Department of Clinical Psychopharmacology and Neurotoxicology, National Institute of Mental Health and Neurosciences, Bangalore, India (
J Clin Psychiatry. 2023 Jul 31;84(4):23f15009. doi: 10.4088/JCP.23f15009.
Delusions and hallucinations are common in Alzheimer disease (AD) and Parkinson disease (PD), especially in the later stages of illness. Antipsychotic drugs are effective in treating these psychotic symptoms but are associated with an increased risk of serious adverse events, including mortality. There is therefore a need to explore other treatment approaches. In this context, a recent individual patient data meta-analysis of 17 randomized controlled trials (RCTs) conducted in AD (12 RCTs) and PD (5 RCTs) found that the cholinesterase inhibitor (ChEI) drugs donepezil, rivastigmine, and galantamine attenuated the severity of both delusions and hallucinations in both AD and PD. Most of these trials were 24 weeks in duration. The effect sizes, expressed as standardized mean differences (SMDs), were, however, small, lying in the -0.08 to -0.14 range. These values are so small as to be perhaps clinically insignificant. When analyses were restricted to data from patients who actually had delusions and hallucinations at baseline, all effect sizes became larger, lying in the -0.13 to -0.39 range; however, after correcting for multiple hypothesis testing, only the finding for delusions in PD remained statistically significant. The meta-analysis did not provide information on what the best doses were, how long it took for improvement to become evident, and what proportion of patients showed remission from psychotic symptoms. Whereas the signal identified in this meta-analysis merits examination in appropriately designed RCTs, the findings of the meta-analysis may not much change current treatment strategies because patients with dementia would probably anyway receive a ChEI. Therefore, if psychotic symptoms persist for 24 weeks despite optimally dosed ChEI treatment, and if behavioral and psychosocial interventions do not help, clinicians may need to consider the potential benefits vs risks of other drugs, such as atypical antipsychotics and pimavanserin, in a shared decision-making process.
妄想和幻觉在阿尔茨海默病（AD）和帕金森病（PD）中很常见，尤其是在疾病的后期。抗精神病药物在治疗这些精神病症状方面非常有效，但与严重不良事件风险增加相关，包括死亡。因此，需要探索其他治疗方法。在这种情况下，最近对 17 项在 AD（12 项 RCT）和 PD（5 项 RCT）中进行的随机对照试验（RCT）的个体患者数据进行的荟萃分析发现，胆碱酯酶抑制剂（ChEI）药物多奈哌齐、利伐斯的明和加兰他敏可减轻 AD 和 PD 中妄想和幻觉的严重程度。这些试验大多持续 24 周。然而，表达为标准化均数差（SMD）的效应大小很小，范围在-0.08 至-0.14 之间。这些值很小，可能在临床上无意义。当分析仅限于基线时有妄想和幻觉的患者的数据时，所有的效应大小都变得更大，范围在-0.13 至-0.39 之间；然而，在进行多次假设检验校正后，只有 PD 中的妄想发现具有统计学意义。荟萃分析没有提供最佳剂量是多少、改善需要多长时间才能显现以及有多少患者从精神病症状中缓解的信息。尽管荟萃分析中确定的信号值得在适当设计的 RCT 中进行检查，但荟萃分析的结果可能不会对当前的治疗策略产生太大影响，因为痴呆症患者可能无论如何都会接受 ChEI 治疗。因此，如果尽管使用最佳剂量的 ChEI 治疗但精神病症状仍持续 24 周，并且行为和心理社会干预没有帮助，临床医生可能需要在共同决策过程中考虑其他药物（如非典型抗精神病药和 pimavanserin）的潜在益处与风险。
