In people with intellectual disability (ID) and challenging behaviour, antipsychotics (AP) are often used off-label and for a long period. Despite a lack of evidence for efficacy for challenging behaviour and concerns about common and clinically relevant side effects, complete withdrawal often fails. We postulate three possible hypotheses for withdrawal failure: 1. Influence of subjective interpretation of behavioural symptoms by caregivers and family; 2. Beneficial effects from AP treatment on undiagnosed psychiatric illness, through improvement in sleep or a direct effect on behaviour; and 3. Misinterpretation of withdrawal symptoms as a recurrence of challenging behaviour. To investigate our hypotheses, we have designed a multicentre double-blind, placebo-controlled randomised trial in which AP (pipamperone or risperidone) are withdrawn. In the withdrawal group, the AP dose is reduced by 25% every 4 weeks and in the control group the dose remains unaltered. Behaviour, sleep, psychiatric disorders, withdrawal symptoms and side effects will be measured and compared between the two groups. If drop-out from the protocol is similar in both groups (non-inferiority), the first hypothesis will be supported. If drop-out is higher in the withdrawal group and an increase is seen in psychiatric disorders, sleep problems and/or behavioural problems compared to the control group, this suggests effectiveness of AP, and indications for AP use should be reconsidered. If drop-out is higher in the withdrawal group and withdrawal symptoms and side effects are more common in the withdrawal group compared to the control group, this supports the hypothesis that withdrawal symptoms contribute to withdrawal failure. In order to develop AP withdrawal guidelines for people with ID, we need to understand why withdrawal of AP is not successful in the majority of people with ID and challenging behaviour. With this study, we will bridge the gap between the lack of available evidence on AP use and withdrawal on the one hand and the international policy drive to reduce prescription of AP in people with ID and challenging behaviour on the other hand. This trial is registered in the Netherlands Trial Register (NTR 7232) on October 6, 2018 ( www.trialregister.nl ).

中文翻译：

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智力障碍和具有挑战性行为的成人戒断抗精神病药：多中心双盲安慰剂对照随机试验的研究方案

对于有智力障碍 (ID) 和具有挑战性行为的人，抗精神病药 (AP) 经常在标签外长期使用。尽管缺乏挑战行为的有效性证据以及对常见和临床相关副作用的担忧，但完全戒断往往失败。我们假设戒断失败的三种可能假设： 1. 照顾者和家人对行为症状的主观解释的影响；2. AP 治疗对未确诊的精神疾病的有益影响，通过改善睡眠或直接影响行为；3. 将戒断症状误解为挑战性行为的复发。为了研究我们的假设，我们设计了一项多中心双盲、安慰剂对照随机试验，其中停用 AP（哌帕酮或利培酮）。在戒断组中，AP 剂量每 4 周减少 25%，而在对照组中，剂量保持不变。将测量并比较两组之间的行为、睡眠、精神障碍、戒断症状和副作用。如果退出协议在两组中相似（非劣效性），则第一个假设将得到支持。如果与对照组相比，戒断组的辍学率更高，并且精神障碍、睡眠问题和/或行为问题有所增加，这表明 AP 的有效性，应重新考虑 AP 使用的指征。如果戒断组的退出率更高，并且与对照组相比，戒断组的戒断症状和副作用更常见，这支持了戒断症状导致戒断失败的假设。为了为有 ID 的人制定 AP 戒断指南，我们需要了解为什么大多数有 ID 和具有挑战性行为的人不能成功戒除 AP。通过这项研究，我们将弥补一方面缺乏关于 AP 使用和戒断的可用证据，另一方面是国际政策驱动以减少对智障人士和具有挑战性行为的人的 AP 处方之间的差距。该试验于 2018 年 10 月 6 日在荷兰试验注册 (NTR 7232) ( www.trialregister.nl ) 中注册。我们将弥补一方面缺乏关于 AP 使用和戒断的可用证据与另一方面国际政策驱动以减少对智障人士和具有挑战性行为的人的 AP 处方之间的差距。该试验于 2018 年 10 月 6 日在荷兰试验注册 (NTR 7232) ( www.trialregister.nl ) 中注册。我们将弥补一方面缺乏关于 AP 使用和戒断的可用证据与另一方面国际政策驱动以减少对智障人士和具有挑战性行为的人的 AP 处方之间的差距。该试验于 2018 年 10 月 6 日在荷兰试验注册 (NTR 7232) ( www.trialregister.nl ) 中注册。