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OBJECTIVE--To assess treatment discontinuation rates with selective serotonin reuptake inhibitors compared with tricyclic antidepressants. DESIGN--Meta-analysis of 62 randomised controlled trials. SUBJECTS--6029 patients with major unipolar depression. MAIN OUTCOME MEASURES--Pooled risk ratios for drop out rates with respect to all cases of discontinuation and those due to side effects and treatment failure. RESULTS--The total discontinuation rate was 10% lower with selective serotonin reuptake inhibitors than with tricyclic antidepressants (risk ratio 0.90; 95% confidence interval 0.84 to 0.97) and the drop out rate due to side effects was 25% lower (risk ratio 0.75; 0.66 to 0.84). There was no significant difference between drug classes in the drop out rates for treatment failure. The risk ratios for drop out did not differ significantly between individual selective serotonin reuptake inhibitors. CONCLUSIONS--Selective serotonin reuptake inhibitors are better tolerated than tricyclic antidepressants as measured by total numbers of drop outs. The definite advantage to selective serotonin reuptake inhibitors is explained by fewer drop outs due to side effects. The overall difference, however, is comparatively small and may not be clinically relevant. Analyses of cost effectiveness should not overestimate the advantage to selective serotonin reuptake inhibitors.