The effect of olanzapine on lipid profiles in humans: a time and dose response meta-analysis of randomized controlled trials.

Abstract

<h4>Background and aim</h4>Olanzapine, a widely used second-generation antipsychotic, is associated with notable metabolic side effects, particularly dyslipidemia. However, the extent, timing, and dose-dependence of these lipid alterations remain inadequately defined. This meta-analysis aimed to quantify the effects of olanzapine on lipid profiles in humans and to evaluate how dosage and treatment duration influence these changes.<h4>Methods</h4>A systematic search of Scopus, Web of Science, Embase, and PubMed/MEDLINE was conducted to identify randomized controlled trials (RCTs) published up to December 1, 2025. Studies were eligible if they reported lipid outcomes (triglycerides [TG], total cholesterol [TC], high-density lipoprotein cholesterol [HDL-C], and low-density lipoprotein cholesterol [LDL-C]) before and after olanzapine treatment. Pooled weighted mean differences (WMDs) with 95% confidence intervals (CIs) were calculated using a random-effects model. Subgroup, dose-response, and sensitivity analyses were performed to explore sources of heterogeneity and assess result robustness.<h4>Results</h4>Seventeen trials were included. Olanzapine significantly increased TG (WMD: 24.96 mg/dL), TC (WMD: 6.57 mg/dL), and LDL-C (WMD: 4.30 mg/dL), while HDL-C decreased non-significantly (WMD: - 1.33 mg/dL). Subgroup analyses revealed that lipid alterations were more pronounced with higher doses (≥ 10 mg/day), shorter treatment durations (< 12 weeks), and in individuals with baseline body mass index (BMI) < 25 kg/m². Dose-response analysis showed a positive correlation between olanzapine dose and increases in TG and TC, and a negative correlation with HDL-C. Sensitivity analyses confirmed the robustness of findings, and no publication bias was detected for TG or HDL-C.<h4>Conclusion</h4>Olanzapine treatment is associated with a distinct dyslipidemic profile, characterized by increased TG, TC, and LDL-C and reduced HDL-C, particularly at higher doses and during early treatment. These findings underscore the need for proactive lipid monitoring and cardiovascular risk assessment, especially in patients with low baseline BMI, who appear more susceptible to rapid lipid alterations, and in those with existing metabolic risk factors or multiple cardiometabolic comorbidities.