Amitriptyline v. the rest: still the leading antidepressant after 40 yearsof randomised controlled trials

Background Tricyclic antidepressants have similar efficacy and slightly low er tolerability than selective serotonin reuptake inhibitors (SSRls). Howev er, there are no systematic reviews assessing amitriptyline, the reference tricyclic drug, v. other tricyclics and SSRls directly. Aims To review the tolerability and efficacy of amitriptyline in the manage ment of depression. Method Asystematic review of randomised controlled trials (RCTs) comparing amitriptyline with other tricyclics/heterocyclics or with an SSRl. Results We reviewed 186 RCTs. The overall estimate of the efficacy of amitr iptyline revealed a standardised mean difference of 0.147 (95% CI 0.05-0.24 3), significantly favouring amitriptyline. The overall OR for dropping out was 0.99 (95% CI 0.91-1.08) and that For side-effects was 0.62 (95% Cl 0.54 -0.70), Favouring the control drugs. With drop-outs included as treatment f ailures, the estimate of the effectiveness of amitriptyline v. tricyclics/h eterocyclics and SSRls showed a 2.5% difference in the proportion of respon ders in favour of amitriptyline (number needed to treat 40, Cl 21-694; OR 1 .12 (95% Cl 1.01-1.24)). Conclusions Amitriptyline is less well tolerated than tricyclics/hetrocycli cs and SSRls, but slightly more patients treated on it recover than on alte rnative antidepressants.