Medication review has been proposed to achieve improved use of psychotropic drugs, but benefits have not been confirmed. To synthesize evidence for focused psychotropic medication review in medication optimization. Medline, PsycINFO, EMBASE, and CINAHL Plus were searched from inception to February 2018 using the index terms "drug utilization review" and "psychotropic drugs" and synonyms. Additional articles were retrieved using citation tracking and reference checking. Full-length, peer-reviewed articles that reported focused psychotropic medication review were included. Inclusion was determined against prespecified criteria and assessed independently. Study quality was assessed using National Institutes for Health appraisal tools and informed a structured synthesis of results. Meta-analysis using a random effects model was conducted. Change in the number or dosage of psychotropic medications, change in clinical parameters, change in patient-reported outcomes, and economic data were collected. A total of 26 studies met the inclusion criteria. Four studies were randomized clinical trials (n = 712 participants), while the remainder were before-after studies (n = 7844 participants). Most studies were conducted in elderly individuals, people with dementia, and adults with intellectual disability. Focused psychotropic medication review is a complex intervention; the professional(s) involved, target drug, degree of integration with usual care, and participant involvement varied greatly among the studies. Meta-analysis included 3 studies (n = 652 participants). Psychotropic medication review was associated with a reduction in prescribing of psychotropic drugs compared with control (pooled odds ratio, 0.24; 95% CI, 0.14-0.39) in elderly participants with cognitive impairment living in nursing homes. Before-after studies consistently reported a change in psychotropic drug prescribing after medication review, regardless of the population. Studies that reported the effects of psychotropic medication review on clinical outcomes failed to demonstrate benefit. Economic implications of focused psychotropic medication review were not adequately assessed. The quality of evidence is poor and studies are at risk of bias. Focused psychotropic medication review was associated with a reduction in prescribing of psychotropic drugs, but has not been shown to improve clinical outcomes or to provide economic benefit. More robust evidence is needed before programs of focused psychotropic medication review can be recommended as part of routine care for any patient group.