Amitriptyline versus other types of pharmacotherapy for depression

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 the selective serotonin reuptake inhibitors have been introduced on the market with the claim of a more favourable tolerability/efficacy profile.

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.

The Cochrane Collaboration Depression, Anxiety and Neurosis Controlled Trials Register (2002-3) and the Cochrane Central Register of Controlled Trials (CENTRAL) were searched. Key journals and conference abstracts were handsearched. Pharmaceutical companies were contacted for information on unpublished materials.

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 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 was extracted.

The estimate of the overall odds ratio for responders showed that more subjects responded to amitriptyline in comparison with the control antidepressant group (odds ratio 1.12, 95% confidence interval 1.01, 1.23, number needed to treat 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 0.13, 95% confidence interval 0.04, 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 (odds ratio 0.63, 95% confidence interval 0.56, 0.71). 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 (odds ratio 0.84, 95% confidence interval 0.75,0.95, number needed to harm 40). When the responder analysis was stratified by study setting amitriptyline was more effective than control ADs in inpatients (odds ratio 1.22, 95% confidence interval 1.04, 1.42, number needed to treat 24), but not in outpatients (odds ratio 1.01, 95% confidence interval 0.88, 1.17, number needed to treat = 200).

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 the selective serotonin reuptake inhibitors amitriptyline was less well tolerated, and although counterbalanced by a higher proportion of responders, the difference was not statistically significant.