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Antipsychotic medications demonstrate a variable range of efficacy and side effects in patients with mental illness. Research has attempted to identify biomarkers associated with antipsychotic effects in various populations. Research designs utilizing healthy volunteers may have the added benefit of measuring the effect of antipsychotics on a given biomarker (s) independent of the varied environmental and clinical factors that often accompany patient populations. The aim of this systematic review and meta‐analysis was to synthesize the current evidence of hormonal, inflammatory, and metabolic biomarker studies of antipsychotic treatment in study designs using healthy volunteers. The systematic review was performed according to established guidelines and a random effects meta‐analysis of biomarkers appearing in at least three studies was performed while biomarkers in two or less studies were qualitatively summarized. A total of 28 studies including 28 biomarkers were identified. Meta‐analyses were carried out for 14 biomarkers, showing significant effects within six biomarkers (cortisol, C‐peptide, free fatty acids, leptin, thyroid‐stimulating hormone, and prolactin). Many of these effects were associated with olanzapine, the most used antipsychotic amongst the trials, observed on sub‐analyses. When combining biomarkers into categories, some additional effects were observed, for example, when grouping inflammatory biomarkers. These findings suggest that antipsychotics exert potentially strong effects on several biomarkers of interest independent of psychiatric disease which could be used to spur future investigations, however, replication work is needed for many biomarkers included in this review. [ABSTRACT FROM AUTHOR]

The pharmacoepigenetics of antipsychotic treatment in severe mental illness is a growing area of research that aims to understand the interface between antipsychotic treatment and genetic regulation. Pharmacoepigenetics may some day assist in identifying treatment response mechanisms or become one of the components in the implementation of precision medicine. To understand the current evidence regarding the effects of antipsychotics on DNA methylation a systematic review with qualitative synthesis was performed through Pubmed, Embase and Psychinfo from earliest data to June 2019. Studies were included if they analyzed DNA methylation in an antipsychotic‐treated population of patients with schizophrenia or bipolar disorder. Data extraction occurred via a standardized format and study quality was assessed. Twenty‐nine studies were identified for inclusion. Study design, antipsychotic type, sample source, and methods of DNA methylation measurement varied across all studies. Eighteen studies analyzed methylation in patients with schizophrenia, four studies in patients with bipolar disorder, and seven studies in a combined sample of schizophrenia and bipolar disorder. Twenty‐two studies used observational samples whereas the remainder used prospectively treated samples. Six studies assessed global methylation, five assessed epigenome‐wide, and 15 performed a candidate epigenetic study. Two studies analyzed both global and gene‐specific methylation, whereas one study performed a simultaneous epigenome‐wide and gene‐specific study. Only three genes were analyzed in more than one gene‐specific study and the findings were discordant. The state of the pharmacoepigenetic literature on antipsychotic use is still in its early stages and uniform reporting of methylation site information is needed. Future work should concentrate on using prospective sampling with appropriate control groups and begin to replicate many of the novel associations that have been reported. [ABSTRACT FROM AUTHOR]