Nutt John G, Carter Julie H, Carlson Nichole E
Department of Neurology, and Public Health and Preventative Medicine, Division of Biostatistics, Oregon Health and Science University, Portland, OR 97239, USA.
Arch Neurol. 2007 Mar;64(3):319-23. doi: 10.1001/archneur.64.3.319.
To determine if repeated dosing with methylphenidate hydrochloride (MPD) (Ritalin; Novartis Pharmaceuticals, East Hanover, NJ), an inhibitor of the dopamine transporter, would augment the effects of oral levodopa in patients with Parkinson disease.
The study was a double-blind, randomized, placebo-controlled crossover trial.
The trial was conducted at the General Clinical Research Center (GCRC) as an inpatient study. Subjects Thirteen people with idiopathic Parkinson disease and a fluctuating motor response to levodopa were recruited from movement disorder clinics as a convenience sample. One subject was excluded because he did not have a 10% increase in tapping speed in response to levodopa. The remaining 12 subjects completed the protocol.
A 0.4-mg/kg dose of MPD was administered orally at 8 am, noon, and 4 pm in conjunction with the subjects' normal oral antiparkinsonian medications. Oral levodopa dosage was decreased as clinically feasible during the first 4 days in the GCRC during open-label administration of MPD and hourly monitoring of parkinsonism and vital signs between 7 am and 8 pm. Subjects were discharged taking their usual antiparkinsonian medications without MPD. They returned 1 and 2 weeks later to the GCRC for 1 day of hourly monitoring of their response to the medication regimen derived during the 4 days in the GCRC, once with MPD and once with identical-appearing placebo, in a randomized sequence and double-blind conditions.
The main outcome measure was the duration of "on" time between 9 am and 8 pm measured by an increase in tapping speed by 10% over the average of the 7 am to 8 am predosing tapping speed measurements. Secondary measures were estimates of "on" time obtained with the timed walking task, tremor scores, and dyskinesia scores. In addition, averages of hourly tapping speeds, walking speed, tremor scores, dyskinesia scores, vital signs, and analog scale scores for mood, anxiety, and fatigue between 9 am and 8 pm were examined. Adverse events on the double-blinded days were compared.
Methylphenidate tended to increase the time "on" as measured by tapping (P = .09) but not by walking time or dyskinesia scores (P = .40 and .42, respectively). Methylphenidate tended to increase average tapping speed, decrease time to perform walking task, decrease tremor, and increase dyskinesia score but only the decrease in tremor reached significance. Neither the investigators nor the subjects could reliably identify active drug. Methylphenidate was well tolerated.
The effects of 0.4 mg/kg of MPD 3 times per day on the motor response to levodopa were small and variable and judged to be clinically insignificant. Trial Registration clinicaltrials.gov Identifier: NCT00359723.
确定多巴胺转运体抑制剂盐酸哌甲酯（MPD，商品名利他林；诺华制药公司，新泽西州东哈嫩）重复给药是否会增强帕金森病患者口服左旋多巴的疗效。
该研究为双盲、随机、安慰剂对照交叉试验。
试验在综合临床研究中心（GCRC）作为住院研究进行。
从运动障碍门诊方便抽样招募了13例特发性帕金森病患者，其对左旋多巴的运动反应波动。1例受试者因对左旋多巴反应时敲击速度未增加10%而被排除。其余12例受试者完成了研究方案。
上午8点、中午和下午4点口服0.4mg/kg剂量的MPD，同时服用受试者常规的口服抗帕金森病药物。在GCRC开放标签给予MPD的前4天，根据临床情况可行时减少口服左旋多巴剂量，并在上午7点至晚上8点每小时监测帕金森症状和生命体征。受试者出院时服用其常规抗帕金森病药物，但不服用MPD。他们在1周和2周后返回GCRC，进行1天的每小时监测，观察其对在GCRC的4天期间所采用药物治疗方案的反应，一次服用MPD，一次服用外观相同的安慰剂，顺序随机且处于双盲状态。
主要观察指标是上午9点至晚上8点“开”期的持续时间，通过敲击速度比上午7点至8点给药前敲击速度平均值增加10%来测量。次要指标是通过定时步行任务、震颤评分和异动症评分获得的“开”期估计值。此外，还检查了上午9点至晚上8点每小时的敲击速度、步行速度、震颤评分、异动症评分、生命体征以及情绪、焦虑和疲劳的视觉模拟量表评分的平均值。比较双盲日的不良事件。
以敲击测量，哌甲酯倾向于增加“开”期时间（P = 0.09），但以步行时间或异动症评分测量则不然（分别为P = 0.40和0.42）。哌甲酯倾向于增加平均敲击速度、减少完成步行任务的时间、减少震颤并增加异动症评分，但只有震颤的减少具有统计学意义。研究者和受试者均无法可靠地识别活性药物。哌甲酯耐受性良好。
每天3次服用0.4mg/kg的MPD对左旋多巴运动反应的影响较小且不稳定，临床意义不大。试验注册 clinicaltrials.gov标识符：NCT00359723。
