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Relative effectiveness of augmentation treatments for treatment-resistant depression: a systematic review and network meta-analysis

Ben Carter, Rebecca Strawbridge, Muhammad Ishrat Husain, Brett D. M. Jones, Roxanna Short, Anthony J. Cleare, Dimosthenis Tsapekos, Fiona Patrick, Lindsey Marwood, R. Taylor, Tim Mantingh, Valeria de Angel, Viktoriya L. Nikolova, André F. Carvalho, Allan H. Young

International Review of Psychiatry June 5, 2020 DOI: 10.1080/09540261.2020.1765748 (opens in new tab)

Study at a glance

AI-extracted from the abstract
Characteristics Systematic review and network meta-analysis Randomized Peer reviewed
Population Adults meeting common clinical criteria for treatment-resistant depression
Interventions antipsychotics mood stabilizers NMDA-targeting medications
Topics Depression
Keywords Meta-analysis Placebo Depression economics Clinical trial Randomized controlled trial Psychological intervention Mood Systematic review Medline Alternative medicine
Citations 45
Key findings NMDA-targeting medications are markedly superior to placebo and have the highest chance of being an effective augmentation treatment for treatment-resistant depression.

Abstract

Most interventions for treatment-resistant depression (TRD) are added as augmenters. We aimed to determine the relative effectiveness of augmentation treatments for TRD. This systematic review and network meta-analysis (NMA) sought all randomized trials of pharmacological and psychological augmentation interventions for adults meeting the most common clinical criteria for TRD. The NMA compared the intervention effectiveness of depressive symptoms for TRD augmentation. Of 36 included trials, 27 were suitable for inclusion in NMA, and no psychological trials could be included in the absence of a common comparator. Antipsychotics (13 trials), mood stabilizers (three trials), NMDA-targeting medications (five trials), and other mechanisms (3 trials) were compared against placebo. NMDA treatments were markedly superior to placebo (ES = 0.91, 95% CI 0.67 to 1.16) and head-to-head NMA suggested that NMDA therapies had the highest chance of being an effective treatment option compared to other pharmacological classes. This study provides the most comprehensive evidence of augmenters' effectiveness for TRD, and our GRADE recommendations can be used to guide guidelines to optimize treatment choices. Although conclusions are limited by paucity of, and heterogeneity between, trials as well as inconsistent reports of treatment safety. This work supports the use of NMDA-targeting medications such as ketamine.

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