Centre for Trials Research, Cardiff University, Cardiff, UK.
Division of Population Medicine, Cardiff University, Cardiff, UK.
Health Technol Assess. 2017 Aug;21(47):1-92. doi: 10.3310/hta21470.
Data suggest that approximately 50,000 adults with learning disabilities (LDs) in England and Wales are currently prescribed antipsychotic medication. Illness in this population is common, including significant rates of challenging behaviour and mental illness, but there is particular concern over the use of antipsychotics prescribed for reasons other than the treatment of psychosis. Control of challenging behaviour is the primary reason why such medications are prescribed despite the absence of good evidence for any therapeutic effect for this purpose.
To assess the feasibility of recruitment and retention and to explore non-efficacy-based barriers to a blinded antipsychotic medication withdrawal programme for adults with LDs without psychosis compared with treatment as usual. A secondary objective was to compare trial arms regarding clinical outcomes.
A two-arm individually randomised double-blind placebo-controlled drug reduction trial.
Recruitment was through community learning disability teams (CLDTs) in south Wales and south-west England.
Adults with LDs who are prescribed risperidone for treatment of challenging behaviour with no known current psychosis or previous recurrence of psychosis following prior drug reduction.
A double-blind drug reduction programme leading to full withdrawal within 6 months. Treatment in the intervention group was gradually reduced over a 6-month period and then maintained at the same level for a further 3 months, still under blind conditions. In the control group, the baseline level of medication was maintained throughout the 9-month period. The blind was broken at 9 months, following final data collection.
Feasibility outcomes were (1) the number and proportion of general practices/CLDTs that progressed from initial approach to recruitment of participants and (2) the number and proportion of recruited participants who progressed through the various stages of the study. Trial arms were also compared regarding clinical outcomes, the Modified Overt Aggression Scale, the Aberrant Behaviour Checklist, the Psychiatric Assessment Schedule for Adults with Developmental Disability checklist, the Antipsychotic Side-effect Checklist, the Dyskinesia Identification System Condensed User Scale, the Client Service Receipt Inventory, use of other interventions to manage challenging behaviour, use of as-required (pro re nata) medication and level of psychotropic medication use.
Of the 22 participants randomised (intervention, = 11; control, = 11), 13 (59%) achieved progression through all four stages of reduction. Follow-up data at 6 and 9 months were obtained for 17 participants (intervention, = 10; and control, = 7; 77% of those randomised). There were no clinically important changes in participants' levels of aggression or challenging behaviour at the end of the study. There were no expedited safety reports. Four adverse events and one serious adverse event were reported during the trial.
Recruitment was challenging, which was largely a result of difficulty in identifying appropriate persons to consent and carer concerns regarding re-emergence of challenging behaviour. Reduced recruitment meant that the full trial became an exploratory pilot study.
The results indicate that drug reduction is possible and safe. However, concerns about taking part were probably exacerbated by limited availability of alternative (behavioural) interventions to manage behaviour; therefore, focused support and alternative interventions are required. The results of the qualitative study provide important insights into the experiences of people taking part in drug reduction studies that should influence future trial development.
We recommend that further work focuses on support for practitioners, carers and patients in reducing antipsychotic medication.
Current Controlled Trials ISRCTN38126962.
This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in ; Vol. 21, No. 47. See the NIHR Journals Library website for further project information.
数据显示，目前英格兰和威尔士约有 5 万名患有学习障碍 (LDs) 的成年人正在服用抗精神病药物。该人群中疾病很常见，包括严重的挑战性行为和精神疾病，但特别令人关注的是，出于治疗精神病以外的原因而开处抗精神病药物。尽管没有任何证据表明这种药物对控制挑战性行为有任何治疗效果，但仍将其作为控制这种行为的主要手段。
评估招募和保留的可行性，并探讨对于没有精神病的 LDs 成年人，与常规治疗相比，盲法抗精神病药物停药方案的非疗效相关障碍。次要目的是比较试验组的临床结果。
一项两臂、个体随机、双盲、安慰剂对照的药物减量试验。
通过南威尔士和英格兰西南部的社区学习障碍团队 (CLDT) 进行招募。
正在服用利培酮治疗挑战性行为的 LDs 成年人，且无已知当前精神病或既往药物减量后精神病复发。
一项双盲药物减量方案，在 6 个月内实现完全停药。干预组的治疗逐渐减少 6 个月，然后在盲态下维持相同水平再持续 3 个月。在对照组中，药物的基线水平在整个 9 个月期间保持不变。在最后一次数据收集后 9 个月时打破盲法。
可行性结局包括：(1) 从初步接触到招募参与者的各个普通实践/CLDT 的数量和比例；(2) 通过研究各个阶段的参与者数量和比例。还比较了试验组的临床结果，使用改良外显攻击量表、异常行为检查表、成人发育障碍精神病学评估量表检查表、抗精神病药物副作用检查表、运动障碍识别系统简化用户量表、客户服务收据清单、用于管理挑战性行为的其他干预措施、按需（pro re nata）药物的使用以及精神药物使用水平。
在随机分配的 22 名参与者中（干预组，n=11；对照组，n=11），有 13 名（59%）成功完成了所有四个阶段的减量。在 6 个月和 9 个月时，对 17 名参与者（干预组，n=10；对照组，n=7；随机分配的参与者的 77%）进行了随访数据收集。在研究结束时，参与者的攻击水平或挑战性行为没有出现任何临床意义上的变化。没有紧急安全报告。在试验期间报告了四起不良事件和一起严重不良事件。
招募工作具有挑战性，这主要是由于难以确定适当的同意人以及照顾者对挑战性行为再次出现的担忧所致。由于招募人数减少，完整的试验成为了一项探索性试点研究。
结果表明药物减量是可行且安全的。然而，参与的担忧可能因缺乏管理行为的替代（行为）干预措施而加剧；因此，需要提供有针对性的支持和替代干预措施。定性研究的结果提供了关于参与药物减量研究的人的重要经验见解，这些见解应影响未来的试验发展。
我们建议进一步关注为从业者、照顾者和患者提供支持，以减少抗精神病药物的使用。
当前对照试验 ISRCTN38126962。
该项目由英国国家卫生研究院 (NIHR) 健康技术评估计划资助，将在 ; Vol. 21, No. 47 中全文发表。请访问 NIHR 期刊库网站以获取该项目的更多信息。
