The Pharmaceutical Journal
Vol 270 No 7237 p256
22 February 2003

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The Lancet (www.thelancet.com)

Longer-term use of antidepressants could reduce patients' risk of relapse

Longer-term use of antidepressants could reduce the risk of relapse for patients with depressive disorders. This would involve giving antidepressants for courses of one or two years, rather than the currently recommended periods of four to nine months, after management of an acute episode.

The suggested new approach is the outcome of an overview led by Professor John Geddes, department of psychiatry, Oxford University, published in The Lancet (2003; 361:653). Professor Geddes and colleagues pooled data from 31 randomised trials involving over 4,400 patients. Most trials were of 12 months' antidepressant therapy, although duration ranged from six months to three years. All participants had received treatment for acute depressive episodes and were randomised either to continue treatment or to switch to placebo.

The researchers found that continued treatment reduced the chance of depressive relapse by around two-thirds. The average rate of relapse on placebo was 41 per cent, compared with 18 per cent on active treatment. The effect was similar across different classes of antidepressant. The reduction in risk was generally independent of the underlying risk of relapse and the duration of treatment before randomisation.

The authors call for further trials to establish the optimum length of therapy. They say that trials should include patients with milder disease, since most of the trials they examined involved patients at high risk of relapse. "We cannot make specific recommendations about which patients should or should not be offered long-term treatment with antidepressants, because treatment will depend on an individual's baseline risk, patients' treatment preferences and the clinician's prior beliefs," they state.

But co-author Professor Guy Goodwin, of Oxford University clinical trial service unit, adds: "We know that many patients remain at appreciable risk of recurrence after four to six months of treatment with antidepressants, and another one or two years of continuation treatment will approximately halve their risk of another episode. In other words, the positive effects of antidepressants do not wear off over time. Many patients who do exceptionally well may elect to take such medicine indefinitely rather than increase the risk of further illness by stopping."

The researchers conceded that the risk of relapse or recurrence of depression might be increased by a direct pharmacological response to the withdrawal of medicines rather than the underlying disorder. "If there is an effect, the effectiveness of continuation therapy could have been overestimated," they say.

David Taylor, chief pharmacist, South London and Maudsley NHS Trust, commented that there had been a lack of information on the issue of antidepressant continuation. He drew attention to other new theories proposing that, although antidepressants were crucial in treating major depressive episodes, long-term treatment might actually worsen the course of depression in certain patients.