Abstract: Two trials including a total of 81 participants fulfilled the inclusion criteria for this review. All participants in both studies had a history of postnatal depression and were not taking antidepressant medication at baseline. Both trials were conducted by the same research group. Risk of bias was low or unclear in most domains for both studies. We were unable to perform a meta-analysis due to the small number of studies. One study compared nortriptyline with placebo and did not find any evidence that nortriptyline was effective in preventing postnatal depression. In this study, 23% (6/26) of women who took nortriptyline and 24% (6/25) of women who took placebo experienced postnatal depression (RR 0.96, 95% CI 0.36 to 2.59, very low quality evidence) in the first 17 weeks postpartum. One woman taking nortriptyline developed mania; and one side effect, constipation, was more common among women taking nortriptyline than those taking placebo. The second study compared sertraline with placebo. In this study, 7% (1/14) of women who took sertraline developed postnatal depression in the first 17 weeks postpartum compared with 50% (4/8) of women who took placebo. It is uncertain whether sertraline reduces the risk of postnatal depression (RR 0.14, 95% CI 0.02 to 1.07, very low quality evidence). One woman taking sertraline had a hypomanic episode. Two side effects (dizziness and drowsiness) were more common among women taking sertraline than women taking placebo. Conclusions are limited by the small number of studies, small sample sizes and incomplete outcome data due to study drop-out which may have led to bias in the results. We have assessed the certainty of the evidence as very low, based on the GRADE system. No data were available on secondary outcomes of interest including child development, the mother‒infant relationship, breastfeeding, maternal daily functioning, family relationships or maternal satisfaction. Due to the limitations of the current evidence base, such as the low statistical power of the included studies, it is not possible to draw any clear conclusions about the effectiveness of antidepressants for the prevention of postnatal depression. It is striking that no new eligible trials have been completed in the period of over a decade since the last published version of this review. Larger trials are needed which include comparisons of antidepressant drugs with other prophylactic treatments (e.g. psychological interventions), and examine adverse effects for the fetus or infant. Future reviews in this area may benefit from broadening their focus to examine the effectiveness of antidepressants for the prevention of perinatal (i.e. antenatal or postnatal) depression, which could include studies comparing antidepressant discontinuation with continuation for the prevention of relapse of depression during pregnancy and the postnatal period.

Plain-language summary: We identified two small, relevant trials. All the women in these trials had a history of postnatal depression, but were not depressed or using antidepressants at the beginning of the studies. Both studies compared antidepressant medicine with placebo. Women started taking the medicine or placebo on the first day after giving birth. In the larger study (56 women), the antidepressant given to women was nortriptyline, which is a tricyclic antidepressant. In the other study (25 women), the antidepressant used was sertraline which is a selective serotonin reuptake inhibitor (SSRI); these types of antidepressants work in different ways. The women and the researchers assessing the outcomes in both studies did not know which women were taking antidepressants and which placebo (i.e. both studies were 'double-blind'). Both studies were funded by the National Institute of Mental Health (NIMH), a US government organisation. There was no evidence that nortriptyline prevented postnatal depression. During the 17-week treatment period, 6 of the 26 women taking nortriptyline experienced postnatal depression compared with 6 of the 25 women taking placebo. One woman taking nortriptyline developed mania (a state of abnormally high arousal and energy level), and constipation was more common among women taking nortriptyline, but other unwanted, or harmful, effects did not differ between groups. In the sertraline study, 1 of the 14 women taking sertraline developed postnatal depression compared with 4 of the 8 women taking placebo (during the 17-week treatment period). This study was very small, so we can't be sure whether the difference between sertraline and placebo is due to chance, or whether sertraline does prevent postnatal depression among women with a history of postnatal depression. One woman taking sertraline experienced a hypomanic episode (a state like mania but less severe); and dizziness and drowsiness were more common among women taking sertraline than women taking placebo. This evidence is current to February 2018. We could only identify two relevant studies, which had small numbers of participants and inconsistent findings, and were conducted by the same research group. Therefore we consider the quality of evidence in this review to be very low. Further studies with larger samples are needed before we can know whether antidepressants can prevent postnatal depression. It is worth noting that no new relevant trials have been completed in the 10 years since we last examined this evidence. It may be useful for future medical studies to investigate whether antidepressants can prevent depression during pregnancy as well as during the postnatal period; and whether women who continue to take antidepressants during pregnancy (compared with stopping medication) are less likely to have a relapse of depression at this time. We also need studies which have longer follow-ups periods; examine outcomes and side effects for both the mother and fetus or breastfeeding infant; and compare antidepressants with other preventative interventions (such as psychological therapies).