Comment: The quality of evidence is downgraded by study quality (unclear allocation concealment) and indirectness (short follow-up time).
A Cochrane review 1 [Abstract] included 194 RCTs. A total of 147 RCTs compared amitriptyline with another TCA or related antidepressive drug (AD), and 47 RCTs compared amitriptyline with one of the SSRIs. The mean length of follow-up was 5.2 weeks. More subjects responded to amitriptyline in comparison with the control antidepressant group (OR 1.12, 95% CI 1.01 to 1.23, NNT 50). The estimate of the efficacy of amitriptyline and control agents on a continuous outcome also significantly favoured amitriptyline (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 SSRI comparators. The dropout rate in patients taking amitriptyline and control agents was similar; however, the proportion of patients with side-effects significantly favoured control agents (OR 0.63, 95%CI 0.56 to 0.71). When the tolerability analysis was stratified by drug class, the dropout rate significantly favoured SSRIs (OR 0.84, 95%CI 0.75 to 0.95, NNH 40). When the responder analysis was stratified by study setting amitriptyline was more effective than control ADs in inpatients (OR 1.22, 95%CI 1.04 to 1.42, NNT 24), but not in outpatients (OR 1.01, 95%CI 0.88 to 1.17, NNT=200).
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