Abstract: We included six trials with 596 participants in this review. All studies had a randomised controlled parallel group design, with two conducted in the UK, three in the US and one in Israel. Meta-analyses were performed to pool data on response and remission from studies comparing antidepressants with placebo. No meta-analyses could be conducted for other comparisons due to the small number of trials identified. Four studies compared selective serotonin reuptake inhibitors (SSRIs) with placebo (two using sertraline, one using paroxetine and one using fluoxetine; 233 participants in total). In two of these studies both the experimental and placebo groups also received psychological therapy. Pooled risk ratios based on data from three of these studies (146 participants) showed that women randomised to SSRIs had higher rates of response and remission than those randomised to placebo (response: RR 1.43, 95% CI 1.01 to 2.03; remission: RR 1.79, 95% CI 1.08 to 2.98); the fourth study did not report data on response or remission. One study (254 participants) compared antidepressant treatment with treatment as usual (for the first four weeks) followed by listening visits. The study found significantly higher rates of improvement in the antidepressant group than treatment-as-usual group after the first four weeks, but no difference between antidepressants and listening visits at the later follow-up. In addition, one study comparing sertraline with nortriptyline (a tricyclic antidepressant) found no difference in effectiveness (109 participants). Side effects were experienced by a substantial proportion of women, but there was no evidence of a meaningful difference in the number of adverse effects between treatment arms in any study. There were very limited data on adverse effects experienced by breastfed infants, with no long-term follow-up. All but one of the studies were assessed as being at high or uncertain risk of attrition bias and selective outcome reporting. In particular, one of the placebo-controlled studies had over 50% drop-out. The evidence base for this review was very limited, with a small number of studies and little information on a number of important outcomes, particularly regarding potential effects on the child. Risk of bias, for example from high attrition rates, as well as low representativeness of participants (e.g. exclusion of women with severe or chronic depression in several trials) also limit the conclusions that can be drawn. Pooled estimates for response and remission found that SSRIs were significantly more effective than placebo for women with postnatal depression. However the quality of evidence contributing to this comparison was assessed as very low owing to the small sample size for this comparison (146 participants from three studies), the risk of bias in included studes and the inclusion of one study where all participants in both study arms additionally received psychological therapy. There was insufficient evidence to conclude whether, and for whom, antidepressant or psychological/psychosocial treatments are more effective, or whether some antidepressants are more effective or better tolerated than others. There is also inadequate evidence on whether the benefits of antidepressants persist beyond eight weeks or whether they have short- or long-term adverse effects on breastfeeding infants. Professionals treating women with severe depression in the postnatal period will need to draw on other evidence, including trials among general adult populations and observational studies of antidepressant safety when breastfeeding (although the potential for confounding in non-randomised studies must be considered). More RCTs are needed with larger sample sizes and longer follow-up, including assessment of the impact on the child and safety of breastfeeding. Further larger-scale trials comparing antidepressants with alternative treatment modalities are also required.

Plain-language summary: The quality of evidence from this review was assessed as being very low quality due to the small number of studies, risk of bias in the included studies (in particular, high proportions of participants dropped out) and the fact that many studies excluded women with chronic (i.e. long lasting) or severe depression, or both. We were able to combine data from three studies comparing a type of commonly used antidepressant called selective serotonin reuptake inhibitors (SSRIs) with placebo. The results showed that women with postnatal depression who were given SSRIs were more likely to improve or recover than those given placebo. We were unable to combine the data from studies comparing antidepressants with other treatments or treatment as usual due to the very small number of studies identified for these comparisons. There was insufficient evidence to conclude whether, and for whom, antidepressant or psychosocial/psychological treatments are more effective, or whether some antidepressants are more effective or better tolerated (or both) than others. Conclusions were also limited by the lack of data on long-term follow-up, the safety of breastfeeding or child outcomes. Larger studies need to be done, and treatment decisions for women with postnatal depression will need to use evidence from other sources such as trials in general adult populations and observational studies of antidepressant safety in the postnatal period. The review authors recommend that future studies in this area should include women with severe postnatal depression, long-term follow-up on psychiatric symptoms and quality of life in mothers who have been treated for postnatal depression. In addition, more evidence is needed on outcomes for infants, particularly with regards to the safety of breastfeeding and effect of treatment for postnatal depression on the maternal-infant relationship.