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

Department of Psychological Medicine, Institute of Psychiatry, London, and Istituto di Ricerche Farmacologiche "Mario Negri" Milan, and Dipartimento di Medicina e Sanità Pubblica, Sezione di Psichiatria, Università di Verona, Italy

MATTHEW HOTOPF, MRCPsych

Department of Psychological Medicine, Guy's, King's and St Thomas' Schools of Medicine, and Institute of Psychiatry, London

Correspondence: Dr Corrado Barbui, Istituto di Ricerche Farmacologiche "Mario Negri", Via Eritrea 62, 20157 Milano, Italy. Tel: 0039 02 39014 431; fax: 0039 02 33 2000 49; e-mail: barbui{at}marionegri.it

Declaration of interest None.

See editorial, pp. 99-100, this issue.

Background Tricyclic antidepressants have similar efficacy and slightly lower tolerability than selective serotonin reuptake inhibitors (SSRIs). However, there are no systematic reviews assessing amitriptyline, the reference tricyclic drug, v. other tricyclics and SSRIs directly.

Aims To review the tolerability and efficacy of amitriptyline in the management of depression.

Method A systematic review of randomised controlled trials (RCTs) comparing amitriptyline with other tricyclics/heterocyclics or with an SSRI.

Results We reviewed 186 RCTs. The overall estimate of the efficacy of amitriptyline revealed a standardised mean difference of 0.147 (95% CI 0.05-0.243), 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% CI 0.54-0.70), favouring the control drugs. With drop-outs included as treatment failures, the estimate of the effectiveness of amitriptyline v. tricyclics/heterocyclics and SSRIs showed a 2.5% difference in the proportion of responders in favour of amitriptyline (number needed to treat 40, CI 21-694; OR 1.12 (95% CI 1.01-1.24)).

Conclusions Amitriptyline is less well tolerated than tricyclics/heterocyclics and SSRIs, but slightly more patients treated on it recover than on alternative antidepressants.

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