A four-year naturalistic prospective study of cardiometabolic disease in antipsychotic-treated patients.

The relationship between antipsychotic use and cardiovascular morbidity and mortality is controversial. There is a lack of long-term prospective studies investigating changes in cardiometabolic risk in patients treated with antipsychotic drugs. We report data from a 4-year prospective study. Patients (89) underwent detailed metabolic and cardiovascular risk assessment at 4-years which included anthropometric assessment, blood pressure, lipid profile, and an oral glucose tolerance test. We used the homeostatic model assessment to determine insulin resistance, and calculated 10-year cardiovascular risk scores. Mean age of subjects was 44.7 (± 11.5) years, and 52% were male. The prevalence of type 2 diabetes was 8%, and 38.4% fulfilled diagnostic criteria for the metabolic syndrome. With the exception of increased central adiposity over the 4-year follow-up period (p < 0.001), other cardiometabolic parameters were generally unchanged. There was a high prevalence of dyslipidaemia, but only 16.9% were prescribed lipid-lowering treatment. Commencing lipid-lowering therapy was associated with a reduction in cardiovascular risk score (OR 7.9, 95% CI = 1.3 to 48.7; p = 0.02). Patients established on longer-term antipsychotic treatment show less dramatic metabolic changes than those occurring in the early stages of treatment, but have a high burden of cardiovascular risk. Lipid-lowering therapy is associated with a significant reduction in cardiovascular risk.

A prospective study of glycaemic status in anti-psychotic-treated patients.

Anti-psychotic drugs, particularly the second generation, or ;atypical' agents, have been implicated in the development of metabolic dysfunction such as diabetes mellitus. There is a paucity of longitudinal data on the natural history of glucose homeostasis in anti-psychotic-treated patients, and there are no universally accepted strategies for managing worsening glycaemic control in this population. Notwithstanding, several guidelines recommend switching to a ;lower risk' agent if patients develop worsening glycaemic control during anti-psychotic treatment. We prospectively followed a cohort of 106 anti-psychotic-treated patients from across the diagnostic spectrum, and investigated changes in glycaemic status. Between baseline and follow-up assessment (mean follow-up time, 599.3 [SD+/-235.4] days glycaemic status was unchanged in 78 (86.7%) patients; 5 (5.6%) reverted from impaired fasting glucose (IFG) to normoglycaemia in the absence of any pharmacological or lifestyle intervention and all were taking a ;high risk' drug (clozapine or olanzapine). These preliminary data suggest that progression to overt diabetes mellitus is not inevitable in patients who develop IFG during anti-psychotic treatment. Switching to another agent simply on the basis of the development of IFG may not offer any advantage, especially if the mental state is stable.

Prevalence of obesity, glucose homeostasis disorders and metabolic syndrome in psychiatric patients taking typical or atypical antipsychotic drugs: a cross-sectional study.

AIMS/HYPOTHESIS: Atypical antipsychotic drugs may be associated with obesity and other components of the metabolic syndrome, but this relationship is controversial. We investigated the hypothesis that atypical antipsychotics are associated with a greater degree of metabolic dysfunction than typical agents. METHODS: Metabolic parameters were measured in 103 diagnostically heterogeneous psychiatric out-patients. Patients had been taking typical or atypical antipsychotic drugs for a minimum of six months. RESULTS: Sixty-nine patients were taking atypical agents, 20 typical agents and 14 a combination. Mean values (+/-SD) for the whole group were: age 43.8 years (11.4); BMI 29.1 kg/m(2) (5.1); W:H ratio 0.88 (0.09). Metabolic parameters, including beta cell function and insulin sensitivity, measured by HOMA, did not differ with regard to the prescribed antipsychotic drug. Six patients had undiagnosed diabetes, six patients had impaired fasting glucose, and eight fulfilled criteria for the metabolic syndrome, all of whom were taking atypical agents (p=0.07 vs typical agents). Subgroup analyses of those taking atypical agents revealed differences in BMI (mean, +/-SD) between olanzapine (27.3 kg/m(2)+/-5.1) and quetiapine (31.9 kg/m(2)+/-5.1), p=0.01, and HbA(1c) (olanzapine, 5.1%+/-0.6 vs quetiapine, 5.6%+/-0.6; p=0.03). Other atypical agents were intermediate with regard to these parameters. CONCLUSIONS: Obesity, dyslipidaemia and abnormalities of glucose homeostasis are prevalent in this group. Patients taking atypical agents showed a trend towards abnormalities of glucose homeostasis. Prospective studies are needed to explore the precise relationship between antipsychotic drugs, glucose homeostasis, obesity and the metabolic syndrome.