Influence of olanzapine on human liver function markers: evidence from a systematic review and meta-analysis of RCTs

Although olanzapine is widely prescribed as a second-generation antipsychotic, its cardiometabolic adverse effects have been investigated more extensively than its hepatic safety profile. Evidence from randomized controlled trials (RCTs) evaluating liver-related biomarkers has remained limited and inconsistent. Therefore, we conducted a systematic review and meta-analysis of RCTs to evaluate the effects of olanzapine on hepatic biochemical markers in psychiatric populations. We systematically searched PubMed/MEDLINE, Embase, Scopus, and Web of Science from inception to July 17, 2026, for RCTs comparing olanzapine with placebo or no active treatment in psychiatric populations. Outcomes included alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transferase (GGT), albumin, and total bilirubin. Pooled effects were calculated using random-effects models and expressed as mean differences (MDs) with 95% confidence intervals (CIs). Heterogeneity, subgroup analyses according to dose and treatment duration, sensitivity analyses, and publication bias assessments were performed. Five RCTs comprising six comparison arms and 999 participants met the inclusion criteria. Olanzapine treatment was associated with significant increases in ALT (MD: 11.39 U/L; 95% CI: 4.10–18.68; P = 0.002), AST (MD: 4.15 U/L; 95% CI: 1.56–6.74; P = 0.002), and GGT (MD: 11.00 U/L; 95% CI: 3.21–18.79; P = 0.006). Higher olanzapine doses ( ≥ 10 mg/day) were associated with greater elevations in ALT and AST. Albumin concentrations decreased significantly, whereas total bilirubin remained unchanged. In psychiatric populations, olanzapine treatment is associated with mild but significant elevations in hepatic enzymes, particularly ALT, AST, and GGT, while markers of hepatic synthetic and excretory function are largely preserved. These findings suggest predominantly biochemical rather than clinically overt hepatic dysfunction and support routine monitoring of liver enzymes, particularly during treatment initiation and when higher olanzapine doses are prescribed.