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Treatment-Resistant Geriatric Depression: Augmenting vs. Switching Antidepressants

In the Optimizing Outcomes of Treatment-Resistant Depression in Older Adults (OPTIMUM) trial, outcomes were better when current antidepressants were augmented with aripiprazole rather than discontinued and replaced by bupropion. “This pragmatic trial involving older persons with treatment-resistant depression showed greater improvement in psychological well-being and a numerically higher incidence of remission with aripiprazole augmentation than with a switch to bupropion,” the authors conclude. “Improvement in psychological well-being and incidences of remission were low but similar with lithium augmentation or a switch to nortriptyline after the failure of initial trial treatment.”

The open-label trial consisted of 2 10-week steps: patients were randomly assigned to augmentation of existing antidepressant medication with aripiprazole, augmentation with bupropion, or a switch from existing antidepressant medication to bupropion (step 1) and those not benefitting from or ineligible for step 1 were randomly assigned to augmentation with lithium or a switch to nortriptyline (step 2).

Based on a primary outcome of the change from baseline in psychological well-being (assessed with the NIH Toolbox Positive Affect and General Life Satisfaction subscales (population mean, 50; higher scores indicate greater well-being), the study produced the following results: “In step 1, a total of 619 patients were enrolled; 211 were assigned to aripiprazole augmentation, 206 to bupropion augmentation, and 202 to a switch to bupropion. Well-being scores improved by 4.83 points, 4.33 points, and 2.04 points, respectively. The difference between the aripiprazole-augmentation group and the switch-to-bupropion group was 2.79 points (95% CI, 0.56 to 5.02; P = 0.014, with a prespecified threshold P value of 0.017); the between-group differences were not significant for aripiprazole augmentation versus bupropion augmentation or for bupropion augmentation versus a switch to bupropion. Remission occurred in 28.9% of patients in the aripiprazole-augmentation group, 28.2% in the bupropion-augmentation group, and 19.3% in the switch-to-bupropion group. The rate of falls was highest with bupropion augmentation. In step 2, a total of 248 patients were enrolled; 127 were assigned to lithium augmentation and 121 to a switch to nortriptyline. Well-being scores improved by 3.17 points and 2.18 points, respectively (difference, 0.99; 95% CI, −1.92 to 3.91). Remission occurred in 18.9% of patients in the lithium-augmentation group and 21.5% in the switch-to-nortriptyline group; rates of falling were similar in the two groups.”

Editorial: “Depression among older persons is often under-recognized or minimized, perhaps misattributed as a normal or inevitable part of aging,” editorialists write. “Given the high prevalence of depression and the extent of nonresponses to first-line therapies, treatment resistance is a great clinical concern and has poor outcomes. The findings from this trial should help clinicians and older adult patients make informed decisions regarding the next steps, in the absence of a response to conventional pharmacologic approaches.”

Source: New England Journal of Medicine