Amitriptyline for depression (Withdrawn Paper. 2007, art. no. CD004186)

Background For many years amitriptyline has been considered one of the reference compounds for the pharmacological treatment of depression. However, new tricyclic drugs, heterocyclic compounds and selective serotonin reuptake inhibitors have been introduced on the market with the claim of a more favourable tolerability/efficacy profile. Objectives The aim of the present systematic review was to investigate the tolerability and efficacy of amitriptyline in comparison with the other tricyclic/heterocyclic antidepressants and with the selective serotonin reuptake inhibitors. Search strategy The Cochrane Collaboration Depression, Anxiety and Neurosis Controlled Trials Register (CCDANCTR-Studies) was searched on 28-11-2005. Reference lists of all included studies were checked. Selection criteria Only randomised controlled trials were included. Study participants were of either sex and any age with a primary diagnosis of depression. Included trials compared amitriptyline with another tricyclic/heterocyclic antidepressant or with one of the selective serotonin reuptake inhibitors. Data collection and analysis Data were extracted using a standardised form. The number of patients undergoing the randomisation procedure, the number of patients who completed the study and the number of improved patients were extracted. In addition, group mean scores at the end of the trial on Hamilton Depression Scale or any other depression scale were extracted. In the tolerability analysis, the number of patients failing to complete the study and the number of patients complaining of side-effects were extracted. Main results A total number of 194 studies were included in the review. The estimate of the overall odds ratio (OR) for responders showed that more subjects responded to amitriptyline in comparison with the control antidepressant group (OR 1.12 to 95% confidence interval (CI) 1.02 to 1.23, number needed to treat to benefit (NNTB) = 50). The estimate of the efficacy of amitriptyline and control agents on a continuous outcome revealed an effect size which also significantly favoured amitriptyline (Standardised Mean Difference (SMD) 0.13, 95% CI 0.04 to 0.23). Whilst these differences are statistically significant, their clinical significance is less clear. When the efficacy analysis was stratified by drug class, no difference in outcome emerged between amitriptyline and either tricyclic or selective serotonin reuptake inhibitor comparators. The dropout rate in patients taking amitriptyline and control agents was similar; however, the estimate of the proportion of patients who experienced side-effects significantly favoured control agents in comparison with amitriptyline (OR 0.66, 95% CI 0.59 to 0.74). When the tolerability analysis was stratified by drug class, the dropout rate in patients taking amitriptyline and the selective serotonin reuptake inhibitors significantly favoured the latter (OR 0.84, 95% CI 0.75 to 0.95, number needed to treat to harm (NNTH) = 40). When the responder analysis was stratified by study setting amitriptyline was more effective than control antidepressants in inpatients (OR 1.22, 95% CI 1.04 to 1.42, NNTB = 24), but not in outpatients (OR 1.01, 95% CI 0.88 to 1.17, NNTB = 200). Authors' conclusions This present systematic review indicates that amitriptyline is at least as efficacious as other tricyclics or newer compounds. However, the burden of side-effects in patients receiving it was greater. In comparison with selective serotonin reuptake inhibitors amitriptyline was less well tolerated, and although counterbalanced by a higher proportion of responders, the difference was not statistically significant.