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Objectives: Both antidepressant medications and psychological therapy are common treatments for depression in postpartum women. Antidepressant treatment may have a number of practical disadvantages, including a preference by women to avoid medication while breastfeeding. Consequently, more information about the relative benefits of the two modalities in the perinatal period is helpful. In the treatment of depressive disorders there is some evidence that combination therapies (pharmacological plus psychological treatment) may be more efficacious than either form of mono-therapy in isolation. However, in the treatment of postnatal depression, such evidence is limited. Method: Forty five postpartum women with a DSM-IV diagnosis of depression were randomised to receive either: 1) cognitive behavioural therapy (CBT); 2) sertraline, or 3) a combination of both treatment modalities. Psychometric measures were collected weekly for 12 weeks, with a follow-up at 24 weeks. Results: Symptoms of depression and anxiety were reduced to a significant degree following all three treatments. CBT mono-therapy was found to be superior to both sertraline mono-therapy and combination therapy after 12 weeks. The CBT mono-therapy group appeared to display the most rapid initial gains after treatment commencement. Conclusions: In this sample, a specialised CBT program for postnatal depression was found to be superior as a mono-therapy compared to sertraline, a commonly prescribed SSRI antidepressant. This is in contrast to previous studies which have found no detectable difference in the efficacies of drug and psychological treatment for postnatal depression. Unlike some previous work, this study allowed a statistically independent evaluation of CBT mono-therapy for postnatal depression compared to both antidepressant and combination therapy. In line with previous studies in postpartum women, there was no detectable advantage of combining pharmacological and psychological treatments in the short term.