Saturday, February 14, 2004

Weight Gain and Antipsychotic Medications There has been a great deal of interest recently concerning weight gain and the risk of diabetes. Last month a joint panel composed of the American Diabetes Association, the American Psychiatric Association, the American Association of Clinical Endocrinologists, and the North American Association for the Study of Obesity outlined recommendations for monitoring, management, and counseling. They also note that not all second-generation antipsychotics (SGAs) are associated with increased risk. The consensus panel reviewed current published studies then heard presentations from experts drawn from the areas of psychiatry, obesity, and diabetes. Presentations were also made by a representative from the U.S. Food and Drug Administration (FDA) and by representatives from the AstraZeneca, Bristol-Myers Squibb, Janssen, Lilly, and Pfizer pharmaceutical companies. Antipsychotic medications have been an important component in the medical management of many psychotic conditions. Initially many of the side effects were overlooked since the properties of the SGAs showed notable improvement in the mental status and social functioning in a patient population that has been difficult to treat. It became clear that some of the SGAs were more prone to an increased risk of weight gain and and related difficulties glucose metabolism (clozapine and olanzapine). There were numerous reports of dramatic weight gain, diabetes (including diabetic ketoacidosis), and an atherogenic lipid profile (increased LDL cholesterol and triglyceride levels and decreased HDL cholesterol) in these patients. In addition, quality of life (both physical and psychosocial) became as important as minimizing psychotic symptoms. Compliance with the treatment regimens also became an important issue since patients were choosing symptoms over side effects. Medscape Medical News published a CME news report on the consensus panel that describes the study's highlights. (registration required but free) Interventions There are various approaches to countering the weight gain and related glucose metabolism difficulties from weight management/education programs to medications. The consensus panel only went a far as recommending the following 1. Consideration of metabolic risks when starting SGAs 2. Patient, family, and care giver education 3. Baseline screening 4. Regular monitoring 5. Referral to specialized services, when appropriate New Research from the Biological Psychiatry Meeting in Sydney One of the best things about scientific meetings is the new research that is presented. Whether in the form of posters or presentations, looking at works in progress and new small preliminary studies offers a preview of things to come and presents new ideas to the psychiatric and neuroscience community. David C. Henderson, MD from Massachusetts General Hospital, Schizophrenia Program presented a number of preliminary studies that attracted the attention of conference attendees and will probably stimulate additional research. He looked at weight and weight management in a chronic, difficult to treat population of patients. According the the author's experience with this population of clinic patients, traditional weight loss programs and/or medications did not work for those who were taking clozapine or olanzapine. Three studies In his first study, Dr. Henderson set a baseline for the subsequent studies. He looked at glucose metabolism in patients with schizophrenia who were treated with atypical antipsychotics and concluded that patients treated with clozapine or olanzapine may be at increased risk for insulin resistance, even if not obese. He recommended routine screening, counseling and early intervention. In the second study (12 week, double-blind placebo-controlled), he used sibutramine, an FDA approved weight loss agent (or a placebo) added to olanzapine. His results showed that the sibutramine treated group improved in a number of ways, BMI and total cholesterol were significantly reduced when compared to placebo. In the third study (exploratory, open label), Dr. Henderson added aripiprazole, a new atypical antipsychotic agent, to clozapine. He was initially looking for a reduction in symptomatology and an increase in activity and motivation in these patients, since aripiprazole is reportedly more energizing than many of the other atypicals and with minimal weight gain. Not only did he find general improvement in symptoms (using the PANSS) but to his surprise, there were very significant reductions in weight, total cholesterol and triglycerides. Clearly, long-term placebo-controlled studies are warranted to further evaluate this combination but the results were striking. Dr. Henderson describes his research in a Medscape Psychiatry Newsmaker Interview with Dr. Henderson Other studies by Dr. Henderson Consensus Development Conference on Antipsychotic Drugs and Obesity and Diabetes from Disbetes Care - Diabetes Care 27:596-601, 2004 Medline Drug Information on Sibutramine Information on aripiprazole 1:53:07 PM    comment []

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