Mostert Jop, Heersema Thea, Mahajan Manju, Van Der Grond Jeroen, Van Buchem Mark A, De Keyser Jacques
Department of Neurology, University Medical Center Groningen, University of Groningen, Postbus 30.001, 9700 RB Groningen, The Netherlands ; Department of Neurology, Rijnstate Hospital, Postbus 9555, 6800 TA Arnhem, The Netherlands.
ISRN Neurol. 2013 Jul 29;2013:370943. doi: 10.1155/2013/370943. eCollection 2013.
Preclinical studies suggest that fluoxetine may have neuroprotective properties. In this pilot study forty-two patients with secondary or primary progressive MS were randomized to receive fluoxetine 20 mg twice daily or placebo for 2 years. Every 3 months the Expanded Disability Status Scale (EDSS), 9-hole peg test (9-HPT) and ambulation index (AI) were assessed. Brain MRI scans, Multiple Sclerosis Functional Composite, Fatigue Impact Scale, Guy's neurological disability Scale and SF-36 were performed at baseline, year 1 and year 2. Seven out of 20 (35%) patients in the fluoxetine group and 7 out of 22 (32%) patients in the placebo group had sustained progression on the EDSS, 9-HPT, or AI at 2 years. No differences were identified between the 2 treatment groups with respect to secondary clinical outcomes and T2 lesion load, grey matter volume and white matter volume. An unanticipated low rate of disability progression in the placebo group decreased the statistical power. At least 200 patients would have been needed to detect a 50% treatment effect. This trial shows that fluoxetine was generally well tolerated, but no assumptions can be made about a possible treatment effect. An adequately powered controlled trial of fluoxetine in progressive MS is still warranted. This trial is registered with Current Controlled Trials ISRCTN38456328.
临床前研究表明，氟西汀可能具有神经保护特性。在这项试点研究中，42例继发或原发进展型多发性硬化症患者被随机分为两组，一组每天两次服用20毫克氟西汀，另一组服用安慰剂，为期2年。每3个月评估一次扩展残疾状态量表（EDSS）、9孔插钉试验（9-HPT）和步行指数（AI）。在基线、第1年和第2年进行脑部磁共振成像扫描、多发性硬化症功能综合评分、疲劳影响量表、盖伊神经功能障碍量表和SF-36评估。氟西汀组20例患者中有7例（35%），安慰剂组22例患者中有7例（32%）在2年时EDSS、9-HPT或AI持续进展。两个治疗组在次要临床结局以及T2病变负荷、灰质体积和白质体积方面未发现差异。安慰剂组意外的低残疾进展率降低了统计效力。至少需要200例患者才能检测到50%的治疗效果。该试验表明，氟西汀总体耐受性良好，但无法对可能的治疗效果做出任何假设。仍有必要对氟西汀在进展型多发性硬化症中进行一项有足够效力的对照试验。该试验已在当前对照试验注册中心注册，注册号为ISRCTN38456328。
