Clozapine, Diabetes Mellitus, Cardiovascular Risk and Mortality: Results of a 21-Year Naturalistic Study in Patients with Schizophrenia and Schizoaffective Disorder

Abstract

The goal of this 21-year naturalistic study of clozapine treated patients was to examine the cardiovascular risk factors following clozapine initiation and resultant mortality estimates from cardiovascular disease. Data was collected from medical records of clozapine treated patients with schizophrenia or schizoaffective disorder from January 1992 to February 2012. Demographics, clozapine dosage and laboratory results were extracted at 12-month intervals. At clozapine initiation, the mean age of 96 patients was 36.4 years ±7.6 years; N=27(28%) were women. The mean duration of clozapine use was 13 years. The Kaplan-Meier estimate for 21-year cardiovascular events was 29%, while the Kaplan-Meier estimate for 21-year mortality from cardiovascular disease was 10%. The mean cardiovascular risk increased during the first ten years (p<.01), while a slight decrease occurred beyond ten years (p<.01). Patients involved in cardiometabolic research showed a greater decrease in cardiovascular risk factors over 21 years (p = .05). The Kaplan-Meier estimate for 21-year all-cause mortality was 22%. Forty-one patients were diagnosed with diabetes (42.7%), compared to a nationwide prevalence of 13.7% in a similar age group. These results support the hypothesis that clozapine-treated patients are at risk for cardiovascular events and death secondary to an increased risk of medical disorders. Interventions that target weight loss, smoking cessation, and lipid profile improvement may alleviate the increased risk of cardiovascular mortality.

Ethnic inequalities in clozapine use among people with treatment-resistant schizophrenia: a retrospective cohort study using data from electronic clinical records

“…For instance, diabetes, hypertension and cardiovascular disease seem to be more prevalent among Black communities than White British people [45][46][47]. The potential impact of clozapine on these conditions may discourage clinicians and service-users from choosing this treatment [48], even though there may not be safe alternatives to clozapine, given that other antipsychotics with high efficacy, such as olanzapine, or zotepine, also have metabolic sideeffects [49,50]. Nonetheless, in a previous study in the USA, diabetes and cardiovascular illness had little association with clozapine treatment, and ethnic disparities persisted when controlling for those [24].…”

Clozapine Worsens Glucose Intolerance, Nonalcoholic Fatty Liver Disease, Kidney Damage, and Retinal Injury and Increases Renal Reactive Oxygen Species Production and Chromium Loss in Obese Mice

“…By contrast, mice treated with clozapine over 30 consecutive days had lower body weight and fasting glucose levels than had mice without clozapine treatment [21]. However, another study discovered that approximately two-thirds of patients taking clozapine did not develop diabetes mellitus, and that clozapine-treated patients had a risk profile linked to possible metabolic side effects and weight gain [22].…”

Atypical Antipsychotic Administration in Schizophrenic Patients Leads to Elevated Lipoprotein‐Associated Phospholipase A2 Levels and Increased Cardiovascular Risk: A Retrospective Cohort Study

“…Atypical antipsychotics are the first‐line pharmacological intervention for schizophrenia. Oral AAP, especially olanzapine and clozapine, are associated with weight gain , which can lead to overweight or obesity and other serious metabolic disorders including hyperlipidaemia and type II diabetes mellitus, substantially increasing the risk of CVD . However, some schizophrenia patients with AAP may have few or none of the risk factors such as overweight and metabolic comorbidities, but still be at risk of CVD .…”