Update on guidelines on biological treatment of depressive disorder Dr. Henry CHEUNG Psychiatrist in private practice
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)
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 )
MDD: most meaning in terms of consequences as well as socio economic implications. Treatment: acute phase, maintenance; focus of this guidelines.
MDD: single or recurrent major depressive episodes (MDE). Essential feature: at least 2 weeks of depressed mood with abnormal neurovegetative function, psychomotor activity, cognition, anxiety, suicidal ideation. Symptoms: most of the day and nearly everyday.
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.
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.
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.
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.
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).
Maintenance treatment: aim at preventing recurrence of depression and suicide and also full and lasting functional recovery.
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.
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.
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.
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.
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.
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 +mirtazapineor SSRI + TCA are superior to SSRI alone. Other studiers: showed no superiority of combination.
Paroxetine and venafaxine are effective in melancholic depression. Clomipramine is superior to paroxetine, citalopram in other study.
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.
Atypical depression Hypersomnia, wt gain, intense fatigue, rejection sensitively. Irreversible MAOI Lack of evidence about SSRI or newer antidepressants.
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
Suicidal depression Toxicity of antidepressants TCA: most Venafaxine, Mitrazapine: higher than SSRI SSRI: lower Recommend to prescribe a limited supply.
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
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.
Non responder?persistent psychosocial stressors Adherence of the medications Therapeutic drug monitoring Drug drug interactions
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.
Adjunctive therapy Benzodiazepine: possible side effects: sedation, psychomotor and cognitive impairment, dependence etc Duration: max 4 6 weeks
Treatment resistant depression 50% of non responder to first antidepressant fail to respond to second antidepressant.
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.
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