Patients on Atypical Antipsychotic Drugs

Patients with schizophrenia are more likely than the general population to develop diabetes, which contributes to a high risk of cardiovascular complications; individuals with schizophrenia are two to three times more likely to die from cardiovascular disease than the general population. The risk of diabetes, and hence cardiovascular disease, is particularly increased by some of the new atypical antipsychotic drugs. Individuals taking an atypical antipsychotic drug, particularly younger patients under 40 years of age (odds ratio 1.63, 95% CI 1.23–2.16), represent an underrecognized group at high risk of type 2 diabetes. The mechanisms responsible for antipsychotic-induced diabetes remain unclear. Hypotheses include these drugs’ potential to cause weight gain, possibly through antagonism at the H1, 5-HT2A, or 5-HT2C receptors. Other mechanisms independent of weight gain lead to elevation of serum leptin and insulin resistance. Patients with psychoses have difficulties with diet and lifestyle interventions for diabetes and weight management. If hyperglycemia develops, withdrawal from antipsychotic medication will often be inappropriate, and a change to an atypical antipsychotic drug with lower diabetogenic potential should be considered, especially in younger patients. Management of psychoses should routinely include body weight and blood glucose monitoring and steps to promote exercise and minimize weight gain. Careful collaboration between the psychiatric and diabetology teams is essential to minimize the risk of diabetes in patients taking atypical antipsychotic medication and for effective management when it develops. This collaboration will also help minimize the already high risk of cardiovascular disease in individuals with schizophrenia. Diabetes Care 26:1597–1605, 2003 T he number of individuals in the population receiving antipsychotic drugs is surprisingly high. The most common reason is schizophrenia, although antipsychotic drugs are widely used in other psychiatric conditions (e.g., bipolar disorder and Alzheimer’s disease). Schizophrenia is far more common than is generally appreciated. For example, as many as 1 in 100 individuals in the population will suffer one or more episodes of schizophrenia in a lifetime, and for at least half of these individuals, the illness will be lifelong, probably requiring long-term medication. Schizophrenia causes social disability and also carries a high mortality—approximately twice as high as in the general population (1). It has a strikingly high suicide rate of 10% (2,3), but the most common cause of death is accelerated heart disease (two to three times that in the general population) (4). Despite its relatively low prevalence, the early age at onset and its chronic nature means that schizophrenia is an expensive medical condition to health care systems and to society in general (5,6). The introduction of chlorpromazine after 1956 transformed the lives of many sufferers. Several major chemical classes of antipsychotic drugs were developed, principally the phenothiazines (including chlorpromazine itself), the butyrophenones (e.g., haloperidol), and the thioxanthines (e.g., flupenthixol). All these “conventional neuroleptics” are effective because they are dopamine D2 antagonists (7), but they all have major drawbacks and contribute their own stigmata to schizophrenia. These drugs share a set of Parkinsonian-like movement-disorder side effects, the “extrapyramidal side effects” (EPSs), resulting from antagonism at dopamine D2 receptors in the basal ganglia. Many conventional neuroleptics cause excessive daytime sedation, and many are muscarinic antagonists, causing dry mouth, blurred vision, and constipation, and may precipitate glaucoma in