Effectiveness of antidepressants. Meta-analysis of dose-effect relationships in randomised clinical trials

Antidepressant drugs are usually prescribed at low doses, possibly to avoid adverse reactions. No comprehensive review has addressed the issue of dose, clinical response and tolerability in a quantitative way.

To determine whether high doses of antidepressants are more effective than low doses, and how safety is affected by dose.

Trials comparing two or more doses of the same antidepressant were located, and all antidepressants administered were converted to the equivalent dose of imipramine. Generalised estimating equations were used to analyse percentage improvement and adverse event rate according to dose level.

Thirty-three studies were identified. The dose level 100-200 mg imipramine equivalents showed an average improvement of 53% by 'intention-to-treat'. Higher doses were not accompanied by increased efficacy, while lower doses showed reduction in efficacy. Adverse events significantly increased with dose.

With a low dose of antidepressants, clinicians trade off a slightly reduced chance of improvement for a higher chance of avoiding adverse reactions.