Katzenschlager R, Manson A J, Evans A, Watt H, Lees A J
Reta Lila Weston Institute of Neurological Studies, University College London, National Hospital for Neurology and Neurosurgery, UK.
J Neurol Neurosurg Psychiatry. 2004 Feb;75(2):295-7.
Drug induced dyskinesias remain a challenging problem in the long term management of Parkinson's disease (PD). We have assessed the effect of quetiapine on dyskinesias in a double blind placebo controlled cross over study.
Nine patients with PD were enrolled and received 25 mg of quetiapine or placebo at night for two weeks in prerandomised order, with one week of wash out between treatment periods. Assessments were made using on-off diaries, self assessment of dyskinesias, and L-dopa challenges at baseline and after each treatment period. Videotapes were rated blindly by two raters using modified Abnormal Involuntary Movement Scale and Goetz scores. Patients subsequently went on open label quetiapine at 50 mg/day, for a mean duration of 30 days, and completed the same self assessment forms.
During the double blind phase, no significant change in dyskinesias was found on either 25 mg of quetiapine or placebo. Duration of off states and Unified PD Rating Scale motor scores also remained unchanged. Moderate tiredness and daytime sleepiness occurred in two patients on quetiapine. One patient dropped out early for unrelated reasons. Eight patients completed the open label phase. On 50 mg/day of quetiapine, a slight reduction in dyskinesias occurred on some scales. Reduction in dyskinesia severity on visual analogue scales was by 50.1%. Off time was not significantly increased. This improvement was not strongly reflected in patients' overall impression of treatment effect. Drowsiness and daytime sleep episodes led to discontinuation in four patients, after completion of the study, and two additional patients stopped treatment after the study because of lack of effect.
Our study failed to demonstrate an antidyskinetic effect of low dose (25 mg) quetiapine. The absence of an increase in parkinsonism combined with a possible antidyskinetic effect on higher doses warrants further investigation.
在帕金森病(PD)的长期管理中,药物诱发的运动障碍仍然是一个具有挑战性的问题。我们在一项双盲安慰剂对照交叉研究中评估了喹硫平对运动障碍的影响。
招募了9名PD患者,按预先随机分组的顺序,在夜间服用25mg喹硫平或安慰剂,为期两周,治疗期间之间有一周的洗脱期。在基线期和每个治疗期后,使用“开-关”日记、运动障碍自我评估以及左旋多巴激发试验进行评估。由两名评估者使用改良的异常不自主运动量表和戈茨评分对录像带进行盲法评分。患者随后接受50mg/天的开放标签喹硫平治疗,平均持续30天,并填写相同的自我评估表格。
在双盲阶段,服用25mg喹硫平或安慰剂后,运动障碍均未发现明显变化。“关”期时长和统一帕金森病评定量表运动评分也保持不变。两名服用喹硫平的患者出现了中度疲劳和日间嗜睡。一名患者因无关原因提前退出。8名患者完成了开放标签阶段。服用50mg/天喹硫平后,某些量表上的运动障碍略有减轻。视觉模拟量表上运动障碍严重程度的降低为50.1%。“关”期时间没有显著增加。这种改善在患者对治疗效果的总体印象中没有得到强烈体现。嗜睡和日间睡眠发作导致4名患者在研究结束后停药,另有2名患者在研究结束后因无效而停止治疗。
我们的研究未能证明低剂量(25mg)喹硫平具有抗运动障碍作用。高剂量时帕金森症状没有加重,同时可能具有抗运动障碍作用,这值得进一步研究。