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Am Fam Physician. 2024;109(2):online

Author disclosure: No relevant financial relationships.

Details for This Review

Study Population: Nine randomized controlled trials from 16 high-income countries, including 3,424 adults with treatment-resistant depression (lack of response after at least two trials of antidepressant monotherapy) who met the Diagnostic and Statistical Manual of Mental Disorders, 4th and 5th eds., criteria for major depressive disorder and were having a current depressive episode

Efficacy End Points: Primary outcome: response to treatment (greater than 50% improvement in depressive symptoms on validated depression score) at eight weeks; secondary outcomes: response to treatment after two and 18 weeks, remission after eight weeks, social functioning or adjustment, health-related quality of life

Harm End Points: Primary outcomes: dropouts due to any cause or adverse effects at eight weeks; secondary outcomes: any adverse effects, specific adverse effects (e.g., akathisia [restlessness], weight gain)

1 in 16 had positive response to treatment at eight weeks
1 in 22 had remission of depression at eight weeks
1 in 38 withdrew from the study due to any cause
1 in 58 withdrew from the study due to adverse effects
1 in 20 experienced akathisia or weight gain
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This series is coordinated by Christopher W. Bunt, MD, AFP assistant medical editor, and the NNT Group.

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