Antiaggressive effect of cyproterone versus haloperidol in Alzheimer's disease: a randomized double-blind pilot study.

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 >or=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.