Tyrer Peter, Oliver-Africano Patricia C, Ahmed Zed, Bouras Nick, Cooray Sherva, Deb Shoumitro, Murphy Declan, Hare Monica, Meade Michael, Reece Ben, Kramo Kofi, Bhaumik Sabyasachi, Harley David, Regan Adrienne, Thomas David, Rao Bharti, North Bernard, Eliahoo Joseph, Karatela Shamshad, Soni Anju, Crawford Mike
Department of Psychological Medicine, Imperial College, London, UK.
Lancet. 2008 Jan 5;371(9606):57-63. doi: 10.1016/S0140-6736(08)60072-0.
Aggressive challenging behaviour is frequently reported in adults with intellectual disability and it is often treated with antipsychotic drugs. However, no adequate evidence base for this practice exists. We compared flexible doses of haloperidol (a typical, first-generation antipsychotic drug), risperidone (an atypical, second-generation antipsychotic), and placebo, in the treatment of this behaviour.
86 non-psychotic patients presenting with aggressive challenging behaviour from ten centres in England and Wales, and one in Queensland, Australia, were randomly assigned to haloperidol (n=28), risperidone (n=29), or placebo (n=29). Clinical assessments of aggression, aberrant behaviour, quality of life, adverse drug effects, and carer uplift (positive feelings about the care of the disabled person) and burden, together with total costs, were recorded at 4, 12, and 26 weeks. The primary outcome was change in aggression after 4 weeks' treatment, which was recorded with the modified overt aggression scale (MOAS). Analysis was by intention to treat. This study is registered as ISRCTN 11736448.
80 patients had adherence of 80% or more to prescribed drug. Aggression decreased substantially with all three treatments by 4 weeks, with the placebo group showing the greatest change (median decrease in MOAS score after 4 weeks=9 [95% CI 5-14] for placebo, 79% from baseline; 7 [4-14] for risperidone, 58% from baseline; 6.5 [5-14] for haloperidol, 65% from baseline; p=0.06). Furthermore, although no important differences between the treatments were recorded, including adverse effects, patients given placebo showed no evidence at any time points of worse response than did patients assigned to either of the antipsychotic drugs.
Antipsychotic drugs should no longer be regarded as an acceptable routine treatment for aggressive challenging behaviour in people with intellectual disability.
有智力障碍的成年人中经常出现攻击性行为，且常用抗精神病药物进行治疗。然而，这种治疗方法缺乏充分的证据支持。我们比较了灵活剂量的氟哌啶醇（一种典型的第一代抗精神病药物）、利培酮（一种非典型的第二代抗精神病药物）和安慰剂对这种行为的治疗效果。
来自英格兰和威尔士十个中心以及澳大利亚昆士兰州一个中心的86名有攻击性行为的非精神病患者被随机分配到氟哌啶醇组（n = 28）、利培酮组（n = 29）或安慰剂组（n = 29）。在第4周、12周和26周记录攻击行为、异常行为、生活质量、药物不良反应、照顾者的积极感受（对照顾残疾人的积极情绪）和负担以及总成本的临床评估。主要结局是治疗4周后攻击行为的变化，用改良的明显攻击量表（MOAS）记录。分析采用意向性分析。本研究已在国际标准随机对照试验编号系统（ISRCTN）注册，注册号为11736448。
80名患者对规定药物的依从性达到80%或更高。所有三种治疗方法在4周时攻击行为均大幅减少，安慰剂组变化最大（4周后MOAS评分中位数下降：安慰剂组为9[95%置信区间5 - 14]，较基线下降79%；利培酮组为7[4 - 14]，较基线下降58%；氟哌啶醇组为6.5[5 - 14]，较基线下降65%；p = 0.06）。此外，尽管各治疗组之间未记录到重要差异，包括不良反应，但服用安慰剂的患者在任何时间点均未显示出比服用抗精神病药物的患者反应更差的证据。
抗精神病药物不应再被视为治疗智力障碍者攻击性行为的可接受常规治疗方法。
