AbstractObjectiveAtypical features are common among depressed primary care patients, but clinical trials testing the efficacy of psychopharmacological and/or psychotherapeutic treatment are lacking. This paper examines the efficacy of sertraline and cognitive behavioural therapy (CBT) among depressed patients with atypical features.Subjects and methodsAnalyses involve a double-blind comparison of sertraline versus placebo (N = 47) and a single-blind comparison between CBT versus a guided self-help group (GSG) (N = 48), with primary efficacy endpoints being the Inventory of Depressive Symptomatology (IDS_C) and Hamilton Depression Scale (HAMD-17).ResultsIn intent-to-treat (ITT) analyses, the decrease on the IDS_C scale (and HAMD-17) was greater after CBT compared to GSG: p = 0.01 (HAMD-17: p = 0.01). The difference between selective serotonin reuptake inhibitors (SSRI) versus placebo was not significant: p = 0.22 (HAMD-17: p = 0.36).LimitationsThe number of cases in each treatment group was small, thereby limiting statistical power. Patients medicated with sertraline were 10 to 15 years younger than those included in the other groups of treatment.ConclusionsCBT may be an effective alternative to GSG for mildly depressed patients with atypical features. Although SSRI were not superior to placebo, it would be premature to rule out SSRI as efficacious in atypical depression.