Originally published by 2 Minute Medicine® (view original article). Reused on AccessMedicine with permission.

1. Selective serotonin reuptake inhibitors (SSRIs) are not associated with significant short-term reductions in depressive symptoms in the primary care setting, but reduce short-term anxiety and improve mental health and health-related quality of life.

Evidence Rating Level: 1 (Excellent)

While most patients with depression are managed in the primary care setting, there is limited evidence regarding the effectiveness of antidepressants across different severities of illness in the outpatient setting. This is largely due to the narrow eligibility criteria used in studies conducted thus far, specifically concerning the diagnoses and severity of disease in research participants. The PANDA trial examined the effectiveness of sertraline in primary care patients with all severities of depression. Using a pragmatic, multi-centre double-blind design, 655 patients age 18 to 74 years with clinical uncertainty regarding benefit of antidepressants were randomly assigned to sertraline 50 mg daily or placebo, for a maximum of 11 weeks. Through the inclusion of patients where there was clinical uncertainty, the authors were able to generate a study sample more generalizable to the general population currently receiving antidepressant medications. The primary outcome was depressive symptoms 6 weeks after randomization, and was measured using the Patient Health Questionnaire 9-item version (PHQ-9). Researchers found no clinically meaningful difference in depressive symptoms after 6 weeks of therapy with sertraline compared to placebo, with mean PHQ-9 scores of 7.98 (SD 5.63) and 8.76 (SD 5.86) in the two groups, respectively (adjusted proportional difference 0.95, 95% CI 0.85 to 1.07, p=0.41). Sertraline was however found to reduce anxiety symptoms (adjusted proportional difference 0.79, 95% CI 0.70 to 0.89 at 6 weeks), improve mental health-related quality of life (2.41, 95% CI 1.14 to 3.96, p=0·00021), and enhance self-reported mental health improvement (adjusted OR 1.96, 95% CI 1.45 to 2.63, p<0·0001), compared to placebo. Adverse events were comparable between groups. The findings of the PANDA trial therefore suggest that while sertraline is not associated with reductions in 6-week depressive symptoms, benefits in anxiety, quality of life and self-rated mental health may support selective serotonin reuptake inhibitor use in primary care for mild to moderate symptoms of depression and/or generalized anxiety.

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