cyproterone and Psychomotor-Agitation

Aggressivity is a common problem in the management of elderly patients with dementia. Medications currently used to diminish aggressive behaviour in dementia can have problematic side effects. We present a case and systematic review of the current knowledge about the use of cyproterone acetate to treat aggressivity (excluding hypersexuality related behaviours) in dementia. An 82-year-old man required psychiatric inpatient admission due to agitation and aggressivity and was diagnosed with Alzheimer's disease. After failed trials of atypical antipsychotics (quetiapine 100 mg/day and risperidone 1 mg/day), drugs for dementia (memantine 20 mg/day and rivastigmine 9 mg/day) and benzodiazepines (lorazepam 0.5-1 mg prn) he was started on cyproterone acetate titrated up to 50 mg twice daily. After two weeks he was calmer and did not express aggressivity. Two months later he was discharged to a community placement where he subsequently remained settled on cyproterone. We reviewed literature on the use of cyproterone in aggressivity (excluding hypersexuality) associated with dementia. We searched the main medical databases including articles in English, Spanish, French and Italian. Only one randomized double-blind trial was found, comparing cyproterone with haloperidol (n = 27). Cyproterone was more effective controlling aggressivity and had lower incidence of side effects. In the one uncontrolled naturalistic observational study identified (n = 19), cyproterone was associated with significant reductions in aggressivity without causing major side effects. Further literature was limited to theoretical discussions. Despite there being evidence to support our observations of a useful role for cyproterone in aggressivity in dementia, further studies are needed to establish the efficacy and safety of this therapeutic option.

Topics: Aged, 80 and over; Aggression; Androgen Antagonists; Antipsychotic Agents; Clinical Trials as Topic; Cyproterone; Dementia; Humans; Male; Psychomotor Agitation

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.. 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.. 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.. 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.

Topics: Aged; Aggression; Alzheimer Disease; Androgen Antagonists; Antipsychotic Agents; Cyproterone; Dementia; Dementia, Vascular; Drug Administration Schedule; Female; Humans; Huntington Disease; Impulsive Behavior; Male; Pilot Projects; Psychomotor Agitation; Severity of Illness Index