Amitriptyline versus placebo for major depressive disorder

Area of Science:

• Psychiatry
• Clinical Pharmacology
• Evidence-Based Medicine

Background:

• Amitriptyline, a tricyclic antidepressant synthesized in 1960, remains in regular clinical use.
• It has served as a benchmark in trials for newer antidepressants.
• A systematic review and meta-analysis on its efficacy and safety versus placebo for major depression was lacking.

Purpose of the Study:

• To systematically assess the efficacy and safety of amitriptyline compared to placebo or no treatment in adults with major depressive disorder.

Main Methods:

• A comprehensive search of multiple databases (Cochrane, EMBASE, MEDLINE, PsycINFO) up to August 2012.
• Inclusion of randomized controlled trials (RCTs) diagnosing major depressive disorder using operationalized criteria.
• Data extraction and analysis using random-effects models, calculating odds ratios (OR) and standardized mean differences (SMD) with 95% confidence intervals (CI).

Main Results:

• The review included 39 trials with 3509 participants, showing amitriptyline significantly improved acute response compared to placebo (OR 2.67, 95% CI 2.21 to 3.23).
• Fewer participants withdrew due to inefficacy with amitriptyline, but more withdrew due to side effects (OR 4.15, 95% CI 2.71 to 6.35).
• Common side effects included anticholinergic effects, sedation, and weight gain; higher baseline depression severity correlated with greater amitriptyline superiority.

Conclusions:

• Amitriptyline is an efficacious antidepressant for major depressive disorder.
• The drug is associated with a notable incidence of side effects.
• The degree of placebo response and baseline depression severity may influence the observed differences in efficacy between amitriptyline and placebo.