The report from the Consensus Development Conference on Antipsychotic Drugs and Obesity and Diabetes Consensus Panel (1) contains valuable advice for the appropriate and prudent monitoring of patients who are at risk for type 2 diabetes. The recommendations made are similar to a prior consensus conference (2) and, if they are followed, will benefit our vulnerable patients by the early identification and treatment of metabolic disorders.
However, the report probably overreaches available evidence when suggesting that clinicians should consider prescribing one antipsychotic over another with the aim of avoiding diabetes. Although clear differences exist in liability for weight gain (and consequently dyslipidemias), quantifiable risk differences among the second-generation antipsychotics regarding an association with diabetes have been inconsistent in large published pharmacoepidemiological studies (3). For this reason, the U.S. Food and Drug Administration has notified the manufacturers of the second-generation antipsychotics that product labeling for all drugs in that class will require a new warning about hyperglycemia and diabetes (4). Furthermore, the risk attributable to antipsychotics appears small compared with established risk factors such as family history and advancing age. From the evidence, choosing a second-generation antipsychotic medication does not, in and of itself, have significant predictive value for treatment-emergent diabetes.
Moreover, the report did not adequately address the complex issues regarding antipsychotic efficacy. Although clinical trials may not show big differences in efficacy among antipsychotic groups, modest differences do exist, favoring not only clozapine but also risperidone and olanzapine (5). Although the consensus panel report acknowledged the primacy of appropriate treatment, for example with clozapine having unique benefits for treatment-refractory patients and those at significant risk for suicidal behavior, other antipsychotics may also have a favorable efficacy profile among treatment-refractory patients in specific treatment domains such as cognitive dysfunction (favoring risperidone and olanzapine) (6). Efficacy considerations are particularly important among patients with persistent aggressive behavior (again, favoring clozapine). Further complicating the risk-benefit equation is the observation that weight gain may be associated with response in about half of the responders to clozapine or olanzapine (7). In addition, interindividual differences in response may be huge, leading to patients receiving several sequential medication trials over the years to find the optimal regimen for that individual.
As clinicians and researchers in a state-operated psychiatric center, where the average patient has failed a number of medication trials, we find obtaining an adequate antipsychotic medication response to be a major challenge. When such a response is achieved, a major focus is to manage somatic problems should they emerge. Efficacy is the prime mover for treatment decisions (8). A switch from a beneficial antipsychotic regimen is usually the last resort after other management approaches have not been successful. Taken out of context, the consensus conference report might lead the inexperienced practitioner to switch medications prematurely and thus expose the patient to the risk of a deterioration in their symptoms and, ultimately, relapse.
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L.C. has received honoraria from Abbott Laboratories, AstraZeneca, Bristol-Myers-Squibb, Eli Lilly, Novartis, and Pfizer; has received research support from Abbott Laboratories, Bristol-Myers-Squibb, Janssen, Eli Lilly, and Repligen; and holds stock in Bristol-Meyers-Squibb, Eli Lilly, Merck, and Pfizer. J.V. has received honoraria from AstraZeneca, Bristol-Myers-Squibb, GlaxoSmithKline, and Eli Lilly and research support from GlaxoSmithKline.
