Caparros-Lefebvre D, Dewailly D
Val d'Escaut, Centre Hospitalier, Valenciennes.
Rev Neurol (Paris). 2005 Nov;161(11):1071-8. doi: 10.1016/s0035-3787(05)85174-4.
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.
行为症状在痴呆症中很常见，而且在男性中似乎比女性更频繁。激越常常导致照料者精疲力竭，并导致患者被送进养老院。阿尔茨海默病及相关疾病患病率的急剧上升需要更好地管理行为症状。尽管最近有人提出环境适应的方法，但多年来，精神活性药物和身体约束一直是主要的治疗方法。然而，在重度痴呆患者中，药物和非药物治疗均无效。在这种情况下，应该测试替代的药物治疗方法。醋酸环丙孕酮是一种抗雄激素和孕激素类甾体，从未被用于预防痴呆症中的攻击行为，但其在大鼠和猴子攻击行为方面的良好效果已有充分描述。
19例出现严重攻击行为或对精神活性药物（即使联合使用）或环境适应无反应的激越的痴呆患者接受了醋酸环丙孕酮治疗。在醋酸环丙孕酮治疗前和治疗期间，使用科恩-曼斯菲尔德激越量表并结合日常生活活动能力依赖性评估进行临床和行为分析。行为状态稳定，存在持续性或重复性激越。7例患者患有血管性痴呆，7例患有阿尔茨海默病，2例患有额颞叶变性，2例患有亨廷顿病，1例可能患有弥漫性路易体病。15例患者有明显的攻击行为，4例有以攻击行为为主的异常运动行为。
醋酸环丙孕酮（50至100毫克 - 平均每日92.5毫克）显著改善了与阿尔茨海默病或血管性痴呆相关的攻击和冲动行为，但对异常运动行为无效。当停用醋酸环丙孕酮时，血管性痴呆患者的攻击行为复发更快。
当精神药物不能改善攻击行为时，醋酸环丙孕酮是一个有意思的选择。需要进行详细的临床分析，以避免在无攻击和无冲动的患者中使用醋酸环丙孕酮。这项初步研究的结果表明，应在不久的将来开展随机双盲研究。行为改善可能与雄激素受体的阻断有关，同时也与孕激素类药物的镇静作用有关。
