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Antiaggressive Effect of Cyproterone Versus Haloperidol in Alzheimer's Disease: A Randomized Double-Blind Pilot Study
David Huertas, M.D., Ph.D.; Juan J. López-Ibor Aliño, M.D., Ph.D.; Juan D. Molina, M.D., Ph.D.; Lorenzo Chamorro, M.D.; Juana Balanza, M.D.; María P. Jiménez, M.D.; and Mercedes Hornillos, M.D., Ph.D.
Objective: Alzheimer's disease (AD) is commonly accompanied by aggressive behavior. In the elderly, effective and safe antiaggressive treatment is lacking. Risks of antipsychotics in this population demand therapeutic alternatives. This randomized, double-blind, pilot trial examined the efficacy and safety of cyproterone in the treatment of agitated AD.
Method: The subjects were 27 elderly patients referred to the University Hospital of Guadalajara Psychogeriatric Clinic diagnosed with AD and associated aggressive behavior (mean Staff Observation Aggression Scale [SOAS] score >= 2). Each patient underwent a 15-day washout for psychotropics and then was randomly assigned to receive stable doses of either cyproterone (100 mg/day) or haloperidol (2 mg/day) for 90 days. The primary outcome measure was the SOAS score. This trial was conducted between October 27, 1993, and March 24, 1998.
Results: Of the 27 patients, 19 (70.4%) were women, and the mean age was 80.7 years. The trial was completed by 24 (88.9%) of the subjects (13 in the cyproterone group and 11 in the haloperidol group for 90 days). Three patients (11.1%) dropped out, all after adverse effects in the haloperidol group. Baseline aggression level in the sample was mild (mean SOAS score of 4.48 [SD = 2.04]). Efficacy analyses for all intent-to-treat patients showed that 9 (69.2%) in the cyproterone group achieved complete elimination of aggression at endpoint, in contrast to 2 patients (14.2%) in the haloperidol group (p = .012). Ten patients (71.4%) taking haloperidol had adverse events, compared with 4 (30.7%) taking cyproterone (p = .035).
Conclusion: Cyproterone showed significantly better efficacy and safety than haloperidol in controlling mild aggression associated with AD. Additional research is needed to confirm if these results can be ratified in a larger study and generalized to patients whose aggression is more severe.
(J Clin Psychiatry 2007;68:439-444)
Received May 8, 2006; accepted Aug. 29, 2006. From the University of Alcalá, Madrid (Drs. Huertas, Chamorro, and Hornillos); the Department of Psychiatry (Drs. Huertas, Chamorro, and Balanza), and the Department of Geriatric Medicine (Drs. Jiménez and Hornillos), University Hospital of Guadalajara, Guadalajara; the Complutense University of Madrid (Drs. López-Ibor Aliño and Balanza); the Institute of Psychiatry and Mental Health, San Carlos University Hospital (Dr. López-Ibor Aliño); University Camilo José Cela and the Department of Psychiatry, Dr. Rodríguez Lafora Hospital (Dr. Molina), Madrid, Spain; and the Linda Pollin Institute, Harvard Medical School, Boston, Mass. (Dr. Huertas).
This investigator-initiated study was supported by a grant from the Social Security Investigation Fund, Spanish National Institute of Health (No. 93/1317).
The authors acknowledge Jan Volavka, M.D., Ph.D., from New York University, for his contributions to the correction of earlier versions of the paper and editorial assistance; and Fernando Carballo, M.D., Ph.D., from the University Hospital of Guadalajara Research Unit (currently employed by the University of Alcalá, Madrid, Spain), who served as project manager from 1993 to 1998, for his support with data analysis and guidance. These individuals disclose no conflict of interest.
The authors report no other significant commercial relationships relevant to the study.
Corresponding author and reprints: David Huertas, M.D., Ph.D., Servicio de Psiquiatría, Hospital Universitario de Guadalajara, Donantes de Sangre s/n, 19002 Guadalajara, Spain (e-mail: email@example.com).