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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 low doses, 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. [ABSTRACT FROM AUTHOR]

The strategy of high-dose intramuscular haloperidol as routinely applied in a general hospital psychiatric ward to 74 successive patients, 33 of whom stayed only up to seven days, and a further 34 up to 15 days, led to a complete recovery in only six, and complete lack of change in 23. Adverse reactions were recorded in 42, severe enough to stop treatment in eight; there were three deaths. In view of this risk-benefit analysis, systematic application of this high dose strategy to get a more rapid turnover of patients is unjustified. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to comments made on the authors' paper about high-dose neuroleptics in Italy.