dr. henry cheung psychiatristcme.hkdu.org/files/symposia/handouts/symposium710-handout-201… ·...
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Update on guidelines on biological treatment of depressive disorder
Dr. Henry CHEUNG
Psychiatrist in private practice
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• 2013 update• International Task Force of World Federation
of Societies of Biological Psychiatry (WFSBP)
• Based on 2007 guidelines (for use in primary care based on review of all available evidence)
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Definition
• ICD 10• DSM IV• Depressive episode or recurrent depressive
disorder(DSM IV: major depressive disorder (MDD)‐single episode or recurrent);
• Dysthymia(DSM IV:
Dysthymic
disorder and other chronic depressive disorder(MDD in incomplete
remission and chronic MDD));• Depressive episode, unspecified, brief recurrent
depressives (DSM IV:”sub‐threshold depressions”)
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• MDD: most meaning in terms of consequences as well as socio‐economic
implications.
• Treatment: acute phase, maintenance; focus of this guidelines.
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• MDD: single or recurrent major depressive episodes (MDE).
• Essential feature: at least 2 weeks of depressed mood with abnormal
neuro‐
vegetative function, psychomotor activity, cognition, anxiety, suicidal ideation.
• Symptoms: most of the day and nearly everyday.
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• MDD: median lifetime prevalence of 16.1% (range 4.4 ‐
18).
• 5‐10% of adult population during any 1 year period of time.
• Male : female (1:2)• At least 10% of all patients presenting in
primary care settings suffer from depression, with 50% presenting with primarily or only
with somatic symptoms.
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• 25% classify as having MDD;
• 30% classify as having minor depression;
• 45% classify as having non‐specific depressive disorder.
• MDD cab begin at any age;
• Two peaks: 20s and 40s.• Mean age of onset: 30.
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• Untreated: last about 6 months or longer.
• 50‐85 % of patients will eventually have another.
• 20‐30 % remission will be incomplete.
• Most serious consequence: suicide.
• Life time prevalence of suicide of general population: 0.5%; 2.2 for all affective disorder
patients, 8.6% for history of hospitalized.
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Indications and treatment goals
• Comprehensive treatment plan based on history of previous treatments, current clinical
findings, severity and risk of suicide.
• 1) acute; 2)continuation therapy; and 3) maintenance therapy.
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• Acute phase: initiation of treatment to remission; (remission: 2 goals:
asymptomatic
and improvement in psychosocial and occupational functioning.
• Continuation phase: follows acute phase to preserve and stabilize remission, treatment is
extended for a period to prevent return of depression(relapse).
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• Maintenance treatment: aim at preventing recurrence of depression and suicide and also
full and lasting functional recovery.
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Acute phase treatment
• Antidepressants:
imipramine
(developed in 1957), now about 40 available.
• Newer antidepressants: less side effects.• All produce treatment response of 50‐75%.• Choice of antidepressant: patient’s past response,
concurrent medical condition, concomitant use of other medications, drug side effects, physician
experience on different antidepressants, first degree relative’s response to antidepressant, patent preference and cost.
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classification
• TCA(both non selective
serotonin
and norepinephrine
reuptake inhibitors), SSRI, NRI,
SNRI, MAOI and other.
• No clinically significant differences in efficacy and effectiveness between TCA and SSRI.
• Mitrazapine
vs
TCA: no significant difference.
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• Side effect varies between classes.• SSRI generally better tolerated, lower rate of
treatment discontinuation.• SSRI: safer and higher tolerability profile, fewer
anticholinergic
side effects and cardiovascular toxicities.
• Most frequent side effect of TCA, tetracyclics: anticholingeric/ antimuscarinergic, CVS,
antihistaminergic
and
neurologic.• TCA not to be used in : moderate to severe CVS
disorder, narrow angle glaucoma, BPH, cognitive impairment, seizure, delirium. Nortriptyline
safer CVS
profile.
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• Most freq side effect of SSRI: GI upset, restlessness, sexual dysfunction and
neurological.
• SSRI cab alter platelet function, SIADH.• High dose SSRI: QTc
prolongation.
• SSRI is contraindicated in combination with MAOI,
serotonin
syndrome.
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• SNRI: more discontinuation as
comparted
to SSRI. Possible BP elevation.
• Mirtazapine: discontinuation syndrome, weight gain, sedation; less nausea and sexual
dysfunction.
• Agomelatine: risk of liver damage.
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• WFSBP recommendation: SSRI first line options, followed by
Mirtazapine, SNRI and
tetracyclics,
bupropion, tianeptin
and agomelatine.
• TCA considered as second line.• Small scales studies: SSRI + mirtazapine or
SSRI + TCA are superior to SSRI alone.• Other studiers: showed no superiority of
combination.
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• Paroxetine
and venafaxine
are effective in melancholic depression.
• Clomipramine
is superior to
paroxetine, citalopram
in other study.
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Psychotic depression
• Benefit from combination of antidepressant and
antipsychotics.
• Atypical
antipsychotics
are sometimes preferred due to lower risk of extra‐pyramidal
side effects.
• Higher risk of metabolic syndrome.
• Usually lower dose then those used in schizophrenia.
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Atypical depression
• Hypersomnia, wt gain, intense fatigue, rejection sensitively.
• Irreversible MAOI
• Lack of evidence about SSRI or newer antidepressants.
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Suicidal depression
• Male: 20‐30, over 50, esp
the very old.
• Female: 40‐60.
• History of previous suicidal attempts.
• Family history
• Marital statue,
• Lack of support, substance abuse.• Lithium, ECT
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Suicidal depression
• Toxicity of antidepressants• TCA: most
• Venafaxine, Mitrazapine: higher than SSRI
• SSRI: lower• Recommend to prescribe a limited supply.
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Evaluating efficacy of initial treatment
• By rating scales• HRSD, MADRS,BDI, PHQ
• Non‐response: <25%• Partial response: 26‐49%• Response: >50%• Response with residual symptoms
• remission
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• First 14 days can assess.• Improvement in the early phase: predict of a
positive final treatment outcome.
• Onset of improvement: 20% for a HAMD score 17 out of 20.
• Less than 10% non responder will become responder or remitter in 6 weeks course.
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Non responder
• ?persistent psychosocial stressors• Adherence of the medications
• Therapeutic drug monitoring
• Drug drug interactions
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Treatment options for partial and non responders
• At least 30% will not respond sufficiently.• 1) step up dose• 2)switch to another class• 3) switch to another in the same class• 4) combination of antidepressants• 5) augmentation (lithium, T3, atypical
antipsychotics)• 6) combination with psychotherapy• 7) combine with other bio treatment ECT, Light
therapy and ECT.
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Adjunctive therapy
• Benzodiazepine: possible side effects: sedation, psychomotor and cognitive
impairment, dependence etc
• Duration: max 4‐6 weeks
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Treatment resistant depression
• 50% of non responder to first antidepressant fail to respond to second antidepressant.
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Continuation‐phase treatment
• Last at least 6 months following remission of the acute
symptomatology.
• Prolonged to 9 months in patients with a history of long previous episodes and even
longer in cases of residual
symptomatology
, until such symptoms have subsided.
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Special circumstances
• 1) co‐morbidity of depression with other psychiatric disorder;
• 2) co‐morbid with OCD;
• 3) substance abuse;• 4) older age group;• 5) depression due to a general medical
condition;
• 6) during pregnancy and breast feeding