Antipsychotic Monotherapy Worth a Try

Fran Lowry

July 11, 2011

July 11, 2011 — Adult outpatients with schizophrenia who are receiving antipsychotic polypharmacy can be safely tried on monotherapy, according to new research published in the July issue of the American Journal of Psychiatry.

If monotherapy proves unsatisfactory, patients can always be switched back to polypharmacy, the researchers, led by Susan M. Essock, PhD, Edna L. Edison Professor of Psychiatry at Columbia University, New York, New York, suggest.

"Antipsychotic polypharmacy is prescribed for a nontrivial amount of people in the psychiatric population, and it is a practice that continues without evidence of effectiveness,” senior author Nancy H. Covell, PhD, from the Department of Psychiatry, Columbia University, told Medscape Medical News.

The rate of polypharmacy ranges from 10% to 30% and is increasing, despite lack of studies, Dr. Covell said. "We wanted to take a closer look because there are added risks to taking more than 1 medication. You’re exposed to the side effects from both, there’s extra cost, all without any evidence as to whether polypharmacy is more effective."

To begin to answer that question, the investigators recruited 127 adults 18 years of age and older with schizophrenia from 15 study sites in the National Institute of Mental Health Schizophrenia Trials Network and 5 sites in Connecticut’s public mental health system between December 2004 and March 2008. All patients were taking 2 antipsychotic medications when they entered the study.

They were randomly assigned to continue receiving polypharmacy or switch to monotherapy by discontinuing 1 of their antipsychotic medications. The choice of which medication to discontinue was left to the patient and the prescriber. The dose of the remaining medication could also be raised or lowered or kept the same, again at the discretion of patient and prescriber.

The patients were asked to stay in their assigned condition for 6 months unless there was a clear clinical indication that they needed to discontinue. After 6 months, the patients were free to continue in their assigned condition if they wished, and all were followed for another 6 months of naturalistic follow-up.

Monotherapy Associated With Weight Loss

Patients who continued to receive polypharmacy had a longer time to all-cause discontinuation than patients who were randomly assigned to monotherapy. By the sixth month, 86% of those assigned to continue polypharmacy were still taking both medications, but among patients assigned to monotherapy, 69% were still taking the same medication. Most of the time, patients who stopped monotherapy resumed their original polypharmacy regimen.

The groups did not differ with respect to symptom control.

The study also found that patients in the monotherapy group lost weight, whereas those receiving polypharmacy gained weight. Among those who switched to monotherapy, body mass index (BMI) decreased by a mean of 0.50 (standard deviation, 2.32) point, and among those who continued polypharmacy, BMI increased by 0.28 (standard deviation, 2.31) point.

"The groups didn’t differ with respect to symptom control, and those on monotherapy had some weight loss, so there was some benefit going from polypharmacy to monotherapy," Dr. Covell said. "There does seem to be some advantage for being on 1 drug rather than 2. If monotherapy is not working, they can always go back to polypharmacy."

She suggested that a future study should examine antipsychotic monotherapy to which a second drug is added. "The next iteration of studies that would be useful would be to start with monotherapy and see what happens when someone switches to polypharmacy. This is definitely an area that could use further study," she said.

For Some, Polypharmacy Might Be Preferred

In an accompanying editorial, Donald C. Goff, MD, professor of psychiatry at Harvard Medical School, Boston, Massachusetts, and Lisa Dixon, MD, MPH, professor of psychiatry at the University of Maryland School of Medicine, Baltimore, point out that polypharmacy in and of itself does not produce side effects, and write, "it is the specific drugs and doses that matter."

They note that relatively few patients continue to receive a single antipsychotic agent for long, and adherence is often poor, even with monotherapy.

"In some patients, combination treatment may be preferred after all other reasonable options have failed" they write. "In such patients, combination treatment using the lowest possible dose of each drug should be evaluated in a systematic, time-limited trial, and the evidence for benefit should be clear and well-documented if the combination is to be continued. As always, clinician judgment combined with patient preference must take over when treatment algorithms fall short," they conclude.

Dr. Essock and Dr. Covell have disclosed no relevant financial relationships. Dr. Goff reports financial relationships with Abbott Laboratories, Astra-Zeneca, Biovail, Bristol-Myers Squibb, Cypress, Dainippon Sumitomo, Eli Lilly, Endo Pharmaceuticals, Forest Laboratories, H. Lundbeck, Hoffman-La Roche, Indevus Pharmaceuticals, Merck, Organon, Ortho-McNeil-Janssen, Otsuka, Pfizer, Proteus, Schering-Plough, Solvay, Takeda, Vanda, Wyeth, XenoPort, and Xytis. Dr. Dixon reports financial relationships with Ortho-McNeil-Janssen Scientific Affairs.

Am J. Psychiatry. 2011;168:702-708. Abstract