Aripiprazole augmentation of antidepressants may be an effective long-term strategy for the treatment of patients with refractory major depressive disorder, according to a systematic review and meta-analysis published in The Primary Care Companion for CNS Disorders.

“These long-term studies do not provide data to recommend optimal duration of maintenance therapy,” researchers wrote. “However, relative safety of low-dose augmentation and suggestion of increasing benefit from longer treatment duration suggest aripiprazole could be a safe long-term maintenance strategy for up to 52 weeks.”

The review included 4 open-label studies investigating aripiprazole, an atypical antipsychotic approved in 2007 as an adjunct for major depressive disorder, as augmentation therapy for 6 months to 1 year in a total 2632 participants. Two studies were conducted in the United States, 1 in Italy, and 1 in Japan.

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Random effects meta-analysis of 3 aripiprazole augmentation studies involving 2117 participants identified a weighted remission proportion of 0.33, suggesting a third of participants achieved remission of depression with long-term treatment. Researchers reported a trend of increased treatment response with increased duration of treatment.

One study reported no significant adverse effects with aripiprazole augmentation, while 3 provided adverse effect data. Weight gain considered medically significant occurred in a quarter of participants receiving mean doses of 5 mg or more but in just 3.5% of participants with mean doses less than 5 mg.

Doses higher than 5 mg were also associated with akathisia (15%–16%), insomnia (12%–17%), somnolence (14%), and fatigue (18%), according to the study. The risk of tardive dyskinesia was low, at less than 1%, at 1-year follow-up.

“However, it must be noted that the studies reporting treatment response data included in this review were open-label studies with no control groups, making firm conclusions on efficacy difficult,” researchers wrote. “Additionally, side effects such as tardive dyskinesia could emerge many years after treatment.”

Reference

Seshadri A, Wermers ME, Habermann TJ, Singh B. Long-term efficacy and tolerability of adjunctive aripiprazole for major depressive disorder: systematic review and meta-analysis. Prim Care Companion CNS Disord. 2021;23(4):20r02799. doi: 10.4088/PCC.20r02799