Is Amitriptyline the Reference Antidepressant?

Article type
Year
Authors
Barbui C, Hotopf M
Abstract
Introduction:

Objectives: For many years the tricyclic antidepressant (AD) amitriptyline has been considered the reference compound for the treatment of depression; in the last 10 years, however, new tricyclic drugs, heterocyclic ADs and the selective serotonin reuptake inhibitors (SSRIs) have been introduced in the market. As a result, little consensus exists on which drug should be considered the reference AD. The present systematic review was therefore undertaken to investigate the tolerability and efficacy of amitriptyline in comparison with the other tricyclic/heterocyclic ADs and with the SSRIs.

Methods: Only randomised controlled trials (RCTs) comparing amitriptyline with tricyclic/heterocyclic drugs and SSRIs were included. Studies were identified by searching the Depression, Anxiety and Neurosis Register of RCTs and electronic databases (Medline, 1966 onwards; Embase, 1974 onwards). Outcomes of interests were: treatment response as defined in the studies; numbers of people dropping out during the trial; number of people reporting side-effects. All randomised patients were included in the effectiveness evaluation (intent-to-treat analysis),

Results: Nearly 200 RCTs were included in the analysis. The estimate of the overall effectiveness of amitriptyline versus tricyclic/heterocyclic drugs and SSRIs was 1.13 (95% CI 1.02, 1.25), favouring amitriptyline. The overall odds ratio for drop-outs was 0.99 (95% CI 0.91, 1.08) and that for side-effects was 0.61 (95% CI 0.54, 0.70), favouring the control drugs. No differences were seen between amitriptyline and the other tricyclic/heterocyclic AD in terms of responders and drop-outs. A difference in terms of drop-outs was found between amitriptyline and SSRIs, favouring SSRIs. However, the odds ratio of the effectiveness of amitriptyline versus SSRI was 1.18 (95% CI 0.96, 1.44).

Discussion: Amitriptyline is at least as effective as the other AD. In comparison to SSRIs amitriptyline showed a worse tolerability profile. When drop-outs were included in the analysis, no differences in outcome were seen. These data support the notion that amitriptyline should still be considered the reference AD in the pharmacological treatment of depression.