Amitriptyline for major depression

Evidence Summaries

Level of Evidence = B
Amitriptyline appears to be efficient in the treatment of depression but is also associated with a number of side effects.

A Cochrane review 1 included 39 studies with a total of 3509 participants with major depression. Most of the participants were outpatients. The mean age was 40 years. All studies compared amitriptyline with placebo, study duration ranged between 3 and 12 weeks. Amitriptyline was significantly more effective than placebo in achieving acute response (OR 2.67, 95% CI 2.21 to 3.23; 18 RCTs, n = 1987). Higher severity at baseline was associated with higher superiority of amitriptyline (p = 0.02). Significantly fewer participants on amitriptyline withdrew from trials due to inefficacy of treatment (OR 0.20, 95% CI 0.14 to 0.28; 19 RCTs, n = 2017), but more amitriptyline-treated participants withdrew due to side effects (OR 4.15, 95% CI 2.71 to 6.35; 19 RCTs, n = 2174). Amitriptyline also caused more anticholinergic side effects, tachycardia, dizziness, nervousness, sedation, tremor, dyspepsia, sedation, sexual dysfunction and weight gain. The results of the primary outcome were rather homogeneous, reflecting comparability of the trials.

Comment: The quality of the evidence is downgraded by study quality (inadequate allocation concealment, short follow-up time).


1. Leucht C, Huhn M, Leucht S. Amitriptyline versus placebo for major depressive disorder. Cochrane Database Syst Rev 2012;12():CD009138.  [PMID:23235671]
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