Concomitant Medications May Not Improve Outcome of Antipsychotic Monotherapy for Stabilized Patients With Nonacute Schizophrenia

Ira D. Glick, M.D.; Diana Pham; and John M. Davis, M.D.

Background: There are virtually no controlled data suggesting that concomitant psychotropic medications (CPMs) improve outcome in schizophrenia after the acute phase. Despite that, polypharmacy (with all of its disadvantages) is far more common than monotherapy. To our knowledge, there have been no published reports of prospective systematic investigations of the efficacy of unrestricted CPM use in nonacute schizophrenia.

Method: This was a naturalistic, systematic study using a sample of 53 stabilized patients with DSM-IV-TR schizophrenia from 1 clinical practice setting including both private patients and patients from controlled research studies of the effectiveness of antipsychotics. Since there are meager controlled or systematic data on the effectiveness of CPM use with antipsychotics in nonacute schizophrenia, we tested the clinical strategy of CPM use by gradually tapering all CPMs (except antianxiety agents). The aim was to determine if the CPM improved outcome, had no effect, or worsened outcome using the Clinical Global Impressions-Improvement scale before and after taper, over at least 3 months and in some cases up to 18 months after discontinuation. Data were gathered from July 2002 to June 2005.

Results: For 21 patients undergoing 22 antidepressant tapers, no change was noted in 18 of 22 tapers, while in 3 improvement was noted and in 1 worsening was noted. For the 12 patients on treatment with mood stabilizers, no change was noted in 10 of 13 discontinuations, while in 3 mild worsening was noted. One patient was on treatment with both modafinil and trazodone and reported no change after tapering each in separate discontinuation trials, while another 3 patients were taking sleeping medications and also noted no change after discontinuation.

Conclusion: For most stabilized, chronic patients with schizophrenia, tapering adjunctive medications did not change outcome. This naturalistic study further defines the limits of efficacy of some concomitant classes of medications in patients with chronic schizophrenia who are already receiving adequate antipsychotic therapy.

(J Clin Psychiatry 2006;67:1261-1265)

Received Sept. 20, 2005; accepted Jan. 24, 2006. From the Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, Calif. (Dr. Glick and Ms. Pham); and the Department of Psychiatry, University of Illinois at Chicago (Dr. Davis).

There was no industry support for this article.

In the spirit of full disclosure and in compliance with all ACCME Essential Areas and Policies, the faculty for this CME article were asked to complete a statement regarding all relevant financial relationships between themselves or their spouse/partner and any commercial interest (i.e., a proprietary entity producing health care goods or services) occurring within at least 12 months prior to joining this activity. The CME Institute has resolved any conflicts of interest that were identified. The disclosures are as follows: Dr. Glick has received grant/research support from Bristol-Myers Squibb, Glaxo, Solvay, and Shire; is a member of the speakers/advisory boards for Bristol-Myers Squibb, AstraZeneca, Janssen, and Pfizer; and is a stock shareholder in Johnson & Johnson and Forest. Ms. Pham and Dr. Davis have no personal affiliations or financial relationships with any proprietary entity producing health care goods or services to disclose relative to the article.

The authors thank Donald F. Klein, M.D.; Alec Miller, M.D.; Andres Tapp, M.D.; Del Miller, M.D.; and Robert Rosenheck, M.D., for critical review and Uma Suryadevara, M.D., and Nabanita Basu, M.D., for help in compiling the data.

Corresponding author and reprints: Ira D. Glick, M.D., Stanford University School of Medicine, 401 Quarry Rd., #2122, Stanford, CA 94305 (e-mail: iraglick@stanford.edu).