Remission, dropouts, and adverse drug reaction rates in major depressive disorder: a meta-analysis of head-to-head trials.
OBJECTIVE
To summarize remission rates and dropouts due to adverse drug reactions (ADRs) or lack of efficacy (LoE) of serotonin-norepinephrine reuptake inhibitors (SNRIs), selective serotonin-reuptake inhibitors (SSRIs), and tricyclic antidepressants (TCAs) in treating major depressive disorder.


METHODS
We searched MEDLINE, EMBASE, IPA, and the Cochrane International Library from 1980-2005. Meta-analysis summarized outcomes from head-to-head randomized clinical trials comparing >or= 2 drugs from three antidepressants classes (SNRIs, and/or SSRIs, and/or TCAs) followed by >or= 6 weeks of treatment. Remission was a final Hamilton Depression Rating Scale (HAMD) score <or= 7 or Montgomery-Asberg Depression Rating Scale (MADRS) <or= 12. Intent-to-treat data were combined across study arms using random effects models, producing point estimates with 95% confidence intervals.


RESULTS
We obtained data from 30 arms of 15 head-to-head trials with 2458 patients. SNRIs had the highest ITT remission rate (49.0%), then TCAs (44.1%), and SSRIs (37.7%) (p > 0.05 for SNRIs versus TCAs; p < 0.001 for TCAs versus SSRIs and SNRIs versus SSRIs). When categorized as inpatients (n = 582) and outpatients (n = 1613), SNRIs had the highest remission rates (52.0% for 144 inpatients and 49.3% for 559 outpatients). SNRIs had lowest overall dropouts (26.1%), followed by SSRIs (28.4%), and TCAs (35.7%). Dropouts due to ADRs and LoE were 10.3% and 6.2% for SNRIs, 8.3% and 7.2% for SSRIs, and 19.8% and 9.9% for TCAs, respectively (p > 0.05 for ADR dropouts only). One limitation was the inclusion of only venlafaxine-XR; results may not be the same for immediate release forms. In addition, few studies reported remission rates.


CONCLUSIONS
SNRIs had the highest efficacy remission rates (statistically significant for inpatients and outpatients), and the lowest overall dropout rates, suggesting clinical superiority in treating major depression.
Machado
Márcio
M
Universidad de Chile, Santiago, Chile.
Iskedjian
Michael
M
Ruiz
Inés
I
Einarson
Thomas R
TR
D018759:Adrenergic Uptake Inhibitors / Q000009:adverse effects* / Q000627:therapeutic use; D000929:Antidepressive Agents, Tricyclic / Q000009:adverse effects* / Q000627:therapeutic use; D003865:Major Depressive Disorder / Q000188:drug therapy* / Q000523:psychology; D006801:Humans; D010352:Patient Dropouts; D016032:Randomized Controlled Trials as Topic; D012075:Remission, Spontaneous; D017367:Selective Serotonin Reuptake Inhibitors / Q000009:adverse effects* / Q000627:therapeutic use
D018759:Adrenergic Uptake Inhibitors; D000929:Antidepressive Agents, Tricyclic; D017367:Selective Serotonin Reuptake Inhibitors