Antipsychotic-induced weight gain (AIWG) is a clinically relevant and concerning adverse effect of contemporary antipsychotic medications. Lumateperone is a novel antipsychotic, which became commercially available in 2020 and received Food and Drug Administration approval for schizophrenia and bipolar disorder in 2019 and 2021, respectively. To date, no comprehensive review exists on its AIWG profile. This systematic review aims to assess the association between lumateperone and AIWG.

Data Sources: A comprehensive search of published studies on “lumateperone” OR “ITI-007” OR “Caplyta” was conducted on PubMed, CINAHL Complete, APA PsychInfo, Cochrane Library, and Embase databases until January 2022.

Study Selection: A total of 149 articles in English were collected. After removing duplicates, all human trials on lumateperone were screened for the inclusion criteria.

Data Extraction: Two reviewers conducted an independent screening followed by full-text analysis of extracted studies adhering to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Third reviewer resolved the conflicts as tiebreaker.

Primary search generated 77 articles, excluding 72 duplicates, of which 51 were deemed appropriate for exclusion. Full-text analysis of the remaining 26 articles concluded with 5 studies for finalized review per inclusion criteria. Excluded studies were manually reviewed for relevant citation of studies per inclusion criteria. Three randomized, double-blinded, placebo-controlled clinical trials and 2 open-label trials were derived from this systematic review. Lumateperone showed a favorable weight profile compared with placebo and alternate antipsychotics.

Lumateperone displays minimal to no weight gain among participants in the studies reviewed.