Objectives To evaluate the effectiveness of different antidepressant drugs in addition to standard clinical care in the prevention of postnatal depression. To compare the effectiveness of different antidepressant drugs and with any other form of intervention for postnatal depression i.e. hormonal, psychological or social support. To assess any adverse effects of antidepressant drugs in either the mother or the foetus/infant.Methods The register of clinical trials maintained and updated by the Cochrane Depression, Anxiety and Neurosis Group and the Cochrane Pregnancy and Childbirth Group.Randomised studies of antidepressants alone or in combination with another treatment, compared with placebo or a psychosocial intervention in non-depressed pregnant women or women who had given birth in the previous six weeks (i.e. women at risk of postnatal depression). Data were extracted independently from the trial reports by the authors.Missing information was requested from investigators wherever possible. Data were sought to allow an intention to treat analysis.Results Two trials fullled the inclusion criteria for this review. Both looked at women with a past history of postpartum depression.Nortriptyline (n=26) did not show any benefit over placebo (n=25). Sertraline (n=14) reduced the recurrence of postnatal depression and the time to recurrence when compared with placebo (n=8). Intention to treat analyses were not carried out in either trial.Conclusions It is not possible to draw any clear conclusions about the effectiveness of antidepressants given immediately postpartum in preventing postnatal depression and, therefore, cannot be recommended for prophylaxis of postnatal depression, due to the lack of clear evidence. Larger trials are needed which also include comparisons of antidepressant drugs with other prophylactic treatments to reect clinical practice, and examine adverse effects for the foetus and infant, as well as assess womens’ attitudes to the use of antidepressants at this time.