Better Options for People with Treatment-Resistant Schizophrenia

Schizophrenia is a serious mental disorder affecting up to one percent of the adult population. Antipsychotics are effective at relieving symptoms for most patients, but up to 30% do not respond well to standard treatments and are considered to have treatment-resistant schizophrenia. While trials have indicated that clozapine is effective for these cases, the effectiveness of clozapine in clinical practice has not previously been studied in depth.

Often when one traditional antipsychotic medication does not work, clinicians change to another traditional antipsychotic. Clozapine is often seen as a drug of last resort, although it is the only medication approved by the FDA for treatment-resistant schizophrenia.

The new study was conducted using national Medicaid data from 6,246 patients whose treatment patterns were consistent with treatment resistance. It is the largest study directly comparing the effectiveness of clozapine with standard antipsychotics in this population in routine practice settings.

The results are encouraging and timely because the FDA recently broadened access to clozapine. In the past access was limited, in part because of the risk of agranulocytosis, a condition that can make people susceptible to infections. A system has been in place for 25 years to successfully manage the risks of agranulocytosis, using regular monitoring of white blood cell levels. Leading clinicians thus believe the limits on use of clozapine have been overly restrictive. The new FDA rules still require regular blood monitoring, but allow prescribers to make decisions based on benefits and risks for individual patients rather than rigidly following universal standards.

“These results give clinicians important guidance for how to help an extremely vulnerable group of people,” said T. Scott Stroup, MD, lead author of the study, and professor of psychiatry at Columbia University Medical Center and a research psychiatrist at New York State Psychiatric Institute. “By helping individuals with treatment-resistant schizophrenia get effective treatment sooner we can expect better outcomes.”

“Comparative Effectiveness of Clozapine and Standard Antipsychotic Treatment in Adults With Schizophrenia,” was published in the American Journal of Psychiatry. The authors are T. Scott Stroup, M.D., M.P.H., Tobias Gerhard, Ph.D., Stephen Crystal, Ph.D., Cecilia Huang, Ph.D., Mark Olfson, M.D., M.P.H. Drs. Stroup and Olfson are affiliated with the Department of Psychiatry, Columbia University, and the New York State Psychiatric Institute; Drs. Gerhard, Huang, and Crystal are affiliated with the Institute for Health, Health Care Policy and Aging Research, Rutgers University, New Brunswick, N.J.

Funding for this study was provided by the Agency for Healthcare Research and Quality.

Dr. Stroup serves as an investigator in a study sponsored by Auspex Pharmaceuticals; and he has participated in CME activities sponsored by Genentech. Dr. Gerhard serves on an external safety review committee for a Merck study; he has provided expert consultation to a law firm on behalf of Roche; and he has received compensation from Boehringer for a talk at an internal CER symposium. Dr. Olfson serves as principal investigator on a grant to Columbia University from Sunovion Pharmaceuticals. All other authors report no financial relationships with commercial interests.