BACKGROUND: Approximately 10% to 16% of women experience a major depressive episode after childbirth. A significant proportion of these women also suffer from comorbid anxiety disorders. The purpose of this study was to evaluate whether the addition of cognitive-behavioral therapy (CBT) to standard antidepressant therapy offers additional benefits in the treatment of post-partum depression with comorbid anxiety disorders. METHOD: Thirty-five women referred to a tertiary care hospital outpatient program with a DSM-IV diagnosis of postpartum depression with comorbid anxiety disorder were randomly assigned to 1 of 2 treatment groups-paroxetine-only monotherapy group (N = 16) or paroxetine plus 12 sessions of CBT combination therapy group (N = 19)-for a 12-week trial. Progress was monitored by a psychiatrist blinded to treatment group, using the Hamilton Rating Scale for Depression, Hamilton Rating Scale for Anxiety, Yale-Brown Obsessive Compulsive Scale, Clinical Global Impressions scale, and Edinburgh Postnatal Depression Scale. Data were analyzed using 2-tailed statistical tests at an alpha level of.05. The study was conducted from April 1, 2002, to June 30, 2003. RESULTS: Both treatment groups showed a highly significant improvement (p <.01) in mood and anxiety symptoms. Groups did not differ significantly in week of recovery, dose of paroxetine at remission, or measures of depression, anxiety, and obsessive-compulsive symptoms at outcome. CONCLUSION: Antidepressant monotherapy and combination therapy with antidepressants and CBT were both efficacious in reducing depression and anxiety symptoms. However, in this sample of acutely depressed/anxious postpartum women, there were no additional benefits from combining the 2 treatment modalities. Further research into the efficacy of combination therapy in the treatment of moderate-to-severe depression with comorbid disorders in postpartum women is recommended.