Patients with schizophrenia who take a combination of 3 or more different psychotropic medications have an increased risk for type 2 diabetes, according to a study published in BMC Psychiatry.

This nested case control study sought to investigate the effect of pharmacological, anthropometric, clinical, and lifestyle measurements of patients with schizophrenia in association with developing type 2 diabetes. In addition, this Genetic Overlap between Metabolic and Psychiatric disease (GOMAP) study attempted to understand the underlying mechanisms linking psychiatric disorders and type 2 diabetes.

The GOMAP study included 1653 patients diagnosed with schizophrenia recruited from 2 hospitals in Athens, Greece. Treatment history and medication data was drawn from medical records as well as the National Organization for Health Care Services Provision database. Investigators assessed the effects of psychotropic medications, body mass index, duration of schizophrenia, hospitalizations, and physical activity on the risk of developing type 2 diabetes between January 2012 and May 2014. Crude and adjusted odds ratios (OR) were calculated using logistic regression to identify associations between demographic characteristics and psychiatric drugs.

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Of the 1653 study participants, 611 (36.96%) also had type 2 diabetes. After adjusting for age, body mass index, gender, and disease duration, patients with schizophrenia on a combination of 3 or more different classes of psychiatric medications demonstrated a higher risk of developing type 2 diabetes (OR 1.81; 95% CI, 1.22-2.69; P=.003) compared with monotherapy with first-generation antipsychotics. The use of second-generation antipsychotics (OR 1.27; 95% CI, 0.84-1.93; P=.259) or a combination of 2 different classes of psychiatric medications (OR 0.98; 95% CI, 0.71-1.35; P=.885) did not reveal an increased risk for type 2 diabetes compared to first-generation antipsychotic use. No significant findings were observed when examining the genetic relationship between a polypharmacy medication regimen and risk for type 2 diabetes.

A limitation of the study was the inability to assess the effect of each specific psychotropic drug regimen or the various combinations thereof. In addition, the investigators’ access to retrospective medication information was limited to only 6 months prior to study commencement. Finally, causality could not be inferred regarding type 2 diabetes and various medication effects (dose-effect, category effect, or the effect on drug-naïve or first episode patients).

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Patients with schizophrenia who followed a triple-drug combination therapy were associated with an increased risk for type 2 diabetes compared to monotherapy with first-generation antipsychotics. Further studies are needed to explore if different antipsychotic classes or maximizing monotherapy doses can decrease diabetogenic effects in this population.


Mamakou V, Hackinger S, Zengini E, et al. Combination therapy as a potential risk factor for the development of type 2 diabetes in patients with schizophrenia: the GOMAP study. BMC Psychiatry. 2018; 18(1):249.

This article originally appeared on Psychiatry Advisor