La depressione nelle malattie neurologiche

Roberto Ceravolo

Department of Clinical and Experimental MedicineUniversity of Pisa

Depressione

e

Malattie neurologiche

MALATTIA DI

ALZHEIMERDEMENZA FRONTO

TEMPORALE

MALATTIA DI

PARKINSON

Epilessia

Neuro-

miopatie

Cefalea

SM

Stroke

Sclerosi laterale

amiotrofica

Irritabilitagrave 46

Apatia 48

Ansia68

Depressione69

hanno almeno 1 sintomoneuropsichiatrico in unapopolazione con etagrave media di70 aa e una durata media dimalattia di 5 aa

87Kulisevsky et al 2008

Disinibizione 11

Comport Motori

aberranti 13

Allucinazioni16

Agitazione

22Euforia

12Deliri14

Depression in PD Unmet needs

Depression is the factor most significantly associated with QoL and isan important contributor to caregiver distress (Hobson et al 1999Schrag et al 2000)

In general practice registries 64 of PD patients reported clinicallysignificant depression on GDS scale but only 7 were treated withADs (Meara et al Age Ageing 19992838)

In a movement disorder clinic 34 of patients met diagnostic criteriafor depressive disorder but 65 were not treated with ADs(Weintraub J Geriatr Psych Neurol 200316178-83)

Over 1000 PD patients in 6 countries 50 had significant depressionas measured by BDI however only 1 of patients had revealeddepressive symptoms to the clinicians (GPDS Mov Disord 20021760-67)

Inclusion criteria Antidepressanttreatment in PD reporting outcomemeasure

27 studies from 1965 to 2003 total patient population=772 subjects

1627 were specifically designed fordepression in PD

Only 1127 studies suitable formeta-analysis

Only 2 studies with Double Blindversus placebo design

Depression in PD

Under recognized

Misdiagnosed

Under treated

Depression NICE criteria

Depressive syndrome

AFFECTIVEdomain

COGNITIVE domain

PHYSICAL

domainBEHAVIORAL

domain

Low mood

Pessimism

Desperation

Guilty feeling

Suicide ideation

Weight change

Insomnia

Loss of libido

Somatic symptoms

Aches and pain

Anhedonia

Slowness

Hypomimia

Irritability

Anxiety

Modified from NICE National Institute of Clinical Excellence

Slowness of thinking

Attention memoryreduction

Guilty ideas

Self reproching

Guilt thoughts Depression

Sleepchanges

Anxiety

Anorexiabulimia

Fatigue

Tiredness

Reduced energy

Anhedonia

DEPRESSION GALAXY

Aches and Pains

Suicidal ideation

Brooding

Loss of libido

Weight

change

Phobic

features

Hypochondria

Motor

slowness

Guilty thoughts Depression

Sleep changes

Anxiety

Anorexiabulimia

Fatigue

Tiredness

Reduced energy

Anhedonia

Aches and Pains

Suicidal ideation

Brooding

Loss of libido

Weight

change

Phobic

features

Hypochondria

Motor

slowness

PD DEPRESSION GALAXY

Cheng-Che Shen Neurology 2013

Ris

chio

di M

P

Periodo di follow-up

4636 p con depressione

18544 controlli

Malattia di Pakinson 142 (plt 0001)

Rischio di MP aumenta quando crsquoegrave una

diagnosi di depressione HR=324

letagrave egrave piugrave alta nei pazienti con depressione e

PD rispetto ai pazienti depressi non PD

Depressione difficile da trattare egrave un fattore di

rischio per MP indipendente

8166 PD patients

46755 individualswithout PD

NON MOTOR SYMPTOMS were assessed by a custom-made questionnaire in 109 newly diagnosed untreated PD patients and 107 controls

bull Anhedonia apathy memory complaints and inattentionoccurred more frequently during the 2-year premotor period

bull Smell loss mood disturbances taste loss excessive sweatingfatigue and pain were more frequently reported in the 2- to10-year premotor period

bull Constipation dream-enacting behavior excessive daytimesleepiness and postprandial fullness were frequentlyperceived more than 10 years before motor symptoms

Mov Dis 2014

Alexander StorchNeurology 2013

Nonmotor fluctuations in Parkinson

diseaseSeverity and correlation with motor complications

Fluttuazioni non motorie (NMS) presenti nel 100 dei pz con fluttuazioni motorie tutti i SNM sono peggiori nelle fasi OFF

La gravitagrave dei NMS non correla con lrsquoentitagrave delle variazioni motorie

in circa 23 dei pzlrsquoansia e la depressione erano presenti solo in fase off

Barone et al2009

bull La diagnosi dovrebbe essere fatta seguendo i criteri DSM-V

bull La depressione sub-sindromica dovrebbe essere inclusa come

categoria diagnostica negli studi

bull Il momento della valutazione dovrebbe essere (on o off)

bull Per i paziente con demenza dovrebbero essere interrogati i caregivers

bull Lrsquoanedonia dovrebbe essere considerata solo sulla base della perdita di

piacere

DepressioneMP

Mov Disord 2006

[

DepressioneMP

I sintomi di depressione in MP sono diversi

rispetto a quelli solitamente presenti nella

depressione primaria i pazienti con MP

hanno meno senso di colpa meno biasimo

ma maggiore irritabilitagrave tristezza che

correlano con lo stato di salute raro il

suicidioDepression in Parkinsons diseaseMust be properly diagnosed and treated to avoid serious morbidityBMJ VOLUME 320 13 MAY 2000

Associata con aumento della disabilitagrave

Peggiora la qualitagrave della vita

Tende ad essere sottodiagnosticatasottotrattata

Solo 20-26 dei p con MP e depressione ricevono un trattamento

(Richard IH Neurology 1997 Oct)(Weintraub D J Geriatr Psyc Neurol 2003)

DepressioneMP

Depressione

e

Malattie neurologiche

MALATTIA DI

ALZHEIMERDEMENZA FRONTO

TEMPORALE

MALATTIA DI

PARKINSON

Epilessia

Neuro-

miopatie

Cefalea

SM

Stroke

Sclerosi laterale

amiotrofica

Irritabilitagrave 46

Apatia 48

Ansia68

Depressione69

hanno almeno 1 sintomoneuropsichiatrico in unapopolazione con etagrave media di70 aa e una durata media dimalattia di 5 aa

87Kulisevsky et al 2008

Disinibizione 11

Comport Motori

aberranti 13

Allucinazioni16

Agitazione

22Euforia

12Deliri14

Depression in PD Unmet needs

Depression is the factor most significantly associated with QoL and isan important contributor to caregiver distress (Hobson et al 1999Schrag et al 2000)

In general practice registries 64 of PD patients reported clinicallysignificant depression on GDS scale but only 7 were treated withADs (Meara et al Age Ageing 19992838)

In a movement disorder clinic 34 of patients met diagnostic criteriafor depressive disorder but 65 were not treated with ADs(Weintraub J Geriatr Psych Neurol 200316178-83)

Over 1000 PD patients in 6 countries 50 had significant depressionas measured by BDI however only 1 of patients had revealeddepressive symptoms to the clinicians (GPDS Mov Disord 20021760-67)

Inclusion criteria Antidepressanttreatment in PD reporting outcomemeasure

27 studies from 1965 to 2003 total patient population=772 subjects

1627 were specifically designed fordepression in PD

Only 1127 studies suitable formeta-analysis

Only 2 studies with Double Blindversus placebo design

Depression in PD

Under recognized

Misdiagnosed

Under treated

Depression NICE criteria

Depressive syndrome

AFFECTIVEdomain

COGNITIVE domain

PHYSICAL

domainBEHAVIORAL

domain

Low mood

Pessimism

Desperation

Guilty feeling

Suicide ideation

Weight change

Insomnia

Loss of libido

Somatic symptoms

Aches and pain

Anhedonia

Slowness

Hypomimia

Irritability

Anxiety

Modified from NICE National Institute of Clinical Excellence

Slowness of thinking

Attention memoryreduction

Guilty ideas

Self reproching

Guilt thoughts Depression

Sleepchanges

Anxiety

Anorexiabulimia

Fatigue

Tiredness

Reduced energy

Anhedonia

DEPRESSION GALAXY

Aches and Pains

Suicidal ideation

Brooding

Loss of libido

Weight

change

Phobic

features

Hypochondria

Motor

slowness

Guilty thoughts Depression

Sleep changes

Anxiety

Anorexiabulimia

Fatigue

Tiredness

Reduced energy

Anhedonia

Aches and Pains

Suicidal ideation

Brooding

Loss of libido

Weight

change

Phobic

features

Hypochondria

Motor

slowness

PD DEPRESSION GALAXY

Cheng-Che Shen Neurology 2013

Ris

chio

di M

P

Periodo di follow-up

4636 p con depressione

18544 controlli

Malattia di Pakinson 142 (plt 0001)

Rischio di MP aumenta quando crsquoegrave una

diagnosi di depressione HR=324

letagrave egrave piugrave alta nei pazienti con depressione e

PD rispetto ai pazienti depressi non PD

Depressione difficile da trattare egrave un fattore di

rischio per MP indipendente

8166 PD patients

46755 individualswithout PD

NON MOTOR SYMPTOMS were assessed by a custom-made questionnaire in 109 newly diagnosed untreated PD patients and 107 controls

bull Anhedonia apathy memory complaints and inattentionoccurred more frequently during the 2-year premotor period

bull Smell loss mood disturbances taste loss excessive sweatingfatigue and pain were more frequently reported in the 2- to10-year premotor period

bull Constipation dream-enacting behavior excessive daytimesleepiness and postprandial fullness were frequentlyperceived more than 10 years before motor symptoms

Mov Dis 2014

Alexander StorchNeurology 2013

Nonmotor fluctuations in Parkinson

diseaseSeverity and correlation with motor complications

Fluttuazioni non motorie (NMS) presenti nel 100 dei pz con fluttuazioni motorie tutti i SNM sono peggiori nelle fasi OFF

La gravitagrave dei NMS non correla con lrsquoentitagrave delle variazioni motorie

in circa 23 dei pzlrsquoansia e la depressione erano presenti solo in fase off

Barone et al2009

bull La diagnosi dovrebbe essere fatta seguendo i criteri DSM-V

bull La depressione sub-sindromica dovrebbe essere inclusa come

categoria diagnostica negli studi

bull Il momento della valutazione dovrebbe essere (on o off)

bull Per i paziente con demenza dovrebbero essere interrogati i caregivers

bull Lrsquoanedonia dovrebbe essere considerata solo sulla base della perdita di

piacere

DepressioneMP

Mov Disord 2006

[

DepressioneMP

I sintomi di depressione in MP sono diversi

rispetto a quelli solitamente presenti nella

depressione primaria i pazienti con MP

hanno meno senso di colpa meno biasimo

ma maggiore irritabilitagrave tristezza che

correlano con lo stato di salute raro il

suicidioDepression in Parkinsons diseaseMust be properly diagnosed and treated to avoid serious morbidityBMJ VOLUME 320 13 MAY 2000

Associata con aumento della disabilitagrave

Peggiora la qualitagrave della vita

Tende ad essere sottodiagnosticatasottotrattata

Solo 20-26 dei p con MP e depressione ricevono un trattamento

(Richard IH Neurology 1997 Oct)(Weintraub D J Geriatr Psyc Neurol 2003)

DepressioneMP

Irritabilitagrave 46

Apatia 48

Ansia68

Depressione69

hanno almeno 1 sintomoneuropsichiatrico in unapopolazione con etagrave media di70 aa e una durata media dimalattia di 5 aa

87Kulisevsky et al 2008

Disinibizione 11

Comport Motori

aberranti 13

Allucinazioni16

Agitazione

22Euforia

12Deliri14

Depression in PD Unmet needs

Depression is the factor most significantly associated with QoL and isan important contributor to caregiver distress (Hobson et al 1999Schrag et al 2000)

In general practice registries 64 of PD patients reported clinicallysignificant depression on GDS scale but only 7 were treated withADs (Meara et al Age Ageing 19992838)

In a movement disorder clinic 34 of patients met diagnostic criteriafor depressive disorder but 65 were not treated with ADs(Weintraub J Geriatr Psych Neurol 200316178-83)

Over 1000 PD patients in 6 countries 50 had significant depressionas measured by BDI however only 1 of patients had revealeddepressive symptoms to the clinicians (GPDS Mov Disord 20021760-67)

Inclusion criteria Antidepressanttreatment in PD reporting outcomemeasure

27 studies from 1965 to 2003 total patient population=772 subjects

1627 were specifically designed fordepression in PD

Only 1127 studies suitable formeta-analysis

Only 2 studies with Double Blindversus placebo design

Depression in PD

Under recognized

Misdiagnosed

Under treated

Depression NICE criteria

Depressive syndrome

AFFECTIVEdomain

COGNITIVE domain

PHYSICAL

domainBEHAVIORAL

domain

Low mood

Pessimism

Desperation

Guilty feeling

Suicide ideation

Weight change

Insomnia

Loss of libido

Somatic symptoms

Aches and pain

Anhedonia

Slowness

Hypomimia

Irritability

Anxiety

Modified from NICE National Institute of Clinical Excellence

Slowness of thinking

Attention memoryreduction

Guilty ideas

Self reproching

Guilt thoughts Depression

Sleepchanges

Anxiety

Anorexiabulimia

Fatigue

Tiredness

Reduced energy

Anhedonia

DEPRESSION GALAXY

Aches and Pains

Suicidal ideation

Brooding

Loss of libido

Weight

change

Phobic

features

Hypochondria

Motor

slowness

Guilty thoughts Depression

Sleep changes

Anxiety

Anorexiabulimia

Fatigue

Tiredness

Reduced energy

Anhedonia

Aches and Pains

Suicidal ideation

Brooding

Loss of libido

Weight

change

Phobic

features

Hypochondria

Motor

slowness

PD DEPRESSION GALAXY

Cheng-Che Shen Neurology 2013

Ris

chio

di M

P

Periodo di follow-up

4636 p con depressione

18544 controlli

Malattia di Pakinson 142 (plt 0001)

Rischio di MP aumenta quando crsquoegrave una

diagnosi di depressione HR=324

letagrave egrave piugrave alta nei pazienti con depressione e

PD rispetto ai pazienti depressi non PD

Depressione difficile da trattare egrave un fattore di

rischio per MP indipendente

8166 PD patients

46755 individualswithout PD

NON MOTOR SYMPTOMS were assessed by a custom-made questionnaire in 109 newly diagnosed untreated PD patients and 107 controls

bull Anhedonia apathy memory complaints and inattentionoccurred more frequently during the 2-year premotor period

bull Smell loss mood disturbances taste loss excessive sweatingfatigue and pain were more frequently reported in the 2- to10-year premotor period

bull Constipation dream-enacting behavior excessive daytimesleepiness and postprandial fullness were frequentlyperceived more than 10 years before motor symptoms

Mov Dis 2014

Alexander StorchNeurology 2013

Nonmotor fluctuations in Parkinson

diseaseSeverity and correlation with motor complications

Fluttuazioni non motorie (NMS) presenti nel 100 dei pz con fluttuazioni motorie tutti i SNM sono peggiori nelle fasi OFF

La gravitagrave dei NMS non correla con lrsquoentitagrave delle variazioni motorie

in circa 23 dei pzlrsquoansia e la depressione erano presenti solo in fase off

Barone et al2009

bull La diagnosi dovrebbe essere fatta seguendo i criteri DSM-V

bull La depressione sub-sindromica dovrebbe essere inclusa come

categoria diagnostica negli studi

bull Il momento della valutazione dovrebbe essere (on o off)

bull Per i paziente con demenza dovrebbero essere interrogati i caregivers

bull Lrsquoanedonia dovrebbe essere considerata solo sulla base della perdita di

piacere

DepressioneMP

Mov Disord 2006

[

DepressioneMP

I sintomi di depressione in MP sono diversi

rispetto a quelli solitamente presenti nella

depressione primaria i pazienti con MP

hanno meno senso di colpa meno biasimo

ma maggiore irritabilitagrave tristezza che

correlano con lo stato di salute raro il

suicidioDepression in Parkinsons diseaseMust be properly diagnosed and treated to avoid serious morbidityBMJ VOLUME 320 13 MAY 2000

Associata con aumento della disabilitagrave

Peggiora la qualitagrave della vita

Tende ad essere sottodiagnosticatasottotrattata

Solo 20-26 dei p con MP e depressione ricevono un trattamento

(Richard IH Neurology 1997 Oct)(Weintraub D J Geriatr Psyc Neurol 2003)

DepressioneMP

Depression in PD Unmet needs

Depression is the factor most significantly associated with QoL and isan important contributor to caregiver distress (Hobson et al 1999Schrag et al 2000)

In general practice registries 64 of PD patients reported clinicallysignificant depression on GDS scale but only 7 were treated withADs (Meara et al Age Ageing 19992838)

In a movement disorder clinic 34 of patients met diagnostic criteriafor depressive disorder but 65 were not treated with ADs(Weintraub J Geriatr Psych Neurol 200316178-83)

Over 1000 PD patients in 6 countries 50 had significant depressionas measured by BDI however only 1 of patients had revealeddepressive symptoms to the clinicians (GPDS Mov Disord 20021760-67)

Inclusion criteria Antidepressanttreatment in PD reporting outcomemeasure

27 studies from 1965 to 2003 total patient population=772 subjects

1627 were specifically designed fordepression in PD

Only 1127 studies suitable formeta-analysis

Only 2 studies with Double Blindversus placebo design

Depression in PD

Under recognized

Misdiagnosed

Under treated

Depression NICE criteria

Depressive syndrome

AFFECTIVEdomain

COGNITIVE domain

PHYSICAL

domainBEHAVIORAL

domain

Low mood

Pessimism

Desperation

Guilty feeling

Suicide ideation

Weight change

Insomnia

Loss of libido

Somatic symptoms

Aches and pain

Anhedonia

Slowness

Hypomimia

Irritability

Anxiety

Modified from NICE National Institute of Clinical Excellence

Slowness of thinking

Attention memoryreduction

Guilty ideas

Self reproching

Guilt thoughts Depression

Sleepchanges

Anxiety

Anorexiabulimia

Fatigue

Tiredness

Reduced energy

Anhedonia

DEPRESSION GALAXY

Aches and Pains

Suicidal ideation

Brooding

Loss of libido

Weight

change

Phobic

features

Hypochondria

Motor

slowness

Guilty thoughts Depression

Sleep changes

Anxiety

Anorexiabulimia

Fatigue

Tiredness

Reduced energy

Anhedonia

Aches and Pains

Suicidal ideation

Brooding

Loss of libido

Weight

change

Phobic

features

Hypochondria

Motor

slowness

PD DEPRESSION GALAXY

Cheng-Che Shen Neurology 2013

Ris

chio

di M

P

Periodo di follow-up

4636 p con depressione

18544 controlli

Malattia di Pakinson 142 (plt 0001)

Rischio di MP aumenta quando crsquoegrave una

diagnosi di depressione HR=324

letagrave egrave piugrave alta nei pazienti con depressione e

PD rispetto ai pazienti depressi non PD

Depressione difficile da trattare egrave un fattore di

rischio per MP indipendente

8166 PD patients

46755 individualswithout PD

NON MOTOR SYMPTOMS were assessed by a custom-made questionnaire in 109 newly diagnosed untreated PD patients and 107 controls

bull Anhedonia apathy memory complaints and inattentionoccurred more frequently during the 2-year premotor period

bull Smell loss mood disturbances taste loss excessive sweatingfatigue and pain were more frequently reported in the 2- to10-year premotor period

bull Constipation dream-enacting behavior excessive daytimesleepiness and postprandial fullness were frequentlyperceived more than 10 years before motor symptoms

Mov Dis 2014

Alexander StorchNeurology 2013

Nonmotor fluctuations in Parkinson

diseaseSeverity and correlation with motor complications

Fluttuazioni non motorie (NMS) presenti nel 100 dei pz con fluttuazioni motorie tutti i SNM sono peggiori nelle fasi OFF

La gravitagrave dei NMS non correla con lrsquoentitagrave delle variazioni motorie

in circa 23 dei pzlrsquoansia e la depressione erano presenti solo in fase off

Barone et al2009

bull La diagnosi dovrebbe essere fatta seguendo i criteri DSM-V

bull La depressione sub-sindromica dovrebbe essere inclusa come

categoria diagnostica negli studi

bull Il momento della valutazione dovrebbe essere (on o off)

bull Per i paziente con demenza dovrebbero essere interrogati i caregivers

bull Lrsquoanedonia dovrebbe essere considerata solo sulla base della perdita di

piacere

DepressioneMP

Mov Disord 2006

[

DepressioneMP

I sintomi di depressione in MP sono diversi

rispetto a quelli solitamente presenti nella

depressione primaria i pazienti con MP

hanno meno senso di colpa meno biasimo

ma maggiore irritabilitagrave tristezza che

correlano con lo stato di salute raro il

suicidioDepression in Parkinsons diseaseMust be properly diagnosed and treated to avoid serious morbidityBMJ VOLUME 320 13 MAY 2000

Associata con aumento della disabilitagrave

Peggiora la qualitagrave della vita

Tende ad essere sottodiagnosticatasottotrattata

Solo 20-26 dei p con MP e depressione ricevono un trattamento

(Richard IH Neurology 1997 Oct)(Weintraub D J Geriatr Psyc Neurol 2003)

DepressioneMP

Inclusion criteria Antidepressanttreatment in PD reporting outcomemeasure

27 studies from 1965 to 2003 total patient population=772 subjects

1627 were specifically designed fordepression in PD

Only 1127 studies suitable formeta-analysis

Only 2 studies with Double Blindversus placebo design

Depression in PD

Under recognized

Misdiagnosed

Under treated

Depression NICE criteria

Depressive syndrome

AFFECTIVEdomain

COGNITIVE domain

PHYSICAL

domainBEHAVIORAL

domain

Low mood

Pessimism

Desperation

Guilty feeling

Suicide ideation

Weight change

Insomnia

Loss of libido

Somatic symptoms

Aches and pain

Anhedonia

Slowness

Hypomimia

Irritability

Anxiety

Modified from NICE National Institute of Clinical Excellence

Slowness of thinking

Attention memoryreduction

Guilty ideas

Self reproching

Guilt thoughts Depression

Sleepchanges

Anxiety

Anorexiabulimia

Fatigue

Tiredness

Reduced energy

Anhedonia

DEPRESSION GALAXY

Aches and Pains

Suicidal ideation

Brooding

Loss of libido

Weight

change

Phobic

features

Hypochondria

Motor

slowness

Guilty thoughts Depression

Sleep changes

Anxiety

Anorexiabulimia

Fatigue

Tiredness

Reduced energy

Anhedonia

Aches and Pains

Suicidal ideation

Brooding

Loss of libido

Weight

change

Phobic

features

Hypochondria

Motor

slowness

PD DEPRESSION GALAXY

Cheng-Che Shen Neurology 2013

Ris

chio

di M

P

Periodo di follow-up

4636 p con depressione

18544 controlli

Malattia di Pakinson 142 (plt 0001)

Rischio di MP aumenta quando crsquoegrave una

diagnosi di depressione HR=324

letagrave egrave piugrave alta nei pazienti con depressione e

PD rispetto ai pazienti depressi non PD

Depressione difficile da trattare egrave un fattore di

rischio per MP indipendente

8166 PD patients

46755 individualswithout PD

NON MOTOR SYMPTOMS were assessed by a custom-made questionnaire in 109 newly diagnosed untreated PD patients and 107 controls

bull Anhedonia apathy memory complaints and inattentionoccurred more frequently during the 2-year premotor period

bull Smell loss mood disturbances taste loss excessive sweatingfatigue and pain were more frequently reported in the 2- to10-year premotor period

bull Constipation dream-enacting behavior excessive daytimesleepiness and postprandial fullness were frequentlyperceived more than 10 years before motor symptoms

Mov Dis 2014

Alexander StorchNeurology 2013

Nonmotor fluctuations in Parkinson

diseaseSeverity and correlation with motor complications

Fluttuazioni non motorie (NMS) presenti nel 100 dei pz con fluttuazioni motorie tutti i SNM sono peggiori nelle fasi OFF

La gravitagrave dei NMS non correla con lrsquoentitagrave delle variazioni motorie

in circa 23 dei pzlrsquoansia e la depressione erano presenti solo in fase off

Barone et al2009

bull La diagnosi dovrebbe essere fatta seguendo i criteri DSM-V

bull La depressione sub-sindromica dovrebbe essere inclusa come

categoria diagnostica negli studi

bull Il momento della valutazione dovrebbe essere (on o off)

bull Per i paziente con demenza dovrebbero essere interrogati i caregivers

bull Lrsquoanedonia dovrebbe essere considerata solo sulla base della perdita di

piacere

DepressioneMP

Mov Disord 2006

[

DepressioneMP

I sintomi di depressione in MP sono diversi

rispetto a quelli solitamente presenti nella

depressione primaria i pazienti con MP

hanno meno senso di colpa meno biasimo

ma maggiore irritabilitagrave tristezza che

correlano con lo stato di salute raro il

suicidioDepression in Parkinsons diseaseMust be properly diagnosed and treated to avoid serious morbidityBMJ VOLUME 320 13 MAY 2000

Associata con aumento della disabilitagrave

Peggiora la qualitagrave della vita

Tende ad essere sottodiagnosticatasottotrattata

Solo 20-26 dei p con MP e depressione ricevono un trattamento

(Richard IH Neurology 1997 Oct)(Weintraub D J Geriatr Psyc Neurol 2003)

DepressioneMP

Depression in PD

Under recognized

Misdiagnosed

Under treated

Depression NICE criteria

Depressive syndrome

AFFECTIVEdomain

COGNITIVE domain

PHYSICAL

domainBEHAVIORAL

domain

Low mood

Pessimism

Desperation

Guilty feeling

Suicide ideation

Weight change

Insomnia

Loss of libido

Somatic symptoms

Aches and pain

Anhedonia

Slowness

Hypomimia

Irritability

Anxiety

Modified from NICE National Institute of Clinical Excellence

Slowness of thinking

Attention memoryreduction

Guilty ideas

Self reproching

Guilt thoughts Depression

Sleepchanges

Anxiety

Anorexiabulimia

Fatigue

Tiredness

Reduced energy

Anhedonia

DEPRESSION GALAXY

Aches and Pains

Suicidal ideation

Brooding

Loss of libido

Weight

change

Phobic

features

Hypochondria

Motor

slowness

Guilty thoughts Depression

Sleep changes

Anxiety

Anorexiabulimia

Fatigue

Tiredness

Reduced energy

Anhedonia

Aches and Pains

Suicidal ideation

Brooding

Loss of libido

Weight

change

Phobic

features

Hypochondria

Motor

slowness

PD DEPRESSION GALAXY

Cheng-Che Shen Neurology 2013

Ris

chio

di M

P

Periodo di follow-up

4636 p con depressione

18544 controlli

Malattia di Pakinson 142 (plt 0001)

Rischio di MP aumenta quando crsquoegrave una

diagnosi di depressione HR=324

letagrave egrave piugrave alta nei pazienti con depressione e

PD rispetto ai pazienti depressi non PD

Depressione difficile da trattare egrave un fattore di

rischio per MP indipendente

8166 PD patients

46755 individualswithout PD

NON MOTOR SYMPTOMS were assessed by a custom-made questionnaire in 109 newly diagnosed untreated PD patients and 107 controls

bull Anhedonia apathy memory complaints and inattentionoccurred more frequently during the 2-year premotor period

bull Smell loss mood disturbances taste loss excessive sweatingfatigue and pain were more frequently reported in the 2- to10-year premotor period

bull Constipation dream-enacting behavior excessive daytimesleepiness and postprandial fullness were frequentlyperceived more than 10 years before motor symptoms

Mov Dis 2014

Alexander StorchNeurology 2013

Nonmotor fluctuations in Parkinson

diseaseSeverity and correlation with motor complications

Fluttuazioni non motorie (NMS) presenti nel 100 dei pz con fluttuazioni motorie tutti i SNM sono peggiori nelle fasi OFF

La gravitagrave dei NMS non correla con lrsquoentitagrave delle variazioni motorie

in circa 23 dei pzlrsquoansia e la depressione erano presenti solo in fase off

Barone et al2009

bull La diagnosi dovrebbe essere fatta seguendo i criteri DSM-V

bull La depressione sub-sindromica dovrebbe essere inclusa come

categoria diagnostica negli studi

bull Il momento della valutazione dovrebbe essere (on o off)

bull Per i paziente con demenza dovrebbero essere interrogati i caregivers

bull Lrsquoanedonia dovrebbe essere considerata solo sulla base della perdita di

piacere

DepressioneMP

Mov Disord 2006

[

DepressioneMP

I sintomi di depressione in MP sono diversi

rispetto a quelli solitamente presenti nella

depressione primaria i pazienti con MP

hanno meno senso di colpa meno biasimo

ma maggiore irritabilitagrave tristezza che

correlano con lo stato di salute raro il

suicidioDepression in Parkinsons diseaseMust be properly diagnosed and treated to avoid serious morbidityBMJ VOLUME 320 13 MAY 2000

Associata con aumento della disabilitagrave

Peggiora la qualitagrave della vita

Tende ad essere sottodiagnosticatasottotrattata

Solo 20-26 dei p con MP e depressione ricevono un trattamento

(Richard IH Neurology 1997 Oct)(Weintraub D J Geriatr Psyc Neurol 2003)

DepressioneMP

Depression NICE criteria

Depressive syndrome

AFFECTIVEdomain

COGNITIVE domain

PHYSICAL

domainBEHAVIORAL

domain

Low mood

Pessimism

Desperation

Guilty feeling

Suicide ideation

Weight change

Insomnia

Loss of libido

Somatic symptoms

Aches and pain

Anhedonia

Slowness

Hypomimia

Irritability

Anxiety

Modified from NICE National Institute of Clinical Excellence

Slowness of thinking

Attention memoryreduction

Guilty ideas

Self reproching

Guilt thoughts Depression

Sleepchanges

Anxiety

Anorexiabulimia

Fatigue

Tiredness

Reduced energy

Anhedonia

DEPRESSION GALAXY

Aches and Pains

Suicidal ideation

Brooding

Loss of libido

Weight

change

Phobic

features

Hypochondria

Motor

slowness

Guilty thoughts Depression

Sleep changes

Anxiety

Anorexiabulimia

Fatigue

Tiredness

Reduced energy

Anhedonia

Aches and Pains

Suicidal ideation

Brooding

Loss of libido

Weight

change

Phobic

features

Hypochondria

Motor

slowness

PD DEPRESSION GALAXY

Cheng-Che Shen Neurology 2013

Ris

chio

di M

P

Periodo di follow-up

4636 p con depressione

18544 controlli

Malattia di Pakinson 142 (plt 0001)

Rischio di MP aumenta quando crsquoegrave una

diagnosi di depressione HR=324

letagrave egrave piugrave alta nei pazienti con depressione e

PD rispetto ai pazienti depressi non PD

Depressione difficile da trattare egrave un fattore di

rischio per MP indipendente

8166 PD patients

46755 individualswithout PD

NON MOTOR SYMPTOMS were assessed by a custom-made questionnaire in 109 newly diagnosed untreated PD patients and 107 controls

bull Anhedonia apathy memory complaints and inattentionoccurred more frequently during the 2-year premotor period

bull Smell loss mood disturbances taste loss excessive sweatingfatigue and pain were more frequently reported in the 2- to10-year premotor period

bull Constipation dream-enacting behavior excessive daytimesleepiness and postprandial fullness were frequentlyperceived more than 10 years before motor symptoms

Mov Dis 2014

Alexander StorchNeurology 2013

Nonmotor fluctuations in Parkinson

diseaseSeverity and correlation with motor complications

Fluttuazioni non motorie (NMS) presenti nel 100 dei pz con fluttuazioni motorie tutti i SNM sono peggiori nelle fasi OFF

La gravitagrave dei NMS non correla con lrsquoentitagrave delle variazioni motorie

in circa 23 dei pzlrsquoansia e la depressione erano presenti solo in fase off

Barone et al2009

bull La diagnosi dovrebbe essere fatta seguendo i criteri DSM-V

bull La depressione sub-sindromica dovrebbe essere inclusa come

categoria diagnostica negli studi

bull Il momento della valutazione dovrebbe essere (on o off)

bull Per i paziente con demenza dovrebbero essere interrogati i caregivers

bull Lrsquoanedonia dovrebbe essere considerata solo sulla base della perdita di

piacere

DepressioneMP

Mov Disord 2006

[

DepressioneMP

I sintomi di depressione in MP sono diversi

rispetto a quelli solitamente presenti nella

depressione primaria i pazienti con MP

hanno meno senso di colpa meno biasimo

ma maggiore irritabilitagrave tristezza che

correlano con lo stato di salute raro il

suicidioDepression in Parkinsons diseaseMust be properly diagnosed and treated to avoid serious morbidityBMJ VOLUME 320 13 MAY 2000

Associata con aumento della disabilitagrave

Peggiora la qualitagrave della vita

Tende ad essere sottodiagnosticatasottotrattata

Solo 20-26 dei p con MP e depressione ricevono un trattamento

(Richard IH Neurology 1997 Oct)(Weintraub D J Geriatr Psyc Neurol 2003)

DepressioneMP

Guilt thoughts Depression

Sleepchanges

Anxiety

Anorexiabulimia

Fatigue

Tiredness

Reduced energy

Anhedonia

DEPRESSION GALAXY

Aches and Pains

Suicidal ideation

Brooding

Loss of libido

Weight

change

Phobic

features

Hypochondria

Motor

slowness

Guilty thoughts Depression

Sleep changes

Anxiety

Anorexiabulimia

Fatigue

Tiredness

Reduced energy

Anhedonia

Aches and Pains

Suicidal ideation

Brooding

Loss of libido

Weight

change

Phobic

features

Hypochondria

Motor

slowness

PD DEPRESSION GALAXY

Cheng-Che Shen Neurology 2013

Ris

chio

di M

P

Periodo di follow-up

4636 p con depressione

18544 controlli

Malattia di Pakinson 142 (plt 0001)

Rischio di MP aumenta quando crsquoegrave una

diagnosi di depressione HR=324

letagrave egrave piugrave alta nei pazienti con depressione e

PD rispetto ai pazienti depressi non PD

Depressione difficile da trattare egrave un fattore di

rischio per MP indipendente

8166 PD patients

46755 individualswithout PD

NON MOTOR SYMPTOMS were assessed by a custom-made questionnaire in 109 newly diagnosed untreated PD patients and 107 controls

bull Anhedonia apathy memory complaints and inattentionoccurred more frequently during the 2-year premotor period

bull Smell loss mood disturbances taste loss excessive sweatingfatigue and pain were more frequently reported in the 2- to10-year premotor period

bull Constipation dream-enacting behavior excessive daytimesleepiness and postprandial fullness were frequentlyperceived more than 10 years before motor symptoms

Mov Dis 2014

Alexander StorchNeurology 2013

Nonmotor fluctuations in Parkinson

diseaseSeverity and correlation with motor complications

Fluttuazioni non motorie (NMS) presenti nel 100 dei pz con fluttuazioni motorie tutti i SNM sono peggiori nelle fasi OFF

La gravitagrave dei NMS non correla con lrsquoentitagrave delle variazioni motorie

in circa 23 dei pzlrsquoansia e la depressione erano presenti solo in fase off

Barone et al2009

bull La diagnosi dovrebbe essere fatta seguendo i criteri DSM-V

bull La depressione sub-sindromica dovrebbe essere inclusa come

categoria diagnostica negli studi

bull Il momento della valutazione dovrebbe essere (on o off)

bull Per i paziente con demenza dovrebbero essere interrogati i caregivers

bull Lrsquoanedonia dovrebbe essere considerata solo sulla base della perdita di

piacere

DepressioneMP

Mov Disord 2006

[

DepressioneMP

I sintomi di depressione in MP sono diversi

rispetto a quelli solitamente presenti nella

depressione primaria i pazienti con MP

hanno meno senso di colpa meno biasimo

ma maggiore irritabilitagrave tristezza che

correlano con lo stato di salute raro il

suicidioDepression in Parkinsons diseaseMust be properly diagnosed and treated to avoid serious morbidityBMJ VOLUME 320 13 MAY 2000

Associata con aumento della disabilitagrave

Peggiora la qualitagrave della vita

Tende ad essere sottodiagnosticatasottotrattata

Solo 20-26 dei p con MP e depressione ricevono un trattamento

(Richard IH Neurology 1997 Oct)(Weintraub D J Geriatr Psyc Neurol 2003)

DepressioneMP

Guilty thoughts Depression

Sleep changes

Anxiety

Anorexiabulimia

Fatigue

Tiredness

Reduced energy

Anhedonia

Aches and Pains

Suicidal ideation

Brooding

Loss of libido

Weight

change

Phobic

features

Hypochondria

Motor

slowness

PD DEPRESSION GALAXY

Cheng-Che Shen Neurology 2013

Ris

chio

di M

P

Periodo di follow-up

4636 p con depressione

18544 controlli

Malattia di Pakinson 142 (plt 0001)

Rischio di MP aumenta quando crsquoegrave una

diagnosi di depressione HR=324

letagrave egrave piugrave alta nei pazienti con depressione e

PD rispetto ai pazienti depressi non PD

Depressione difficile da trattare egrave un fattore di

rischio per MP indipendente

8166 PD patients

46755 individualswithout PD

NON MOTOR SYMPTOMS were assessed by a custom-made questionnaire in 109 newly diagnosed untreated PD patients and 107 controls

bull Anhedonia apathy memory complaints and inattentionoccurred more frequently during the 2-year premotor period

bull Smell loss mood disturbances taste loss excessive sweatingfatigue and pain were more frequently reported in the 2- to10-year premotor period

bull Constipation dream-enacting behavior excessive daytimesleepiness and postprandial fullness were frequentlyperceived more than 10 years before motor symptoms

Mov Dis 2014

Alexander StorchNeurology 2013

Nonmotor fluctuations in Parkinson

diseaseSeverity and correlation with motor complications

Fluttuazioni non motorie (NMS) presenti nel 100 dei pz con fluttuazioni motorie tutti i SNM sono peggiori nelle fasi OFF

La gravitagrave dei NMS non correla con lrsquoentitagrave delle variazioni motorie

in circa 23 dei pzlrsquoansia e la depressione erano presenti solo in fase off

Barone et al2009

bull La diagnosi dovrebbe essere fatta seguendo i criteri DSM-V

bull La depressione sub-sindromica dovrebbe essere inclusa come

categoria diagnostica negli studi

bull Il momento della valutazione dovrebbe essere (on o off)

bull Per i paziente con demenza dovrebbero essere interrogati i caregivers

bull Lrsquoanedonia dovrebbe essere considerata solo sulla base della perdita di

piacere

DepressioneMP

Mov Disord 2006

[

DepressioneMP

I sintomi di depressione in MP sono diversi

rispetto a quelli solitamente presenti nella

depressione primaria i pazienti con MP

hanno meno senso di colpa meno biasimo

ma maggiore irritabilitagrave tristezza che

correlano con lo stato di salute raro il

suicidioDepression in Parkinsons diseaseMust be properly diagnosed and treated to avoid serious morbidityBMJ VOLUME 320 13 MAY 2000

Associata con aumento della disabilitagrave

Peggiora la qualitagrave della vita

Tende ad essere sottodiagnosticatasottotrattata

Solo 20-26 dei p con MP e depressione ricevono un trattamento

(Richard IH Neurology 1997 Oct)(Weintraub D J Geriatr Psyc Neurol 2003)

DepressioneMP

Cheng-Che Shen Neurology 2013

Ris

chio

di M

P

Periodo di follow-up

4636 p con depressione

18544 controlli

Malattia di Pakinson 142 (plt 0001)

Rischio di MP aumenta quando crsquoegrave una

diagnosi di depressione HR=324

letagrave egrave piugrave alta nei pazienti con depressione e

PD rispetto ai pazienti depressi non PD

Depressione difficile da trattare egrave un fattore di

rischio per MP indipendente

8166 PD patients

46755 individualswithout PD

NON MOTOR SYMPTOMS were assessed by a custom-made questionnaire in 109 newly diagnosed untreated PD patients and 107 controls

bull Anhedonia apathy memory complaints and inattentionoccurred more frequently during the 2-year premotor period

bull Smell loss mood disturbances taste loss excessive sweatingfatigue and pain were more frequently reported in the 2- to10-year premotor period

bull Constipation dream-enacting behavior excessive daytimesleepiness and postprandial fullness were frequentlyperceived more than 10 years before motor symptoms

Mov Dis 2014

Alexander StorchNeurology 2013

Nonmotor fluctuations in Parkinson

diseaseSeverity and correlation with motor complications

Fluttuazioni non motorie (NMS) presenti nel 100 dei pz con fluttuazioni motorie tutti i SNM sono peggiori nelle fasi OFF

La gravitagrave dei NMS non correla con lrsquoentitagrave delle variazioni motorie

in circa 23 dei pzlrsquoansia e la depressione erano presenti solo in fase off

Barone et al2009

bull La diagnosi dovrebbe essere fatta seguendo i criteri DSM-V

bull La depressione sub-sindromica dovrebbe essere inclusa come

categoria diagnostica negli studi

bull Il momento della valutazione dovrebbe essere (on o off)

bull Per i paziente con demenza dovrebbero essere interrogati i caregivers

bull Lrsquoanedonia dovrebbe essere considerata solo sulla base della perdita di

piacere

DepressioneMP

Mov Disord 2006

[

DepressioneMP

I sintomi di depressione in MP sono diversi

rispetto a quelli solitamente presenti nella

depressione primaria i pazienti con MP

hanno meno senso di colpa meno biasimo

ma maggiore irritabilitagrave tristezza che

correlano con lo stato di salute raro il

suicidioDepression in Parkinsons diseaseMust be properly diagnosed and treated to avoid serious morbidityBMJ VOLUME 320 13 MAY 2000

Associata con aumento della disabilitagrave

Peggiora la qualitagrave della vita

Tende ad essere sottodiagnosticatasottotrattata

Solo 20-26 dei p con MP e depressione ricevono un trattamento

(Richard IH Neurology 1997 Oct)(Weintraub D J Geriatr Psyc Neurol 2003)

DepressioneMP

8166 PD patients

46755 individualswithout PD

NON MOTOR SYMPTOMS were assessed by a custom-made questionnaire in 109 newly diagnosed untreated PD patients and 107 controls

bull Anhedonia apathy memory complaints and inattentionoccurred more frequently during the 2-year premotor period

bull Smell loss mood disturbances taste loss excessive sweatingfatigue and pain were more frequently reported in the 2- to10-year premotor period

bull Constipation dream-enacting behavior excessive daytimesleepiness and postprandial fullness were frequentlyperceived more than 10 years before motor symptoms

Mov Dis 2014

Alexander StorchNeurology 2013

Nonmotor fluctuations in Parkinson

diseaseSeverity and correlation with motor complications

Fluttuazioni non motorie (NMS) presenti nel 100 dei pz con fluttuazioni motorie tutti i SNM sono peggiori nelle fasi OFF

La gravitagrave dei NMS non correla con lrsquoentitagrave delle variazioni motorie

in circa 23 dei pzlrsquoansia e la depressione erano presenti solo in fase off

Barone et al2009

bull La diagnosi dovrebbe essere fatta seguendo i criteri DSM-V

bull La depressione sub-sindromica dovrebbe essere inclusa come

categoria diagnostica negli studi

bull Il momento della valutazione dovrebbe essere (on o off)

bull Per i paziente con demenza dovrebbero essere interrogati i caregivers

bull Lrsquoanedonia dovrebbe essere considerata solo sulla base della perdita di

piacere

DepressioneMP

Mov Disord 2006

[

DepressioneMP

I sintomi di depressione in MP sono diversi

rispetto a quelli solitamente presenti nella

depressione primaria i pazienti con MP

hanno meno senso di colpa meno biasimo

ma maggiore irritabilitagrave tristezza che

correlano con lo stato di salute raro il

suicidioDepression in Parkinsons diseaseMust be properly diagnosed and treated to avoid serious morbidityBMJ VOLUME 320 13 MAY 2000

Associata con aumento della disabilitagrave

Peggiora la qualitagrave della vita

Tende ad essere sottodiagnosticatasottotrattata

Solo 20-26 dei p con MP e depressione ricevono un trattamento

(Richard IH Neurology 1997 Oct)(Weintraub D J Geriatr Psyc Neurol 2003)

DepressioneMP

NON MOTOR SYMPTOMS were assessed by a custom-made questionnaire in 109 newly diagnosed untreated PD patients and 107 controls

bull Anhedonia apathy memory complaints and inattentionoccurred more frequently during the 2-year premotor period

bull Smell loss mood disturbances taste loss excessive sweatingfatigue and pain were more frequently reported in the 2- to10-year premotor period

bull Constipation dream-enacting behavior excessive daytimesleepiness and postprandial fullness were frequentlyperceived more than 10 years before motor symptoms

Mov Dis 2014

Alexander StorchNeurology 2013

Nonmotor fluctuations in Parkinson

diseaseSeverity and correlation with motor complications

Fluttuazioni non motorie (NMS) presenti nel 100 dei pz con fluttuazioni motorie tutti i SNM sono peggiori nelle fasi OFF

La gravitagrave dei NMS non correla con lrsquoentitagrave delle variazioni motorie

in circa 23 dei pzlrsquoansia e la depressione erano presenti solo in fase off

Barone et al2009

bull La diagnosi dovrebbe essere fatta seguendo i criteri DSM-V

bull La depressione sub-sindromica dovrebbe essere inclusa come

categoria diagnostica negli studi

bull Il momento della valutazione dovrebbe essere (on o off)

bull Per i paziente con demenza dovrebbero essere interrogati i caregivers

bull Lrsquoanedonia dovrebbe essere considerata solo sulla base della perdita di

piacere

DepressioneMP

Mov Disord 2006

[

DepressioneMP

I sintomi di depressione in MP sono diversi

rispetto a quelli solitamente presenti nella

depressione primaria i pazienti con MP

hanno meno senso di colpa meno biasimo

ma maggiore irritabilitagrave tristezza che

correlano con lo stato di salute raro il

suicidioDepression in Parkinsons diseaseMust be properly diagnosed and treated to avoid serious morbidityBMJ VOLUME 320 13 MAY 2000

Associata con aumento della disabilitagrave

Peggiora la qualitagrave della vita

Tende ad essere sottodiagnosticatasottotrattata

Solo 20-26 dei p con MP e depressione ricevono un trattamento

(Richard IH Neurology 1997 Oct)(Weintraub D J Geriatr Psyc Neurol 2003)

DepressioneMP

Alexander StorchNeurology 2013

Nonmotor fluctuations in Parkinson

diseaseSeverity and correlation with motor complications

Fluttuazioni non motorie (NMS) presenti nel 100 dei pz con fluttuazioni motorie tutti i SNM sono peggiori nelle fasi OFF

La gravitagrave dei NMS non correla con lrsquoentitagrave delle variazioni motorie

in circa 23 dei pzlrsquoansia e la depressione erano presenti solo in fase off

Barone et al2009

bull La diagnosi dovrebbe essere fatta seguendo i criteri DSM-V

bull La depressione sub-sindromica dovrebbe essere inclusa come

categoria diagnostica negli studi

bull Il momento della valutazione dovrebbe essere (on o off)

bull Per i paziente con demenza dovrebbero essere interrogati i caregivers

bull Lrsquoanedonia dovrebbe essere considerata solo sulla base della perdita di

piacere

DepressioneMP

Mov Disord 2006

[

DepressioneMP

I sintomi di depressione in MP sono diversi

rispetto a quelli solitamente presenti nella

depressione primaria i pazienti con MP

hanno meno senso di colpa meno biasimo

ma maggiore irritabilitagrave tristezza che

correlano con lo stato di salute raro il

suicidioDepression in Parkinsons diseaseMust be properly diagnosed and treated to avoid serious morbidityBMJ VOLUME 320 13 MAY 2000

Associata con aumento della disabilitagrave

Peggiora la qualitagrave della vita

Tende ad essere sottodiagnosticatasottotrattata

Solo 20-26 dei p con MP e depressione ricevono un trattamento

(Richard IH Neurology 1997 Oct)(Weintraub D J Geriatr Psyc Neurol 2003)

DepressioneMP

Barone et al2009

bull La diagnosi dovrebbe essere fatta seguendo i criteri DSM-V

bull La depressione sub-sindromica dovrebbe essere inclusa come

categoria diagnostica negli studi

bull Il momento della valutazione dovrebbe essere (on o off)

bull Per i paziente con demenza dovrebbero essere interrogati i caregivers

bull Lrsquoanedonia dovrebbe essere considerata solo sulla base della perdita di

piacere

DepressioneMP

Mov Disord 2006

[

DepressioneMP

I sintomi di depressione in MP sono diversi

rispetto a quelli solitamente presenti nella

depressione primaria i pazienti con MP

hanno meno senso di colpa meno biasimo

ma maggiore irritabilitagrave tristezza che

correlano con lo stato di salute raro il

suicidioDepression in Parkinsons diseaseMust be properly diagnosed and treated to avoid serious morbidityBMJ VOLUME 320 13 MAY 2000

Associata con aumento della disabilitagrave

Peggiora la qualitagrave della vita

Tende ad essere sottodiagnosticatasottotrattata

Solo 20-26 dei p con MP e depressione ricevono un trattamento

(Richard IH Neurology 1997 Oct)(Weintraub D J Geriatr Psyc Neurol 2003)

DepressioneMP

bull La diagnosi dovrebbe essere fatta seguendo i criteri DSM-V

bull La depressione sub-sindromica dovrebbe essere inclusa come

categoria diagnostica negli studi

bull Il momento della valutazione dovrebbe essere (on o off)

bull Per i paziente con demenza dovrebbero essere interrogati i caregivers

bull Lrsquoanedonia dovrebbe essere considerata solo sulla base della perdita di

piacere

DepressioneMP

Mov Disord 2006

[

DepressioneMP

I sintomi di depressione in MP sono diversi

rispetto a quelli solitamente presenti nella

depressione primaria i pazienti con MP

hanno meno senso di colpa meno biasimo

ma maggiore irritabilitagrave tristezza che

correlano con lo stato di salute raro il

suicidioDepression in Parkinsons diseaseMust be properly diagnosed and treated to avoid serious morbidityBMJ VOLUME 320 13 MAY 2000

Associata con aumento della disabilitagrave

Peggiora la qualitagrave della vita

Tende ad essere sottodiagnosticatasottotrattata

Solo 20-26 dei p con MP e depressione ricevono un trattamento

(Richard IH Neurology 1997 Oct)(Weintraub D J Geriatr Psyc Neurol 2003)

DepressioneMP

[

DepressioneMP

I sintomi di depressione in MP sono diversi

rispetto a quelli solitamente presenti nella

depressione primaria i pazienti con MP

hanno meno senso di colpa meno biasimo

ma maggiore irritabilitagrave tristezza che

correlano con lo stato di salute raro il

suicidioDepression in Parkinsons diseaseMust be properly diagnosed and treated to avoid serious morbidityBMJ VOLUME 320 13 MAY 2000

Associata con aumento della disabilitagrave

Peggiora la qualitagrave della vita

Tende ad essere sottodiagnosticatasottotrattata

Solo 20-26 dei p con MP e depressione ricevono un trattamento

(Richard IH Neurology 1997 Oct)(Weintraub D J Geriatr Psyc Neurol 2003)

DepressioneMP

Associata con aumento della disabilitagrave

Peggiora la qualitagrave della vita

Tende ad essere sottodiagnosticatasottotrattata

Solo 20-26 dei p con MP e depressione ricevono un trattamento

(Richard IH Neurology 1997 Oct)(Weintraub D J Geriatr Psyc Neurol 2003)

DepressioneMP

Scale cliniche depressione in MP

screening monitoraggio

HAM-D

MADRSUPDRS

BDI I-IIGDS

Scala clinica Cut-off suggerito nella MP

Hamilton Depression (HAM-D) 9-10

Beck Depression Inventory (BDI) 13-14

Geriatric Depression Scale 30 (GDS 30) 9-10

Geriatric Depression Scale 15 (GDS 15) 4-5

Montgomery-Asberg Depression Rating Scale (MADRS) 14-15

+frequentemente utilizzate

breve autosomministrata risposte sino

DepressioneMP

Prevalence of Depressive Disorder and

Depressive symptoms in PD

Major depression 17

Minor depression 22

Dysthymia 13

Reijnders et al Mov Disord 2007

Clinically significant

depressive symptoms 361

DepressionPD

22

ldquoDEPRESSIONrdquo in PDwhat should we treat

Depressive Disorder

(Major Minor Dysthimia)

Depressive Symptoms

DSM-V criteria for

Diagnosis of depression

screening for depressive

symptoms

Low mood AnxietyDepression

Depression in PD not ONE disease

DEPRESSIONE E SEROTONINA

Pazienti con MP

Ridotti trasportatori SERT nella regione orbitofrontale corteccia del cingolo insula amigdala e ippocampo

(Kish S Brain 2008)

(Guttman Eur J Neurol 2007)

(Albin J Cereb Blood Flow Metab 2008)

Riduzione dei livelli di 5-HT e dei trasportatori SERT a livello striatale (soprattutto caudato)

Riduzione dei neuroni serotoninergici nucleo dorsale del rafe

Pazienti con MP e depressione

Ridotta ecogenicitagrave nel rafe mesencefalico alla sonografia transcranica

(Pauls J Neuropathol Exp Neurol 1991)

(Berg J Neurol 1999)

Natural history of degenerative parkinsonism

Department of Clinical and Experimental Medicine University of Pisa

Possible correlation anatomo-clinic

SALAT D et al Lancet Neurology 2016

11C-DASB11C-MADAM

Serotonintransporter

5-HT

Imaging

serotonin terminal function

AADC

TRYP

5-HTP

5-HT

TH

Serotonin

receptors

5-HT1A

1B1C

1E

1D1F5-HT2A

2B2C

5-HT4

67

5-HT5

5-HT1A

5-HT1B

5-HT3

18F-dopa

11C-AMT

123I-beta CIT 123I-FP-CIT

11C-DASB

Serotonin transporter

11C-WAY100635

Serotonin HT1A receptor

123I-FP-CIT

Serotonin and Dopamine

transporter

PETSPECT ligands

11C-AZ10419369

Serotonin HT1B receptor

18F-altanserin

Serotonin HT2A receptor

[11C]DASB binding positively correlated with

depression but not with disease severityduration

wide-spread increase in [11C]DASB in

PDdepression

1 dorsolateral cortices

2 prefrontal cortices

Lower uptake in depressedvs non-depressed PD

bull 8 non depressedPD patients

bull 4 depressed PD patients

Ballanger et al 2011

x= 6 plt0001 y= 8 plt0001

y= -1 plt001z= 43 plt0001

z= 10 plt0001

Lower 11C-DASB uptake

in PD with depression

7 PD depr lt 7 PD without depression

amygdalacingulate

cingulate

thalamus

thalamus

striatum

Courtesy of Nicola Pavese

Autore

annoCampione Disegno Farmaco

Scala

usata

Risultati(decremento punteggio

scala)

Follow up

Leentjens200333

6

6Doppio cieco

Sertralina

PlaceboMADRS

-9

-1110 settimane

Fregni200434

21

21Doppio cieco

Fluoxetina

TMS

HAM D

BDI

-9sect-8sect

-10sect-8sect8 settimane

Serrano Duenas200235

37

40Randomizzato

Fluoxetina

AmitriptilinaHAM D

Inefficace

Efficace 12 mesi

Avila200336

7

9Randomizzato

Fluoxetina

NefazodoneBDI

Ugualmente

efficaci sect12 settimane

Antonini200637

12

11Doppio cieco

Sertralina

AmitriptilinaHAM D

-12sect

-11sect3 mesi

Barone200638

33

34Doppio cieco

Pramipexole

SertralineHAM D

-10sect

-9sect12 settimane

Devos200823

16

15

17

Doppio cieco

Placebo

Citalopram

Desimipramina

MADRS

-9

-14

-20

4 settimane

Menza200921

17

18

17

Doppio cieco

Placebo

Paroxetina

Nortriptilina

HAM D

-4

-6

-11

8 settimane

Richard201224

39

42

34

Doppio cieco

Placebo

Paroxetina

Venlafaxina ER

HAM D

-68

-13

-11

12 settimane

differenza significativa rispetto al placebo

sect differenza significativa rispetto al basale

Studi sullrsquoutilizzo di SSRI nei pazienti con Malattia di Parkinson e depressione (2003-2013)

Efficacy and Acceptability of selective serotoninreuptake inhibitors for the treatment of depression in Parkinsons disease

a systematic review andmeta-analysis of randomized controlled trials

Petros Skapinakis et all

BMC Neurology 2010 1049

bull Il 63 degli antidepressivi prescritti sono SSRI e nel 7 sono TCAbull Crsquoegrave ancora incertezza sullrsquoefficacia degli SSRI nella depressione in MPbull I risultati di questo studio mostrano che la pratica clinica attuale non

egrave supportata da forti evidenze

Trattamento della depressione in MP

DepressioneMP

Depression and PD clinical features

Anhedonia

Low mood and impaired interest or

ability to experience pleasure

Core symptomOther clinical features

1 Altered sleep patterns

2 Change in weight

3 Loss of libido

4 Psychomotor retardation

5 Reduced energy

Starkstein Mov Disord 2008

Imaging del rilascio di dopamina

10 di riduzione

del 11C raclopride

BP riflette un

incremento di 5

volte del rilascio di

Dopamina

Journal of Psychiatric Research 2006

DAergic

PRE -

SYNAPTIC

NEURON

DAT

Tracer

PET SPECTPOST -

SYNAPTIC

NEURON

DAT TRACER BINDING = Density of DAergic terminals

Healthy Control Parkinsonrsquos disease

11C-RTI 3218F-CFT123I-beta CIT 123I-FP-CIT123I-altropane99mTc-TroDAT

Depressive symptoms in Parkinsons disease are related to reduced [123I]FP-CIT binding in the caudate nucleus

Vriend 2014

Frosini D et al 2015

Mesolimbic dopaminergic dysfunction in Parkinsonrsquos disease-depression evidence from a 123I-FP-CIT SPECT investigation

Pd-nd (35) PD-d (15)

MeanplusmnSD MeanplusmnSD

Age at onset (years) 683plusmn71 661plusmn55

Disease duration (years) 12plusmn10 10plusmn05

Age at scan (years) 671plusmn69 668plusmn54

UPDRS II 58plusmn36 70plusmn34

UPDRS III 156plusmn70 157plusmn53

MMSE 279plusmn17 275plusmn13

BDI 25plusmn09 168plusmn38

Left caudate FP-CIT uptake 32 plusmn12 34plusmn 11

Right caudate FP-CIT uptake 33plusmn11 34 plusmn11

Left putamen FP-CIT uptake 17plusmn 10 18 plusmn09

Right putamen FP-CIT uptake 18plusmn 08 12 plusmn08

Pramipexole for the treatment of depressive symptomsin patients with Parkinsonrsquos disease a randomised

double-blind placebo-controlled trialPaolo Barone Werner Poewe Stefan Albrecht Catherine Debieuvre Dan Massey Olivier Rascol Eduardo Tolosa Daniel Weintraub

Lancet Neurol 2010 9 573ndash80

Miglioramento dello scoreBeck depression Inventory(BDI) Geriatric DepressionScale (GDS) UPDRS II e EQ-5D vs placebo

Lrsquoeffetto del trattamento sui sintomi depressivi egrave

stato per un 80 diretto sulla depressione

valutato con la BDI per un 20 indiretto legato ad un miglioramento dellrsquo UPDRS III

Trattamento della depressione in MP

DepressioneMP

PD (90)

HC (90)

Major Depression 211 33

Dysthymia 188 44

DAP 30 33

Anxiety 111 144

DOC 33 22

Mov Disord 2010

Depressed compared to non depressed dopaminergic and noradrenergic denervation

Locus coeruleus

Medial thalamus

Left

Ventral

striatum

Right Amigdala

Remy et al Brain 2005

[11C]RTI 32 PET

Biochemical Pharmacology 2007

0 20 40 60 80 100

SNc

DRN

LC

DVN

DPDNDPD

0 20 40 60 80 100

SNc

DRN

LC

DVN

DPDNDPD

GLIOSIS

NEURONAL LOSS

DVN dorsal vagus nerveLC locus coeruleusDRN dorsal raphe nucleiSNc substantia nigra c

Frisina et al 2009 modified

Mapping the norepinephrine transporter

NETSCAN

A Varrone et al 2010

Prevalence of Depressive Disorder and

Depressive symptoms in PD

Major depression 17

Minor depression 22

Dysthymia 13

Reijnders et al Mov Disord 2007

Clinically significant

depressive symptoms 361

DepressionPD

22

ldquoDEPRESSIONrdquo in PDwhat should we treat

Depressive Disorder

(Major Minor Dysthimia)

Depressive Symptoms

DSM-V criteria for

Diagnosis of depression

screening for depressive

symptoms

Low mood AnxietyDepression

Depression in PD not ONE disease

DEPRESSIONE E SEROTONINA

Pazienti con MP

Ridotti trasportatori SERT nella regione orbitofrontale corteccia del cingolo insula amigdala e ippocampo

(Kish S Brain 2008)

(Guttman Eur J Neurol 2007)

(Albin J Cereb Blood Flow Metab 2008)

Riduzione dei livelli di 5-HT e dei trasportatori SERT a livello striatale (soprattutto caudato)

Riduzione dei neuroni serotoninergici nucleo dorsale del rafe

Pazienti con MP e depressione

Ridotta ecogenicitagrave nel rafe mesencefalico alla sonografia transcranica

(Pauls J Neuropathol Exp Neurol 1991)

(Berg J Neurol 1999)

Natural history of degenerative parkinsonism

Department of Clinical and Experimental Medicine University of Pisa

Possible correlation anatomo-clinic

SALAT D et al Lancet Neurology 2016

11C-DASB11C-MADAM

Serotonintransporter

5-HT

Imaging

serotonin terminal function

AADC

TRYP

5-HTP

5-HT

TH

Serotonin

receptors

5-HT1A

1B1C

1E

1D1F5-HT2A

2B2C

5-HT4

67

5-HT5

5-HT1A

5-HT1B

5-HT3

18F-dopa

11C-AMT

123I-beta CIT 123I-FP-CIT

11C-DASB

Serotonin transporter

11C-WAY100635

Serotonin HT1A receptor

123I-FP-CIT

Serotonin and Dopamine

transporter

PETSPECT ligands

11C-AZ10419369

Serotonin HT1B receptor

18F-altanserin

Serotonin HT2A receptor

[11C]DASB binding positively correlated with

depression but not with disease severityduration

wide-spread increase in [11C]DASB in

PDdepression

1 dorsolateral cortices

2 prefrontal cortices

Lower uptake in depressedvs non-depressed PD

bull 8 non depressedPD patients

bull 4 depressed PD patients

Ballanger et al 2011

x= 6 plt0001 y= 8 plt0001

y= -1 plt001z= 43 plt0001

z= 10 plt0001

Lower 11C-DASB uptake

in PD with depression

7 PD depr lt 7 PD without depression

amygdalacingulate

cingulate

thalamus

thalamus

striatum

Courtesy of Nicola Pavese

Autore

annoCampione Disegno Farmaco

Scala

usata

Risultati(decremento punteggio

scala)

Follow up

Leentjens200333

6

6Doppio cieco

Sertralina

PlaceboMADRS

-9

-1110 settimane

Fregni200434

21

21Doppio cieco

Fluoxetina

TMS

HAM D

BDI

-9sect-8sect

-10sect-8sect8 settimane

Serrano Duenas200235

37

40Randomizzato

Fluoxetina

AmitriptilinaHAM D

Inefficace

Efficace 12 mesi

Avila200336

7

9Randomizzato

Fluoxetina

NefazodoneBDI

Ugualmente

efficaci sect12 settimane

Antonini200637

12

11Doppio cieco

Sertralina

AmitriptilinaHAM D

-12sect

-11sect3 mesi

Barone200638

33

34Doppio cieco

Pramipexole

SertralineHAM D

-10sect

-9sect12 settimane

Devos200823

16

15

17

Doppio cieco

Placebo

Citalopram

Desimipramina

MADRS

-9

-14

-20

4 settimane

Menza200921

17

18

17

Doppio cieco

Placebo

Paroxetina

Nortriptilina

HAM D

-4

-6

-11

8 settimane

Richard201224

39

42

34

Doppio cieco

Placebo

Paroxetina

Venlafaxina ER

HAM D

-68

-13

-11

12 settimane

differenza significativa rispetto al placebo

sect differenza significativa rispetto al basale

Studi sullrsquoutilizzo di SSRI nei pazienti con Malattia di Parkinson e depressione (2003-2013)

Efficacy and Acceptability of selective serotoninreuptake inhibitors for the treatment of depression in Parkinsons disease

a systematic review andmeta-analysis of randomized controlled trials

Petros Skapinakis et all

BMC Neurology 2010 1049

bull Il 63 degli antidepressivi prescritti sono SSRI e nel 7 sono TCAbull Crsquoegrave ancora incertezza sullrsquoefficacia degli SSRI nella depressione in MPbull I risultati di questo studio mostrano che la pratica clinica attuale non

egrave supportata da forti evidenze

Trattamento della depressione in MP

DepressioneMP

Depression and PD clinical features

Anhedonia

Low mood and impaired interest or

ability to experience pleasure

Core symptomOther clinical features

1 Altered sleep patterns

2 Change in weight

3 Loss of libido

4 Psychomotor retardation

5 Reduced energy

Starkstein Mov Disord 2008

Imaging del rilascio di dopamina

10 di riduzione

del 11C raclopride

BP riflette un

incremento di 5

volte del rilascio di

Dopamina

Journal of Psychiatric Research 2006

DAergic

PRE -

SYNAPTIC

NEURON

DAT

Tracer

PET SPECTPOST -

SYNAPTIC

NEURON

DAT TRACER BINDING = Density of DAergic terminals

Healthy Control Parkinsonrsquos disease

11C-RTI 3218F-CFT123I-beta CIT 123I-FP-CIT123I-altropane99mTc-TroDAT

Depressive symptoms in Parkinsons disease are related to reduced [123I]FP-CIT binding in the caudate nucleus

Vriend 2014

Frosini D et al 2015

Mesolimbic dopaminergic dysfunction in Parkinsonrsquos disease-depression evidence from a 123I-FP-CIT SPECT investigation

Pd-nd (35) PD-d (15)

MeanplusmnSD MeanplusmnSD

Age at onset (years) 683plusmn71 661plusmn55

Disease duration (years) 12plusmn10 10plusmn05

Age at scan (years) 671plusmn69 668plusmn54

UPDRS II 58plusmn36 70plusmn34

UPDRS III 156plusmn70 157plusmn53

MMSE 279plusmn17 275plusmn13

BDI 25plusmn09 168plusmn38

Left caudate FP-CIT uptake 32 plusmn12 34plusmn 11

Right caudate FP-CIT uptake 33plusmn11 34 plusmn11

Left putamen FP-CIT uptake 17plusmn 10 18 plusmn09

Right putamen FP-CIT uptake 18plusmn 08 12 plusmn08

Pramipexole for the treatment of depressive symptomsin patients with Parkinsonrsquos disease a randomised

double-blind placebo-controlled trialPaolo Barone Werner Poewe Stefan Albrecht Catherine Debieuvre Dan Massey Olivier Rascol Eduardo Tolosa Daniel Weintraub

Lancet Neurol 2010 9 573ndash80

Miglioramento dello scoreBeck depression Inventory(BDI) Geriatric DepressionScale (GDS) UPDRS II e EQ-5D vs placebo

Lrsquoeffetto del trattamento sui sintomi depressivi egrave

stato per un 80 diretto sulla depressione

valutato con la BDI per un 20 indiretto legato ad un miglioramento dellrsquo UPDRS III

Trattamento della depressione in MP

DepressioneMP

PD (90)

HC (90)

Major Depression 211 33

Dysthymia 188 44

DAP 30 33

Anxiety 111 144

DOC 33 22

Mov Disord 2010

Depressed compared to non depressed dopaminergic and noradrenergic denervation

Locus coeruleus

Medial thalamus

Left

Ventral

striatum

Right Amigdala

Remy et al Brain 2005

[11C]RTI 32 PET

Biochemical Pharmacology 2007

0 20 40 60 80 100

SNc

DRN

LC

DVN

DPDNDPD

0 20 40 60 80 100

SNc

DRN

LC

DVN

DPDNDPD

GLIOSIS

NEURONAL LOSS

DVN dorsal vagus nerveLC locus coeruleusDRN dorsal raphe nucleiSNc substantia nigra c

Frisina et al 2009 modified

Mapping the norepinephrine transporter

NETSCAN

A Varrone et al 2010

22

ldquoDEPRESSIONrdquo in PDwhat should we treat

Depressive Disorder

(Major Minor Dysthimia)

Depressive Symptoms

DSM-V criteria for

Diagnosis of depression

screening for depressive

symptoms

Low mood AnxietyDepression

Depression in PD not ONE disease

DEPRESSIONE E SEROTONINA

Pazienti con MP

Ridotti trasportatori SERT nella regione orbitofrontale corteccia del cingolo insula amigdala e ippocampo

(Kish S Brain 2008)

(Guttman Eur J Neurol 2007)

(Albin J Cereb Blood Flow Metab 2008)

Riduzione dei livelli di 5-HT e dei trasportatori SERT a livello striatale (soprattutto caudato)

Riduzione dei neuroni serotoninergici nucleo dorsale del rafe

Pazienti con MP e depressione

Ridotta ecogenicitagrave nel rafe mesencefalico alla sonografia transcranica

(Pauls J Neuropathol Exp Neurol 1991)

(Berg J Neurol 1999)

Natural history of degenerative parkinsonism

Department of Clinical and Experimental Medicine University of Pisa

Possible correlation anatomo-clinic

SALAT D et al Lancet Neurology 2016

11C-DASB11C-MADAM

Serotonintransporter

5-HT

Imaging

serotonin terminal function

AADC

TRYP

5-HTP

5-HT

TH

Serotonin

receptors

5-HT1A

1B1C

1E

1D1F5-HT2A

2B2C

5-HT4

67

5-HT5

5-HT1A

5-HT1B

5-HT3

18F-dopa

11C-AMT

123I-beta CIT 123I-FP-CIT

11C-DASB

Serotonin transporter

11C-WAY100635

Serotonin HT1A receptor

123I-FP-CIT

Serotonin and Dopamine

transporter

PETSPECT ligands

11C-AZ10419369

Serotonin HT1B receptor

18F-altanserin

Serotonin HT2A receptor

[11C]DASB binding positively correlated with

depression but not with disease severityduration

wide-spread increase in [11C]DASB in

PDdepression

1 dorsolateral cortices

2 prefrontal cortices

Lower uptake in depressedvs non-depressed PD

bull 8 non depressedPD patients

bull 4 depressed PD patients

Ballanger et al 2011

x= 6 plt0001 y= 8 plt0001

y= -1 plt001z= 43 plt0001

z= 10 plt0001

Lower 11C-DASB uptake

in PD with depression

7 PD depr lt 7 PD without depression

amygdalacingulate

cingulate

thalamus

thalamus

striatum

Courtesy of Nicola Pavese

Autore

annoCampione Disegno Farmaco

Scala

usata

Risultati(decremento punteggio

scala)

Follow up

Leentjens200333

6

6Doppio cieco

Sertralina

PlaceboMADRS

-9

-1110 settimane

Fregni200434

21

21Doppio cieco

Fluoxetina

TMS

HAM D

BDI

-9sect-8sect

-10sect-8sect8 settimane

Serrano Duenas200235

37

40Randomizzato

Fluoxetina

AmitriptilinaHAM D

Inefficace

Efficace 12 mesi

Avila200336

7

9Randomizzato

Fluoxetina

NefazodoneBDI

Ugualmente

efficaci sect12 settimane

Antonini200637

12

11Doppio cieco

Sertralina

AmitriptilinaHAM D

-12sect

-11sect3 mesi

Barone200638

33

34Doppio cieco

Pramipexole

SertralineHAM D

-10sect

-9sect12 settimane

Devos200823

16

15

17

Doppio cieco

Placebo

Citalopram

Desimipramina

MADRS

-9

-14

-20

4 settimane

Menza200921

17

18

17

Doppio cieco

Placebo

Paroxetina

Nortriptilina

HAM D

-4

-6

-11

8 settimane

Richard201224

39

42

34

Doppio cieco

Placebo

Paroxetina

Venlafaxina ER

HAM D

-68

-13

-11

12 settimane

differenza significativa rispetto al placebo

sect differenza significativa rispetto al basale

Studi sullrsquoutilizzo di SSRI nei pazienti con Malattia di Parkinson e depressione (2003-2013)

Efficacy and Acceptability of selective serotoninreuptake inhibitors for the treatment of depression in Parkinsons disease

a systematic review andmeta-analysis of randomized controlled trials

Petros Skapinakis et all

BMC Neurology 2010 1049

bull Il 63 degli antidepressivi prescritti sono SSRI e nel 7 sono TCAbull Crsquoegrave ancora incertezza sullrsquoefficacia degli SSRI nella depressione in MPbull I risultati di questo studio mostrano che la pratica clinica attuale non

egrave supportata da forti evidenze

Trattamento della depressione in MP

DepressioneMP

Depression and PD clinical features

Anhedonia

Low mood and impaired interest or

ability to experience pleasure

Core symptomOther clinical features

1 Altered sleep patterns

2 Change in weight

3 Loss of libido

4 Psychomotor retardation

5 Reduced energy

Starkstein Mov Disord 2008

Imaging del rilascio di dopamina

10 di riduzione

del 11C raclopride

BP riflette un

incremento di 5

volte del rilascio di

Dopamina

Journal of Psychiatric Research 2006

DAergic

PRE -

SYNAPTIC

NEURON

DAT

Tracer

PET SPECTPOST -

SYNAPTIC

NEURON

DAT TRACER BINDING = Density of DAergic terminals

Healthy Control Parkinsonrsquos disease

11C-RTI 3218F-CFT123I-beta CIT 123I-FP-CIT123I-altropane99mTc-TroDAT

Depressive symptoms in Parkinsons disease are related to reduced [123I]FP-CIT binding in the caudate nucleus

Vriend 2014

Frosini D et al 2015

Mesolimbic dopaminergic dysfunction in Parkinsonrsquos disease-depression evidence from a 123I-FP-CIT SPECT investigation

Pd-nd (35) PD-d (15)

MeanplusmnSD MeanplusmnSD

Age at onset (years) 683plusmn71 661plusmn55

Disease duration (years) 12plusmn10 10plusmn05

Age at scan (years) 671plusmn69 668plusmn54

UPDRS II 58plusmn36 70plusmn34

UPDRS III 156plusmn70 157plusmn53

MMSE 279plusmn17 275plusmn13

BDI 25plusmn09 168plusmn38

Left caudate FP-CIT uptake 32 plusmn12 34plusmn 11

Right caudate FP-CIT uptake 33plusmn11 34 plusmn11

Left putamen FP-CIT uptake 17plusmn 10 18 plusmn09

Right putamen FP-CIT uptake 18plusmn 08 12 plusmn08

Pramipexole for the treatment of depressive symptomsin patients with Parkinsonrsquos disease a randomised

double-blind placebo-controlled trialPaolo Barone Werner Poewe Stefan Albrecht Catherine Debieuvre Dan Massey Olivier Rascol Eduardo Tolosa Daniel Weintraub

Lancet Neurol 2010 9 573ndash80

Miglioramento dello scoreBeck depression Inventory(BDI) Geriatric DepressionScale (GDS) UPDRS II e EQ-5D vs placebo

Lrsquoeffetto del trattamento sui sintomi depressivi egrave

stato per un 80 diretto sulla depressione

valutato con la BDI per un 20 indiretto legato ad un miglioramento dellrsquo UPDRS III

Trattamento della depressione in MP

DepressioneMP

PD (90)

HC (90)

Major Depression 211 33

Dysthymia 188 44

DAP 30 33

Anxiety 111 144

DOC 33 22

Mov Disord 2010

Depressed compared to non depressed dopaminergic and noradrenergic denervation

Locus coeruleus

Medial thalamus

Left

Ventral

striatum

Right Amigdala

Remy et al Brain 2005

[11C]RTI 32 PET

Biochemical Pharmacology 2007

0 20 40 60 80 100

SNc

DRN

LC

DVN

DPDNDPD

0 20 40 60 80 100

SNc

DRN

LC

DVN

DPDNDPD

GLIOSIS

NEURONAL LOSS

DVN dorsal vagus nerveLC locus coeruleusDRN dorsal raphe nucleiSNc substantia nigra c

Frisina et al 2009 modified

Mapping the norepinephrine transporter

NETSCAN

A Varrone et al 2010

Low mood AnxietyDepression

Depression in PD not ONE disease

DEPRESSIONE E SEROTONINA

Pazienti con MP

Ridotti trasportatori SERT nella regione orbitofrontale corteccia del cingolo insula amigdala e ippocampo

(Kish S Brain 2008)

(Guttman Eur J Neurol 2007)

(Albin J Cereb Blood Flow Metab 2008)

Riduzione dei livelli di 5-HT e dei trasportatori SERT a livello striatale (soprattutto caudato)

Riduzione dei neuroni serotoninergici nucleo dorsale del rafe

Pazienti con MP e depressione

Ridotta ecogenicitagrave nel rafe mesencefalico alla sonografia transcranica

(Pauls J Neuropathol Exp Neurol 1991)

(Berg J Neurol 1999)

Natural history of degenerative parkinsonism

Department of Clinical and Experimental Medicine University of Pisa

Possible correlation anatomo-clinic

SALAT D et al Lancet Neurology 2016

11C-DASB11C-MADAM

Serotonintransporter

5-HT

Imaging

serotonin terminal function

AADC

TRYP

5-HTP

5-HT

TH

Serotonin

receptors

5-HT1A

1B1C

1E

1D1F5-HT2A

2B2C

5-HT4

67

5-HT5

5-HT1A

5-HT1B

5-HT3

18F-dopa

11C-AMT

123I-beta CIT 123I-FP-CIT

11C-DASB

Serotonin transporter

11C-WAY100635

Serotonin HT1A receptor

123I-FP-CIT

Serotonin and Dopamine

transporter

PETSPECT ligands

11C-AZ10419369

Serotonin HT1B receptor

18F-altanserin

Serotonin HT2A receptor

[11C]DASB binding positively correlated with

depression but not with disease severityduration

wide-spread increase in [11C]DASB in

PDdepression

1 dorsolateral cortices

2 prefrontal cortices

Lower uptake in depressedvs non-depressed PD

bull 8 non depressedPD patients

bull 4 depressed PD patients

Ballanger et al 2011

x= 6 plt0001 y= 8 plt0001

y= -1 plt001z= 43 plt0001

z= 10 plt0001

Lower 11C-DASB uptake

in PD with depression

7 PD depr lt 7 PD without depression

amygdalacingulate

cingulate

thalamus

thalamus

striatum

Courtesy of Nicola Pavese

Autore

annoCampione Disegno Farmaco

Scala

usata

Risultati(decremento punteggio

scala)

Follow up

Leentjens200333

6

6Doppio cieco

Sertralina

PlaceboMADRS

-9

-1110 settimane

Fregni200434

21

21Doppio cieco

Fluoxetina

TMS

HAM D

BDI

-9sect-8sect

-10sect-8sect8 settimane

Serrano Duenas200235

37

40Randomizzato

Fluoxetina

AmitriptilinaHAM D

Inefficace

Efficace 12 mesi

Avila200336

7

9Randomizzato

Fluoxetina

NefazodoneBDI

Ugualmente

efficaci sect12 settimane

Antonini200637

12

11Doppio cieco

Sertralina

AmitriptilinaHAM D

-12sect

-11sect3 mesi

Barone200638

33

34Doppio cieco

Pramipexole

SertralineHAM D

-10sect

-9sect12 settimane

Devos200823

16

15

17

Doppio cieco

Placebo

Citalopram

Desimipramina

MADRS

-9

-14

-20

4 settimane

Menza200921

17

18

17

Doppio cieco

Placebo

Paroxetina

Nortriptilina

HAM D

-4

-6

-11

8 settimane

Richard201224

39

42

34

Doppio cieco

Placebo

Paroxetina

Venlafaxina ER

HAM D

-68

-13

-11

12 settimane

differenza significativa rispetto al placebo

sect differenza significativa rispetto al basale

Studi sullrsquoutilizzo di SSRI nei pazienti con Malattia di Parkinson e depressione (2003-2013)

Efficacy and Acceptability of selective serotoninreuptake inhibitors for the treatment of depression in Parkinsons disease

a systematic review andmeta-analysis of randomized controlled trials

Petros Skapinakis et all

BMC Neurology 2010 1049

bull Il 63 degli antidepressivi prescritti sono SSRI e nel 7 sono TCAbull Crsquoegrave ancora incertezza sullrsquoefficacia degli SSRI nella depressione in MPbull I risultati di questo studio mostrano che la pratica clinica attuale non

egrave supportata da forti evidenze

Trattamento della depressione in MP

DepressioneMP

Depression and PD clinical features

Anhedonia

Low mood and impaired interest or

ability to experience pleasure

Core symptomOther clinical features

1 Altered sleep patterns

2 Change in weight

3 Loss of libido

4 Psychomotor retardation

5 Reduced energy

Starkstein Mov Disord 2008

Imaging del rilascio di dopamina

10 di riduzione

del 11C raclopride

BP riflette un

incremento di 5

volte del rilascio di

Dopamina

Journal of Psychiatric Research 2006

DAergic

PRE -

SYNAPTIC

NEURON

DAT

Tracer

PET SPECTPOST -

SYNAPTIC

NEURON

DAT TRACER BINDING = Density of DAergic terminals

Healthy Control Parkinsonrsquos disease

11C-RTI 3218F-CFT123I-beta CIT 123I-FP-CIT123I-altropane99mTc-TroDAT

Depressive symptoms in Parkinsons disease are related to reduced [123I]FP-CIT binding in the caudate nucleus

Vriend 2014

Frosini D et al 2015

Mesolimbic dopaminergic dysfunction in Parkinsonrsquos disease-depression evidence from a 123I-FP-CIT SPECT investigation

Pd-nd (35) PD-d (15)

MeanplusmnSD MeanplusmnSD

Age at onset (years) 683plusmn71 661plusmn55

Disease duration (years) 12plusmn10 10plusmn05

Age at scan (years) 671plusmn69 668plusmn54

UPDRS II 58plusmn36 70plusmn34

UPDRS III 156plusmn70 157plusmn53

MMSE 279plusmn17 275plusmn13

BDI 25plusmn09 168plusmn38

Left caudate FP-CIT uptake 32 plusmn12 34plusmn 11

Right caudate FP-CIT uptake 33plusmn11 34 plusmn11

Left putamen FP-CIT uptake 17plusmn 10 18 plusmn09

Right putamen FP-CIT uptake 18plusmn 08 12 plusmn08

Pramipexole for the treatment of depressive symptomsin patients with Parkinsonrsquos disease a randomised

double-blind placebo-controlled trialPaolo Barone Werner Poewe Stefan Albrecht Catherine Debieuvre Dan Massey Olivier Rascol Eduardo Tolosa Daniel Weintraub

Lancet Neurol 2010 9 573ndash80

Miglioramento dello scoreBeck depression Inventory(BDI) Geriatric DepressionScale (GDS) UPDRS II e EQ-5D vs placebo

Lrsquoeffetto del trattamento sui sintomi depressivi egrave

stato per un 80 diretto sulla depressione

valutato con la BDI per un 20 indiretto legato ad un miglioramento dellrsquo UPDRS III

Trattamento della depressione in MP

DepressioneMP

PD (90)

HC (90)

Major Depression 211 33

Dysthymia 188 44

DAP 30 33

Anxiety 111 144

DOC 33 22

Mov Disord 2010

Depressed compared to non depressed dopaminergic and noradrenergic denervation

Locus coeruleus

Medial thalamus

Left

Ventral

striatum

Right Amigdala

Remy et al Brain 2005

[11C]RTI 32 PET

Biochemical Pharmacology 2007

0 20 40 60 80 100

SNc

DRN

LC

DVN

DPDNDPD

0 20 40 60 80 100

SNc

DRN

LC

DVN

DPDNDPD

GLIOSIS

NEURONAL LOSS

DVN dorsal vagus nerveLC locus coeruleusDRN dorsal raphe nucleiSNc substantia nigra c

Frisina et al 2009 modified

Mapping the norepinephrine transporter

NETSCAN

A Varrone et al 2010

DEPRESSIONE E SEROTONINA

Pazienti con MP

Ridotti trasportatori SERT nella regione orbitofrontale corteccia del cingolo insula amigdala e ippocampo

(Kish S Brain 2008)

(Guttman Eur J Neurol 2007)

(Albin J Cereb Blood Flow Metab 2008)

Riduzione dei livelli di 5-HT e dei trasportatori SERT a livello striatale (soprattutto caudato)

Riduzione dei neuroni serotoninergici nucleo dorsale del rafe

Pazienti con MP e depressione

Ridotta ecogenicitagrave nel rafe mesencefalico alla sonografia transcranica

(Pauls J Neuropathol Exp Neurol 1991)

(Berg J Neurol 1999)

Natural history of degenerative parkinsonism

Department of Clinical and Experimental Medicine University of Pisa

Possible correlation anatomo-clinic

SALAT D et al Lancet Neurology 2016

11C-DASB11C-MADAM

Serotonintransporter

5-HT

Imaging

serotonin terminal function

AADC

TRYP

5-HTP

5-HT

TH

Serotonin

receptors

5-HT1A

1B1C

1E

1D1F5-HT2A

2B2C

5-HT4

67

5-HT5

5-HT1A

5-HT1B

5-HT3

18F-dopa

11C-AMT

123I-beta CIT 123I-FP-CIT

11C-DASB

Serotonin transporter

11C-WAY100635

Serotonin HT1A receptor

123I-FP-CIT

Serotonin and Dopamine

transporter

PETSPECT ligands

11C-AZ10419369

Serotonin HT1B receptor

18F-altanserin

Serotonin HT2A receptor

[11C]DASB binding positively correlated with

depression but not with disease severityduration

wide-spread increase in [11C]DASB in

PDdepression

1 dorsolateral cortices

2 prefrontal cortices

Lower uptake in depressedvs non-depressed PD

bull 8 non depressedPD patients

bull 4 depressed PD patients

Ballanger et al 2011

x= 6 plt0001 y= 8 plt0001

y= -1 plt001z= 43 plt0001

z= 10 plt0001

Lower 11C-DASB uptake

in PD with depression

7 PD depr lt 7 PD without depression

amygdalacingulate

cingulate

thalamus

thalamus

striatum

Courtesy of Nicola Pavese

Autore

annoCampione Disegno Farmaco

Scala

usata

Risultati(decremento punteggio

scala)

Follow up

Leentjens200333

6

6Doppio cieco

Sertralina

PlaceboMADRS

-9

-1110 settimane

Fregni200434

21

21Doppio cieco

Fluoxetina

TMS

HAM D

BDI

-9sect-8sect

-10sect-8sect8 settimane

Serrano Duenas200235

37

40Randomizzato

Fluoxetina

AmitriptilinaHAM D

Inefficace

Efficace 12 mesi

Avila200336

7

9Randomizzato

Fluoxetina

NefazodoneBDI

Ugualmente

efficaci sect12 settimane

Antonini200637

12

11Doppio cieco

Sertralina

AmitriptilinaHAM D

-12sect

-11sect3 mesi

Barone200638

33

34Doppio cieco

Pramipexole

SertralineHAM D

-10sect

-9sect12 settimane

Devos200823

16

15

17

Doppio cieco

Placebo

Citalopram

Desimipramina

MADRS

-9

-14

-20

4 settimane

Menza200921

17

18

17

Doppio cieco

Placebo

Paroxetina

Nortriptilina

HAM D

-4

-6

-11

8 settimane

Richard201224

39

42

34

Doppio cieco

Placebo

Paroxetina

Venlafaxina ER

HAM D

-68

-13

-11

12 settimane

differenza significativa rispetto al placebo

sect differenza significativa rispetto al basale

Studi sullrsquoutilizzo di SSRI nei pazienti con Malattia di Parkinson e depressione (2003-2013)

Efficacy and Acceptability of selective serotoninreuptake inhibitors for the treatment of depression in Parkinsons disease

a systematic review andmeta-analysis of randomized controlled trials

Petros Skapinakis et all

BMC Neurology 2010 1049

bull Il 63 degli antidepressivi prescritti sono SSRI e nel 7 sono TCAbull Crsquoegrave ancora incertezza sullrsquoefficacia degli SSRI nella depressione in MPbull I risultati di questo studio mostrano che la pratica clinica attuale non

egrave supportata da forti evidenze

Trattamento della depressione in MP

DepressioneMP

Depression and PD clinical features

Anhedonia

Low mood and impaired interest or

ability to experience pleasure

Core symptomOther clinical features

1 Altered sleep patterns

2 Change in weight

3 Loss of libido

4 Psychomotor retardation

5 Reduced energy

Starkstein Mov Disord 2008

Imaging del rilascio di dopamina

10 di riduzione

del 11C raclopride

BP riflette un

incremento di 5

volte del rilascio di

Dopamina

Journal of Psychiatric Research 2006

DAergic

PRE -

SYNAPTIC

NEURON

DAT

Tracer

PET SPECTPOST -

SYNAPTIC

NEURON

DAT TRACER BINDING = Density of DAergic terminals

Healthy Control Parkinsonrsquos disease

11C-RTI 3218F-CFT123I-beta CIT 123I-FP-CIT123I-altropane99mTc-TroDAT

Depressive symptoms in Parkinsons disease are related to reduced [123I]FP-CIT binding in the caudate nucleus

Vriend 2014

Frosini D et al 2015

Mesolimbic dopaminergic dysfunction in Parkinsonrsquos disease-depression evidence from a 123I-FP-CIT SPECT investigation

Pd-nd (35) PD-d (15)

MeanplusmnSD MeanplusmnSD

Age at onset (years) 683plusmn71 661plusmn55

Disease duration (years) 12plusmn10 10plusmn05

Age at scan (years) 671plusmn69 668plusmn54

UPDRS II 58plusmn36 70plusmn34

UPDRS III 156plusmn70 157plusmn53

MMSE 279plusmn17 275plusmn13

BDI 25plusmn09 168plusmn38

Left caudate FP-CIT uptake 32 plusmn12 34plusmn 11

Right caudate FP-CIT uptake 33plusmn11 34 plusmn11

Left putamen FP-CIT uptake 17plusmn 10 18 plusmn09

Right putamen FP-CIT uptake 18plusmn 08 12 plusmn08

Pramipexole for the treatment of depressive symptomsin patients with Parkinsonrsquos disease a randomised

double-blind placebo-controlled trialPaolo Barone Werner Poewe Stefan Albrecht Catherine Debieuvre Dan Massey Olivier Rascol Eduardo Tolosa Daniel Weintraub

Lancet Neurol 2010 9 573ndash80

Miglioramento dello scoreBeck depression Inventory(BDI) Geriatric DepressionScale (GDS) UPDRS II e EQ-5D vs placebo

Lrsquoeffetto del trattamento sui sintomi depressivi egrave

stato per un 80 diretto sulla depressione

valutato con la BDI per un 20 indiretto legato ad un miglioramento dellrsquo UPDRS III

Trattamento della depressione in MP

DepressioneMP

PD (90)

HC (90)

Major Depression 211 33

Dysthymia 188 44

DAP 30 33

Anxiety 111 144

DOC 33 22

Mov Disord 2010

Depressed compared to non depressed dopaminergic and noradrenergic denervation

Locus coeruleus

Medial thalamus

Left

Ventral

striatum

Right Amigdala

Remy et al Brain 2005

[11C]RTI 32 PET

Biochemical Pharmacology 2007

0 20 40 60 80 100

SNc

DRN

LC

DVN

DPDNDPD

0 20 40 60 80 100

SNc

DRN

LC

DVN

DPDNDPD

GLIOSIS

NEURONAL LOSS

DVN dorsal vagus nerveLC locus coeruleusDRN dorsal raphe nucleiSNc substantia nigra c

Frisina et al 2009 modified

Mapping the norepinephrine transporter

NETSCAN

A Varrone et al 2010

Natural history of degenerative parkinsonism

Department of Clinical and Experimental Medicine University of Pisa

Possible correlation anatomo-clinic

SALAT D et al Lancet Neurology 2016

11C-DASB11C-MADAM

Serotonintransporter

5-HT

Imaging

serotonin terminal function

AADC

TRYP

5-HTP

5-HT

TH

Serotonin

receptors

5-HT1A

1B1C

1E

1D1F5-HT2A

2B2C

5-HT4

67

5-HT5

5-HT1A

5-HT1B

5-HT3

18F-dopa

11C-AMT

123I-beta CIT 123I-FP-CIT

11C-DASB

Serotonin transporter

11C-WAY100635

Serotonin HT1A receptor

123I-FP-CIT

Serotonin and Dopamine

transporter

PETSPECT ligands

11C-AZ10419369

Serotonin HT1B receptor

18F-altanserin

Serotonin HT2A receptor

[11C]DASB binding positively correlated with

depression but not with disease severityduration

wide-spread increase in [11C]DASB in

PDdepression

1 dorsolateral cortices

2 prefrontal cortices

Lower uptake in depressedvs non-depressed PD

bull 8 non depressedPD patients

bull 4 depressed PD patients

Ballanger et al 2011

x= 6 plt0001 y= 8 plt0001

y= -1 plt001z= 43 plt0001

z= 10 plt0001

Lower 11C-DASB uptake

in PD with depression

7 PD depr lt 7 PD without depression

amygdalacingulate

cingulate

thalamus

thalamus

striatum

Courtesy of Nicola Pavese

Autore

annoCampione Disegno Farmaco

Scala

usata

Risultati(decremento punteggio

scala)

Follow up

Leentjens200333

6

6Doppio cieco

Sertralina

PlaceboMADRS

-9

-1110 settimane

Fregni200434

21

21Doppio cieco

Fluoxetina

TMS

HAM D

BDI

-9sect-8sect

-10sect-8sect8 settimane

Serrano Duenas200235

37

40Randomizzato

Fluoxetina

AmitriptilinaHAM D

Inefficace

Efficace 12 mesi

Avila200336

7

9Randomizzato

Fluoxetina

NefazodoneBDI

Ugualmente

efficaci sect12 settimane

Antonini200637

12

11Doppio cieco

Sertralina

AmitriptilinaHAM D

-12sect

-11sect3 mesi

Barone200638

33

34Doppio cieco

Pramipexole

SertralineHAM D

-10sect

-9sect12 settimane

Devos200823

16

15

17

Doppio cieco

Placebo

Citalopram

Desimipramina

MADRS

-9

-14

-20

4 settimane

Menza200921

17

18

17

Doppio cieco

Placebo

Paroxetina

Nortriptilina

HAM D

-4

-6

-11

8 settimane

Richard201224

39

42

34

Doppio cieco

Placebo

Paroxetina

Venlafaxina ER

HAM D

-68

-13

-11

12 settimane

differenza significativa rispetto al placebo

sect differenza significativa rispetto al basale

Studi sullrsquoutilizzo di SSRI nei pazienti con Malattia di Parkinson e depressione (2003-2013)

Efficacy and Acceptability of selective serotoninreuptake inhibitors for the treatment of depression in Parkinsons disease

a systematic review andmeta-analysis of randomized controlled trials

Petros Skapinakis et all

BMC Neurology 2010 1049

bull Il 63 degli antidepressivi prescritti sono SSRI e nel 7 sono TCAbull Crsquoegrave ancora incertezza sullrsquoefficacia degli SSRI nella depressione in MPbull I risultati di questo studio mostrano che la pratica clinica attuale non

egrave supportata da forti evidenze

Trattamento della depressione in MP

DepressioneMP

Depression and PD clinical features

Anhedonia

Low mood and impaired interest or

ability to experience pleasure

Core symptomOther clinical features

1 Altered sleep patterns

2 Change in weight

3 Loss of libido

4 Psychomotor retardation

5 Reduced energy

Starkstein Mov Disord 2008

Imaging del rilascio di dopamina

10 di riduzione

del 11C raclopride

BP riflette un

incremento di 5

volte del rilascio di

Dopamina

Journal of Psychiatric Research 2006

DAergic

PRE -

SYNAPTIC

NEURON

DAT

Tracer

PET SPECTPOST -

SYNAPTIC

NEURON

DAT TRACER BINDING = Density of DAergic terminals

Healthy Control Parkinsonrsquos disease

11C-RTI 3218F-CFT123I-beta CIT 123I-FP-CIT123I-altropane99mTc-TroDAT

Depressive symptoms in Parkinsons disease are related to reduced [123I]FP-CIT binding in the caudate nucleus

Vriend 2014

Frosini D et al 2015

Mesolimbic dopaminergic dysfunction in Parkinsonrsquos disease-depression evidence from a 123I-FP-CIT SPECT investigation

Pd-nd (35) PD-d (15)

MeanplusmnSD MeanplusmnSD

Age at onset (years) 683plusmn71 661plusmn55

Disease duration (years) 12plusmn10 10plusmn05

Age at scan (years) 671plusmn69 668plusmn54

UPDRS II 58plusmn36 70plusmn34

UPDRS III 156plusmn70 157plusmn53

MMSE 279plusmn17 275plusmn13

BDI 25plusmn09 168plusmn38

Left caudate FP-CIT uptake 32 plusmn12 34plusmn 11

Right caudate FP-CIT uptake 33plusmn11 34 plusmn11

Left putamen FP-CIT uptake 17plusmn 10 18 plusmn09

Right putamen FP-CIT uptake 18plusmn 08 12 plusmn08

Pramipexole for the treatment of depressive symptomsin patients with Parkinsonrsquos disease a randomised

double-blind placebo-controlled trialPaolo Barone Werner Poewe Stefan Albrecht Catherine Debieuvre Dan Massey Olivier Rascol Eduardo Tolosa Daniel Weintraub

Lancet Neurol 2010 9 573ndash80

Miglioramento dello scoreBeck depression Inventory(BDI) Geriatric DepressionScale (GDS) UPDRS II e EQ-5D vs placebo

Lrsquoeffetto del trattamento sui sintomi depressivi egrave

stato per un 80 diretto sulla depressione

valutato con la BDI per un 20 indiretto legato ad un miglioramento dellrsquo UPDRS III

Trattamento della depressione in MP

DepressioneMP

PD (90)

HC (90)

Major Depression 211 33

Dysthymia 188 44

DAP 30 33

Anxiety 111 144

DOC 33 22

Mov Disord 2010

Depressed compared to non depressed dopaminergic and noradrenergic denervation

Locus coeruleus

Medial thalamus

Left

Ventral

striatum

Right Amigdala

Remy et al Brain 2005

[11C]RTI 32 PET

Biochemical Pharmacology 2007

0 20 40 60 80 100

SNc

DRN

LC

DVN

DPDNDPD

0 20 40 60 80 100

SNc

DRN

LC

DVN

DPDNDPD

GLIOSIS

NEURONAL LOSS

DVN dorsal vagus nerveLC locus coeruleusDRN dorsal raphe nucleiSNc substantia nigra c

Frisina et al 2009 modified

Mapping the norepinephrine transporter

NETSCAN

A Varrone et al 2010

11C-DASB11C-MADAM

Serotonintransporter

5-HT

Imaging

serotonin terminal function

AADC

TRYP

5-HTP

5-HT

TH

Serotonin

receptors

5-HT1A

1B1C

1E

1D1F5-HT2A

2B2C

5-HT4

67

5-HT5

5-HT1A

5-HT1B

5-HT3

18F-dopa

11C-AMT

123I-beta CIT 123I-FP-CIT

11C-DASB

Serotonin transporter

11C-WAY100635

Serotonin HT1A receptor

123I-FP-CIT

Serotonin and Dopamine

transporter

PETSPECT ligands

11C-AZ10419369

Serotonin HT1B receptor

18F-altanserin

Serotonin HT2A receptor

[11C]DASB binding positively correlated with

depression but not with disease severityduration

wide-spread increase in [11C]DASB in

PDdepression

1 dorsolateral cortices

2 prefrontal cortices

Lower uptake in depressedvs non-depressed PD

bull 8 non depressedPD patients

bull 4 depressed PD patients

Ballanger et al 2011

x= 6 plt0001 y= 8 plt0001

y= -1 plt001z= 43 plt0001

z= 10 plt0001

Lower 11C-DASB uptake

in PD with depression

7 PD depr lt 7 PD without depression

amygdalacingulate

cingulate

thalamus

thalamus

striatum

Courtesy of Nicola Pavese

Autore

annoCampione Disegno Farmaco

Scala

usata

Risultati(decremento punteggio

scala)

Follow up

Leentjens200333

6

6Doppio cieco

Sertralina

PlaceboMADRS

-9

-1110 settimane

Fregni200434

21

21Doppio cieco

Fluoxetina

TMS

HAM D

BDI

-9sect-8sect

-10sect-8sect8 settimane

Serrano Duenas200235

37

40Randomizzato

Fluoxetina

AmitriptilinaHAM D

Inefficace

Efficace 12 mesi

Avila200336

7

9Randomizzato

Fluoxetina

NefazodoneBDI

Ugualmente

efficaci sect12 settimane

Antonini200637

12

11Doppio cieco

Sertralina

AmitriptilinaHAM D

-12sect

-11sect3 mesi

Barone200638

33

34Doppio cieco

Pramipexole

SertralineHAM D

-10sect

-9sect12 settimane

Devos200823

16

15

17

Doppio cieco

Placebo

Citalopram

Desimipramina

MADRS

-9

-14

-20

4 settimane

Menza200921

17

18

17

Doppio cieco

Placebo

Paroxetina

Nortriptilina

HAM D

-4

-6

-11

8 settimane

Richard201224

39

42

34

Doppio cieco

Placebo

Paroxetina

Venlafaxina ER

HAM D

-68

-13

-11

12 settimane

differenza significativa rispetto al placebo

sect differenza significativa rispetto al basale

Studi sullrsquoutilizzo di SSRI nei pazienti con Malattia di Parkinson e depressione (2003-2013)

Efficacy and Acceptability of selective serotoninreuptake inhibitors for the treatment of depression in Parkinsons disease

a systematic review andmeta-analysis of randomized controlled trials

Petros Skapinakis et all

BMC Neurology 2010 1049

bull Il 63 degli antidepressivi prescritti sono SSRI e nel 7 sono TCAbull Crsquoegrave ancora incertezza sullrsquoefficacia degli SSRI nella depressione in MPbull I risultati di questo studio mostrano che la pratica clinica attuale non

egrave supportata da forti evidenze

Trattamento della depressione in MP

DepressioneMP

Depression and PD clinical features

Anhedonia

Low mood and impaired interest or

ability to experience pleasure

Core symptomOther clinical features

1 Altered sleep patterns

2 Change in weight

3 Loss of libido

4 Psychomotor retardation

5 Reduced energy

Starkstein Mov Disord 2008

Imaging del rilascio di dopamina

10 di riduzione

del 11C raclopride

BP riflette un

incremento di 5

volte del rilascio di

Dopamina

Journal of Psychiatric Research 2006

DAergic

PRE -

SYNAPTIC

NEURON

DAT

Tracer

PET SPECTPOST -

SYNAPTIC

NEURON

DAT TRACER BINDING = Density of DAergic terminals

Healthy Control Parkinsonrsquos disease

11C-RTI 3218F-CFT123I-beta CIT 123I-FP-CIT123I-altropane99mTc-TroDAT

Depressive symptoms in Parkinsons disease are related to reduced [123I]FP-CIT binding in the caudate nucleus

Vriend 2014

Frosini D et al 2015

Mesolimbic dopaminergic dysfunction in Parkinsonrsquos disease-depression evidence from a 123I-FP-CIT SPECT investigation

Pd-nd (35) PD-d (15)

MeanplusmnSD MeanplusmnSD

Age at onset (years) 683plusmn71 661plusmn55

Disease duration (years) 12plusmn10 10plusmn05

Age at scan (years) 671plusmn69 668plusmn54

UPDRS II 58plusmn36 70plusmn34

UPDRS III 156plusmn70 157plusmn53

MMSE 279plusmn17 275plusmn13

BDI 25plusmn09 168plusmn38

Left caudate FP-CIT uptake 32 plusmn12 34plusmn 11

Right caudate FP-CIT uptake 33plusmn11 34 plusmn11

Left putamen FP-CIT uptake 17plusmn 10 18 plusmn09

Right putamen FP-CIT uptake 18plusmn 08 12 plusmn08

Pramipexole for the treatment of depressive symptomsin patients with Parkinsonrsquos disease a randomised

double-blind placebo-controlled trialPaolo Barone Werner Poewe Stefan Albrecht Catherine Debieuvre Dan Massey Olivier Rascol Eduardo Tolosa Daniel Weintraub

Lancet Neurol 2010 9 573ndash80

Miglioramento dello scoreBeck depression Inventory(BDI) Geriatric DepressionScale (GDS) UPDRS II e EQ-5D vs placebo

Lrsquoeffetto del trattamento sui sintomi depressivi egrave

stato per un 80 diretto sulla depressione

valutato con la BDI per un 20 indiretto legato ad un miglioramento dellrsquo UPDRS III

Trattamento della depressione in MP

DepressioneMP

PD (90)

HC (90)

Major Depression 211 33

Dysthymia 188 44

DAP 30 33

Anxiety 111 144

DOC 33 22

Mov Disord 2010

Depressed compared to non depressed dopaminergic and noradrenergic denervation

Locus coeruleus

Medial thalamus

Left

Ventral

striatum

Right Amigdala

Remy et al Brain 2005

[11C]RTI 32 PET

Biochemical Pharmacology 2007

0 20 40 60 80 100

SNc

DRN

LC

DVN

DPDNDPD

0 20 40 60 80 100

SNc

DRN

LC

DVN

DPDNDPD

GLIOSIS

NEURONAL LOSS

DVN dorsal vagus nerveLC locus coeruleusDRN dorsal raphe nucleiSNc substantia nigra c

Frisina et al 2009 modified

Mapping the norepinephrine transporter

NETSCAN

A Varrone et al 2010

11C-DASB

Serotonin transporter

11C-WAY100635

Serotonin HT1A receptor

123I-FP-CIT

Serotonin and Dopamine

transporter

PETSPECT ligands

11C-AZ10419369

Serotonin HT1B receptor

18F-altanserin

Serotonin HT2A receptor

[11C]DASB binding positively correlated with

depression but not with disease severityduration

wide-spread increase in [11C]DASB in

PDdepression

1 dorsolateral cortices

2 prefrontal cortices

Lower uptake in depressedvs non-depressed PD

bull 8 non depressedPD patients

bull 4 depressed PD patients

Ballanger et al 2011

x= 6 plt0001 y= 8 plt0001

y= -1 plt001z= 43 plt0001

z= 10 plt0001

Lower 11C-DASB uptake

in PD with depression

7 PD depr lt 7 PD without depression

amygdalacingulate

cingulate

thalamus

thalamus

striatum

Courtesy of Nicola Pavese

Autore

annoCampione Disegno Farmaco

Scala

usata

Risultati(decremento punteggio

scala)

Follow up

Leentjens200333

6

6Doppio cieco

Sertralina

PlaceboMADRS

-9

-1110 settimane

Fregni200434

21

21Doppio cieco

Fluoxetina

TMS

HAM D

BDI

-9sect-8sect

-10sect-8sect8 settimane

Serrano Duenas200235

37

40Randomizzato

Fluoxetina

AmitriptilinaHAM D

Inefficace

Efficace 12 mesi

Avila200336

7

9Randomizzato

Fluoxetina

NefazodoneBDI

Ugualmente

efficaci sect12 settimane

Antonini200637

12

11Doppio cieco

Sertralina

AmitriptilinaHAM D

-12sect

-11sect3 mesi

Barone200638

33

34Doppio cieco

Pramipexole

SertralineHAM D

-10sect

-9sect12 settimane

Devos200823

16

15

17

Doppio cieco

Placebo

Citalopram

Desimipramina

MADRS

-9

-14

-20

4 settimane

Menza200921

17

18

17

Doppio cieco

Placebo

Paroxetina

Nortriptilina

HAM D

-4

-6

-11

8 settimane

Richard201224

39

42

34

Doppio cieco

Placebo

Paroxetina

Venlafaxina ER

HAM D

-68

-13

-11

12 settimane

differenza significativa rispetto al placebo

sect differenza significativa rispetto al basale

Studi sullrsquoutilizzo di SSRI nei pazienti con Malattia di Parkinson e depressione (2003-2013)

Efficacy and Acceptability of selective serotoninreuptake inhibitors for the treatment of depression in Parkinsons disease

a systematic review andmeta-analysis of randomized controlled trials

Petros Skapinakis et all

BMC Neurology 2010 1049

bull Il 63 degli antidepressivi prescritti sono SSRI e nel 7 sono TCAbull Crsquoegrave ancora incertezza sullrsquoefficacia degli SSRI nella depressione in MPbull I risultati di questo studio mostrano che la pratica clinica attuale non

egrave supportata da forti evidenze

Trattamento della depressione in MP

DepressioneMP

Depression and PD clinical features

Anhedonia

Low mood and impaired interest or

ability to experience pleasure

Core symptomOther clinical features

1 Altered sleep patterns

2 Change in weight

3 Loss of libido

4 Psychomotor retardation

5 Reduced energy

Starkstein Mov Disord 2008

Imaging del rilascio di dopamina

10 di riduzione

del 11C raclopride

BP riflette un

incremento di 5

volte del rilascio di

Dopamina

Journal of Psychiatric Research 2006

DAergic

PRE -

SYNAPTIC

NEURON

DAT

Tracer

PET SPECTPOST -

SYNAPTIC

NEURON

DAT TRACER BINDING = Density of DAergic terminals

Healthy Control Parkinsonrsquos disease

11C-RTI 3218F-CFT123I-beta CIT 123I-FP-CIT123I-altropane99mTc-TroDAT

Depressive symptoms in Parkinsons disease are related to reduced [123I]FP-CIT binding in the caudate nucleus

Vriend 2014

Frosini D et al 2015

Mesolimbic dopaminergic dysfunction in Parkinsonrsquos disease-depression evidence from a 123I-FP-CIT SPECT investigation

Pd-nd (35) PD-d (15)

MeanplusmnSD MeanplusmnSD

Age at onset (years) 683plusmn71 661plusmn55

Disease duration (years) 12plusmn10 10plusmn05

Age at scan (years) 671plusmn69 668plusmn54

UPDRS II 58plusmn36 70plusmn34

UPDRS III 156plusmn70 157plusmn53

MMSE 279plusmn17 275plusmn13

BDI 25plusmn09 168plusmn38

Left caudate FP-CIT uptake 32 plusmn12 34plusmn 11

Right caudate FP-CIT uptake 33plusmn11 34 plusmn11

Left putamen FP-CIT uptake 17plusmn 10 18 plusmn09

Right putamen FP-CIT uptake 18plusmn 08 12 plusmn08

Pramipexole for the treatment of depressive symptomsin patients with Parkinsonrsquos disease a randomised

double-blind placebo-controlled trialPaolo Barone Werner Poewe Stefan Albrecht Catherine Debieuvre Dan Massey Olivier Rascol Eduardo Tolosa Daniel Weintraub

Lancet Neurol 2010 9 573ndash80

Miglioramento dello scoreBeck depression Inventory(BDI) Geriatric DepressionScale (GDS) UPDRS II e EQ-5D vs placebo

Lrsquoeffetto del trattamento sui sintomi depressivi egrave

stato per un 80 diretto sulla depressione

valutato con la BDI per un 20 indiretto legato ad un miglioramento dellrsquo UPDRS III

Trattamento della depressione in MP

DepressioneMP

PD (90)

HC (90)

Major Depression 211 33

Dysthymia 188 44

DAP 30 33

Anxiety 111 144

DOC 33 22

Mov Disord 2010

Depressed compared to non depressed dopaminergic and noradrenergic denervation

Locus coeruleus

Medial thalamus

Left

Ventral

striatum

Right Amigdala

Remy et al Brain 2005

[11C]RTI 32 PET

Biochemical Pharmacology 2007

0 20 40 60 80 100

SNc

DRN

LC

DVN

DPDNDPD

0 20 40 60 80 100

SNc

DRN

LC

DVN

DPDNDPD

GLIOSIS

NEURONAL LOSS

DVN dorsal vagus nerveLC locus coeruleusDRN dorsal raphe nucleiSNc substantia nigra c

Frisina et al 2009 modified

Mapping the norepinephrine transporter

NETSCAN

A Varrone et al 2010

[11C]DASB binding positively correlated with

depression but not with disease severityduration

wide-spread increase in [11C]DASB in

PDdepression

1 dorsolateral cortices

2 prefrontal cortices

Lower uptake in depressedvs non-depressed PD

bull 8 non depressedPD patients

bull 4 depressed PD patients

Ballanger et al 2011

x= 6 plt0001 y= 8 plt0001

y= -1 plt001z= 43 plt0001

z= 10 plt0001

Lower 11C-DASB uptake

in PD with depression

7 PD depr lt 7 PD without depression

amygdalacingulate

cingulate

thalamus

thalamus

striatum

Courtesy of Nicola Pavese

Autore

annoCampione Disegno Farmaco

Scala

usata

Risultati(decremento punteggio

scala)

Follow up

Leentjens200333

6

6Doppio cieco

Sertralina

PlaceboMADRS

-9

-1110 settimane

Fregni200434

21

21Doppio cieco

Fluoxetina

TMS

HAM D

BDI

-9sect-8sect

-10sect-8sect8 settimane

Serrano Duenas200235

37

40Randomizzato

Fluoxetina

AmitriptilinaHAM D

Inefficace

Efficace 12 mesi

Avila200336

7

9Randomizzato

Fluoxetina

NefazodoneBDI

Ugualmente

efficaci sect12 settimane

Antonini200637

12

11Doppio cieco

Sertralina

AmitriptilinaHAM D

-12sect

-11sect3 mesi

Barone200638

33

34Doppio cieco

Pramipexole

SertralineHAM D

-10sect

-9sect12 settimane

Devos200823

16

15

17

Doppio cieco

Placebo

Citalopram

Desimipramina

MADRS

-9

-14

-20

4 settimane

Menza200921

17

18

17

Doppio cieco

Placebo

Paroxetina

Nortriptilina

HAM D

-4

-6

-11

8 settimane

Richard201224

39

42

34

Doppio cieco

Placebo

Paroxetina

Venlafaxina ER

HAM D

-68

-13

-11

12 settimane

differenza significativa rispetto al placebo

sect differenza significativa rispetto al basale

Studi sullrsquoutilizzo di SSRI nei pazienti con Malattia di Parkinson e depressione (2003-2013)

Efficacy and Acceptability of selective serotoninreuptake inhibitors for the treatment of depression in Parkinsons disease

a systematic review andmeta-analysis of randomized controlled trials

Petros Skapinakis et all

BMC Neurology 2010 1049

bull Il 63 degli antidepressivi prescritti sono SSRI e nel 7 sono TCAbull Crsquoegrave ancora incertezza sullrsquoefficacia degli SSRI nella depressione in MPbull I risultati di questo studio mostrano che la pratica clinica attuale non

egrave supportata da forti evidenze

Trattamento della depressione in MP

DepressioneMP

Depression and PD clinical features

Anhedonia

Low mood and impaired interest or

ability to experience pleasure

Core symptomOther clinical features

1 Altered sleep patterns

2 Change in weight

3 Loss of libido

4 Psychomotor retardation

5 Reduced energy

Starkstein Mov Disord 2008

Imaging del rilascio di dopamina

10 di riduzione

del 11C raclopride

BP riflette un

incremento di 5

volte del rilascio di

Dopamina

Journal of Psychiatric Research 2006

DAergic

PRE -

SYNAPTIC

NEURON

DAT

Tracer

PET SPECTPOST -

SYNAPTIC

NEURON

DAT TRACER BINDING = Density of DAergic terminals

Healthy Control Parkinsonrsquos disease

11C-RTI 3218F-CFT123I-beta CIT 123I-FP-CIT123I-altropane99mTc-TroDAT

Depressive symptoms in Parkinsons disease are related to reduced [123I]FP-CIT binding in the caudate nucleus

Vriend 2014

Frosini D et al 2015

Mesolimbic dopaminergic dysfunction in Parkinsonrsquos disease-depression evidence from a 123I-FP-CIT SPECT investigation

Pd-nd (35) PD-d (15)

MeanplusmnSD MeanplusmnSD

Age at onset (years) 683plusmn71 661plusmn55

Disease duration (years) 12plusmn10 10plusmn05

Age at scan (years) 671plusmn69 668plusmn54

UPDRS II 58plusmn36 70plusmn34

UPDRS III 156plusmn70 157plusmn53

MMSE 279plusmn17 275plusmn13

BDI 25plusmn09 168plusmn38

Left caudate FP-CIT uptake 32 plusmn12 34plusmn 11

Right caudate FP-CIT uptake 33plusmn11 34 plusmn11

Left putamen FP-CIT uptake 17plusmn 10 18 plusmn09

Right putamen FP-CIT uptake 18plusmn 08 12 plusmn08

Pramipexole for the treatment of depressive symptomsin patients with Parkinsonrsquos disease a randomised

double-blind placebo-controlled trialPaolo Barone Werner Poewe Stefan Albrecht Catherine Debieuvre Dan Massey Olivier Rascol Eduardo Tolosa Daniel Weintraub

Lancet Neurol 2010 9 573ndash80

Miglioramento dello scoreBeck depression Inventory(BDI) Geriatric DepressionScale (GDS) UPDRS II e EQ-5D vs placebo

Lrsquoeffetto del trattamento sui sintomi depressivi egrave

stato per un 80 diretto sulla depressione

valutato con la BDI per un 20 indiretto legato ad un miglioramento dellrsquo UPDRS III

Trattamento della depressione in MP

DepressioneMP

PD (90)

HC (90)

Major Depression 211 33

Dysthymia 188 44

DAP 30 33

Anxiety 111 144

DOC 33 22

Mov Disord 2010

Depressed compared to non depressed dopaminergic and noradrenergic denervation

Locus coeruleus

Medial thalamus

Left

Ventral

striatum

Right Amigdala

Remy et al Brain 2005

[11C]RTI 32 PET

Biochemical Pharmacology 2007

0 20 40 60 80 100

SNc

DRN

LC

DVN

DPDNDPD

0 20 40 60 80 100

SNc

DRN

LC

DVN

DPDNDPD

GLIOSIS

NEURONAL LOSS

DVN dorsal vagus nerveLC locus coeruleusDRN dorsal raphe nucleiSNc substantia nigra c

Frisina et al 2009 modified

Mapping the norepinephrine transporter

NETSCAN

A Varrone et al 2010

Lower uptake in depressedvs non-depressed PD

bull 8 non depressedPD patients

bull 4 depressed PD patients

Ballanger et al 2011

x= 6 plt0001 y= 8 plt0001

y= -1 plt001z= 43 plt0001

z= 10 plt0001

Lower 11C-DASB uptake

in PD with depression

7 PD depr lt 7 PD without depression

amygdalacingulate

cingulate

thalamus

thalamus

striatum

Courtesy of Nicola Pavese

Autore

annoCampione Disegno Farmaco

Scala

usata

Risultati(decremento punteggio

scala)

Follow up

Leentjens200333

6

6Doppio cieco

Sertralina

PlaceboMADRS

-9

-1110 settimane

Fregni200434

21

21Doppio cieco

Fluoxetina

TMS

HAM D

BDI

-9sect-8sect

-10sect-8sect8 settimane

Serrano Duenas200235

37

40Randomizzato

Fluoxetina

AmitriptilinaHAM D

Inefficace

Efficace 12 mesi

Avila200336

7

9Randomizzato

Fluoxetina

NefazodoneBDI

Ugualmente

efficaci sect12 settimane

Antonini200637

12

11Doppio cieco

Sertralina

AmitriptilinaHAM D

-12sect

-11sect3 mesi

Barone200638

33

34Doppio cieco

Pramipexole

SertralineHAM D

-10sect

-9sect12 settimane

Devos200823

16

15

17

Doppio cieco

Placebo

Citalopram

Desimipramina

MADRS

-9

-14

-20

4 settimane

Menza200921

17

18

17

Doppio cieco

Placebo

Paroxetina

Nortriptilina

HAM D

-4

-6

-11

8 settimane

Richard201224

39

42

34

Doppio cieco

Placebo

Paroxetina

Venlafaxina ER

HAM D

-68

-13

-11

12 settimane

differenza significativa rispetto al placebo

sect differenza significativa rispetto al basale

Studi sullrsquoutilizzo di SSRI nei pazienti con Malattia di Parkinson e depressione (2003-2013)

Efficacy and Acceptability of selective serotoninreuptake inhibitors for the treatment of depression in Parkinsons disease

a systematic review andmeta-analysis of randomized controlled trials

Petros Skapinakis et all

BMC Neurology 2010 1049

bull Il 63 degli antidepressivi prescritti sono SSRI e nel 7 sono TCAbull Crsquoegrave ancora incertezza sullrsquoefficacia degli SSRI nella depressione in MPbull I risultati di questo studio mostrano che la pratica clinica attuale non

egrave supportata da forti evidenze

Trattamento della depressione in MP

DepressioneMP

Depression and PD clinical features

Anhedonia

Low mood and impaired interest or

ability to experience pleasure

Core symptomOther clinical features

1 Altered sleep patterns

2 Change in weight

3 Loss of libido

4 Psychomotor retardation

5 Reduced energy

Starkstein Mov Disord 2008

Imaging del rilascio di dopamina

10 di riduzione

del 11C raclopride

BP riflette un

incremento di 5

volte del rilascio di

Dopamina

Journal of Psychiatric Research 2006

DAergic

PRE -

SYNAPTIC

NEURON

DAT

Tracer

PET SPECTPOST -

SYNAPTIC

NEURON

DAT TRACER BINDING = Density of DAergic terminals

Healthy Control Parkinsonrsquos disease

11C-RTI 3218F-CFT123I-beta CIT 123I-FP-CIT123I-altropane99mTc-TroDAT

Depressive symptoms in Parkinsons disease are related to reduced [123I]FP-CIT binding in the caudate nucleus

Vriend 2014

Frosini D et al 2015

Mesolimbic dopaminergic dysfunction in Parkinsonrsquos disease-depression evidence from a 123I-FP-CIT SPECT investigation

Pd-nd (35) PD-d (15)

MeanplusmnSD MeanplusmnSD

Age at onset (years) 683plusmn71 661plusmn55

Disease duration (years) 12plusmn10 10plusmn05

Age at scan (years) 671plusmn69 668plusmn54

UPDRS II 58plusmn36 70plusmn34

UPDRS III 156plusmn70 157plusmn53

MMSE 279plusmn17 275plusmn13

BDI 25plusmn09 168plusmn38

Left caudate FP-CIT uptake 32 plusmn12 34plusmn 11

Right caudate FP-CIT uptake 33plusmn11 34 plusmn11

Left putamen FP-CIT uptake 17plusmn 10 18 plusmn09

Right putamen FP-CIT uptake 18plusmn 08 12 plusmn08

Pramipexole for the treatment of depressive symptomsin patients with Parkinsonrsquos disease a randomised

double-blind placebo-controlled trialPaolo Barone Werner Poewe Stefan Albrecht Catherine Debieuvre Dan Massey Olivier Rascol Eduardo Tolosa Daniel Weintraub

Lancet Neurol 2010 9 573ndash80

Miglioramento dello scoreBeck depression Inventory(BDI) Geriatric DepressionScale (GDS) UPDRS II e EQ-5D vs placebo

Lrsquoeffetto del trattamento sui sintomi depressivi egrave

stato per un 80 diretto sulla depressione

valutato con la BDI per un 20 indiretto legato ad un miglioramento dellrsquo UPDRS III

Trattamento della depressione in MP

DepressioneMP

PD (90)

HC (90)

Major Depression 211 33

Dysthymia 188 44

DAP 30 33

Anxiety 111 144

DOC 33 22

Mov Disord 2010

Depressed compared to non depressed dopaminergic and noradrenergic denervation

Locus coeruleus

Medial thalamus

Left

Ventral

striatum

Right Amigdala

Remy et al Brain 2005

[11C]RTI 32 PET

Biochemical Pharmacology 2007

0 20 40 60 80 100

SNc

DRN

LC

DVN

DPDNDPD

0 20 40 60 80 100

SNc

DRN

LC

DVN

DPDNDPD

GLIOSIS

NEURONAL LOSS

DVN dorsal vagus nerveLC locus coeruleusDRN dorsal raphe nucleiSNc substantia nigra c

Frisina et al 2009 modified

Mapping the norepinephrine transporter

NETSCAN

A Varrone et al 2010

x= 6 plt0001 y= 8 plt0001

y= -1 plt001z= 43 plt0001

z= 10 plt0001

Lower 11C-DASB uptake

in PD with depression

7 PD depr lt 7 PD without depression

amygdalacingulate

cingulate

thalamus

thalamus

striatum

Courtesy of Nicola Pavese

Autore

annoCampione Disegno Farmaco

Scala

usata

Risultati(decremento punteggio

scala)

Follow up

Leentjens200333

6

6Doppio cieco

Sertralina

PlaceboMADRS

-9

-1110 settimane

Fregni200434

21

21Doppio cieco

Fluoxetina

TMS

HAM D

BDI

-9sect-8sect

-10sect-8sect8 settimane

Serrano Duenas200235

37

40Randomizzato

Fluoxetina

AmitriptilinaHAM D

Inefficace

Efficace 12 mesi

Avila200336

7

9Randomizzato

Fluoxetina

NefazodoneBDI

Ugualmente

efficaci sect12 settimane

Antonini200637

12

11Doppio cieco

Sertralina

AmitriptilinaHAM D

-12sect

-11sect3 mesi

Barone200638

33

34Doppio cieco

Pramipexole

SertralineHAM D

-10sect

-9sect12 settimane

Devos200823

16

15

17

Doppio cieco

Placebo

Citalopram

Desimipramina

MADRS

-9

-14

-20

4 settimane

Menza200921

17

18

17

Doppio cieco

Placebo

Paroxetina

Nortriptilina

HAM D

-4

-6

-11

8 settimane

Richard201224

39

42

34

Doppio cieco

Placebo

Paroxetina

Venlafaxina ER

HAM D

-68

-13

-11

12 settimane

differenza significativa rispetto al placebo

sect differenza significativa rispetto al basale

Studi sullrsquoutilizzo di SSRI nei pazienti con Malattia di Parkinson e depressione (2003-2013)

Efficacy and Acceptability of selective serotoninreuptake inhibitors for the treatment of depression in Parkinsons disease

a systematic review andmeta-analysis of randomized controlled trials

Petros Skapinakis et all

BMC Neurology 2010 1049

bull Il 63 degli antidepressivi prescritti sono SSRI e nel 7 sono TCAbull Crsquoegrave ancora incertezza sullrsquoefficacia degli SSRI nella depressione in MPbull I risultati di questo studio mostrano che la pratica clinica attuale non

egrave supportata da forti evidenze

Trattamento della depressione in MP

DepressioneMP

Depression and PD clinical features

Anhedonia

Low mood and impaired interest or

ability to experience pleasure

Core symptomOther clinical features

1 Altered sleep patterns

2 Change in weight

3 Loss of libido

4 Psychomotor retardation

5 Reduced energy

Starkstein Mov Disord 2008

Imaging del rilascio di dopamina

10 di riduzione

del 11C raclopride

BP riflette un

incremento di 5

volte del rilascio di

Dopamina

Journal of Psychiatric Research 2006

DAergic

PRE -

SYNAPTIC

NEURON

DAT

Tracer

PET SPECTPOST -

SYNAPTIC

NEURON

DAT TRACER BINDING = Density of DAergic terminals

Healthy Control Parkinsonrsquos disease

11C-RTI 3218F-CFT123I-beta CIT 123I-FP-CIT123I-altropane99mTc-TroDAT

Depressive symptoms in Parkinsons disease are related to reduced [123I]FP-CIT binding in the caudate nucleus

Vriend 2014

Frosini D et al 2015

Mesolimbic dopaminergic dysfunction in Parkinsonrsquos disease-depression evidence from a 123I-FP-CIT SPECT investigation

Pd-nd (35) PD-d (15)

MeanplusmnSD MeanplusmnSD

Age at onset (years) 683plusmn71 661plusmn55

Disease duration (years) 12plusmn10 10plusmn05

Age at scan (years) 671plusmn69 668plusmn54

UPDRS II 58plusmn36 70plusmn34

UPDRS III 156plusmn70 157plusmn53

MMSE 279plusmn17 275plusmn13

BDI 25plusmn09 168plusmn38

Left caudate FP-CIT uptake 32 plusmn12 34plusmn 11

Right caudate FP-CIT uptake 33plusmn11 34 plusmn11

Left putamen FP-CIT uptake 17plusmn 10 18 plusmn09

Right putamen FP-CIT uptake 18plusmn 08 12 plusmn08

Pramipexole for the treatment of depressive symptomsin patients with Parkinsonrsquos disease a randomised

double-blind placebo-controlled trialPaolo Barone Werner Poewe Stefan Albrecht Catherine Debieuvre Dan Massey Olivier Rascol Eduardo Tolosa Daniel Weintraub

Lancet Neurol 2010 9 573ndash80

Miglioramento dello scoreBeck depression Inventory(BDI) Geriatric DepressionScale (GDS) UPDRS II e EQ-5D vs placebo

Lrsquoeffetto del trattamento sui sintomi depressivi egrave

stato per un 80 diretto sulla depressione

valutato con la BDI per un 20 indiretto legato ad un miglioramento dellrsquo UPDRS III

Trattamento della depressione in MP

DepressioneMP

PD (90)

HC (90)

Major Depression 211 33

Dysthymia 188 44

DAP 30 33

Anxiety 111 144

DOC 33 22

Mov Disord 2010

Depressed compared to non depressed dopaminergic and noradrenergic denervation

Locus coeruleus

Medial thalamus

Left

Ventral

striatum

Right Amigdala

Remy et al Brain 2005

[11C]RTI 32 PET

Biochemical Pharmacology 2007

0 20 40 60 80 100

SNc

DRN

LC

DVN

DPDNDPD

0 20 40 60 80 100

SNc

DRN

LC

DVN

DPDNDPD

GLIOSIS

NEURONAL LOSS

DVN dorsal vagus nerveLC locus coeruleusDRN dorsal raphe nucleiSNc substantia nigra c

Frisina et al 2009 modified

Mapping the norepinephrine transporter

NETSCAN

A Varrone et al 2010

Autore

annoCampione Disegno Farmaco

Scala

usata

Risultati(decremento punteggio

scala)

Follow up

Leentjens200333

6

6Doppio cieco

Sertralina

PlaceboMADRS

-9

-1110 settimane

Fregni200434

21

21Doppio cieco

Fluoxetina

TMS

HAM D

BDI

-9sect-8sect

-10sect-8sect8 settimane

Serrano Duenas200235

37

40Randomizzato

Fluoxetina

AmitriptilinaHAM D

Inefficace

Efficace 12 mesi

Avila200336

7

9Randomizzato

Fluoxetina

NefazodoneBDI

Ugualmente

efficaci sect12 settimane

Antonini200637

12

11Doppio cieco

Sertralina

AmitriptilinaHAM D

-12sect

-11sect3 mesi

Barone200638

33

34Doppio cieco

Pramipexole

SertralineHAM D

-10sect

-9sect12 settimane

Devos200823

16

15

17

Doppio cieco

Placebo

Citalopram

Desimipramina

MADRS

-9

-14

-20

4 settimane

Menza200921

17

18

17

Doppio cieco

Placebo

Paroxetina

Nortriptilina

HAM D

-4

-6

-11

8 settimane

Richard201224

39

42

34

Doppio cieco

Placebo

Paroxetina

Venlafaxina ER

HAM D

-68

-13

-11

12 settimane

differenza significativa rispetto al placebo

sect differenza significativa rispetto al basale

Studi sullrsquoutilizzo di SSRI nei pazienti con Malattia di Parkinson e depressione (2003-2013)

Efficacy and Acceptability of selective serotoninreuptake inhibitors for the treatment of depression in Parkinsons disease

a systematic review andmeta-analysis of randomized controlled trials

Petros Skapinakis et all

BMC Neurology 2010 1049

bull Il 63 degli antidepressivi prescritti sono SSRI e nel 7 sono TCAbull Crsquoegrave ancora incertezza sullrsquoefficacia degli SSRI nella depressione in MPbull I risultati di questo studio mostrano che la pratica clinica attuale non

egrave supportata da forti evidenze

Trattamento della depressione in MP

DepressioneMP

Depression and PD clinical features

Anhedonia

Low mood and impaired interest or

ability to experience pleasure

Core symptomOther clinical features

1 Altered sleep patterns

2 Change in weight

3 Loss of libido

4 Psychomotor retardation

5 Reduced energy

Starkstein Mov Disord 2008

Imaging del rilascio di dopamina

10 di riduzione

del 11C raclopride

BP riflette un

incremento di 5

volte del rilascio di

Dopamina

Journal of Psychiatric Research 2006

DAergic

PRE -

SYNAPTIC

NEURON

DAT

Tracer

PET SPECTPOST -

SYNAPTIC

NEURON

DAT TRACER BINDING = Density of DAergic terminals

Healthy Control Parkinsonrsquos disease

11C-RTI 3218F-CFT123I-beta CIT 123I-FP-CIT123I-altropane99mTc-TroDAT

Depressive symptoms in Parkinsons disease are related to reduced [123I]FP-CIT binding in the caudate nucleus

Vriend 2014

Frosini D et al 2015

Mesolimbic dopaminergic dysfunction in Parkinsonrsquos disease-depression evidence from a 123I-FP-CIT SPECT investigation

Pd-nd (35) PD-d (15)

MeanplusmnSD MeanplusmnSD

Age at onset (years) 683plusmn71 661plusmn55

Disease duration (years) 12plusmn10 10plusmn05

Age at scan (years) 671plusmn69 668plusmn54

UPDRS II 58plusmn36 70plusmn34

UPDRS III 156plusmn70 157plusmn53

MMSE 279plusmn17 275plusmn13

BDI 25plusmn09 168plusmn38

Left caudate FP-CIT uptake 32 plusmn12 34plusmn 11

Right caudate FP-CIT uptake 33plusmn11 34 plusmn11

Left putamen FP-CIT uptake 17plusmn 10 18 plusmn09

Right putamen FP-CIT uptake 18plusmn 08 12 plusmn08

Pramipexole for the treatment of depressive symptomsin patients with Parkinsonrsquos disease a randomised

double-blind placebo-controlled trialPaolo Barone Werner Poewe Stefan Albrecht Catherine Debieuvre Dan Massey Olivier Rascol Eduardo Tolosa Daniel Weintraub

Lancet Neurol 2010 9 573ndash80

Miglioramento dello scoreBeck depression Inventory(BDI) Geriatric DepressionScale (GDS) UPDRS II e EQ-5D vs placebo

Lrsquoeffetto del trattamento sui sintomi depressivi egrave

stato per un 80 diretto sulla depressione

valutato con la BDI per un 20 indiretto legato ad un miglioramento dellrsquo UPDRS III

Trattamento della depressione in MP

DepressioneMP

PD (90)

HC (90)

Major Depression 211 33

Dysthymia 188 44

DAP 30 33

Anxiety 111 144

DOC 33 22

Mov Disord 2010

Depressed compared to non depressed dopaminergic and noradrenergic denervation

Locus coeruleus

Medial thalamus

Left

Ventral

striatum

Right Amigdala

Remy et al Brain 2005

[11C]RTI 32 PET

Biochemical Pharmacology 2007

0 20 40 60 80 100

SNc

DRN

LC

DVN

DPDNDPD

0 20 40 60 80 100

SNc

DRN

LC

DVN

DPDNDPD

GLIOSIS

NEURONAL LOSS

DVN dorsal vagus nerveLC locus coeruleusDRN dorsal raphe nucleiSNc substantia nigra c

Frisina et al 2009 modified

Mapping the norepinephrine transporter

NETSCAN

A Varrone et al 2010

Efficacy and Acceptability of selective serotoninreuptake inhibitors for the treatment of depression in Parkinsons disease

a systematic review andmeta-analysis of randomized controlled trials

Petros Skapinakis et all

BMC Neurology 2010 1049

bull Il 63 degli antidepressivi prescritti sono SSRI e nel 7 sono TCAbull Crsquoegrave ancora incertezza sullrsquoefficacia degli SSRI nella depressione in MPbull I risultati di questo studio mostrano che la pratica clinica attuale non

egrave supportata da forti evidenze

Trattamento della depressione in MP

DepressioneMP

Depression and PD clinical features

Anhedonia

Low mood and impaired interest or

ability to experience pleasure

Core symptomOther clinical features

1 Altered sleep patterns

2 Change in weight

3 Loss of libido

4 Psychomotor retardation

5 Reduced energy

Starkstein Mov Disord 2008

Imaging del rilascio di dopamina

10 di riduzione

del 11C raclopride

BP riflette un

incremento di 5

volte del rilascio di

Dopamina

Journal of Psychiatric Research 2006

DAergic

PRE -

SYNAPTIC

NEURON

DAT

Tracer

PET SPECTPOST -

SYNAPTIC

NEURON

DAT TRACER BINDING = Density of DAergic terminals

Healthy Control Parkinsonrsquos disease

11C-RTI 3218F-CFT123I-beta CIT 123I-FP-CIT123I-altropane99mTc-TroDAT

Depressive symptoms in Parkinsons disease are related to reduced [123I]FP-CIT binding in the caudate nucleus

Vriend 2014

Frosini D et al 2015

Mesolimbic dopaminergic dysfunction in Parkinsonrsquos disease-depression evidence from a 123I-FP-CIT SPECT investigation

Pd-nd (35) PD-d (15)

MeanplusmnSD MeanplusmnSD

Age at onset (years) 683plusmn71 661plusmn55

Disease duration (years) 12plusmn10 10plusmn05

Age at scan (years) 671plusmn69 668plusmn54

UPDRS II 58plusmn36 70plusmn34

UPDRS III 156plusmn70 157plusmn53

MMSE 279plusmn17 275plusmn13

BDI 25plusmn09 168plusmn38

Left caudate FP-CIT uptake 32 plusmn12 34plusmn 11

Right caudate FP-CIT uptake 33plusmn11 34 plusmn11

Left putamen FP-CIT uptake 17plusmn 10 18 plusmn09

Right putamen FP-CIT uptake 18plusmn 08 12 plusmn08

Pramipexole for the treatment of depressive symptomsin patients with Parkinsonrsquos disease a randomised

double-blind placebo-controlled trialPaolo Barone Werner Poewe Stefan Albrecht Catherine Debieuvre Dan Massey Olivier Rascol Eduardo Tolosa Daniel Weintraub

Lancet Neurol 2010 9 573ndash80

Miglioramento dello scoreBeck depression Inventory(BDI) Geriatric DepressionScale (GDS) UPDRS II e EQ-5D vs placebo

Lrsquoeffetto del trattamento sui sintomi depressivi egrave

stato per un 80 diretto sulla depressione

valutato con la BDI per un 20 indiretto legato ad un miglioramento dellrsquo UPDRS III

Trattamento della depressione in MP

DepressioneMP

PD (90)

HC (90)

Major Depression 211 33

Dysthymia 188 44

DAP 30 33

Anxiety 111 144

DOC 33 22

Mov Disord 2010

Depressed compared to non depressed dopaminergic and noradrenergic denervation

Locus coeruleus

Medial thalamus

Left

Ventral

striatum

Right Amigdala

Remy et al Brain 2005

[11C]RTI 32 PET

Biochemical Pharmacology 2007

0 20 40 60 80 100

SNc

DRN

LC

DVN

DPDNDPD

0 20 40 60 80 100

SNc

DRN

LC

DVN

DPDNDPD

GLIOSIS

NEURONAL LOSS

DVN dorsal vagus nerveLC locus coeruleusDRN dorsal raphe nucleiSNc substantia nigra c

Frisina et al 2009 modified

Mapping the norepinephrine transporter

NETSCAN

A Varrone et al 2010

Depression and PD clinical features

Anhedonia

Low mood and impaired interest or

ability to experience pleasure

Core symptomOther clinical features

1 Altered sleep patterns

2 Change in weight

3 Loss of libido

4 Psychomotor retardation

5 Reduced energy

Starkstein Mov Disord 2008

Imaging del rilascio di dopamina

10 di riduzione

del 11C raclopride

BP riflette un

incremento di 5

volte del rilascio di

Dopamina

Journal of Psychiatric Research 2006

DAergic

PRE -

SYNAPTIC

NEURON

DAT

Tracer

PET SPECTPOST -

SYNAPTIC

NEURON

DAT TRACER BINDING = Density of DAergic terminals

Healthy Control Parkinsonrsquos disease

11C-RTI 3218F-CFT123I-beta CIT 123I-FP-CIT123I-altropane99mTc-TroDAT

Depressive symptoms in Parkinsons disease are related to reduced [123I]FP-CIT binding in the caudate nucleus

Vriend 2014

Frosini D et al 2015

Mesolimbic dopaminergic dysfunction in Parkinsonrsquos disease-depression evidence from a 123I-FP-CIT SPECT investigation

Pd-nd (35) PD-d (15)

MeanplusmnSD MeanplusmnSD

Age at onset (years) 683plusmn71 661plusmn55

Disease duration (years) 12plusmn10 10plusmn05

Age at scan (years) 671plusmn69 668plusmn54

UPDRS II 58plusmn36 70plusmn34

UPDRS III 156plusmn70 157plusmn53

MMSE 279plusmn17 275plusmn13

BDI 25plusmn09 168plusmn38

Left caudate FP-CIT uptake 32 plusmn12 34plusmn 11

Right caudate FP-CIT uptake 33plusmn11 34 plusmn11

Left putamen FP-CIT uptake 17plusmn 10 18 plusmn09

Right putamen FP-CIT uptake 18plusmn 08 12 plusmn08

Pramipexole for the treatment of depressive symptomsin patients with Parkinsonrsquos disease a randomised

double-blind placebo-controlled trialPaolo Barone Werner Poewe Stefan Albrecht Catherine Debieuvre Dan Massey Olivier Rascol Eduardo Tolosa Daniel Weintraub

Lancet Neurol 2010 9 573ndash80

Miglioramento dello scoreBeck depression Inventory(BDI) Geriatric DepressionScale (GDS) UPDRS II e EQ-5D vs placebo

Lrsquoeffetto del trattamento sui sintomi depressivi egrave

stato per un 80 diretto sulla depressione

valutato con la BDI per un 20 indiretto legato ad un miglioramento dellrsquo UPDRS III

Trattamento della depressione in MP

DepressioneMP

PD (90)

HC (90)

Major Depression 211 33

Dysthymia 188 44

DAP 30 33

Anxiety 111 144

DOC 33 22

Mov Disord 2010

Depressed compared to non depressed dopaminergic and noradrenergic denervation

Locus coeruleus

Medial thalamus

Left

Ventral

striatum

Right Amigdala

Remy et al Brain 2005

[11C]RTI 32 PET

Biochemical Pharmacology 2007

0 20 40 60 80 100

SNc

DRN

LC

DVN

DPDNDPD

0 20 40 60 80 100

SNc

DRN

LC

DVN

DPDNDPD

GLIOSIS

NEURONAL LOSS

DVN dorsal vagus nerveLC locus coeruleusDRN dorsal raphe nucleiSNc substantia nigra c

Frisina et al 2009 modified

Mapping the norepinephrine transporter

NETSCAN

A Varrone et al 2010

Imaging del rilascio di dopamina

10 di riduzione

del 11C raclopride

BP riflette un

incremento di 5

volte del rilascio di

Dopamina

Journal of Psychiatric Research 2006

DAergic

PRE -

SYNAPTIC

NEURON

DAT

Tracer

PET SPECTPOST -

SYNAPTIC

NEURON

DAT TRACER BINDING = Density of DAergic terminals

Healthy Control Parkinsonrsquos disease

11C-RTI 3218F-CFT123I-beta CIT 123I-FP-CIT123I-altropane99mTc-TroDAT

Depressive symptoms in Parkinsons disease are related to reduced [123I]FP-CIT binding in the caudate nucleus

Vriend 2014

Frosini D et al 2015

Mesolimbic dopaminergic dysfunction in Parkinsonrsquos disease-depression evidence from a 123I-FP-CIT SPECT investigation

Pd-nd (35) PD-d (15)

MeanplusmnSD MeanplusmnSD

Age at onset (years) 683plusmn71 661plusmn55

Disease duration (years) 12plusmn10 10plusmn05

Age at scan (years) 671plusmn69 668plusmn54

UPDRS II 58plusmn36 70plusmn34

UPDRS III 156plusmn70 157plusmn53

MMSE 279plusmn17 275plusmn13

BDI 25plusmn09 168plusmn38

Left caudate FP-CIT uptake 32 plusmn12 34plusmn 11

Right caudate FP-CIT uptake 33plusmn11 34 plusmn11

Left putamen FP-CIT uptake 17plusmn 10 18 plusmn09

Right putamen FP-CIT uptake 18plusmn 08 12 plusmn08

Pramipexole for the treatment of depressive symptomsin patients with Parkinsonrsquos disease a randomised

double-blind placebo-controlled trialPaolo Barone Werner Poewe Stefan Albrecht Catherine Debieuvre Dan Massey Olivier Rascol Eduardo Tolosa Daniel Weintraub

Lancet Neurol 2010 9 573ndash80

Miglioramento dello scoreBeck depression Inventory(BDI) Geriatric DepressionScale (GDS) UPDRS II e EQ-5D vs placebo

Lrsquoeffetto del trattamento sui sintomi depressivi egrave

stato per un 80 diretto sulla depressione

valutato con la BDI per un 20 indiretto legato ad un miglioramento dellrsquo UPDRS III

Trattamento della depressione in MP

DepressioneMP

PD (90)

HC (90)

Major Depression 211 33

Dysthymia 188 44

DAP 30 33

Anxiety 111 144

DOC 33 22

Mov Disord 2010

Depressed compared to non depressed dopaminergic and noradrenergic denervation

Locus coeruleus

Medial thalamus

Left

Ventral

striatum

Right Amigdala

Remy et al Brain 2005

[11C]RTI 32 PET

Biochemical Pharmacology 2007

0 20 40 60 80 100

SNc

DRN

LC

DVN

DPDNDPD

0 20 40 60 80 100

SNc

DRN

LC

DVN

DPDNDPD

GLIOSIS

NEURONAL LOSS

DVN dorsal vagus nerveLC locus coeruleusDRN dorsal raphe nucleiSNc substantia nigra c

Frisina et al 2009 modified

Mapping the norepinephrine transporter

NETSCAN

A Varrone et al 2010

Journal of Psychiatric Research 2006

DAergic

PRE -

SYNAPTIC

NEURON

DAT

Tracer

PET SPECTPOST -

SYNAPTIC

NEURON

DAT TRACER BINDING = Density of DAergic terminals

Healthy Control Parkinsonrsquos disease

11C-RTI 3218F-CFT123I-beta CIT 123I-FP-CIT123I-altropane99mTc-TroDAT

Depressive symptoms in Parkinsons disease are related to reduced [123I]FP-CIT binding in the caudate nucleus

Vriend 2014

Frosini D et al 2015

Mesolimbic dopaminergic dysfunction in Parkinsonrsquos disease-depression evidence from a 123I-FP-CIT SPECT investigation

Pd-nd (35) PD-d (15)

MeanplusmnSD MeanplusmnSD

Age at onset (years) 683plusmn71 661plusmn55

Disease duration (years) 12plusmn10 10plusmn05

Age at scan (years) 671plusmn69 668plusmn54

UPDRS II 58plusmn36 70plusmn34

UPDRS III 156plusmn70 157plusmn53

MMSE 279plusmn17 275plusmn13

BDI 25plusmn09 168plusmn38

Left caudate FP-CIT uptake 32 plusmn12 34plusmn 11

Right caudate FP-CIT uptake 33plusmn11 34 plusmn11

Left putamen FP-CIT uptake 17plusmn 10 18 plusmn09

Right putamen FP-CIT uptake 18plusmn 08 12 plusmn08

Pramipexole for the treatment of depressive symptomsin patients with Parkinsonrsquos disease a randomised

double-blind placebo-controlled trialPaolo Barone Werner Poewe Stefan Albrecht Catherine Debieuvre Dan Massey Olivier Rascol Eduardo Tolosa Daniel Weintraub

Lancet Neurol 2010 9 573ndash80

Miglioramento dello scoreBeck depression Inventory(BDI) Geriatric DepressionScale (GDS) UPDRS II e EQ-5D vs placebo

Lrsquoeffetto del trattamento sui sintomi depressivi egrave

stato per un 80 diretto sulla depressione

valutato con la BDI per un 20 indiretto legato ad un miglioramento dellrsquo UPDRS III

Trattamento della depressione in MP

DepressioneMP

PD (90)

HC (90)

Major Depression 211 33

Dysthymia 188 44

DAP 30 33

Anxiety 111 144

DOC 33 22

Mov Disord 2010

Depressed compared to non depressed dopaminergic and noradrenergic denervation

Locus coeruleus

Medial thalamus

Left

Ventral

striatum

Right Amigdala

Remy et al Brain 2005

[11C]RTI 32 PET

Biochemical Pharmacology 2007

0 20 40 60 80 100

SNc

DRN

LC

DVN

DPDNDPD

0 20 40 60 80 100

SNc

DRN

LC

DVN

DPDNDPD

GLIOSIS

NEURONAL LOSS

DVN dorsal vagus nerveLC locus coeruleusDRN dorsal raphe nucleiSNc substantia nigra c

Frisina et al 2009 modified

Mapping the norepinephrine transporter

NETSCAN

A Varrone et al 2010

DAergic

PRE -

SYNAPTIC

NEURON

DAT

Tracer

PET SPECTPOST -

SYNAPTIC

NEURON

DAT TRACER BINDING = Density of DAergic terminals

Healthy Control Parkinsonrsquos disease

11C-RTI 3218F-CFT123I-beta CIT 123I-FP-CIT123I-altropane99mTc-TroDAT

Depressive symptoms in Parkinsons disease are related to reduced [123I]FP-CIT binding in the caudate nucleus

Vriend 2014

Frosini D et al 2015

Mesolimbic dopaminergic dysfunction in Parkinsonrsquos disease-depression evidence from a 123I-FP-CIT SPECT investigation

Pd-nd (35) PD-d (15)

MeanplusmnSD MeanplusmnSD

Age at onset (years) 683plusmn71 661plusmn55

Disease duration (years) 12plusmn10 10plusmn05

Age at scan (years) 671plusmn69 668plusmn54

UPDRS II 58plusmn36 70plusmn34

UPDRS III 156plusmn70 157plusmn53

MMSE 279plusmn17 275plusmn13

BDI 25plusmn09 168plusmn38

Left caudate FP-CIT uptake 32 plusmn12 34plusmn 11

Right caudate FP-CIT uptake 33plusmn11 34 plusmn11

Left putamen FP-CIT uptake 17plusmn 10 18 plusmn09

Right putamen FP-CIT uptake 18plusmn 08 12 plusmn08

Pramipexole for the treatment of depressive symptomsin patients with Parkinsonrsquos disease a randomised

double-blind placebo-controlled trialPaolo Barone Werner Poewe Stefan Albrecht Catherine Debieuvre Dan Massey Olivier Rascol Eduardo Tolosa Daniel Weintraub

Lancet Neurol 2010 9 573ndash80

Miglioramento dello scoreBeck depression Inventory(BDI) Geriatric DepressionScale (GDS) UPDRS II e EQ-5D vs placebo

Lrsquoeffetto del trattamento sui sintomi depressivi egrave

stato per un 80 diretto sulla depressione

valutato con la BDI per un 20 indiretto legato ad un miglioramento dellrsquo UPDRS III

Trattamento della depressione in MP

DepressioneMP

PD (90)

HC (90)

Major Depression 211 33

Dysthymia 188 44

DAP 30 33

Anxiety 111 144

DOC 33 22

Mov Disord 2010

Depressed compared to non depressed dopaminergic and noradrenergic denervation

Locus coeruleus

Medial thalamus

Left

Ventral

striatum

Right Amigdala

Remy et al Brain 2005

[11C]RTI 32 PET

Biochemical Pharmacology 2007

0 20 40 60 80 100

SNc

DRN

LC

DVN

DPDNDPD

0 20 40 60 80 100

SNc

DRN

LC

DVN

DPDNDPD

GLIOSIS

NEURONAL LOSS

DVN dorsal vagus nerveLC locus coeruleusDRN dorsal raphe nucleiSNc substantia nigra c

Frisina et al 2009 modified

Mapping the norepinephrine transporter

NETSCAN

A Varrone et al 2010

Depressive symptoms in Parkinsons disease are related to reduced [123I]FP-CIT binding in the caudate nucleus

Vriend 2014

Frosini D et al 2015

Mesolimbic dopaminergic dysfunction in Parkinsonrsquos disease-depression evidence from a 123I-FP-CIT SPECT investigation

Pd-nd (35) PD-d (15)

MeanplusmnSD MeanplusmnSD

Age at onset (years) 683plusmn71 661plusmn55

Disease duration (years) 12plusmn10 10plusmn05

Age at scan (years) 671plusmn69 668plusmn54

UPDRS II 58plusmn36 70plusmn34

UPDRS III 156plusmn70 157plusmn53

MMSE 279plusmn17 275plusmn13

BDI 25plusmn09 168plusmn38

Left caudate FP-CIT uptake 32 plusmn12 34plusmn 11

Right caudate FP-CIT uptake 33plusmn11 34 plusmn11

Left putamen FP-CIT uptake 17plusmn 10 18 plusmn09

Right putamen FP-CIT uptake 18plusmn 08 12 plusmn08

Pramipexole for the treatment of depressive symptomsin patients with Parkinsonrsquos disease a randomised

double-blind placebo-controlled trialPaolo Barone Werner Poewe Stefan Albrecht Catherine Debieuvre Dan Massey Olivier Rascol Eduardo Tolosa Daniel Weintraub

Lancet Neurol 2010 9 573ndash80

Miglioramento dello scoreBeck depression Inventory(BDI) Geriatric DepressionScale (GDS) UPDRS II e EQ-5D vs placebo

Lrsquoeffetto del trattamento sui sintomi depressivi egrave

stato per un 80 diretto sulla depressione

valutato con la BDI per un 20 indiretto legato ad un miglioramento dellrsquo UPDRS III

Trattamento della depressione in MP

DepressioneMP

PD (90)

HC (90)

Major Depression 211 33

Dysthymia 188 44

DAP 30 33

Anxiety 111 144

DOC 33 22

Mov Disord 2010

Depressed compared to non depressed dopaminergic and noradrenergic denervation

Locus coeruleus

Medial thalamus

Left

Ventral

striatum

Right Amigdala

Remy et al Brain 2005

[11C]RTI 32 PET

Biochemical Pharmacology 2007

0 20 40 60 80 100

SNc

DRN

LC

DVN

DPDNDPD

0 20 40 60 80 100

SNc

DRN

LC

DVN

DPDNDPD

GLIOSIS

NEURONAL LOSS

DVN dorsal vagus nerveLC locus coeruleusDRN dorsal raphe nucleiSNc substantia nigra c

Frisina et al 2009 modified

Mapping the norepinephrine transporter

NETSCAN

A Varrone et al 2010

Frosini D et al 2015

Mesolimbic dopaminergic dysfunction in Parkinsonrsquos disease-depression evidence from a 123I-FP-CIT SPECT investigation

Pd-nd (35) PD-d (15)

MeanplusmnSD MeanplusmnSD

Age at onset (years) 683plusmn71 661plusmn55

Disease duration (years) 12plusmn10 10plusmn05

Age at scan (years) 671plusmn69 668plusmn54

UPDRS II 58plusmn36 70plusmn34

UPDRS III 156plusmn70 157plusmn53

MMSE 279plusmn17 275plusmn13

BDI 25plusmn09 168plusmn38

Left caudate FP-CIT uptake 32 plusmn12 34plusmn 11

Right caudate FP-CIT uptake 33plusmn11 34 plusmn11

Left putamen FP-CIT uptake 17plusmn 10 18 plusmn09

Right putamen FP-CIT uptake 18plusmn 08 12 plusmn08

Pramipexole for the treatment of depressive symptomsin patients with Parkinsonrsquos disease a randomised

double-blind placebo-controlled trialPaolo Barone Werner Poewe Stefan Albrecht Catherine Debieuvre Dan Massey Olivier Rascol Eduardo Tolosa Daniel Weintraub

Lancet Neurol 2010 9 573ndash80

Miglioramento dello scoreBeck depression Inventory(BDI) Geriatric DepressionScale (GDS) UPDRS II e EQ-5D vs placebo

Lrsquoeffetto del trattamento sui sintomi depressivi egrave

stato per un 80 diretto sulla depressione

valutato con la BDI per un 20 indiretto legato ad un miglioramento dellrsquo UPDRS III

Trattamento della depressione in MP

DepressioneMP

PD (90)

HC (90)

Major Depression 211 33

Dysthymia 188 44

DAP 30 33

Anxiety 111 144

DOC 33 22

Mov Disord 2010

Depressed compared to non depressed dopaminergic and noradrenergic denervation

Locus coeruleus

Medial thalamus

Left

Ventral

striatum

Right Amigdala

Remy et al Brain 2005

[11C]RTI 32 PET

Biochemical Pharmacology 2007

0 20 40 60 80 100

SNc

DRN

LC

DVN

DPDNDPD

0 20 40 60 80 100

SNc

DRN

LC

DVN

DPDNDPD

GLIOSIS

NEURONAL LOSS

DVN dorsal vagus nerveLC locus coeruleusDRN dorsal raphe nucleiSNc substantia nigra c

Frisina et al 2009 modified

Mapping the norepinephrine transporter

NETSCAN

A Varrone et al 2010

Pramipexole for the treatment of depressive symptomsin patients with Parkinsonrsquos disease a randomised

double-blind placebo-controlled trialPaolo Barone Werner Poewe Stefan Albrecht Catherine Debieuvre Dan Massey Olivier Rascol Eduardo Tolosa Daniel Weintraub

Lancet Neurol 2010 9 573ndash80

Miglioramento dello scoreBeck depression Inventory(BDI) Geriatric DepressionScale (GDS) UPDRS II e EQ-5D vs placebo

Lrsquoeffetto del trattamento sui sintomi depressivi egrave

stato per un 80 diretto sulla depressione

valutato con la BDI per un 20 indiretto legato ad un miglioramento dellrsquo UPDRS III

Trattamento della depressione in MP

DepressioneMP

PD (90)

HC (90)

Major Depression 211 33

Dysthymia 188 44

DAP 30 33

Anxiety 111 144

DOC 33 22

Mov Disord 2010

Depressed compared to non depressed dopaminergic and noradrenergic denervation

Locus coeruleus

Medial thalamus

Left

Ventral

striatum

Right Amigdala

Remy et al Brain 2005

[11C]RTI 32 PET

Biochemical Pharmacology 2007

0 20 40 60 80 100

SNc

DRN

LC

DVN

DPDNDPD

0 20 40 60 80 100

SNc

DRN

LC

DVN

DPDNDPD

GLIOSIS

NEURONAL LOSS

DVN dorsal vagus nerveLC locus coeruleusDRN dorsal raphe nucleiSNc substantia nigra c

Frisina et al 2009 modified

Mapping the norepinephrine transporter

NETSCAN

A Varrone et al 2010

PD (90)

HC (90)

Major Depression 211 33

Dysthymia 188 44

DAP 30 33

Anxiety 111 144

DOC 33 22

Mov Disord 2010

Depressed compared to non depressed dopaminergic and noradrenergic denervation

Locus coeruleus

Medial thalamus

Left

Ventral

striatum

Right Amigdala

Remy et al Brain 2005

[11C]RTI 32 PET

Biochemical Pharmacology 2007

0 20 40 60 80 100

SNc

DRN

LC

DVN

DPDNDPD

0 20 40 60 80 100

SNc

DRN

LC

DVN

DPDNDPD

GLIOSIS

NEURONAL LOSS

DVN dorsal vagus nerveLC locus coeruleusDRN dorsal raphe nucleiSNc substantia nigra c

Frisina et al 2009 modified

Mapping the norepinephrine transporter

NETSCAN

A Varrone et al 2010

Mov Disord 2010

Depressed compared to non depressed dopaminergic and noradrenergic denervation

Locus coeruleus

Medial thalamus

Left

Ventral

striatum

Right Amigdala

Remy et al Brain 2005

[11C]RTI 32 PET

Biochemical Pharmacology 2007

0 20 40 60 80 100

SNc

DRN

LC

DVN

DPDNDPD

0 20 40 60 80 100

SNc

DRN

LC

DVN

DPDNDPD

GLIOSIS

NEURONAL LOSS

DVN dorsal vagus nerveLC locus coeruleusDRN dorsal raphe nucleiSNc substantia nigra c

Frisina et al 2009 modified

Mapping the norepinephrine transporter

NETSCAN

A Varrone et al 2010

Depressed compared to non depressed dopaminergic and noradrenergic denervation

Locus coeruleus

Medial thalamus

Left

Ventral

striatum

Right Amigdala

Remy et al Brain 2005

[11C]RTI 32 PET

Biochemical Pharmacology 2007

0 20 40 60 80 100

SNc

DRN

LC

DVN

DPDNDPD

0 20 40 60 80 100

SNc

DRN

LC

DVN

DPDNDPD

GLIOSIS

NEURONAL LOSS

DVN dorsal vagus nerveLC locus coeruleusDRN dorsal raphe nucleiSNc substantia nigra c

Frisina et al 2009 modified

Mapping the norepinephrine transporter

NETSCAN

A Varrone et al 2010

Biochemical Pharmacology 2007

0 20 40 60 80 100

SNc

DRN

LC

DVN

DPDNDPD

0 20 40 60 80 100

SNc

DRN

LC

DVN

DPDNDPD

GLIOSIS

NEURONAL LOSS

DVN dorsal vagus nerveLC locus coeruleusDRN dorsal raphe nucleiSNc substantia nigra c

Frisina et al 2009 modified

Mapping the norepinephrine transporter

NETSCAN

A Varrone et al 2010

0 20 40 60 80 100

SNc

DRN

LC

DVN

DPDNDPD

0 20 40 60 80 100

SNc

DRN

LC

DVN

DPDNDPD

GLIOSIS

NEURONAL LOSS

DVN dorsal vagus nerveLC locus coeruleusDRN dorsal raphe nucleiSNc substantia nigra c

Frisina et al 2009 modified

Mapping the norepinephrine transporter

NETSCAN

A Varrone et al 2010

Mapping the norepinephrine transporter

NETSCAN

A Varrone et al 2010

Weintraub et al 2010

Atomoxetine treatment was not efficacious for the treatment of clinically significantdepressive symptoms in PD but was associated with improvement in globalcognitive performance and daytime sleepiness

115pazientiDoppio cieco vs placeborandomizzato

venlafaxina

paroxetina

12 settimaneplacebo

weeks

SSRI e SNRI sono piugrave efficaci per il trattamento della depressione in MP del placebo

HAM-D

A randomized double-blind

placebo-controlled trial of antidepressants in

Parkinson disease Parkinson disease

IH RichardNeurology 2012

A non-comparative assessment of tolerabilityand efficacy of duloxetine in the treatment ofdepressed patients with Parkinsons disease

Trattamento della depressione in MP

Studio multicentrico non comparativo open-label (151 pazienti)

tollerabilitagrave

sicurezza

efficaciaDuloxetina 60mg 12 settimane

Pazienti con MP e depressione Maggiore

U Bonuccelli Expert Opin Pharmacolther 2012

Miglioramento significativoHAM-17 PDQ39

BDI CGI-S PGI-I

Depressive symptoms are associated whit cholinergic deficit in PD

(corrected for MMSe)

bull 18 PD (6 PDD)bull 10 HS

[11C]PMP PET (attivita Ach Esterasi)

Cornell Scale for Depression

2013

sadness anxiety anhedonia apathy

DEPRESSION

ACETHYLCOLINEDOPAMINENORADRENALINESEROTONIN

Depression-Fatigue-PainAn unique syndrome

Pain

Fatigue

Depression

Apathy

NMS frequency () and PD severityPRIAMO STUDY

Disease severity as Hoehn amp Yahr score

N=1072

1 15ndash2 25ndash3 4ndash5

Pain 509 586 671 796

Urinary 431 517 683 898

Sleep dysfunction 479 606 754 816

Fatigue 377 565 689 816

Apathy 246 268 366 490

Attentionmemory 377 404 517 653

Skin 144 198 345 327

Psychiatric 611 633 732 837

Respiratory 96 155 228 306

Gastrointestinal 455 544 769 735

Adapted from Antonini A et al The PRIAMO study background methods and recruitment Neurol Sci 200829 (2)61ndash5 Barone P et al The PRIAMO study A multicenter assessment of nonmotor symptoms and their impact on quality of life in Parkinsons disease MovDisorders 20091524(11)1641ndash9

8166 PD patients

46755 individualswithout PD

NON MOTOR SYMPTOMS were assessed by a custom-made questionnaire in 109 newly diagnosed untreated PD patients and 107 controls

bull Anhedonia apathy memory complaints and inattentionoccurred more frequently during the 2-year premotor period

bull Smell loss mood disturbances taste loss excessive sweatingfatigue and pain were more frequently reported in the 2- to10-year premotor period

bull Constipation dream-enacting behavior excessive daytimesleepiness and postprandial fullness were frequentlyperceived more than 10 years before motor symptoms

Mov Dis 2014

Edgar Degas (1834-1917) Melancholy late 1860s French Oil on canvasCourtesy of The Phillips Collection Washington DC

bull A total of 402 patients were enrolled and 394 patients completed the PFS-16 questionnaire with a PFS-16 mean score of287 plusmn 099

bull 136 patients (338) reported distressing fatigue (PFS-16 mean score ge33)

bull Patients with distressing fatigue were olderand had a longer duration of PD than thosewithout distressing fatigue

bull Famale gender was a risk factor to developfatigue

bull The presence of distressing fatigue wasassociated with

bull Higher total Unified Parkinsonrsquos DiseaseRating Scale (UPDRS) scores

bull Poorer quality of life (39-item ParkinsonrsquosDisease Questionnaire [PDQ-39])

bull Worse social and psychological behaviorsbull Higher severity of depressive symptomsbull Higher prevalence of sleep disorders

ALL SUBJECTS - 349

PD WITHOUT FATIGUE AT BASELINE - 221

PD WITH FATIGUE AT BASELINE - 128STUDIO ELLDOPA

Fatigue is a frequent symptom in early untreated non-depressed patients with Parkinson disease

Fatigue was associated with the severity of PD and progressed less in patients treated with levodopa

- 10 healty subjects- 7 PD patients with fatigue- 8 PD patientswithout fatigue

Right cingulate and right thalamus

Right and left striatum and left

cingulate

Right and left striatum and right and left thalamus

Right and left cingulatus

Right and left striatum and left

amygdala

11C-DASB uptake

Take home message

bull La depressione nella MP egrave sindrome premotoria molto

frequente durante la malattia e fattore di peggioramento

della qualitagrave della vita

bull Il suo riconoscimento egrave cruciale spesso sottodiagnosticata e

sottotrattata

bull Piu che una diagnosi formale dovremo riconoscere I sintomi

depressivi e trattarli in relazione al loro differente substrato

neurochimico

bull Necessario conoscere la multidimensionalitagrave del quadro per

un precoce ed efficace trattamento

115pazientiDoppio cieco vs placeborandomizzato

venlafaxina

paroxetina

12 settimaneplacebo

weeks

SSRI e SNRI sono piugrave efficaci per il trattamento della depressione in MP del placebo

HAM-D

A randomized double-blind

placebo-controlled trial of antidepressants in

Parkinson disease Parkinson disease

IH RichardNeurology 2012

A non-comparative assessment of tolerabilityand efficacy of duloxetine in the treatment ofdepressed patients with Parkinsons disease

Trattamento della depressione in MP

Studio multicentrico non comparativo open-label (151 pazienti)

tollerabilitagrave

sicurezza

efficaciaDuloxetina 60mg 12 settimane

Pazienti con MP e depressione Maggiore

U Bonuccelli Expert Opin Pharmacolther 2012

Miglioramento significativoHAM-17 PDQ39

BDI CGI-S PGI-I

Depressive symptoms are associated whit cholinergic deficit in PD

(corrected for MMSe)

bull 18 PD (6 PDD)bull 10 HS

[11C]PMP PET (attivita Ach Esterasi)

Cornell Scale for Depression

2013

sadness anxiety anhedonia apathy

DEPRESSION

ACETHYLCOLINEDOPAMINENORADRENALINESEROTONIN

Depression-Fatigue-PainAn unique syndrome

Pain

Fatigue

Depression

Apathy

NMS frequency () and PD severityPRIAMO STUDY

Disease severity as Hoehn amp Yahr score

N=1072

1 15ndash2 25ndash3 4ndash5

Pain 509 586 671 796

Urinary 431 517 683 898

Sleep dysfunction 479 606 754 816

Fatigue 377 565 689 816

Apathy 246 268 366 490

Attentionmemory 377 404 517 653

Skin 144 198 345 327

Psychiatric 611 633 732 837

Respiratory 96 155 228 306

Gastrointestinal 455 544 769 735

Adapted from Antonini A et al The PRIAMO study background methods and recruitment Neurol Sci 200829 (2)61ndash5 Barone P et al The PRIAMO study A multicenter assessment of nonmotor symptoms and their impact on quality of life in Parkinsons disease MovDisorders 20091524(11)1641ndash9

8166 PD patients

46755 individualswithout PD

NON MOTOR SYMPTOMS were assessed by a custom-made questionnaire in 109 newly diagnosed untreated PD patients and 107 controls

bull Anhedonia apathy memory complaints and inattentionoccurred more frequently during the 2-year premotor period

bull Smell loss mood disturbances taste loss excessive sweatingfatigue and pain were more frequently reported in the 2- to10-year premotor period

bull Constipation dream-enacting behavior excessive daytimesleepiness and postprandial fullness were frequentlyperceived more than 10 years before motor symptoms

Mov Dis 2014

Edgar Degas (1834-1917) Melancholy late 1860s French Oil on canvasCourtesy of The Phillips Collection Washington DC

bull A total of 402 patients were enrolled and 394 patients completed the PFS-16 questionnaire with a PFS-16 mean score of287 plusmn 099

bull 136 patients (338) reported distressing fatigue (PFS-16 mean score ge33)

bull Patients with distressing fatigue were olderand had a longer duration of PD than thosewithout distressing fatigue

bull Famale gender was a risk factor to developfatigue

bull The presence of distressing fatigue wasassociated with

bull Higher total Unified Parkinsonrsquos DiseaseRating Scale (UPDRS) scores

bull Poorer quality of life (39-item ParkinsonrsquosDisease Questionnaire [PDQ-39])

bull Worse social and psychological behaviorsbull Higher severity of depressive symptomsbull Higher prevalence of sleep disorders

ALL SUBJECTS - 349

PD WITHOUT FATIGUE AT BASELINE - 221

PD WITH FATIGUE AT BASELINE - 128STUDIO ELLDOPA

Fatigue is a frequent symptom in early untreated non-depressed patients with Parkinson disease

Fatigue was associated with the severity of PD and progressed less in patients treated with levodopa

- 10 healty subjects- 7 PD patients with fatigue- 8 PD patientswithout fatigue

Right cingulate and right thalamus

Right and left striatum and left

cingulate

Right and left striatum and right and left thalamus

Right and left cingulatus

Right and left striatum and left

amygdala

11C-DASB uptake

Take home message

bull La depressione nella MP egrave sindrome premotoria molto

frequente durante la malattia e fattore di peggioramento

della qualitagrave della vita

bull Il suo riconoscimento egrave cruciale spesso sottodiagnosticata e

sottotrattata

bull Piu che una diagnosi formale dovremo riconoscere I sintomi

depressivi e trattarli in relazione al loro differente substrato

neurochimico

bull Necessario conoscere la multidimensionalitagrave del quadro per

un precoce ed efficace trattamento

A non-comparative assessment of tolerabilityand efficacy of duloxetine in the treatment ofdepressed patients with Parkinsons disease

Trattamento della depressione in MP

Studio multicentrico non comparativo open-label (151 pazienti)

tollerabilitagrave

sicurezza

efficaciaDuloxetina 60mg 12 settimane

Pazienti con MP e depressione Maggiore

U Bonuccelli Expert Opin Pharmacolther 2012

Miglioramento significativoHAM-17 PDQ39

BDI CGI-S PGI-I

Depressive symptoms are associated whit cholinergic deficit in PD

(corrected for MMSe)

bull 18 PD (6 PDD)bull 10 HS

[11C]PMP PET (attivita Ach Esterasi)

Cornell Scale for Depression

2013

sadness anxiety anhedonia apathy

DEPRESSION

ACETHYLCOLINEDOPAMINENORADRENALINESEROTONIN

Depression-Fatigue-PainAn unique syndrome

Pain

Fatigue

Depression

Apathy

NMS frequency () and PD severityPRIAMO STUDY

Disease severity as Hoehn amp Yahr score

N=1072

1 15ndash2 25ndash3 4ndash5

Pain 509 586 671 796

Urinary 431 517 683 898

Sleep dysfunction 479 606 754 816

Fatigue 377 565 689 816

Apathy 246 268 366 490

Attentionmemory 377 404 517 653

Skin 144 198 345 327

Psychiatric 611 633 732 837

Respiratory 96 155 228 306

Gastrointestinal 455 544 769 735

Adapted from Antonini A et al The PRIAMO study background methods and recruitment Neurol Sci 200829 (2)61ndash5 Barone P et al The PRIAMO study A multicenter assessment of nonmotor symptoms and their impact on quality of life in Parkinsons disease MovDisorders 20091524(11)1641ndash9

8166 PD patients

46755 individualswithout PD

NON MOTOR SYMPTOMS were assessed by a custom-made questionnaire in 109 newly diagnosed untreated PD patients and 107 controls

bull Anhedonia apathy memory complaints and inattentionoccurred more frequently during the 2-year premotor period

bull Smell loss mood disturbances taste loss excessive sweatingfatigue and pain were more frequently reported in the 2- to10-year premotor period

bull Constipation dream-enacting behavior excessive daytimesleepiness and postprandial fullness were frequentlyperceived more than 10 years before motor symptoms

Mov Dis 2014

Edgar Degas (1834-1917) Melancholy late 1860s French Oil on canvasCourtesy of The Phillips Collection Washington DC

bull A total of 402 patients were enrolled and 394 patients completed the PFS-16 questionnaire with a PFS-16 mean score of287 plusmn 099

bull 136 patients (338) reported distressing fatigue (PFS-16 mean score ge33)

bull Patients with distressing fatigue were olderand had a longer duration of PD than thosewithout distressing fatigue

bull Famale gender was a risk factor to developfatigue

bull The presence of distressing fatigue wasassociated with

bull Higher total Unified Parkinsonrsquos DiseaseRating Scale (UPDRS) scores

bull Poorer quality of life (39-item ParkinsonrsquosDisease Questionnaire [PDQ-39])

bull Worse social and psychological behaviorsbull Higher severity of depressive symptomsbull Higher prevalence of sleep disorders

ALL SUBJECTS - 349

PD WITHOUT FATIGUE AT BASELINE - 221

PD WITH FATIGUE AT BASELINE - 128STUDIO ELLDOPA

Fatigue is a frequent symptom in early untreated non-depressed patients with Parkinson disease

Fatigue was associated with the severity of PD and progressed less in patients treated with levodopa

- 10 healty subjects- 7 PD patients with fatigue- 8 PD patientswithout fatigue

Right cingulate and right thalamus

Right and left striatum and left

cingulate

Right and left striatum and right and left thalamus

Right and left cingulatus

Right and left striatum and left

amygdala

11C-DASB uptake

Take home message

bull La depressione nella MP egrave sindrome premotoria molto

frequente durante la malattia e fattore di peggioramento

della qualitagrave della vita

bull Il suo riconoscimento egrave cruciale spesso sottodiagnosticata e

sottotrattata

bull Piu che una diagnosi formale dovremo riconoscere I sintomi

depressivi e trattarli in relazione al loro differente substrato

neurochimico

bull Necessario conoscere la multidimensionalitagrave del quadro per

un precoce ed efficace trattamento

Depressive symptoms are associated whit cholinergic deficit in PD

(corrected for MMSe)

bull 18 PD (6 PDD)bull 10 HS

[11C]PMP PET (attivita Ach Esterasi)

Cornell Scale for Depression

2013

sadness anxiety anhedonia apathy

DEPRESSION

ACETHYLCOLINEDOPAMINENORADRENALINESEROTONIN

Depression-Fatigue-PainAn unique syndrome

Pain

Fatigue

Depression

Apathy

NMS frequency () and PD severityPRIAMO STUDY

Disease severity as Hoehn amp Yahr score

N=1072

1 15ndash2 25ndash3 4ndash5

Pain 509 586 671 796

Urinary 431 517 683 898

Sleep dysfunction 479 606 754 816

Fatigue 377 565 689 816

Apathy 246 268 366 490

Attentionmemory 377 404 517 653

Skin 144 198 345 327

Psychiatric 611 633 732 837

Respiratory 96 155 228 306

Gastrointestinal 455 544 769 735

Adapted from Antonini A et al The PRIAMO study background methods and recruitment Neurol Sci 200829 (2)61ndash5 Barone P et al The PRIAMO study A multicenter assessment of nonmotor symptoms and their impact on quality of life in Parkinsons disease MovDisorders 20091524(11)1641ndash9

8166 PD patients

46755 individualswithout PD

NON MOTOR SYMPTOMS were assessed by a custom-made questionnaire in 109 newly diagnosed untreated PD patients and 107 controls

bull Anhedonia apathy memory complaints and inattentionoccurred more frequently during the 2-year premotor period

bull Smell loss mood disturbances taste loss excessive sweatingfatigue and pain were more frequently reported in the 2- to10-year premotor period

bull Constipation dream-enacting behavior excessive daytimesleepiness and postprandial fullness were frequentlyperceived more than 10 years before motor symptoms

Mov Dis 2014

Edgar Degas (1834-1917) Melancholy late 1860s French Oil on canvasCourtesy of The Phillips Collection Washington DC

bull A total of 402 patients were enrolled and 394 patients completed the PFS-16 questionnaire with a PFS-16 mean score of287 plusmn 099

bull 136 patients (338) reported distressing fatigue (PFS-16 mean score ge33)

bull Patients with distressing fatigue were olderand had a longer duration of PD than thosewithout distressing fatigue

bull Famale gender was a risk factor to developfatigue

bull The presence of distressing fatigue wasassociated with

bull Higher total Unified Parkinsonrsquos DiseaseRating Scale (UPDRS) scores

bull Poorer quality of life (39-item ParkinsonrsquosDisease Questionnaire [PDQ-39])

bull Worse social and psychological behaviorsbull Higher severity of depressive symptomsbull Higher prevalence of sleep disorders

ALL SUBJECTS - 349

PD WITHOUT FATIGUE AT BASELINE - 221

PD WITH FATIGUE AT BASELINE - 128STUDIO ELLDOPA

Fatigue is a frequent symptom in early untreated non-depressed patients with Parkinson disease

Fatigue was associated with the severity of PD and progressed less in patients treated with levodopa

- 10 healty subjects- 7 PD patients with fatigue- 8 PD patientswithout fatigue

Right cingulate and right thalamus

Right and left striatum and left

cingulate

Right and left striatum and right and left thalamus

Right and left cingulatus

Right and left striatum and left

amygdala

11C-DASB uptake

Take home message

bull La depressione nella MP egrave sindrome premotoria molto

frequente durante la malattia e fattore di peggioramento

della qualitagrave della vita

bull Il suo riconoscimento egrave cruciale spesso sottodiagnosticata e

sottotrattata

bull Piu che una diagnosi formale dovremo riconoscere I sintomi

depressivi e trattarli in relazione al loro differente substrato

neurochimico

bull Necessario conoscere la multidimensionalitagrave del quadro per

un precoce ed efficace trattamento

2013

sadness anxiety anhedonia apathy

DEPRESSION

ACETHYLCOLINEDOPAMINENORADRENALINESEROTONIN

Depression-Fatigue-PainAn unique syndrome

Pain

Fatigue

Depression

Apathy

NMS frequency () and PD severityPRIAMO STUDY

Disease severity as Hoehn amp Yahr score

N=1072

1 15ndash2 25ndash3 4ndash5

Pain 509 586 671 796

Urinary 431 517 683 898

Sleep dysfunction 479 606 754 816

Fatigue 377 565 689 816

Apathy 246 268 366 490

Attentionmemory 377 404 517 653

Skin 144 198 345 327

Psychiatric 611 633 732 837

Respiratory 96 155 228 306

Gastrointestinal 455 544 769 735

Adapted from Antonini A et al The PRIAMO study background methods and recruitment Neurol Sci 200829 (2)61ndash5 Barone P et al The PRIAMO study A multicenter assessment of nonmotor symptoms and their impact on quality of life in Parkinsons disease MovDisorders 20091524(11)1641ndash9

8166 PD patients

46755 individualswithout PD

NON MOTOR SYMPTOMS were assessed by a custom-made questionnaire in 109 newly diagnosed untreated PD patients and 107 controls

bull Anhedonia apathy memory complaints and inattentionoccurred more frequently during the 2-year premotor period

bull Smell loss mood disturbances taste loss excessive sweatingfatigue and pain were more frequently reported in the 2- to10-year premotor period

bull Constipation dream-enacting behavior excessive daytimesleepiness and postprandial fullness were frequentlyperceived more than 10 years before motor symptoms

Mov Dis 2014

Edgar Degas (1834-1917) Melancholy late 1860s French Oil on canvasCourtesy of The Phillips Collection Washington DC

bull A total of 402 patients were enrolled and 394 patients completed the PFS-16 questionnaire with a PFS-16 mean score of287 plusmn 099

bull 136 patients (338) reported distressing fatigue (PFS-16 mean score ge33)

bull Patients with distressing fatigue were olderand had a longer duration of PD than thosewithout distressing fatigue

bull Famale gender was a risk factor to developfatigue

bull The presence of distressing fatigue wasassociated with

bull Higher total Unified Parkinsonrsquos DiseaseRating Scale (UPDRS) scores

bull Poorer quality of life (39-item ParkinsonrsquosDisease Questionnaire [PDQ-39])

bull Worse social and psychological behaviorsbull Higher severity of depressive symptomsbull Higher prevalence of sleep disorders

ALL SUBJECTS - 349

PD WITHOUT FATIGUE AT BASELINE - 221

PD WITH FATIGUE AT BASELINE - 128STUDIO ELLDOPA

Fatigue is a frequent symptom in early untreated non-depressed patients with Parkinson disease

Fatigue was associated with the severity of PD and progressed less in patients treated with levodopa

- 10 healty subjects- 7 PD patients with fatigue- 8 PD patientswithout fatigue

Right cingulate and right thalamus

Right and left striatum and left

cingulate

Right and left striatum and right and left thalamus

Right and left cingulatus

Right and left striatum and left

amygdala

11C-DASB uptake

Take home message

bull La depressione nella MP egrave sindrome premotoria molto

frequente durante la malattia e fattore di peggioramento

della qualitagrave della vita

bull Il suo riconoscimento egrave cruciale spesso sottodiagnosticata e

sottotrattata

bull Piu che una diagnosi formale dovremo riconoscere I sintomi

depressivi e trattarli in relazione al loro differente substrato

neurochimico

bull Necessario conoscere la multidimensionalitagrave del quadro per

un precoce ed efficace trattamento

sadness anxiety anhedonia apathy

DEPRESSION

ACETHYLCOLINEDOPAMINENORADRENALINESEROTONIN

Depression-Fatigue-PainAn unique syndrome

Pain

Fatigue

Depression

Apathy

NMS frequency () and PD severityPRIAMO STUDY

Disease severity as Hoehn amp Yahr score

N=1072

1 15ndash2 25ndash3 4ndash5

Pain 509 586 671 796

Urinary 431 517 683 898

Sleep dysfunction 479 606 754 816

Fatigue 377 565 689 816

Apathy 246 268 366 490

Attentionmemory 377 404 517 653

Skin 144 198 345 327

Psychiatric 611 633 732 837

Respiratory 96 155 228 306

Gastrointestinal 455 544 769 735

Adapted from Antonini A et al The PRIAMO study background methods and recruitment Neurol Sci 200829 (2)61ndash5 Barone P et al The PRIAMO study A multicenter assessment of nonmotor symptoms and their impact on quality of life in Parkinsons disease MovDisorders 20091524(11)1641ndash9

8166 PD patients

46755 individualswithout PD

NON MOTOR SYMPTOMS were assessed by a custom-made questionnaire in 109 newly diagnosed untreated PD patients and 107 controls

bull Anhedonia apathy memory complaints and inattentionoccurred more frequently during the 2-year premotor period

bull Smell loss mood disturbances taste loss excessive sweatingfatigue and pain were more frequently reported in the 2- to10-year premotor period

bull Constipation dream-enacting behavior excessive daytimesleepiness and postprandial fullness were frequentlyperceived more than 10 years before motor symptoms

Mov Dis 2014

Edgar Degas (1834-1917) Melancholy late 1860s French Oil on canvasCourtesy of The Phillips Collection Washington DC

bull A total of 402 patients were enrolled and 394 patients completed the PFS-16 questionnaire with a PFS-16 mean score of287 plusmn 099

bull 136 patients (338) reported distressing fatigue (PFS-16 mean score ge33)

bull Patients with distressing fatigue were olderand had a longer duration of PD than thosewithout distressing fatigue

bull Famale gender was a risk factor to developfatigue

bull The presence of distressing fatigue wasassociated with

bull Higher total Unified Parkinsonrsquos DiseaseRating Scale (UPDRS) scores

bull Poorer quality of life (39-item ParkinsonrsquosDisease Questionnaire [PDQ-39])

bull Worse social and psychological behaviorsbull Higher severity of depressive symptomsbull Higher prevalence of sleep disorders

ALL SUBJECTS - 349

PD WITHOUT FATIGUE AT BASELINE - 221

PD WITH FATIGUE AT BASELINE - 128STUDIO ELLDOPA

Fatigue is a frequent symptom in early untreated non-depressed patients with Parkinson disease

Fatigue was associated with the severity of PD and progressed less in patients treated with levodopa

- 10 healty subjects- 7 PD patients with fatigue- 8 PD patientswithout fatigue

Right cingulate and right thalamus

Right and left striatum and left

cingulate

Right and left striatum and right and left thalamus

Right and left cingulatus

Right and left striatum and left

amygdala

11C-DASB uptake

Take home message

bull La depressione nella MP egrave sindrome premotoria molto

frequente durante la malattia e fattore di peggioramento

della qualitagrave della vita

bull Il suo riconoscimento egrave cruciale spesso sottodiagnosticata e

sottotrattata

bull Piu che una diagnosi formale dovremo riconoscere I sintomi

depressivi e trattarli in relazione al loro differente substrato

neurochimico

bull Necessario conoscere la multidimensionalitagrave del quadro per

un precoce ed efficace trattamento

Depression-Fatigue-PainAn unique syndrome

Pain

Fatigue

Depression

Apathy

NMS frequency () and PD severityPRIAMO STUDY

Disease severity as Hoehn amp Yahr score

N=1072

1 15ndash2 25ndash3 4ndash5

Pain 509 586 671 796

Urinary 431 517 683 898

Sleep dysfunction 479 606 754 816

Fatigue 377 565 689 816

Apathy 246 268 366 490

Attentionmemory 377 404 517 653

Skin 144 198 345 327

Psychiatric 611 633 732 837

Respiratory 96 155 228 306

Gastrointestinal 455 544 769 735

Adapted from Antonini A et al The PRIAMO study background methods and recruitment Neurol Sci 200829 (2)61ndash5 Barone P et al The PRIAMO study A multicenter assessment of nonmotor symptoms and their impact on quality of life in Parkinsons disease MovDisorders 20091524(11)1641ndash9

8166 PD patients

46755 individualswithout PD

NON MOTOR SYMPTOMS were assessed by a custom-made questionnaire in 109 newly diagnosed untreated PD patients and 107 controls

bull Anhedonia apathy memory complaints and inattentionoccurred more frequently during the 2-year premotor period

bull Smell loss mood disturbances taste loss excessive sweatingfatigue and pain were more frequently reported in the 2- to10-year premotor period

bull Constipation dream-enacting behavior excessive daytimesleepiness and postprandial fullness were frequentlyperceived more than 10 years before motor symptoms

Mov Dis 2014

Edgar Degas (1834-1917) Melancholy late 1860s French Oil on canvasCourtesy of The Phillips Collection Washington DC

bull A total of 402 patients were enrolled and 394 patients completed the PFS-16 questionnaire with a PFS-16 mean score of287 plusmn 099

bull 136 patients (338) reported distressing fatigue (PFS-16 mean score ge33)

bull Patients with distressing fatigue were olderand had a longer duration of PD than thosewithout distressing fatigue

bull Famale gender was a risk factor to developfatigue

bull The presence of distressing fatigue wasassociated with

bull Higher total Unified Parkinsonrsquos DiseaseRating Scale (UPDRS) scores

bull Poorer quality of life (39-item ParkinsonrsquosDisease Questionnaire [PDQ-39])

bull Worse social and psychological behaviorsbull Higher severity of depressive symptomsbull Higher prevalence of sleep disorders

ALL SUBJECTS - 349

PD WITHOUT FATIGUE AT BASELINE - 221

PD WITH FATIGUE AT BASELINE - 128STUDIO ELLDOPA

Fatigue is a frequent symptom in early untreated non-depressed patients with Parkinson disease

Fatigue was associated with the severity of PD and progressed less in patients treated with levodopa

- 10 healty subjects- 7 PD patients with fatigue- 8 PD patientswithout fatigue

Right cingulate and right thalamus

Right and left striatum and left

cingulate

Right and left striatum and right and left thalamus

Right and left cingulatus

Right and left striatum and left

amygdala

11C-DASB uptake

Take home message

bull La depressione nella MP egrave sindrome premotoria molto

frequente durante la malattia e fattore di peggioramento

della qualitagrave della vita

bull Il suo riconoscimento egrave cruciale spesso sottodiagnosticata e

sottotrattata

bull Piu che una diagnosi formale dovremo riconoscere I sintomi

depressivi e trattarli in relazione al loro differente substrato

neurochimico

bull Necessario conoscere la multidimensionalitagrave del quadro per

un precoce ed efficace trattamento

NMS frequency () and PD severityPRIAMO STUDY

Disease severity as Hoehn amp Yahr score

N=1072

1 15ndash2 25ndash3 4ndash5

Pain 509 586 671 796

Urinary 431 517 683 898

Sleep dysfunction 479 606 754 816

Fatigue 377 565 689 816

Apathy 246 268 366 490

Attentionmemory 377 404 517 653

Skin 144 198 345 327

Psychiatric 611 633 732 837

Respiratory 96 155 228 306

Gastrointestinal 455 544 769 735

Adapted from Antonini A et al The PRIAMO study background methods and recruitment Neurol Sci 200829 (2)61ndash5 Barone P et al The PRIAMO study A multicenter assessment of nonmotor symptoms and their impact on quality of life in Parkinsons disease MovDisorders 20091524(11)1641ndash9

8166 PD patients

46755 individualswithout PD

NON MOTOR SYMPTOMS were assessed by a custom-made questionnaire in 109 newly diagnosed untreated PD patients and 107 controls

bull Anhedonia apathy memory complaints and inattentionoccurred more frequently during the 2-year premotor period

bull Smell loss mood disturbances taste loss excessive sweatingfatigue and pain were more frequently reported in the 2- to10-year premotor period

bull Constipation dream-enacting behavior excessive daytimesleepiness and postprandial fullness were frequentlyperceived more than 10 years before motor symptoms

Mov Dis 2014

Edgar Degas (1834-1917) Melancholy late 1860s French Oil on canvasCourtesy of The Phillips Collection Washington DC

bull A total of 402 patients were enrolled and 394 patients completed the PFS-16 questionnaire with a PFS-16 mean score of287 plusmn 099

bull 136 patients (338) reported distressing fatigue (PFS-16 mean score ge33)

bull Patients with distressing fatigue were olderand had a longer duration of PD than thosewithout distressing fatigue

bull Famale gender was a risk factor to developfatigue

bull The presence of distressing fatigue wasassociated with

bull Higher total Unified Parkinsonrsquos DiseaseRating Scale (UPDRS) scores

bull Poorer quality of life (39-item ParkinsonrsquosDisease Questionnaire [PDQ-39])

bull Worse social and psychological behaviorsbull Higher severity of depressive symptomsbull Higher prevalence of sleep disorders

ALL SUBJECTS - 349

PD WITHOUT FATIGUE AT BASELINE - 221

PD WITH FATIGUE AT BASELINE - 128STUDIO ELLDOPA

Fatigue is a frequent symptom in early untreated non-depressed patients with Parkinson disease

Fatigue was associated with the severity of PD and progressed less in patients treated with levodopa

- 10 healty subjects- 7 PD patients with fatigue- 8 PD patientswithout fatigue

Right cingulate and right thalamus

Right and left striatum and left

cingulate

Right and left striatum and right and left thalamus

Right and left cingulatus

Right and left striatum and left

amygdala

11C-DASB uptake

Take home message

bull La depressione nella MP egrave sindrome premotoria molto

frequente durante la malattia e fattore di peggioramento

della qualitagrave della vita

bull Il suo riconoscimento egrave cruciale spesso sottodiagnosticata e

sottotrattata

bull Piu che una diagnosi formale dovremo riconoscere I sintomi

depressivi e trattarli in relazione al loro differente substrato

neurochimico

bull Necessario conoscere la multidimensionalitagrave del quadro per

un precoce ed efficace trattamento

8166 PD patients

46755 individualswithout PD

NON MOTOR SYMPTOMS were assessed by a custom-made questionnaire in 109 newly diagnosed untreated PD patients and 107 controls

bull Anhedonia apathy memory complaints and inattentionoccurred more frequently during the 2-year premotor period

bull Smell loss mood disturbances taste loss excessive sweatingfatigue and pain were more frequently reported in the 2- to10-year premotor period

bull Constipation dream-enacting behavior excessive daytimesleepiness and postprandial fullness were frequentlyperceived more than 10 years before motor symptoms

Mov Dis 2014

Edgar Degas (1834-1917) Melancholy late 1860s French Oil on canvasCourtesy of The Phillips Collection Washington DC

bull A total of 402 patients were enrolled and 394 patients completed the PFS-16 questionnaire with a PFS-16 mean score of287 plusmn 099

bull 136 patients (338) reported distressing fatigue (PFS-16 mean score ge33)

bull Patients with distressing fatigue were olderand had a longer duration of PD than thosewithout distressing fatigue

bull Famale gender was a risk factor to developfatigue

bull The presence of distressing fatigue wasassociated with

bull Higher total Unified Parkinsonrsquos DiseaseRating Scale (UPDRS) scores

bull Poorer quality of life (39-item ParkinsonrsquosDisease Questionnaire [PDQ-39])

bull Worse social and psychological behaviorsbull Higher severity of depressive symptomsbull Higher prevalence of sleep disorders

ALL SUBJECTS - 349

PD WITHOUT FATIGUE AT BASELINE - 221

PD WITH FATIGUE AT BASELINE - 128STUDIO ELLDOPA

Fatigue is a frequent symptom in early untreated non-depressed patients with Parkinson disease

Fatigue was associated with the severity of PD and progressed less in patients treated with levodopa

- 10 healty subjects- 7 PD patients with fatigue- 8 PD patientswithout fatigue

Right cingulate and right thalamus

Right and left striatum and left

cingulate

Right and left striatum and right and left thalamus

Right and left cingulatus

Right and left striatum and left

amygdala

11C-DASB uptake

Take home message

bull La depressione nella MP egrave sindrome premotoria molto

frequente durante la malattia e fattore di peggioramento

della qualitagrave della vita

bull Il suo riconoscimento egrave cruciale spesso sottodiagnosticata e

sottotrattata

bull Piu che una diagnosi formale dovremo riconoscere I sintomi

depressivi e trattarli in relazione al loro differente substrato

neurochimico

bull Necessario conoscere la multidimensionalitagrave del quadro per

un precoce ed efficace trattamento

NON MOTOR SYMPTOMS were assessed by a custom-made questionnaire in 109 newly diagnosed untreated PD patients and 107 controls

bull Anhedonia apathy memory complaints and inattentionoccurred more frequently during the 2-year premotor period

bull Smell loss mood disturbances taste loss excessive sweatingfatigue and pain were more frequently reported in the 2- to10-year premotor period

bull Constipation dream-enacting behavior excessive daytimesleepiness and postprandial fullness were frequentlyperceived more than 10 years before motor symptoms

Mov Dis 2014

Edgar Degas (1834-1917) Melancholy late 1860s French Oil on canvasCourtesy of The Phillips Collection Washington DC

bull A total of 402 patients were enrolled and 394 patients completed the PFS-16 questionnaire with a PFS-16 mean score of287 plusmn 099

bull 136 patients (338) reported distressing fatigue (PFS-16 mean score ge33)

bull Patients with distressing fatigue were olderand had a longer duration of PD than thosewithout distressing fatigue

bull Famale gender was a risk factor to developfatigue

bull The presence of distressing fatigue wasassociated with

bull Higher total Unified Parkinsonrsquos DiseaseRating Scale (UPDRS) scores

bull Poorer quality of life (39-item ParkinsonrsquosDisease Questionnaire [PDQ-39])

bull Worse social and psychological behaviorsbull Higher severity of depressive symptomsbull Higher prevalence of sleep disorders

ALL SUBJECTS - 349

PD WITHOUT FATIGUE AT BASELINE - 221

PD WITH FATIGUE AT BASELINE - 128STUDIO ELLDOPA

Fatigue is a frequent symptom in early untreated non-depressed patients with Parkinson disease

Fatigue was associated with the severity of PD and progressed less in patients treated with levodopa

- 10 healty subjects- 7 PD patients with fatigue- 8 PD patientswithout fatigue

Right cingulate and right thalamus

Right and left striatum and left

cingulate

Right and left striatum and right and left thalamus

Right and left cingulatus

Right and left striatum and left

amygdala

11C-DASB uptake

Take home message

bull La depressione nella MP egrave sindrome premotoria molto

frequente durante la malattia e fattore di peggioramento

della qualitagrave della vita

bull Il suo riconoscimento egrave cruciale spesso sottodiagnosticata e

sottotrattata

bull Piu che una diagnosi formale dovremo riconoscere I sintomi

depressivi e trattarli in relazione al loro differente substrato

neurochimico

bull Necessario conoscere la multidimensionalitagrave del quadro per

un precoce ed efficace trattamento

Edgar Degas (1834-1917) Melancholy late 1860s French Oil on canvasCourtesy of The Phillips Collection Washington DC

bull A total of 402 patients were enrolled and 394 patients completed the PFS-16 questionnaire with a PFS-16 mean score of287 plusmn 099

bull 136 patients (338) reported distressing fatigue (PFS-16 mean score ge33)

bull Patients with distressing fatigue were olderand had a longer duration of PD than thosewithout distressing fatigue

bull Famale gender was a risk factor to developfatigue

bull The presence of distressing fatigue wasassociated with

bull Higher total Unified Parkinsonrsquos DiseaseRating Scale (UPDRS) scores

bull Poorer quality of life (39-item ParkinsonrsquosDisease Questionnaire [PDQ-39])

bull Worse social and psychological behaviorsbull Higher severity of depressive symptomsbull Higher prevalence of sleep disorders

ALL SUBJECTS - 349

PD WITHOUT FATIGUE AT BASELINE - 221

PD WITH FATIGUE AT BASELINE - 128STUDIO ELLDOPA

Fatigue is a frequent symptom in early untreated non-depressed patients with Parkinson disease

Fatigue was associated with the severity of PD and progressed less in patients treated with levodopa

- 10 healty subjects- 7 PD patients with fatigue- 8 PD patientswithout fatigue

Right cingulate and right thalamus

Right and left striatum and left

cingulate

Right and left striatum and right and left thalamus

Right and left cingulatus

Right and left striatum and left

amygdala

11C-DASB uptake

Take home message

bull La depressione nella MP egrave sindrome premotoria molto

frequente durante la malattia e fattore di peggioramento

della qualitagrave della vita

bull Il suo riconoscimento egrave cruciale spesso sottodiagnosticata e

sottotrattata

bull Piu che una diagnosi formale dovremo riconoscere I sintomi

depressivi e trattarli in relazione al loro differente substrato

neurochimico

bull Necessario conoscere la multidimensionalitagrave del quadro per

un precoce ed efficace trattamento

bull A total of 402 patients were enrolled and 394 patients completed the PFS-16 questionnaire with a PFS-16 mean score of287 plusmn 099

bull 136 patients (338) reported distressing fatigue (PFS-16 mean score ge33)

bull Patients with distressing fatigue were olderand had a longer duration of PD than thosewithout distressing fatigue

bull Famale gender was a risk factor to developfatigue

bull The presence of distressing fatigue wasassociated with

bull Higher total Unified Parkinsonrsquos DiseaseRating Scale (UPDRS) scores

bull Poorer quality of life (39-item ParkinsonrsquosDisease Questionnaire [PDQ-39])

bull Worse social and psychological behaviorsbull Higher severity of depressive symptomsbull Higher prevalence of sleep disorders

ALL SUBJECTS - 349

PD WITHOUT FATIGUE AT BASELINE - 221

PD WITH FATIGUE AT BASELINE - 128STUDIO ELLDOPA

Fatigue is a frequent symptom in early untreated non-depressed patients with Parkinson disease

Fatigue was associated with the severity of PD and progressed less in patients treated with levodopa

- 10 healty subjects- 7 PD patients with fatigue- 8 PD patientswithout fatigue

Right cingulate and right thalamus

Right and left striatum and left

cingulate

Right and left striatum and right and left thalamus

Right and left cingulatus

Right and left striatum and left

amygdala

11C-DASB uptake

Take home message

bull La depressione nella MP egrave sindrome premotoria molto

frequente durante la malattia e fattore di peggioramento

della qualitagrave della vita

bull Il suo riconoscimento egrave cruciale spesso sottodiagnosticata e

sottotrattata

bull Piu che una diagnosi formale dovremo riconoscere I sintomi

depressivi e trattarli in relazione al loro differente substrato

neurochimico

bull Necessario conoscere la multidimensionalitagrave del quadro per

un precoce ed efficace trattamento

bull The presence of distressing fatigue wasassociated with

bull Higher total Unified Parkinsonrsquos DiseaseRating Scale (UPDRS) scores

bull Poorer quality of life (39-item ParkinsonrsquosDisease Questionnaire [PDQ-39])

bull Worse social and psychological behaviorsbull Higher severity of depressive symptomsbull Higher prevalence of sleep disorders

ALL SUBJECTS - 349

PD WITHOUT FATIGUE AT BASELINE - 221

PD WITH FATIGUE AT BASELINE - 128STUDIO ELLDOPA

Fatigue is a frequent symptom in early untreated non-depressed patients with Parkinson disease

Fatigue was associated with the severity of PD and progressed less in patients treated with levodopa

- 10 healty subjects- 7 PD patients with fatigue- 8 PD patientswithout fatigue

Right cingulate and right thalamus

Right and left striatum and left

cingulate

Right and left striatum and right and left thalamus

Right and left cingulatus

Right and left striatum and left

amygdala

11C-DASB uptake

Take home message

bull La depressione nella MP egrave sindrome premotoria molto

frequente durante la malattia e fattore di peggioramento

della qualitagrave della vita

bull Il suo riconoscimento egrave cruciale spesso sottodiagnosticata e

sottotrattata

bull Piu che una diagnosi formale dovremo riconoscere I sintomi

depressivi e trattarli in relazione al loro differente substrato

neurochimico

bull Necessario conoscere la multidimensionalitagrave del quadro per

un precoce ed efficace trattamento

ALL SUBJECTS - 349

PD WITHOUT FATIGUE AT BASELINE - 221

PD WITH FATIGUE AT BASELINE - 128STUDIO ELLDOPA

Fatigue is a frequent symptom in early untreated non-depressed patients with Parkinson disease

Fatigue was associated with the severity of PD and progressed less in patients treated with levodopa

- 10 healty subjects- 7 PD patients with fatigue- 8 PD patientswithout fatigue

Right cingulate and right thalamus

Right and left striatum and left

cingulate

Right and left striatum and right and left thalamus

Right and left cingulatus

Right and left striatum and left

amygdala

11C-DASB uptake

Take home message

bull La depressione nella MP egrave sindrome premotoria molto

frequente durante la malattia e fattore di peggioramento

della qualitagrave della vita

bull Il suo riconoscimento egrave cruciale spesso sottodiagnosticata e

sottotrattata

bull Piu che una diagnosi formale dovremo riconoscere I sintomi

depressivi e trattarli in relazione al loro differente substrato

neurochimico

bull Necessario conoscere la multidimensionalitagrave del quadro per

un precoce ed efficace trattamento

- 10 healty subjects- 7 PD patients with fatigue- 8 PD patientswithout fatigue

Right cingulate and right thalamus

Right and left striatum and left

cingulate

Right and left striatum and right and left thalamus

Right and left cingulatus

Right and left striatum and left

amygdala

11C-DASB uptake

Take home message

bull La depressione nella MP egrave sindrome premotoria molto

frequente durante la malattia e fattore di peggioramento

della qualitagrave della vita

bull Il suo riconoscimento egrave cruciale spesso sottodiagnosticata e

sottotrattata

bull Piu che una diagnosi formale dovremo riconoscere I sintomi

depressivi e trattarli in relazione al loro differente substrato

neurochimico

bull Necessario conoscere la multidimensionalitagrave del quadro per

un precoce ed efficace trattamento

Take home message

bull La depressione nella MP egrave sindrome premotoria molto

frequente durante la malattia e fattore di peggioramento

della qualitagrave della vita

bull Il suo riconoscimento egrave cruciale spesso sottodiagnosticata e

sottotrattata

bull Piu che una diagnosi formale dovremo riconoscere I sintomi

depressivi e trattarli in relazione al loro differente substrato

neurochimico

bull Necessario conoscere la multidimensionalitagrave del quadro per

un precoce ed efficace trattamento