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Unexplained sudden death in psychiatric patients not directly related to antipsychotic use

Reuters Health • The Doctor's Channel Daily Newscast

NEW YORK (Reuters Health) – The excess risk of unexplained sudden death in psychiatric patients may be related to diabetes and dyslipidemia rather than to the antipsychotic drugs used to treat them, according to a report in the May 3rd online Journal of Clinical Psychiatry.

“The physical health of persons with severe mental illness is poor, due to poverty, lack of access to medical services, substandard medical care, unhealthy lifestyle (smoking, lack of physical activity), and adverse effects of medications,” Dr. Peter Manu from Zucker Hillside Hospital, Glen Oaks, New York told Reuters Health in an email.

“The excess of sudden dying in some segments of this population is a marker of this unfortunate reality. Much more needs to be done to increase these patients’ access to the preventive medical care enjoyed by the majority of U.S. residents.”

Dr. Manu and colleagues reviewed the root cause analyses of 100 consecutive cases of sudden death among patients receiving care in a single behavioral health institution in New York City and compared the groups with explained and unexplained deaths. They expected to find a higher prevalence of coronary artery disease risk factors rather than a greater utilization of antipsychotic drugs.

Forty-eight patients had identifiable causes of death, including most commonly acute coronary syndromes (15 patients), upper airway obstruction (5 patients), pulmonary emboli (4 patients), and thrombotic strokes (3 patients). The cause of death was unknown in the remaining 52 patients.

The explained and unexplained groups were similar in age, sex, primary psychiatric diagnoses, and all medication classes (including first- and second-generation antipsychotics), but significantly more patients in the unexplained sudden death group had a history of dyslipidemia, compared with the explained sudden death group (36.5% versus 14.6%, respectively), and diabetes was more than twice as prevalent in the unexplained group (30.8%) than in the explained group (14.6%).

While there were only 13 cases of sudden death (5 of them unexplained) in the 15 years from 1984 through 1911197, there were 54 cases of sudden death (33 of them unexplained) in the 5 years from 2005 through 2009.

In logistic regression analysis, comorbid presence of dyslipidemia and diabetes were the only factors independently associated with unexplained cause of sudden death.

“This correlation must be confirmed by large longitudinal studies,” the researchers note, “but the signal registered by our study should strengthen efforts to understand the relationship between these metabolic abnormalities and genetic predispositions specific to persons suffering from severe mental illnesses in the global context of rapidly increased prevalence of obesity and diabetes.”

“The combined prevalence of schizophrenia and bipolar disorder in the U.S. is about 5%, and the vast majority of these patients have been or are currently treated with antipsychotic drugs,” Dr. Manu explained. “Antipsychotic drugs are also widely used for behavioral disturbances associated with autism, depression and dementia. The use of modern antipsychotics is associated with higher rates of obesity, prediabetes, and dyslipidemia and requires careful monitoring and treatment of these metabolic abnormalities.”

“Our team has recently completed a cross-sectional study of a cohort of 783 consecutively admitted adult psychiatric patients in which we found that 10.4% had diabetes and that 37% were prediabetic at the time of testing in 2003-2007,” Dr. Manu said.

“The fact that almost half of the patients treated with antipsychotic drugs are diabetic or at high risk of becoming diabetic is extremely worrisome. We will be starting soon the study of health outcomes in this cohort with the goal of identifying predictors of premature dying in the diabetic as well as the prediabetic patients. I feel strongly that the solution lies in the earliest recognition and management of prediabetic patients, to prevent the early atherosclerotic and microangiopathic myocardial changes that contribute to cardiovascular mortality.”

J Clin Psychiatry.