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The aim of the study was to assess a program for detection, prevention and treatment of postpartum depression. The French version of the EPDS (Edinburgh Postnatal Depression Scale; Guedeney & Fermanian, 1998) was used to measure the depressive component of postpartum blues among 859 mothers, during their stay at the obstetrical clinic. Mothers at risk for postpartum depression (N = 258) (EPDS scores ≥ 9) were randomly assigned to a prevention/treatment group or a control group. Counselors were trained Master’s degree level female students in psychology. The prevention group received one counseling prevention session during hospitalization. This prevention session integrated supportive, educational and cognitive-behavioral components. At 4 to 6 weeks postpartum, subjects were screened again with the EPDS. The prevention group showed a significant reduction in the frequency of probable depression (30.2% versus 48.2%; p < 0.01). Mothers with probable depression (EPDS scores ≥ 11) were assessed using the Hamilton Depression Rating Scale (HDRS) and the Beck Depression Inventory (BDI). Mothers with major depression continued in the treatment group (N = 18) or in the control group (N = 30). Treated subjects received a counselling program of 5 to 8 weekly home-visits. The home visits program integrated four components, supportive, educational, cognitive-behavioral and psychodynamic centered on the mother-infant relationship in terms of the mother’s personal history. Counselors participated in clinical training and weekly supervision. All the subjects in the treatment trial completed the protocol. The comparison of the two groups, evaluated 5 to 8 weeks later, showed a high frequency of recovery in the treated group: e.g., recovery rates based on HDRS scores lower than 7 were significantly greater in the treated group than in the control group (66.6% versus 6.6%, p < 0.0001). This study suggests that this program for prevention and treatment of postpartum depression is reasonably well-accepted and efficacious and may represent a solution to the high non-compliance rate for the prescribed treatments for postpartum depression.