T6. ASSOCIATION BETWEEN THE USE OF AN ANTIPSYCHOTIC DRUG AND CHANGES IN LIPID PROFILE: A META-ANALYSIS
Authors: Brierley Beverley , Bak Maarten , Drukker Marjan , Bak Maarten 
Published: May 2020

Abstract

Background
Despite their efficacy, antipsychotic drugs appear to be associated with metabolic side effects such as impaired lipid metabolism and an increased risk for developing metabolic syndrome. The association between individual antipsychotics with a stratification for different durations of exposure and mean changes in the complete lipid profile has not yet been the focus of a meta-analysis. Aim of this meta-analysis was to examine the association between changes in lipid parameters in adults using an antipsychotic drug, irrespective of diagnostic indication.

Methods
This meta-analysis follows the PRISMA guidelines and a protocol has been published in PROSPERO. A systematic search was performed using the databases PubMed, EMBASE, Cochrane, and PsycINFO. Eligible RCTs were identified and no restriction was made regarding diagnosis or publication date. Statistical analysis was based on a random effects model from which forest plots were generated. Effect sizes were reported as the standardized mean difference (SMD) with 95% confidence intervals (CI). Results were presented stratified by four exposure categories, namely &lt; 6 weeks, 6–16 weeks, 16–38 weeks, and ≥ 38 weeks. Outcome measures include mean change from baseline in total cholesterol, high-density lipoprotein cholesterol (HDL), low-density lipoprotein cholesterol (LDL) and triglyceride levels.

Results
The search strategy identified 1144 citations. Of these, 746 abstracts were excluded as being off-topic. A total of 398 full-text articles were assessed for eligibility and 135 RCT’s fulfilled the inclusion criteria. Preliminary results show an overall significant association between olanzapine and mildly elevated triglyceride levels (SMD 0.40, 95% CI 0.02–0.77), risperidone and elevated LDL levels (SMD 0.07, 95% CI 0.01–0.13) and clozapine with elevated total cholesterol and triglyceride levels (SMD 0.59 95% CI 0.26-0.02 and SMD 0.44 95% CI 0.35–0.53, respectively). Final results stratified by exposure category will be presented at the SIRS congress.

Discussion
The preliminary findings of this meta-analysis build upon previous literature and do confirm an association between the use of an antipsychotic drug and changes in lipid parameters. However, changes in the different lipid parameters do not seem to be consistent for each antipsychotic. Tentatively, we may suggest that the duration of exposure to an antipsychotic drug is correlated to the extent of lipid abnormalities. It should be noted that the majority of included studies had a short study duration (&lt; 6 weeks). Monitoring over short periods might give misleading results. Furthermore, literature suggests that the role of lipids should not be seen independently, and interplay exists between lipid metabolism and changes in weight. For example, previous studies suggest that there is a positive association between increases in triglyceride levels and increases in weight, and that once weight has stabilised, triglyceride levels decrease. Further analysis should focus on including longer-term studies in which changes in body weight in relation to changes in lipids should be taken into account. We expect the findings of this study to be of clinical relevance in the management and monitoring of antipsychotic treatment. The knowledge of whether duration of exposure is associated with different lipid changes could provide interesting results benefiting individualised choices, appropriate prevention and early management.