• Gregory E Simon, Nathalie Moise, and David C Mohr.
• Kaiser Permanente Washington Health Research Institute, Seattle.
• JAMA. 2024 Jul 9; 332 (2): 141152141-152.

ImportanceApproximately 9% of US adults experience major depression each year, with a lifetime prevalence of approximately 17% for men and 30% for women.ObservationsMajor depression is defined by depressed mood, loss of interest in activities, and associated psychological and somatic symptoms lasting at least 2 weeks. Evaluation should include structured assessment of severity as well as risk of self-harm, suspected bipolar disorder, psychotic symptoms, substance use, and co-occurring anxiety disorder. First-line treatments include specific psychotherapies and antidepressant medications. A network meta-analysis of randomized clinical trials reported cognitive therapy, behavioral activation, problem-solving therapy, interpersonal therapy, brief psychodynamic therapy, and mindfulness-based psychotherapy all had at least medium-sized effects in symptom improvement over usual care without psychotherapy (standardized mean difference [SMD] ranging from 0.50 [95% CI, 0.20-0.81] to 0.73 [95% CI, 0.52-0.95]). A network meta-analysis of randomized clinical trials reported 21 antidepressant medications all had small- to medium-sized effects in symptom improvement over placebo (SMD ranging from 0.23 [95% CI, 0.19-0.28] for fluoxetine to 0.48 [95% CI, 0.41-0.55] for amitriptyline). Psychotherapy combined with antidepressant medication may be preferred, especially for more severe or chronic depression. A network meta-analysis of randomized clinical trials reported greater symptom improvement with combined treatment than with psychotherapy alone (SMD, 0.30 [95% CI, 0.14-0.45]) or medication alone (SMD, 0.33 [95% CI, 0.20-0.47]). When initial antidepressant medication is not effective, second-line medication treatment includes changing antidepressant medication, adding a second antidepressant, or augmenting with a nonantidepressant medication, which have approximately equal likelihood of success based on a network meta-analysis. Collaborative care programs, including systematic follow-up and outcome assessment, improve treatment effectiveness, with 1 meta-analysis reporting significantly greater symptom improvement compared with usual care (SMD, 0.42 [95% CI, 0.23-0.61]).Conclusions And RelevanceEffective first-line depression treatments include specific forms of psychotherapy and more than 20 antidepressant medications. Close monitoring significantly improves the likelihood of treatment success.

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