ReviewCureus2026
Comparative Augmentative Efficacy of Second-Generation Antipsychotics in Adult Treatment-Resistant Depression: A Systematic Review.
Review in Cureus, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
0 citing papers in PubMed.
No citing paper in PubMed yet.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Treatment-resistant depression (TRD) affects a substantial proportion of patients with major depressive disorder and remains a major therapeutic challenge. Augmentation with second-generation antipsychotics (SGAs) is commonly used; however, comparative evidence regarding their efficacy and safety remains limited. This systematic review aimed to evaluate the augmentative efficacy and tolerability of SGAs in adults with TRD. A systematic search of PubMed/MEDLINE, Embase, Web of Science, Scopus, and the Cochrane Library was conducted for randomized controlled trials published between 2016 and 2025. Eligible studies included adults with TRD receiving SGA augmentation. Two reviewers independently screened studies, extracted data, and assessed risk of bias using the Cochrane RoB 2 tool. Due to clinical heterogeneity across interventions and outcomes, findings were synthesized narratively. Eleven randomized controlled trials including 5,300 participants were analyzed, evaluating brexpiprazole, cariprazine, aripiprazole, and quetiapine XR. Most studies reported greater reductions in depressive symptoms compared with placebo, commonly measured by changes in the Montgomery-Åsberg Depression Rating Scale. Brexpiprazole and the aripiprazole-sertraline combination showed the most consistent improvements, with brexpiprazole augmentation yielding remission rates ranging from 22 to 31% and cariprazine augmentation showing rates of 22-32% across flexible-dose trials. Several agents demonstrated early onset of action within 2-3 weeks. Common adverse events included akathisia, insomnia, restlessness, and weight gain. Discontinuation due to adverse events ranged from 0.4% to 8.6%. Ten studies were assessed as having a low risk of bias. SGA augmentation is an effective treatment strategy for TRD, with brexpiprazole showing particularly consistent benefits. Careful risk-benefit assessment and monitoring for adverse effects are essential. Further head-to-head and long-term studies are needed to guide personalized treatment.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.