Two-thirds of people who were being treated for psychosis with more than one antipsychotic and who were switched to monotherapy did so successfully, without discontinuing therapy and with no difference in symptom control compared with those who stayed on polypharmacy.

Moreover, switching to monotherapy was associated with weight loss, according to a report in the May American Journal of Psychiatry.

The study did find that treatment discontinuation was more common in the group that switched to monotherapy than in the polypharmacy group, but the symptom control and weight loss associated with the switch to monotherapy suggests that monotherapy may be an option worth trying for patients who are relatively stable.

("Discontinuation" in the study was defined as dropping out of the assigned group, not stopping treatment altogether; patients who switched to monotherapy but then "discontinued," for instance, returned to polypharmacy or another form of treatment.)

"I don't think our results say that polypharmacy should not be a part of treatment guidelines, but rather that the guidelines should encourage a trial of monotherapy if it seems reasonable and the patient has a chance to go back to polypharmacy if necessary," said senior author Nancy Covell, Ph.D., an assistant professor of clinical psychology in the Department of Psychiatry at Columbia University.

In the study, adult outpatients with schizophrenia taking two antipsychotics (127 participants across 19 sites) were randomly assigned to stay on polypharmacy or switch to monotherapy by discontinuingone antipsychotic. The trial lasted six months, with a six-month naturalistic follow-up.

The analysis did not examine the relative effects of switching to or from different kinds of antipsychotics.

Results showed that patients assigned to switch to monotherapy had shorter times to all-cause treatment discontinuation than those assigned to stay on polypharmacy. By month 6, 86 percent of those assigned to stay on polypharmacy were still taking both medications, whereas 69 percent of those assigned to switch to monotherapy were still taking the same medication.

However, the two groups did not differ with respect to psychiatric symptoms or hospitalizations. And on average, the monotherapy group lost weight, whereas the polypharmacy group gained weight.

Among those assigned to switch to monotherapy, 18 discontinued their assigned treatment. Of those, 11 reported an increase in symptoms, six expressed a preference to discontinue, and one experienced hyper-lipidemia. Of the 18 monotherapy-switch patients who discontinued, 12 returned to their baseline polypharmacy combination, three began a different polypharmacy combination, one began monotherapy with an agent other than one of the two baseline medications, one began monotherapy with one of the baseline agents and changed to monotherapy with the second baseline agent after 90 days, and one began to taper one of the two agents but did not complete the taper after symptom levels increased.

Covell said that psychosis has a natural variability—some days are better than others—and some of the monotherapy-switch patients who discontinued may have attributed natural variation of the disease to the switch.

"While this study suggests some people taking antipsychotic polypharmacy might benefit from a switch to monotherapy, it does not address the risks and benefits associated with adding a second antipsychotic to monotherapy. Studies addressing the risks and benefits of going from antipsychotic monotherapy to polypharmacy are sorely needed."

"Effectiveness of Switching From Antipsychotic Polypharmacy to Monotherapy" is posted at <http://ajp.psychiatryonline.org/cgi/content/abstract/appi.ajp.2011.10060908v1>.