Department of Psychiatry, Vanderbilt University School of Medicine, Psychiatric Hospital at Vanderbilt, Nashville,TN 37212, USA.
Neuropsychopharmacology. 2010 Mar;35(4):881-92. doi: 10.1038/npp.2009.176. Epub 2009 Nov 11.
Psychotic symptoms occur in up to 40% of patients with Parkinson's disease (PD). Clozapine and quetiapine, two atypical antipsychotic drugs, at doses markedly lower than those effective in schizophrenia, which, nevertheless, still cause sedation, hypotension, and other side effects, are widely used to treat psychotic symptoms in patients with PD psychosis (PDP), although quetiapine has never been shown to be effective in a placebo-controlled study. The demonstrated efficacy of clozapine in PDP has been attributed to serotonin (5-HT(2A)) receptor blockade. We postulated that pimavanserin (ACP-103), a highly selective 5-HT(2A) inverse agonist, would attenuate psychosis in patients with PDP, but avoid motoric worsening and non-motoric side effects. In this double-blind, randomized multicenter 28-day study, the tolerability and efficacy of pimavanserin was compared with placebo in 60 patients with L-DOPA or dopamine (DA) agonist-induced PDP. Motor function was evaluated using the Unified Parkinson's Disease Rating Scale (UPDRS) Parts II and III. Antipsychotic efficacy was evaluated using multiple measures from the Scale for the Assessment of Positive Symptoms (SAPS) and a UPDRS Part I psychosis-relevant item. Pimavanserin did not differentiate from placebo with regard to motor impairment, sedation, hypotension, or other side effects. The principal measures of efficacy of antipsychotic response to pimavanserin, the SAPS total domain score, only showed a trend. However, the pimavanserin-treated patients showed significantly greater improvement in some but not all measures of psychosis, including SAPS global measures of hallucinations and delusions, persecutory delusions, and the UPDRS measure of delusions and hallucinations. Pimavanserin showed significantly greater improvement in psychosis in patients with PDP at a dose which did not impair motor function, or cause sedation or hypotension Thus, pimavanserin may represent a novel treatment for PDP. Furthermore, these results support the hypothesis that attenuation of psychosis secondary to DA receptor stimulation in PDP may be achieved through selective 5-HT(2A) receptor antagonism.
多达 40%的帕金森病（PD）患者会出现精神病症状。氯氮平与喹硫平是两种非典型抗精神病药物，其剂量远低于治疗精神分裂症的有效剂量，但仍会引起镇静、低血压和其他副作用，因此被广泛用于治疗 PD 精神病（PDP）患者的精神病症状，尽管喹硫平从未在安慰剂对照研究中显示出疗效。氯氮平在 PDP 中的疗效被归因于 5-羟色胺（5-HT（2A））受体阻断。我们假设匹莫范色林（ACP-103），一种高度选择性的 5-HT（2A）反向激动剂，将减轻 PDP 患者的精神病，但避免运动恶化和非运动副作用。在这项为期 28 天的双盲、随机、多中心研究中，匹莫范色林的耐受性和疗效与安慰剂在 60 名接受 L-DOPA 或多巴胺（DA）激动剂诱导的 PDP 患者中进行了比较。运动功能使用统一帕金森病评定量表（UPDRS）第二部分和第三部分进行评估。抗精神病疗效使用阳性症状评定量表（SAPS）和 UPDRS 第一部分与精神病相关的项目的多个指标进行评估。匹莫范色林在运动障碍、镇静、低血压或其他副作用方面与安慰剂无差异。匹莫范色林对精神病反应的主要疗效指标，即 SAPS 总分，仅显示出一种趋势。然而，匹莫范色林治疗的患者在某些但不是所有精神病测量指标上显示出显著的改善，包括 SAPS 幻觉和妄想的总体测量、迫害妄想和 UPDRS 妄想和幻觉的测量。匹莫范色林在不损害运动功能、引起镇静或低血压的情况下，对 PDP 患者的精神病显示出显著的改善。因此，匹莫范色林可能为 PDP 提供一种新的治疗方法。此外，这些结果支持了这样一种假设，即通过选择性 5-HT（2A）受体拮抗作用，可以减轻 PDP 中 DA 受体刺激引起的精神病。
