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Effectiveness of antidepressants

Meta-analysis of dose-effect relationships in randomised clinical trials

Published online by Cambridge University Press:  02 January 2018

Paola Bollini*
Affiliation:
for Med, Evolène, Switzerland
Sandro Pampaliona
Affiliation:
for Med, Evolène, Switzerland
Giuseppe Tibaldi
Affiliation:
Centro Studi e Ricerche in Psichiatria, Turin, Italy
Bruce Kupelnick
Affiliation:
for Med, Evolène, Switzerland
Carmine Munizza
Affiliation:
Centro Studi e Richerche in Psichiatria, Turin, Italy
*
Dr Carmine Munizza, Centro Studi e Ricerche in Psichiatria, Piazza del Donatore di Sangue, 3, 10154 Torino, Italy

Abstract

Background

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.

Aims

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

Method

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.

Results

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.

Conclusions

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

Type
Review Articles
Copyright
Copyright © 1999 The Royal College of Psychiatrists 

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Footnotes

Declaration of interest

Supported by the Centro Studi Richerche in Psichiatria (Turin, Italy), and by Angelini, Eli Lilli, Lundbeck, Ravizza. Roerig, Smith Kline Beecham and Solvay Pharma.

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