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

Abstract

BackgroundSchizophrenia (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.MethodsThe 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.ResultsPatients 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.ConclusionsWe 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.Electronic supplementary materialThe online version of this article (10.1186/s12888-018-1826-4) contains supplementary material, which is available to authorized users.

The type rather than the daily dose or number of antipsychotics affects the incidence of hyperglycemic progression

“…The reference group for the type of antipsychotics was initiation of aripiprazole, which is considered to have the lowest risk of hyperglycemic progression among the antipsychotics included in the study (Pillinger et al 2020;Zhang et al, 2017;Carnovale et al, 2021). The number of coadministered antipsychotics and the daily dose (as CPZ) of antipsychotics were classified into three levels based on previous reports (Mamakou et al, 2018;Wubeshet et al, 2019), and the reference group was the number of coadministered antipsychotics = 0 and 300 <daily dose (as CPZ) of antipsychotics, which is considered to have the lowest incidence of hyperglycemic progression. We checked the multicollinearity of the independent variables to assess their validity.…”

“…In contrast, other studies have reported no clear relationship between daily dose and the incidence of diabetes in patients treated with antipsychotics (Henderson, 2001;Bechara, 2001). Regarding the number of antipsychotics, several studies have reported an association between increased risk of diabetes and antipsychotic polypharmacy (Kessing et al, 2010;Mamakou et al, 2018;Kato et al, 2015). In contrast, other studies have reported a lack of any significant difference in the prevalence of diabetes between polypharmacy and monotherapy with either first-generation antipsychotics or second-generation antipsychotics (Ijaz et al, 2018;Correll et al, 2007).…”

Efficacy and Safety of Second-generation Antipsychotics in Schizophrenia Pharmacotherapy: A Comparative Narrative Review

“…Diabetes risk was also affected by the number of antipsychotic medications a patient was prescribed, with those taking three antipsychotics more likely to develop type 2 diabetes than those taking only two (37). A matched cohort study comparing those receiving antipsychotics to those receiving placebo reported a threefold increase in diabetes risk that increased with cumulative dose increment and remained at increased risk one year after treatment discontinuation (38).…”