Treatment discontinuation with selective serotonin reuptake inhibitors compared with tricyclic antidepressants: a meta-analysis

BMJ 1995;310:1433-1438 (3 June)

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Treatment discontinuation with selective serotonin reuptake inhibitors compared with tricyclic antidepressants: a meta-analysis

I M Anderson, senior lecturer,^a B M Tomenson, statistician ^a

^a University of Manchester Department of Psychiatry, Rawnsley Building, Manchester Royal Infirmary, Manchester M13 9WL

Correspondence to: Dr Anderson.

Abstract

Objective: To assess treatment discontinuation rates with selectiveserotonin 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 rateswith respect to all cases of discontinuation and those due toside effects and treatment failure.
Results: The total discontinuation rate was 10% lower with selectiveserotonin reuptake inhibitors than with tricyclic antidepressants(risk ratio 0.90; 95% confidence interval 0.84 to 0.97) andthe drop out rate due to side effects was 25% lower (risk ratio0.75; 0.66 to 0.84). There was no significant difference betweendrug classes in the drop out rates for treatment failure. Therisk ratios for drop out did not differ significantly betweenindividual selective serotonin reuptake inhibitors.
Conclusions: Selective serotonin reuptake inhibitors are bettertolerated than tricyclic antidepressants as measured by totalnumbers of drop outs. The definite advantage to selective serotoninreuptake inhibitors is explained by fewer drop outs due to sideeffects. The overall difference, however, is comparatively smalland may not be clinically relevant. Analyses of cost effectivenessshould not overestimate the advantage to selective serotoninreuptake inhibitors.

Key messages

Key messages
In a meta-analysis of randomised, short term clinical trials selective serotonin reuptake inhibitors were associated with 10% fewer overall drop outs than tricyclic antidepressants (nine drop outs for every 10 with tricyclic agents)
This difference was accounted for by a lower rate of drop out related to side effects of selective serotonin reuptake inhibitors (25% reduction; three drop outs for every four with tricyclic agents)
This comparatively small difference in drop out rate is of uncertain importance clinically and when cost effectiveness is considered
Further studies of the tolerability of selective serotonin reuptake inhibitors compared with that of tricyclic antidepressants are required over a longer period in the setting of clinical practice rather than clinical trials

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