加巴喷丁治疗癫(癎)32例疗效观察

目的观察加巴喷丁抗癫癎作用的有效性与安全性。方法观察各种类型癫癎患者32例,以GBP用药前3个月平均发作频率为基线,与用药3个月后发作频率进行比较,观察疗效及不良反应。结果加巴喷丁对全面性发作治疗疗效优于部分性发作,新诊断癫癎有效率高于难治性癫癎。加巴喷丁不良事件发生率低且症状轻微。结论加巴喷丁对各种类型癫癎发作均有一定疗效,是一种安全性较好的药物。对全身性发作类型有效,对部分性发作疗效欠佳,对新诊断癫癎有效,难治性癫癎疗效欠佳。     

多中心双盲、随机、安慰剂对照评价左乙拉西坦添加治疗难治性部分性癫(癎)发作的疗效及安全性

目的 评价左乙拉西坦(LEV)添加用药治疗难治性部分性癫(癎)发作的临床疗效及安全性.方法 随机、双盲、安慰剂对照、多中心平行设计添加治疗,确诊为有癫(癎)部分性发作的202例癫(癎)患者,平均年龄(32.8±12.7)岁,随机分配入LEV治疗组(n=102)与安慰剂组(n=100).在回顾8周基线期的癫(癎)发作频率后,进入逐量加药期.初始用药剂量为0.5 g,每日2次,2周后增加至1.0 g,每日2次服用,4周后加量至1.5 g,每日2次,随后维持该剂量治疗12周,最后逐渐减量并转入LEV开放治疗期.主要评价指标为16周治疗期内每周癫(癎)发作频率的比较、得出药物治疗发作频率减少50%有效率、安全性和药物不良反应.结果 在16周治疗期内,LEV组每周癫(癎)发作频率明显减少,较安慰剂组减少26.8%;每周发作频率较基线期下降数在LEV组与安慰剂组的组间差异为42.2%;部分性发作频率减少50%有效率为55.9%,与安慰剂组比的OR值为3.6;有11例治疗后完全无发作,两组相比均有显著统计学意义(P＜0.001).LEV组的主要不良事件为嗜睡、头晕、无力及血小板减少,但与安慰剂组比差异无统计学意义.结论 LEV添加用药治疗成人难治性部分性癫(癎)发作,可以显著减少癫(癎)发作频率,安全性良好.     

随机、双盲、安慰剂对照、多中心研究唑尼沙胺添加用药治疗部分性癫(癎)发作的有效性和安全性

目的 评价唑尼沙胺(ZNS)作为添加用药治疗部分性癫(癎)发作的有效性和安全性.方法 采用多中心、随机、双盲、安慰剂对照、平行组、添加治疗设计.240例确诊为癫(癎)部分性发作的受试者按照1:1的比例随机分配到ZNS治疗组或安慰剂组.在前4周加鼋期内受试者自100 mg/d逐渐加量至300 mg/d,随后进入12周的稳定治疗期.在稳定期内可根据患者情况酌情减量,或加量至最大剂量400 mg/d.有效性评价的主要指标为稳定期部分性癫(癎)发作频率较基线值减少百分数的中位值,重要的次要评价指标为有效率,即部分性癫(癎)发作次数减少≥50%者的比例.同时对药物的安全性进行评价.结果 ZNS组受试者稳定期部分性癫(癎)发作频率较基线期减少百分数(48.4%)显著高于安慰剂组(26.6%),组间差异有统计学意义(F=4.904,P=0.028);ZNS组治疗部分性癫(癎)发作的有效率(48.6%)高于安慰剂组(34.9%),差异有统计学意义(X2=4.046,P=0.044),其中以复杂部分性癫(癎)的组间差异最为显著(分别为52.2%和33.3%,X2=5.607,P=0.018).ZNS组与安慰剂组不良事件发生率相当,与ZNS相关的不良事件多为头晕、头痛、嗜睡、食欲下降、恶心等.结论 ZNS能有效治疗部分性癫(癎),降低癫(癎)发作频率,对复杂部分性癫(癎)发作治疗效果尤为突出.ZNS耐受性良好,受试者用药安全性较高.     

加巴喷丁添加治疗难治性癫(癎)局灶性发作的疗效以及对记忆功能的影响

目的 探讨加巴喷丁(GBP)添加治疗对难治性癫(癎)局灶性发作的疗效以及对记忆功能的影响.方法 96例难治性局灶性发作癫(癎)患者随机分为两组,在原用药物基础上,GBP组给予GBP添加治疗,托吡酯(TPM)组给予TPM添加治疗;添加治疗前后应用临床记忆量表(CMS)对入组者进行记忆功能评估及疗效评估.结果 添加治疗20周GBP组总有效率(75.0%)与TPM组(72.9%)相比差异无统计学意义;与添加治疗前比较,添加治疗后GBP组CMS评分差异无统计学意义;TPM组无意义图形再认、自由图像回忆、人像特点回忆和记忆商显著下降(均P<0.05).结论 GBP作为添加药物治疗难治性癫(癎)局灶性发作有效,对患者记忆功能无明显不良影响.     

多中心、随机、双盲、安慰剂对照评价普瑞巴林添加治疗部分性癫癎发作的疗效和安全性

目的 评价普瑞巴林添加治疗部分性癫（癎）发作的疗效和安全性.方法采用随机、双盲、安慰剂对照、多中心平行设计添加治疗的方法,确诊为有部分性癫（癎）发作的225例癫（癎）患者,被随机分配入普瑞巴林治疗组（114例）与安慰剂组（111例）.在6周前瞻性基线期后,采用灵活剂量的普瑞巴林（150～600 mg·d-1）添加治疗成人部分性癫（癎）发作.主要疗效指标：部分性癫（癎）发作28 d-反应率.次要疗效指标：部分性癫（癎）发作28d-减少率、临床疗效评价、16周内癫（癎）无发作和发作减少率≥50％的病例比例、第13～16周癫（癎）无发作和发作减少率≥50％的病例比例以及临床疗效总评量表评分;并观察研究药物的安全性与不良反应情况.结果 普瑞巴林组部分性癫（癎）发作28 d-反应率（-40.24±37.88）％,显著高于安慰剂组（-22.84±37.61）％（F=15.063 9,P=0.000 l）.普瑞巴林组和安慰剂组的不良事件发生率分别为60.53％和47.75％,组间无显著差异;但普瑞巴林组的不良反应发生率较安慰剂组高（45.61％ vs 23.42％,P=0.000 7）,主要不良反应有头晕、嗜睡、视物模糊、乏力等.结论 普瑞巴林组的疗效显著优于安慰剂组.普瑞巴林作为部分性癫（痈）发作的添加药物有确定的疗效,安全耐受性较好,具有一定临床应用价值.     

唑尼沙胺添加治疗部分性癫的临床疗效及安全性:多中心随机双盲安慰剂对照研究

目的观察唑尼沙胺分散片添加治疗部分性发作或继发全面性发作、全面性强直-阵挛发作及失神发作的疗效及安全性。方法 240例诊断明确的部分性发作患者,被随机分为唑尼沙胺组(120例)或对照组(120例)。回顾性基线期(12周)后,予初始剂量唑尼沙胺或安慰剂100mg/次,1次/d,3周内递增至100 mg/次,3次/d;分别在治疗第0、2、4、8和16周时进行随访,评价治疗第5～16周时临床综合疗效的完全控制率和总有效率,以及药物安全性和不良反应。结果治疗第5～16周时,唑尼沙胺组患者癫癎完全控制率为34.04%(32/94)、总有效率74.47%(70/94),对照组分别为13.08%(14/107)和42.99%(46/107);两组临床综合疗效的完全控制率和总有效率比较,差异具有统计学意义(均P=0.000)。唑尼沙胺组患者常见药物不良反应包括食欲不振、嗜睡、疲劳、头晕、肝功能异常等,与对照组不良反应发生率比较差异有统计学意义(P=0.003)。结论唑尼沙胺作为添加药物治疗部分性发作或继发全面性发作、全面性强直-阵挛发作的疗效优于安慰剂,而且有较好的安全性和耐受性,是临床可以选择的新型抗癫癎药物之一。     

左乙拉西坦添加治疗对青年癫(癎)患者生活质量影响的研究

目的 评价新型抗癫(癎)药物左乙拉西坦添加治疗青年难治性部分性癫(癎)患者的疗效,以及对患者生活质量的影响.方法 30例诊断明确的部分性发作青年患者随机分为左乙拉西坦组和吡拉两坦组,计算左乙拉西坦治疗第12周末时治疗有效率;依据癫(癎)生活质量量表-31分别评价两组患者在左乙拉西坦剂量维持期(12周)和开放性治疗期(12周)的生活质量.结果 治疗第12周末时,左乙拉西坦组治疗有效率(43.75%,7/16)高于吡拉两坦组(35.72%,5/14;Fisher精确概率法:P=0.031),生活质最明显改善(与基线比较:t=3.905.P=0.001).治疗第24周末时,两组患者生活质量较治疗前均显著改善(左乙拉西坦组:t=4.940,P:0.021;吡拉西坦组:t=2.575.P=0.023).结论 左乙拉两坦作为抗癫(癎)药的添加治疗药物,能够显著减少青年难治性部分性癫(癎)患者的发作频率,快速有效地提高患者生活质量.     

抗癫(癎)药物应用指南Ⅱ:新型抗癫(癎)药物的药力和耐受性:难治性癫(癎)的治疗美国神经病学学会治疗学和技术评定分委会和质量标准分委会及美国癫(癎)协会报告

目的 对有关7种用以治疗儿童和成人部分性和全面性难治性癫(癎)的新型抗癫(癎)药物(AEDs):加巴喷丁(gabapentin,GBP)、拉莫三嗪(lamotrigine,LTG)、托吡酯(topiramate,TPM)、噻加宾(tiagabine,TGB)、奥卡西平(oxcarbazepine,OXC)、左乙拉西坦(1evetiracetam,LEV)和唑尼沙胺(zonisamide,ZNS)的药力(efficacy)、耐受性和安全性进行评估.方法 由23位成人神经病学家、小儿神经病学家、癫(癎)病学家和药理学家组成的专家组,依据从1987年到2002年9月Medline,Current Contents和Cochrane上发表的相关文献和2003年以前的指南提供的证据进行循证医学评估.结果 所有新型抗癫(癎)药物都适用于成人难治性部分性癫(癎)的添加治疗,加巴喷丁对混合性(癎)性发作有效,加巴喷丁、拉莫三嗪、托吡酯和奥卡西平对儿童难治性部分性癫(癎)有效.有限的证据还表明,拉莫三嗪和托吡酯对成人和儿童特发性全面性发作和Lennox-Gastaut综合征的添加治疗也有效.结论 抗癫(癎)药物的选择要考虑癫瘌发作和/或癫(癎)综合征的类型、患者的年龄、合用的药物、药物的耐受性、安全性和药力等因素.循证医学评估结果提供了难治性癫(癎)患者的抗癫(癎)药物应用指南,但尚需更为有力的证据用以鉴定其在癫(癎)型或综合征中疗效.     

成人幕上脑胶质母细胞瘤术后癫癎发作的预防

目的探讨成人幕上脑胶质母细胞瘤（GBM）术后预防性应用抗癫癎药物对癫癎发作的影响。方法回顾性分析86例术前无癫癎发作的幕上GBM病例资料,根据病人术后预防性应用抗癫癎药物情况分为对照组（不使用抗癫癎药物）、研究1组（使用抗癫癎药物4周）和研究2组（使用抗癫癎药物24周）,统计术后癫癎发作情况和术后24周各组Karnofsky评分。结果术后4周内出现癫癎发作对照组5例（16．7％）,研究组1例（1．8％）,两组癫癎发作有显著性差异（P〈0．05）。术后5～24周新发癫癎发作对照组7例（23．3％）．研究1组7例（25．0％）,研究2组1例（3．6％）,研究2组新发癫癎发作屁著低于对照组和研究1组（P〈0．05）。研究2组术后24周Karnofsky评分为66．96±10．30,明显高于对照组和研究1组（P〈0．05）。结论预防性应用抗癫癎药物可减少GBM术后癫癎发作发病率,术后癫癎发作治疗困难且影响生活质量,术后预防性应用抗癫癎药物应当不少于24周。     

多中心、随机、双盲、安慰剂对照评价唑尼沙胺添加治疗癫(癎)部分性发作的疗效和安全性

目的 评价唑尼沙胺作为添加治疗癫(癎)部分性发作的疗效和安全性.方法 确诊为有癫(癎)部分性发作的217例癫(癎)患者,随机分配入唑尼沙胺治疗组(n=111)与安慰剂组(n=106)进行随机、双盲、安慰剂对照、多中心平行设计添加治疗.在3个月回顾性基线期后,给予患者初始剂量唑尼沙胺(100 mg/片)或安慰剂每次1片,每日1次口服,4周内递增至每次2片,每日2次.分别在治疗0、2、4、8、12和16周时进行随访.主要疗效指标为治疗结束后与基线期比较发作次数减少的中位百分比;次要疗效指标为发作次数减少大于50%的比例.同时观察研究药物的安全性与不良反应情况.结果 总发作次数减少率中位数在唑尼沙胺组为33.33%,安慰剂组为0;唑尼沙胺组总发作次数减少>50%者38例(34.23%),安慰剂组21例(19.81%),差异有统计学意义(χ3=5.7159,P=0.0168).唑尼沙胺组治疗后无发作13例(11.71%),有效25例(22.52%),临床有效率为34.23%;安慰剂组无发作5例(4.72%),有效16例(15.09%),临床有效率为19.81%,2组间比较差异有统计学意义(U=2.4701,P=0.0135).唑尼沙胺组与安慰剂组比较,其不良反应发生率差异无统计学意义,唑尼沙胺组较常见的不良反应有思睡、乏力、食欲下降、胃肠道不适、失眠和便秘.结论 唑尼沙胺作为部分性癫(癎)发作的添加药物有确定的疗效,安全耐受性较好,具有一定临床应用价值.     

Treatment of partial seizures with gabapentin: double-blind, placebo-controlled, parallel-group study

This double-blind study was conducted to evaluate the efficacy and safety of gabapentin 1200 mg/day and 1800 mg/day (t.i.d.) compared to placebo as an adjunctive therapy in patients with refractory epilepsy. Patients were included when they had partial seizures at least eight times during a 12-week baseline period despite treatment with one to two antiepileptic drugs. After baseline, eligible patients were randomized to gabapentin 1200 mg/day, 1800 mg/day, or placebo for 12-week treatment. The primary end-point, response ratio, was derived from seizure frequencies during treatment and baseline period based upon the seizure daily record by a patient. Of the 209 randomized patients, 86 received gabapentin 1200 mg/day, 41 received gabapentin 1800 mg/day, and 82 received placebo. A statistically significant difference was found between each of the two gabapentin groups and placebo for the primary efficacy end-point, response ratio (P < 0.005) with definite dose-response (P < 0.001). More gabapentin patients reported moderate to marked improvement in seizure frequency and intensity/duration of each seizure than placebo patients. Treatment-related adverse events were reported by approximately 65% of patients receiving gabapentin compared to approximately 46% of patients receiving placebo; somnolence and dizziness were the most common events. Gabapentin 1200 mg/day and 1800 mg/day significantly reduced the frequency of refractory seizures compared to placebo. Favorable tolerability of gabapentin was confirmed also in a Japanese population, consistent with previous global studies.     

Efficacy and safety of Losigamone in partial seizures: a randomized double-blind study

The objective of the study was to investigate the efficacy and safety of two different dosages of Losigamone (LSG) in add-on treatment of partial seizures. In a multi-center, double-blind, randomized clinical trial, patients received one of three 12-week treatments: placebo, LSG 1200 mg/day, or 1500 mg/day, in addition to up to three standard anticonvulsants after a prospective period of 12 weeks to assess baseline seizure frequency. The primary efficacy measure was the relative reduction of seizure frequency per 4 weeks in the double-blind phase as compared to baseline. In the intention-to-treat population of 264 patients, the relative median reduction of partial seizure frequency was 3.3% for placebo, 19.7% for LSG 1200 mg/day, and 25.3% for LSG 1500 mg/day. The differences of both LSG groups versus placebo were significant (P<0.01, two-tailed). In the responder analysis, 11.8% of the patients in the placebo group, 17.2% in the LSG 1200 mg/day group, and 29.3% in the LSG 1500 mg/day group showed a seizure reduction versus baseline of at least 50%. A positive association between dosage and response was observed (P=0.003). Adverse events during treatment were reported by 58.8% of the patients for placebo, by 62.1% for LSG 1200 mg/day and by 76.1% for LSG 1500 mg/day. Most events in the LSG groups occurred during the first 4 weeks of double-blind (during or immediately after up-titration) and subsided quickly. Over the last 4 weeks of treatment, the incidence of adverse events in the LSG groups was close to the placebo level. Based on the study's results, LSG is an effective and safe add-on drug for refractory partial epilepsy in adults.     

Remacemide hydrochloride as an add-on therapy in epilepsy: a randomized, placebo-controlled trial of three dose levels (300, 600 and 1200 mg/day) in a Q.I.D. regimen.

Remacemide hydrochloride is a low-affinity, non-competitive N-methyl-D-aspartic acid (NMDA) receptor channel blocker, under investigation in epilepsy. This double-blind, placebo-controlled, multicentre study assessed the safety and efficacy of remacemide hydrochloride or placebo, as adjunctive therapy, in 252 adult patients with refractory epilepsy who were already taking up to three antiepileptic drugs (including an enzyme-inducer). Patients were randomized to one of three doses of remacemide hydrochloride (300, 600 or 1200 mg /day) or placebo Q.I.D., for up to 15 weeks. An increasing percentage of responders (defined as a reduction in seizure frequency from baseline of > or =50%) was seen with increasing remacemide hydrochloride dose. At 1200 mg /day, 23% of patients were responders compared with 7% on placebo. This difference was significant (P = 0.016), as was the overall difference between treatments (P = 0.038). Adverse events: dizziness, abnormal gait, gastrointestinal disturbance, somnolence, diplopia and fatigue were mild or moderate in severity. Carbamazepine and phenytoin plasma concentrations were well controlled and maintained within target ranges, with no evidence of improved seizure control due to increases in the concentrations of these drugs. A dose-dependent, significant, increase in responders following adjunctive remacemide hydrochloride compared with placebo was observed. Remacemide hydrochloride was well tolerated.     

Oxcarbazepine placebo-controlled, dose-ranging trial in refractory partial epilepsy

PURPOSE: The goal of the study was to evaluate the safety and efficacy of a broad oxcarbazepine (OXC) dosage range (600, 1200, and 2400 mg/d) as adjunctive therapy for uncontrolled partial seizures and to determine the relationship between trough plasma 10-monohydroxy derivative concentrations and OXC safety and efficacy. METHODS: This multinational, multicenter, randomized, 28-week, double-blind, placebo-controlled, four-arm, parallel-group trial enrolled 694 patients aged 15-65 years with uncontrolled partial seizures with or without secondarily generalized seizures. The primary efficacy variable was percentage change in seizure frequency per 28 days relative to baseline. RESULTS: The median reduction in seizure frequency was 26%, 40%, 50%, or 8% for patients receiving 600, 1200, or 2400 mg/d OXC or placebo, respectively (all p < or = 0.0001). Of patients in the 600, 1200, or 2400 mg/d OXC groups, 27%, 42%, and 50% respectively, had more than 50% reduction in seizure frequency compared with 13% for placebo (all p < 0.001). Higher plasma 10-monohydroxy derivative concentrations were associated with larger decreases in seizure frequency (p = 0.0001). During the double-blind treatment phase, 84%, 90%, 98%, and 76% of patients receiving 600, 1200, or 2400 mg/d OXC or placebo, respectively, reported one or more adverse events. The most common adverse events were related to the nervous and digestive systems. CONCLUSIONS: OXC is safe and effective as adjunctive therapy in patients with uncontrolled partial seizures. OXC 600 mg/d was the minimum effective dosage; effectiveness of OXC increased with dose. The rapid and fixed titration to high doses was associated with an increased risk of adverse events, which could potentially be reduced by adjusting concomitant antiepileptic medication and by using a slower, flexible OXC titration schedule.     

Gabapentin in childhood epilepsy: a prospective evaluation of efficacy and safety

PURPOSE: To evaluate the efficacy and safety of gabapentin (GBP) in partial epilepsy in children. METHODS: We performed a prospective open label add-on study in 52 children and adolescents (age 1.8-17.5 years, mean 11.1 years) with refractory partial seizures. Gabapentin was added to one other baseline drug and the efficacy was rated according to seizure type and frequency. RESULTS: The GBP dose ranged from 26 to 78 mg/kg per day (mean 52 mg/kg per day) and was well tolerated in most patients. The seizure frequency remained unchanged in 34 patients (65%). We saw a provocation of seizures in three children (6%). Initially 15 patients (29%) benefited from GBP: five (10%) with a seizure reduction of 50-74%, seven (13%) with a reduction of 75-99% and three (6%) became seizure free. All but three experienced a development of tolerance within the next weeks to months. CONCLUSIONS: Although gabapentin seems also to be safe in children, the efficacy in refractory partial seizures was disappointing.     

A randomized open-label study of gabapentin and lamotrigine in adults with learning disability and resistant epilepsy.

The aim of this study was to evaluate the efficacy and safety of gabapentin in patients with learning disabilities and resistant epilepsy, comparing the effects of gabapentin with lamotrigine on efficacy, behaviour and mood. An open-label, randomized, parallel group, multicentre add-on study comparing gabapentin with lamotrigine in 109 patients with drug-resistant localization-related epilepsy and learning disabilities was conducted: 39 patients were randomized to gabapentin and 44 to lamotrigine. The study population had a range of learning disabilities and severe partial epilepsy. The percentage of patients achieving a greater than or equal to 50% reduction in seizure frequency on gabapentin was 50%, (mean reduction in seizures was 51%). Compared to 48.6% of lamotrigine patients, no statistically significant treatment differences could be identified. The safety profile of both drugs was consistent with that seen in previous clinical trials. Carer-rated visual analogue scales detected significant improvements (P< 0.05) for the gabapentin-treated patients in seizure severity, attention, general health and sleeping pattern, while for lamotrigine seizure severity improved significantly. For learning disabled patients with resistant epilepsy, gabapentin and lamotrigine provide safe and effective treatment, with positive benefits on behaviour.     

Randomized polysomnography study of gabapentin enacarbil in subjects with restless legs syndrome

We assessed the efficacy and tolerability of gabapentin enacarbil in the treatment of moderate to severe primary restless legs syndrome and associated sleep disturbance. This was a multicenter, randomized, double‐blind, placebo‐controlled, 2‐period crossover polysomnography study of gabapentin enacarbil 1200 mg or placebo taken once daily. Subjects were randomized 1:1 to a sequence of gabapentin enacarbil:placebo or placebo:gabapentin enacarbil, receiving each treatment for 4 weeks. The primary end point was the mean change from baseline at weeks 4 and 10 (4/10) last observation carried forward in wake time during sleep. The key secondary end point was the mean change from baseline at weeks 4/10 last observation carried forward in periodic limb movements associated with arousal per hour of sleep. Tolerability assessments included adverse events. One hundred thirty‐six subjects were randomized (gabapentin enacarbil:placebo, 67; placebo:gabapentin enacarbil, 69), and 114 (gabapentin enacarbil:placebo, 53; placebo:gabapentin enacarbil, 61) completed the study. Gabapentin enacarbil 1200 mg significantly reduced wake time during sleep (mean change from baseline [adjusted mean treatment difference]: ?26.0 minutes; P < .0001) and periodic limb movements associated with arousal per hour of sleep (adjusted mean treatment difference: ?3.1 periodic limb movements with arousal/hour; P = .002) compared with placebo at weeks 4/10 last observation carried forward. The most commonly reported adverse events were dizziness (gabapentin enacarbil 20%, placebo 2%) and somnolence (gabapentin enacarbil 13%, placebo 2%). Gabapentin enacarbil 1200 mg once daily significantly reduces restless legs syndrome–associated sleep disturbance and periodic limb movements associated with arousal per hour of sleep and is generally well tolerated in adults with moderate to severe primary restless legs syndrome. © 2011 Movement Disorder Society     

Gabapentin and cognition: a double blind, dose ranging, placebo controlled study in refractory epilepsy.

OBJECTIVE: To assess the effect of different doses of gabapentin (GBP) on cognitive function in treated epileptic patients. METHODS: Twenty seven patients with refractory partial seizures commenced a double blind, dose ranging, placebo controlled, crossover study of adjuvant GBP. Each treatment phase lasted three months, during which the dose of GBP or matched placebo was increased stepwise at intervals of four weeks (1200 mg/day, 1800 mg/day, and 2400 mg/day in three daily doses). Psychomotor and memory testing was carried out at the end of each four week period, at which time the patient also completed subjective measures of cognition, fatigue, worry, temper, and dysphoria. A visual analogue scale was used to assess drowsiness and a questionnaire was employed to gauge the severity of side effects. RESULTS: In the 21 patients completing the study, GBP produced a significant reduction in median monthly seizure frequency from 7 to 4.3 (P = 0.02), the decrease being most pronounced for secondarily generalised seizures (from 1.0 to 0.3, P = 0.01). Forty three per cent of patients reported a reduction in seizure frequency of at least 50% throughout all GBP doses. Mean (SD) plasma concentrations of GBP at 1200, 1800, and 2400 mg/day were 4.7 (2.6), 6.8 (3.8), and 8.6 (3.3) mg/l respectively. The drug had no effect on composite psychomotor and memory scores; nor was there alteration in any self assessment subscore. The mean drowsiness (P = 0.03) score was higher during treatment with 2400 mg GBP daily compared with matched placebo. Composite psychomotor (r = -0.47, P < 0.01), tiredness (r = 0.42, P < 0.01), and side effect (r = 0.61, P < 0.001) scores correlated significantly with seizure frequency but not with GBP dose. CONCLUSION: GBP is a well tolerated and effective antiepileptic drug which had no measurable effect on cognition but did produce sedation at the highest dose. This study also supports the suggestion that seizures can cause cognitive impairment.     

A placebo-controlled trial of gabapentin in spinal muscular atrophy.

OBJECTIVE: To evaluate the efficacy of gabapentin in increasing muscle strength of patients with spinal muscular atrophy (SMA). BACKGROUND: Preclinical data in experimental models of motor neuron disease suggest a neuroprotective effect of gabapentin. METHODS: Gabapentin (1200 mg), or placebo, was administered three times daily in a randomized, double-blind trial for 12 months. The primary outcome measure was the average percent change from baseline, based on the measurement of strength in four muscles (elbow flexion and hand grip bilaterally) for each patient. Drug efficacy was examined by comparing the percent change in strength for patients on drug vs. placebo. Secondary efficacy variables included: forced vital capacity (FVC), SMA functional rating scale (SMAFRS), and mini-Sickness Impact Profile (SIP). RESULTS: Eighty-four patients, with type II or III SMA, were enrolled at eight sites across the United States. There were no differences in baseline features. There was no difference between the placebo and drug groups in any outcome measure. CONCLUSIONS: This study demonstrates the feasibility of this trial design and provides data for the design of future clinical trials in SMA.