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 via OpenAlex
Summary
AI-generated from the abstractA network meta-analysis of 27 randomized trials found that NMDA-targeting medications (e.g., ketamine) are markedly more effective than placebo for augmenting treatment-resistant depression (effect size 0.91). Antipsychotics, mood stabilizers, and other pharmacological augmenters were also compared, but NMDA therapies had the highest probability of being effective. No psychological augmentation trials could be included due to the lack of a common comparator. The evidence is limited by few trials, heterogeneity, and inconsistent safety reporting.
Study at a glance
| 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 |
| Citations | 45 |
| Key finding | 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.