Preliminary pilot study of cyproterone acetate for the treatment of aggressive behavior associated with severe dementia

INTRODUCTION: Behavioral symptoms are common in dementia, and seem to be more frequent in men than in women. Agitation is frequently responsible for caregiver burn-out and leads to institutionalization. The dramatic increase in the prevalence of Alzheimer's disease and related disorders requires better management of behavior symptoms. Although environmental adaptation has been proposed recently, for many years, psychoactive medications and physical restraints were the primary approach. However, in severely demented patients, both pharmacologic and non-pharmacologic treatments are inoperative. In this situation, alternative pharmacologic approach should be tested. Cyproterone acetate, an antiandrogen and progestative steroid has never been proposed to prevent aggressive behavior in dementia, but its favorable effect is well described in rat and monkey aggressivity. PATIENTS AND METHODS: Cyproterone acetate was proposed for 19 demented patients who developed severe aggressive behaviors or an agitation unresponsive to psychoactive drugs (even in association) or to environmental adaptation. Clinical and behavioral analysis was carried out using the Cohen-Mansfield agitation inventory associated with an assessment of dependency in daily life activities, before and during treatment with cyproterone acetate. The behavioral status was stable, with permanent or repetitive agitation. Seven patients had vascular dementia, 7 had Alzheimer's disease, 2 had fronto-temporal degeneration, 2 had Huntington's disease and 1 a probable diffuse Lewy bodies disease. Fifteen patients had prominent aggressive behavior and 4 had predominant aberrant motor behavior with aggressive behavior. RESULTS: Cyproterone (50 to 100mg - mean: 92.5mg daily) improved significantly aggressive and impulsive behavior related to Alzheimer's disease or vascular dementia but had no effect on aberrant motor behavior. When cyproterone was stopped, aggressive behaviors reappeared more rapidly in vascular dementia. CONCLUSION: Cyproterone acetate is then an interesting choice when aggressive behavior is not improved with psychotropic drugs. A detailed clinical analysis is required to avoid the use of cyproterone in non-aggressive and non-impulsive patients. The results of this preliminary study suggest a randomized double-blind study should be carried out in the near future. The behavior improvement could be related to the blockage of androgen receptors, and simultaneously to the sedative effect of progestative drugs.