Combination therapy as a potential risk factor for the development of type 2 diabetes in patients with schizophrenia: the GOMAP study.

BACKGROUND: Schizophrenia (SCZ) is associated with increased risk of type 2 diabetes (T2D). The potential diabetogenic effect of concomitant application of psychotropic treatment classes in patients with SCZ has not yet been evaluated. The overarching goal of the Genetic Overlap between Metabolic and Psychiatric disease (GOMAP) study is to assess the effect of pharmacological, anthropometric, lifestyle and clinical measurements, helping elucidate the mechanisms underlying the aetiology of T2D. METHODS: The GOMAP case-control study (Genetic Overlap between Metabolic and Psychiatric disease) includes hospitalized patients with SCZ, some of whom have T2D. We enrolled 1653 patients with SCZ; 611 with T2D and 1042 patients without T2D. This is the first study of SCZ and T2D comorbidity at this scale in the Greek population. We retrieved detailed information on first- and second-generation antipsychotics (FGA, SGA), antidepressants and mood stabilizers, applied as monotherapy, 2-drug combination, or as 3- or more drug combination. We assessed the effects of psychotropic medication, body mass index, duration of schizophrenia, number of hospitalizations and physical activity on risk of T2D. Using logistic regression, we calculated crude and adjusted odds ratios (OR) to identify associations between demographic factors and the psychiatric medications. RESULTS: Patients with SCZ on a combination of at least three different classes of psychiatric drugs had a higher risk of T2D [OR 1.81 (95% CI 1.22-2.69); p = 0.003] compared to FGA alone therapy, after adjustment for age, BMI, sex, duration of SCZ and number of hospitalizations. We did not find evidence for an association of SGA use or the combination of drugs belonging to two different classes of psychiatric medications with increased risk of T2D [1.27 (0.84-1.93), p = 0.259 and 0.98 (0.71-1.35), p = 0.885, respectively] compared to FGA use. CONCLUSIONS: We find an increased risk of T2D in patients with SCZ who take a combination of at least three different psychotropic medication classes compared to patients whose medication consists only of one or two classes of drugs

Additional file 1: of Combination therapy as a potential risk factor for the development of type 2 diabetes in patients with schizophrenia: the GOMAP study

Combination therapy as a potential risk factor for the development of type 2 diabetes in patients with schizophrenia: the GOMAP study. Description of survey flow. Diagnostic assessment of T2D and psychiatric disease. Physical assessments. Table S1. T2D occurrence based on simple logistic regression modelling among patients with SCZ. Figure S1. Manhattan plot of association results from a GWAS on T2D in individuals receiving a combination of three or more psychotropic drugs, including one FGA and one SGA. For each of the 9,565,382 analysed variants the –log10 of the p-value is plotted against its chromosomal position. Blue and red lines indicate suggestive (p < 5*10− 6) and genome-wide (p < 5*10− 8) significance. Figure S2. Quantile-quantile plot of association results from a GWAS on T2D in individuals receiving a combination of three or more psychotropic drugs, including one FGA and one SGA. For each SNP the –log10 of the p-value is plotted against its expected value under the null distribution. (DOCX 219 kb