antidepresivos 2009 -ii

7/27/2019 Antidepresivos 2009 -II

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ANTIDEPRESIVOS Y

ESTABILIZANTES DEL HUMOR

(ESTADO DE ANIMO)

Unidad de Farmacologa

Miguel E MartnezSnchez,MD


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ANTIDEPRESIVOS

TRICCLICOS (HETEROCCLICOS) INHIBIDORES DE LA RECAPTACIN

DE SEROTONINA INHIBIDORES DE LA MONOAMINO -

OXIDASA (MAO)

ESTABILIZANTES DEL HUMOR TRIAZOLOBENZODIACEPINAS


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ANTIDEPRESIVOS

AGONISTAS PARCIALES DELRECEPTOR 5-HT1A INHIBIDOR DE LA RECAPTACIN

DE SEROTONINA Y ANTAGONISTADEL RECEPTOR 5-HT2 INHIBIDOR NO SELECTIVO DE LA

RECAPTACIN DENEUROTRASMISORESAMINERGICOS

TERAPIA ELECTROCONVULSIVATEC


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TEORIAS BIOQUMICAS DEL AFECTO

TEORIA DE LAS AMINASBIOGENAS (1950-1960)

INHIBIDORES DE LA M.A.O EFECTO DE LOS TRICCLICOS EFECTO DE LAS ANFETAMINAS REACCIONES PSICTICAS EFECTO DE LA RESERPINA


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orepinephrine


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Alpha Receptors


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Serotonin


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5-HT: Behavioral Actions

Food intake: increased 5-HT reducesFI (Fenfluramine)

Pain sensitivity (reduced 5-HT =

increased pain sensitivity) 5-HT is low during sleep 5-HT metabolite 5-HIAA is low in

suicides Loss of 5-HT transporters in MDMA

users


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Serotonin

Serotonin(5-HT) cells are mostlylocated in the gut (98%) with only 2%of serotonin cells in brain

Serotonin cell bodies are located in

brainstem raphe nuclei and project tocortex Serotonin systems:

D system originates in the dorsal raphenucleus but does not form synapses (5-HTas a neuromodulator)

M system originates from the median

raphe nucleus and these varicosities formsynapses4.11


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SINTOMAS DEPRESIVOS Y

SU RESPUESTA

NEUROVEGETATIVOS:Trastornos del sueo

Trastornos del apetitoTrastornos de la volicin

Trastornos sexuales

Ritmos diurnos anormales 10 dias a 2 semanas


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SU RESPUESTA

PSICOMOTORES: AGITACIN O LENTIFICACIN 3-4 SEMANAS (MEJORIA 7-14 DIAS)

AFECTIVOS TRISTEZA (MELANCOLIA) INCAPACIDAD DE EXPRESIN LENTAMENTE Y POR ETAPAS


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SU RESPUESTA

COGNOCITIVOS: CONCENTRACIN MEMORIA ATENCIN APRENDIZAJE

PSICTICOS INCAPACIDAD SOCIAL

LENTAMENTE Y POR ETAPAS


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DIMENSIN EXISTENCIAL

SOLEDAD CULPA

RUMIACININCAPACIDAD PARA LA

GRATITUD

CIRCULOS VICIOSOS


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ESTABLECER DIFERENCIAS

DUELO: CULPA/REPROCHE SINT SOMATICOS

MENOS DE SEISMESES FUNCIONAL NO SUICIDIO

DEPRESIN CULPA/REPROCHE SINT SOMATICOS

MAYOR A SEISMESES DEBILITAMIENTO

PROGRESIVO

POTENCIALMENTESUICIDA


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ESTABLECER DIFERENCIAS

DEMENCIAINSIDIOSA PROLONGADA

AFECTOVARIABLE DEF COGNITIVAS

CONSISTENTES

RESP ERRONEASEN EVAL NEUROLAFASIA,APRAXIA,

AGNOSIA

DEPRESINABRUPTA* CORTA*

AFECTODEPRESIVO DEF COGNITIVO

NO

PERSISTENTES NO DEFICIT

NEUROLOGICO


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ANTIDEPRESIVOS HETEROCCL ICOS

Am inas terciar ias

IMIPRAMINA AMITRIPTILINA TRIMIPRAMINA

DOXEPINA CLOMIPRAMINA

Tofranil

Tryptanol Surmontil

Anafranil


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ANTIDEPRESIVOS HETEROCCL ICOS

Am inas secundar ias

DESIPRAMINA NORTRIPTILINA PROTRIPTILINA AMOXAPINA MAPROTILINA Ludiomil


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FARMACODINAMIA

INHIBICIN DE LARECAPTACIN DENORADRENALINA

INHIBICIN DE LARECAPTACIN DE SEROTONINA


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EFECTOS SECUNDARIOS

LOS EFECTOS SECUNDARIOSSE CORRELACIONAN MEJORCON EL PERFIL

FARMACODINAMICO QUE STECON LOS EFECTOS CLNICOS


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EFECTOS SECUNDARIOS

ANTICOLINERGICOS SEQUEDAD DE LA BOCA VISIN BORROSA CONSTIPACIN RETENCIN URINARIA CONFUSIN


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EFECTOS SECUNDARIOS

ANTIHISTAMNICOS SEDACIN

SEROTONINRGICOS SEDACIN Y/O ACATISIA

ADRENRGICOS TEMBLOR, EXCITACIN PALPITACIONES GANANCIA DE PESO


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INHIB IDORES DE LA

RECAPTACIN DE SEROTONINA

FLUOXETINA

TRAZODONE SERTRALINA PAROXETINA FLUVOXAMINA CITALOPRAM


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INDICACIONES

Enfermedad cardiacaconcomitanteIntolerancia a los efectos

secundarios anticolinrgicosAlto riesgo de sobredosis

voluntaria

Aumento de peso excesivo La sedacin no es aconsejable Trastorno obsesivo-compulsivo

asociado


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EFECTOS SECUNDARIOS

Gastrointestinales: nausea,flatulencia, diarrea

S.N.C: insomnio, inquietud,irritabilidad, euforia, agitacin,temblores, distona*

Sexuales: eyaculacinretardada, anorgasmia


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SINDROME SEROTONINERGICO

HipertermiaInquietud, calambres

musculares, rigidez

Convulsiones y coma


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INHIBIDORES DE LA MAO

NO SELECTIVOSISOCARBOXAZI

DA TRANILCIPROMI

NA

SELECTIVOS MOCLOBEMIDA BROMFAROMINE


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EFECTOS SECUNDARIOS

Autonmicos: boca seca,mareo, estreimiento,

dificultad en la miccin,hipotensin postural

Centrales: cefalea, temblores,

parestesia Otros: edema en tobillos,

hepatotoxicidad

Trazodone (Desyrel)


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Trazodone (Desyrel)

SARI (serotonin antagonist/reuptakeinhibitor) Strong 5-HT2Aantagonist, relatively weak 5-HT

reuptake inhibitor Also an 1-adrenergic and H1 antagonist

Introduced in 82 as an atypical orsecond generation antidepressant

Chemically distinct from TCA, resemblesnefazadone

Highly protein bound, metabolized by 3A4,to mCPP (active metabolite), overall half-life < 24 hours.


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Trazodone (Desyrel) cont.

Bottom Line: Almost always used for insomnia. Watch for orthostatic hypotension Caution about priapism Remember, its an antidepressant!


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NEFAZODONE

INHIBIDOR DE LA RECAPTACIONDE SEROTONINA Y ANTAGONISTA

DEL RECEPTOR 5-HT2


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Nefazadone (Serzone)

SARI (serotonin antagonist/reuptakeinhibitor) Strong 5-HT2Aantagonist, relatively weak 5-HT

reuptake inhibitor

Weaker alpha 1 adrenergic and H1 antagonistcompared to trazadone. Approved in 1995, developed to improve

upon trazadone: no priapism and lesssedating.

Unfortunately, cases of liver failure1:200,000-300,000 has limited its use. Ageneric still available. Time to liver injury 2 weeks to 6 months.

Check LFTs


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Mirtazapine (Remeron)

NaSSA (noradrenergic specific

serotonergic antidepressant) Central alpha-2 adrenergic autoreceptorantagonist (leads to net NE and 5-HTneurotransmission

5-HT2A, 5-HT2C, 5-HT3 antagonist H1 antagonist (the most potent action)

Approved for MDD (may work faster thanSSRIs)

Also used for SSRI augmentation, anxiety,nausea Moderately protein bound, metabolized by

1A2, 2D6, 3A4. Half-life 20-40 hours.

Eliminated primarily via urine


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Mirtazapine (Remeron) cont.

Bottom Line: Can be good inpatient choice (helps

sleep, depression, appetite, no drug

interactions) Not popular first choice for outpatients

(oversedation, weight gain).

Avoids sexual dysfunction. Used for augmentation


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Bupropion (Wellbutrin IR, SR, XL)

NDRI (norepinephrine, dopamine receptorinhibitor) Inhibits reuptake of NE, lesser extent

DA but exact mechanism controversial. Initial release of IR delayed due to

seizures, re-released in 89(rarely used).In 96 SR released (now generic) and in03 XL form released.

FDA approved for MDD, smoking cessation(Zyban)

Also used for ADHD, SSRI induced sexualdysfunction, SSRI augmentation Highly protein bound, bupropion and its

active metabolites metabolized by 2B6.

Half life approx 21 hours. Mild 2D6inhibitor.


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Bupropion (Wellbutrin IR, SR, XL) cont.

Bottom Line: Activating so caution for depression with

comorbid panic/anxiety disorders.

Can be useful for anergic depression orwhen you wish to avoid sexualdysfunction.

Relatively ineffective for anxietydisorders. Commonly used to augment SSRIs. Screen for seizure history.


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VENLAFAXINE

INHIBIDOR NO SELECTIVO DELA RECAPTACIN DENEUROTRASMISORES

AMINRGICOS


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Venlafaxine (Effexor XR)

SNRI (serotonin, norepinephrine reuptakeinhibitor) At low doses (75 mg-150 mg), primarily SSRI At moderate/high doses, also NE reuptake

inhibitor FDA approved for MDD, social phobia and GAD

At higher doses, some evidence of higherremission rate for MDD compared to SSRIs.

Some evidence: chronic pain, panic disorder,

ADHD, OCD Poorly protein bound, XR formulation slowsabsorption but half-life still only about 15 hours.Metabolized by 2D6 to active O-desmethylvenlafaxine (ODV) Primarily eliminatedin urine.


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Venlafaxine (Effexor XR) cont.

Bottom Line: Potentiallymodestly more efficacious

antidepressant at high doses but

inconsistent. Watch for discontinuation syndrome. Consider checking BP at doses > 225

mg qd Commonly used after initial trial ofSSRI.


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cymbalta (Duloxetine)

SNRI (serotonin, norepinephrinereuptake inhibitor) Unlike venlafaxine, reuptake of NE, 5-

HT equally affected. Approved for MDD and diabeticperipheral neuropathy Some evidence for chronic pain,

anxiety disorders, urinary stressincontinence. Highly protein bound, metabolized by

2D6 and 1A2, Half life 12 hours

Moderate inhibitor of 2D6


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cymbalta (Duloxetine) cont.

Bottom Line: Newest antidepressant (04) Marketed for physical symptoms of

depression but not unique: tertiaryTCAs, venlafaxine

Some evidence for improved remission

vs SSRIs but jury still out.


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TERAPIA

ELECTROCONVULSIVA

INDICACIONES RIESGO SUICIDA

SINTOMAS CATATNICOSINFORMACIN DEL ELECTROCHOQUE AL TECAR


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THREE PHASES OF TREATMENT

Time

Normal

Acute

Phase (3 months+)

Continuation

Phase (6-12 months)

Maintenance

Phase (years)

Response

Remission

Relapse

Relapse Recurrence

> 50%

STOP

Rx

65 to 70%

STOP

Rx

Recovery


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Potential Adverse Effects of

Antidepressant Therapy

10/31/201345

Cardiac

Orthostasis

hypertension

heart block,

tachycardia

Urogenital

Erectile dysfunction,ejaculation disorder,

anorgasmia,

priapism

Central Nervous System

Dizziness, cognitive impairment,

sedation, light-headedness,

somnolence, nervousness,

insomnia, headache, tremor,

changes in satiety and appetite

Gastrointestinal

Nausea, constipation,

vomiting, dyspepsia,

diarrhea

Autonomic Nervous System

Dry mouth, urinary retention,

blurred vision, sweating


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ESTAB IL IZANTES DEL HUMOR

CARBAMAZEPINAACIDO VALPROICO

CARBONATO DE LITIO


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TRIAZOLOBENZODIACEPINAS

ALPRAZOLAMADINAZOLAM

AGONISTAS RECEPTOR


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AGONISTAS RECEPTOR

5HT1A

GEPIRONA IPSAPIRONA

Symptom Domains of


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Symptom Domains of

Bipolar Disorder

Racing thoughts Distractibility Disorganization

Inattentiveness

Delusions

Hallucinations

Cognitive Symptoms

Psychotic Symptoms

Euphoria Grandiosity Pressured speech Impulsivity Excessive libido Recklessness Social intrusiveness Diminished need

for sleep

Depression Anxiety

Irritability Hostility Violence or

suicide

Manic Mood and Behavior Dysphoric or NegativeMood and Behavior


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Bipolar I,Rapid Cycling and

Mixed State

Bipolar II DisorderCyclothymic Disorder

SchizoaffectiveDisorder,

Bipolar Type

BorderlinePersonality Disorder

Bipolar I,Depressed

Bipolar I,Classic Mania

The Bipolar Spectrum


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Bipolar Disorder: Subtypes of Illness(proposed for the DSM-V)

Bipolar I Mania + Major

Depression

Bipolar II Hypomania + Major

Depression

Bipolar III Cyclothymia

Bipolar IV Anti-depressant-

induced Hypomania

Bipolar V Recurrent MajorDepression with aFamily History ofBipolar Disorder

Bipolar VI Unipolar Mania

po ar sor er:


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po ar sor er:Prevalence and Course of

Illness Lifetime prevalence: 0.81.6% Gender influence: men = women Recurrent illness in >90% of patients Factors :episode frequency and severity

of residual symptoms between episodes Number of episodes may affect

subsequent treatment response 25-50% of patients attempt suicide > 1

time


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Genetic Risk: Bipolar Disorder

First-degree relativeafflicted

Bipolar disorder: 10-15% (10-12 times risk)

Monozygotic twin afflictedBipolar disorder: 60% (40times risk)


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What is the Ideal

Treatment ofBipolar Disorder?

An Ideal Primary Mood


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Any medication that stabilizes acute

manic symptoms, does not inducedepression, and prevents againstfuture relapses into (mania or

depression)

An Ideal Primary Mood

Stabilizer

Mood Stabilizing Agents


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*FDA approved for acute mania.

Mood-Stabilizing Agents Lithium* Antiepileptic medications

Valproate(Depakene,Depakote*,Depakote ER)

Carbamazepine(Tegretol)/Oxcarbazepine(Trileptal)

Gabapentin

(Neurontin

) Topiramate(Topamax)

Lamotrigine(Lamictal)

Typical antipsychotics

Novel antipsychotics Risperidone

(Risperdal) Ziprasidone

(Geodon

) Olanzapine

(Zyprexa)* Clozapine

(Clozaril

) Quetiapine

(Seroquel)


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ESTAB IL IZANTES DEL HUMOR

CARBONATO DE LITIO EVIDENCIA CLINICA USO CLINICO FARMACODINAMIA PROBABLE

SISTEMAS DE TRANSDUCCIN DEMEMBRANA (FOSFATIDIL INOSITOLES)


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EFECTOS SECUNDARIOS

TEMPRANOSsequedad de la bocased diuresis temblorpirosis, sabor metlico debilidad, fatiga


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EFECTOS SECUNDARIOS

TARDIOS temblor levepolidipsia, poliuria aumento de tamao del tiroides hipotiroidismo

alteraciones de memoria cambios en el EKG

TOXICIDAD


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TOXICIDAD

Vmito Diarrea Temblor intensoAtaxia, disartria Calambres musculares,

hiperreflexia Confusin, comaInsuficiencia renal Shock cardiovascular


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INTERACCIONES

Haloperidol Diurticos tiazdicos Relajantes muscularesAINES metronidazol, estreptomicina iECAS, metildopa antipsicticos, ISRS, TECAR


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Who Responds Best

to Lithium?

Factors Associated With


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Factors Associated With

Positive Response to Lithium

Bipolar I (euphoric/elatedmania)

First episode manic Prior response to lithium Limitations

No neurological impairment No substance abuse Relatively few illness episodes

(i.e., no rapid cycling, mixed,

other novel features)


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How are the

Antiepileptic

Medications Used inTreating Bipolar

Mania?

Treatment of Bipolar Mania:


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Treatment of Bipolar Mania:

Divalproex

Efficacy: comparable to lithiumin classic mania

Predictors of responseComparable efficacy in classicmania, mixed states, and rapidcycling

antidepresivos 2009 -ii

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