Neurology Department, Centre Hospitalier Universitaire de Toulouse, Hôpital Purpan, Toulouse, France.
Lancet Neurol. 2011 Feb;10(2):123-30. doi: 10.1016/S1474-4422(10)70314-8. Epub 2011 Jan 7.
Hemiplegia and hemiparesis are the most common deficits caused by stroke. A few small clinical trials suggest that fluoxetine enhances motor recovery but its clinical efficacy is unknown. We therefore aimed to investigate whether fluoxetine would enhance motor recovery if given soon after an ischaemic stroke to patients who have motor deficits.
In this double-blind, placebo-controlled trial, patients from nine stroke centres in France who had ischaemic stroke and hemiplegia or hemiparesis, had Fugl-Meyer motor scale (FMMS) scores of 55 or less, and were aged between 18 years and 85 years were eligible for inclusion. Patients were randomly assigned, using a computer random-number generator, in a 1:1 ratio to fluoxetine (20 mg once per day, orally) or placebo for 3 months starting 5-10 days after the onset of stroke. All patients had physiotherapy. The primary outcome measure was the change on the FMMS between day 0 and day 90 after the start of the study drug. Participants, carers, and physicians assessing the outcome were masked to group assignment. Analysis was of all patients for whom data were available (full analysis set). This trial is registered with ClinicalTrials.gov, number NCT00657163.
118 patients were randomly assigned to fluoxetine (n=59) or placebo (n=59), and 113 were included in the analysis (57 in the fluoxetine group and 56 in the placebo group). Two patients died before day 90 and three withdrew from the study. FMMS improvement at day 90 was significantly greater in the fluoxetine group (adjusted mean 34·0 points [95% CI 29·7-38·4]) than in the placebo group (24·3 points [19·9-28·7]; p=0·003). The main adverse events in the fluoxetine and placebo groups were hyponatraemia (two [4%] vs two [4%]), transient digestive disorders including nausea, diarrhoea, and abdominal pain (14 [25%] vs six [11%]), hepatic enzyme disorders (five [9%] vs ten [18%]), psychiatric disorders (three [5%] vs four [7%]), insomnia (19 [33%] vs 20 [36%]), and partial seizure (one [<1%] vs 0).
In patients with ischaemic stroke and moderate to severe motor deficit, the early prescription of fluoxetine with physiotherapy enhanced motor recovery after 3 months. Modulation of spontaneous brain plasticity by drugs is a promising pathway for treatment of patients with ischaemic stroke and moderate to severe motor deficit.
Public French National Programme for Clinical Research.
偏瘫和轻偏瘫是中风最常见的后遗症。一些小型临床试验表明，氟西汀可增强运动功能恢复，但临床疗效尚不清楚。因此，我们旨在研究如果在中风后不久给患有运动障碍的患者服用氟西汀，是否会增强运动功能恢复。
在这项双盲、安慰剂对照试验中，来自法国 9 个中风中心的年龄在 18 至 85 岁之间、患有缺血性中风和偏瘫或轻偏瘫、Fugl-Meyer 运动量表（FMMS）评分在 55 分或以下的患者符合纳入条件。使用计算机生成的随机数对患者进行随机分组，以 1:1 的比例随机分配至氟西汀（20mg/天，口服）或安慰剂组，治疗 3 个月，起始时间为中风发作后 5-10 天。所有患者均接受物理治疗。主要结局指标是从研究药物开始后的第 0 天至第 90 天，FMMS 的变化。参与者、护理人员和评估结局的医生对分组情况均设盲。分析了所有可获得数据的患者（全分析集）。该试验在 ClinicalTrials.gov 注册，编号为 NCT00657163。
118 名患者被随机分配至氟西汀（n=59）或安慰剂（n=59）组，113 名患者纳入分析（氟西汀组 57 名，安慰剂组 56 名）。两名患者在第 90 天前死亡，三名患者退出研究。氟西汀组在第 90 天的 FMMS 改善程度明显大于安慰剂组（调整后的平均差值 34.0 分[95%CI 29.7-38.4] vs 24.3 分[19.9-28.7]；p=0.003）。氟西汀组和安慰剂组的主要不良事件为低钠血症（2 [4%] vs 2 [4%]）、短暂性消化系统紊乱，包括恶心、腹泻和腹痛（14 [25%] vs 6 [11%]）、肝酶紊乱（5 [9%] vs 10 [18%]）、精神障碍（3 [5%] vs 4 [7%]）、失眠（19 [33%] vs 20 [36%]）和部分性癫痫发作（1 [＜1%] vs 0）。
在缺血性中风和中重度运动障碍患者中，早期联合氟西汀和物理治疗可增强中风后 3 个月的运动功能恢复。药物对自发性脑可塑性的调节是治疗缺血性中风和中重度运动障碍患者的一种有前途的方法。
法国国家临床研究计划的公共资金。
