Antipsychotic medication and risk of metabolic disorders in people with schizophrenia: a longitudinal study using the UK Clinical Practice Research Datalink.

Emily Eyles*, Ruta Margelyte, Hannah B Edwards , Paul A Moran, David S Kessler, Simon J C Davies, Blanca Bolea-Alamanac, Maria Theresa Redaniel, Sarah A Sullivan

*Corresponding author for this work

Research output: Contribution to journalArticle (Academic Journal)peer-review


Background and Hypothesis
Antipsychotics are first-line drug treatments for schizophrenia. When antipsychotic monotherapy is ineffective, combining two antipsychotic drugs is common although treatment guidelines warn of possible increases in side effects. Risks of metabolic side effects with antipsychotic polypharmacy have not been fully investigated. This study examined associations of antipsychotic polypharmacy and risk of developing diabetes, hypertension or hyperlipidaemia in adults with schizophrenia, and impact of co-prescription of first- and second-generation antipsychotics.
Study Design
A population-based prospective cohort study was conducted in the United Kingdom using linked primary care, secondary care, mental health, and social deprivation datasets. Cox proportional hazards models with stabilising weights were used to estimate risk of metabolic disorders among adult patients with schizophrenia, comparing patients on antipsychotic monotherapy vs polypharmacy, adjusting for demographic and clinical characteristics, and antipsychotic dose.
Study Results
Compared to monotherapy, polypharmacy was associated with an increased risk of developing hypertension (adjusted Hazard Ratio= 3.16; p=0.021). Patients exposed to exclusive first-generation antipsychotic polypharmacy had a greater risk of hypertension compared to those exposed to combined first- and second-generation polypharmacy (adjusted HR 0.29, p=0.039). There was no evidence of associations between polypharmacy and risk of diabetes or hyperlipidaemia.
Antipsychotic polypharmacy, and particularly polypharmacy solely comprised of first- generation antipsychotics, increased the risk of hypertension in the study population, though median follow-up time across the three cohorts was approximately 14 months. Future research employing larger sample sizes, longer follow-up, and more complex methodologies would be valuable to confirm the association found in this study.
Original languageEnglish
Article numbersbad126
Number of pages18
JournalSchizophrenia Bulletin
Early online date28 Aug 2023
Publication statusE-pub ahead of print - 28 Aug 2023


Dive into the research topics of 'Antipsychotic medication and risk of metabolic disorders in people with schizophrenia: a longitudinal study using the UK Clinical Practice Research Datalink.'. Together they form a unique fingerprint.

Cite this