A Double-Blind Controlled Study of Adjunctive Treatment With Risperidone in Schizophrenic Patients Partially Responsive to Clozapine: Efficacy and Safety

A. Elif Anil Yagcioglu, M.D.; Berna B. Kivircik Akdede, M.D.;Tolga I. Turgut, M.D.; Mevhibe Tümüklü, M.D.; M. Kâzim Yazici, M.D.;Köksal Alptekin, M.D.; Aygün Ertugrul, M.D.; Karu Jayathilake, M.S.;Ahmet Gögüs¸, M.D.; Zeliha Tunca, M.D.; and Herbert Y. Meltzer, M.D.

Background: Several open trials and case studies have reported beneficial effects following the addition of risperidone for partial responders to clozapine. The purpose of this study was to carry out a placebo-controlled, randomized, double-blind trial of the efficacy, safety, and tolerability of adjunctive treatment with risperidone in patients with schizophrenia partially responsive to clozapine.

Method: In this 6-week double-blind study, 30 patients with DSM-IV schizophrenia who had partial response to clozapine despite being treated for a mean of 32 months were randomly assigned to risperidone (N = 16) up to 6 mg/day or placebo (N = 14). Efficacy assessments included the Positive and Negative Syndrome Scale (PANSS), the Calgary Depression Scale, the Clinical Global Impressions-Severity of Illness scale, the Global Assessment of Functioning scale, and the Quality of Life Scale. A variety of safety and tolerability measures were also obtained. Data were collected between November 2001 and July 2003.

Results: Significant improvement was noted in both groups on a variety of measures of psychopathology, but there was significantly greater improvement in the placebo-treated patients on the primary outcome measure, the PANSS positive symptom subscale. There were no significant differences between the treatment groups regarding extrapyramidal symptoms, weight gain, vital signs, serum clozapine levels, and QTc interval. The only side effect significantly more severe in risperidone-treated compared to placebo-treated patients was sedation. The patients treated with risperidone developed significant increases in plasma prolactin levels.

Conclusion: Adjunctive risperidone treatment in schizophrenia patients partially responsive to clozapine does not significantly improve psychopathology or quality of life compared to placebo in a 6-week period.

(J Clin Psychiatry 2005;66:63-72)

Received April 2, 2004; accepted July 6, 2004. From the Department of Psychiatry, Hacettepe University Faculty of Medicine, Ankara, Turkey (Drs. An¹l Yagc¹oglu, Turgut, Yaz¹c¹, Ertugrul, and Gögüs¸); the Department of Psychiatry, Dokuz Eylül University School of Medicine, Izmir, Turkey (Drs. K¹v¹rc¹k Akdede, Tümüklü, Alptekin, and Tunca); and the Department of Psychiatry, Vanderbilt University Faculty of Medicine, Nashville, Tenn. (Mr. Jayathilake and Dr. Meltzer).

Supported by grants from the Stanley Medical Research Institute, Bethesda, Md. (Drs. An¹l Yagc¹oglu and K¹v¹rc¹k Akdede); Janssen Pharmaceutica, Titusville, N.J.; the Ritter Foundation, New York, N.Y.; and the William K. Warren Medical Research Foundation, Tulsa, Okla. (Dr. Meltzer).

Presented in part at the 39th National Psychiatry Congress, October 14-19, 2003, Antalya, Turkey; and the 24th Collegium Internationale Neuro-Psychopharmacologicum (CINP) Congress, June 20-24, 2004, Paris, France.

Dr. Meltzer has received research grants from or served as a consultant and lecturer for AstraZeneca, Janssen, Novartis, Bristol-Myers Squibb, Eli Lilly, GlaxoSmithKline, Pfizer, Sanofi, and Solvay.

Corresponding author and reprints: A. Elif An¹l Yagc¹oglu, M.D., Hacettepe University Faculty of Medicine, Department of Psychiatry, S¹hhiye, Ankara 06100, Turkey (e-mail: eanil@hacettepe.edu.tr).