拉考沙胺和吡仑帕奈单药治疗癫痫的研究进展

抗癫痫发作药物(Antiseizure medications,ASMs)在癫痫患者的治疗中起着重要的作用,因为大多数患者需要长期的抗惊厥治疗.由于高达30％的患者对药物治疗不耐受,因此需要选择新的治疗.单药治疗是新诊断癫痫治疗的金标准,如果第一次治疗不成功,可以选择第二次单药治疗.拉考沙胺(Lacosamide,LC...     

吡仑帕奈与奥卡西平单药治疗成人局灶性癫痫的有效性和安全性研究

目的 比较吡仑帕奈（Perampanel,PER）和奥卡西平（Oxcarbazepine,OXC）单药治疗成人新诊断局灶性癫痫的有效性和安全性。方法 纳入清远市人民医院2021年8月—2022年10月新诊断的62例成人局灶性癫痫患者,年龄18～79岁,平均（40.53±16.69）岁,随机分为PER组和OXC组。两组均随访12个月,并分析第3、6、12个月的癫痫无发作率、有效率、药物保留率,以及两组的不良反应情况。结果 PER组32例,OXC组30例。3个月时PER组癫痫无发作率62.5%、有效率71.9%、药物保留率87.5%;OXC组癫痫无发作率70.0%、有效率86.7%、药物保留率93.3%。6个月时PER组癫痫无发作率53.1%、有效率65.6%、保留率75.0%;OXC组癫痫无发作率66.7%、有效率73.3%、保留率83.3%。12个月时PER组癫痫无发作率43.8%、有效率46.9%、保留率53.1%;OXC组癫痫无发作率66.7%、有效率66.7%、保留率70.0%。PER组与OXC组不良反应发生率分别为15.6%和16.7%,两组最常见的不良反应均为头晕和嗜睡,无严...     

吡仑帕奈单药治疗儿童局灶性癫痫的临床疗效研究

目的 探讨吡仑帕奈(Perampanel,PER)单药治疗在儿童局灶性癫痫的疗效及安全性。方法 选取2021年1月—2022年6月在无锡市儿童医院神经内科就诊新发、既往未使用过抗癫痫发作药物的局灶性癫痫患儿46例,其中男24例、女22例,平均年龄(7.2±2.4)岁,PER单药治疗组为PER组(23例),左乙拉西坦(Levetiracetam,LEV)单药治疗组为LEV组(23例),对比两组的临床疗效及不良反应发生情况。结果 3个月PER组总有效率为87.0%(20/23),LEV组总有效率为73.9%(17/23),P<0.05,差异有统计学意义;6个月PER组总有效率为78.3%(18/23),LEV组总有效率为60.9%(14/23), P<0.05,差异有统计学意义。PER组有2例患儿出现不良反应,其中嗜睡1例、头晕1例,通过暂时减少药物剂量、减慢加药速度,不良反应均消失。LEV组有3例患儿出现不良反应,均为不同程度的暴躁易怒,通过减慢加药速度,3～6个月期间2例患儿症状消失,1例患儿症状减轻。结论 新型抗癫痫发作药物PER对于局灶性癫痫具有较好的抗癫痫效果,优于L...     

吡仑帕奈治疗局灶性癫痫的研究进展

吡仑帕奈为第三代新型抗癫痫发作药物,通过非竞争性抑制α-氨基-3-羟基-5-甲基-4-异恶唑啉丙酸受体来发挥其抗癫痫发作作用。多个国家已批准用于≥4岁局灶性癫痫患者(伴或不伴继发全面性发作)的单药及添加治疗。该文总结了吡仑帕奈治疗局灶性癫痫患者的作用机制、药代动力学、疗效及不良反应等的相关文献,以期为临床医师治疗局灶性癫痫提供更多的药物选择,从而更好地为临床上合理化用药提供依据。[国际神经病学神经外科学杂志,2023,50(4):85-89]     

吡仑帕奈临床应用研究进展

癫痫是一种常见的神经系统慢性疾病,其对患者的认知、心理及社会功能都有着一定的不良影响。迄今为止,抗癫痫发作药物(Anti-seizure medications,ASMs)仍是癫痫的一线治疗选择,而在癫痫患者人群中,仍有许多癫痫患者在多种ASMs联合使用的情况下仍无法有效控制癫痫发作,因此迫切需要一种新型作用靶点及机制的ASMs来为难治性癫痫患者人群带来新的治疗选择与希望。吡仑帕奈作为一种新型第三代ASMs,相比于第二代ASMs主要倾向于通过调节离子通道或增强γ-氨基丁酸(γ-aminobutyric acid, GABA)作用等相关机制来发挥抗癫痫发作作用,吡仑帕奈主要是通过针对兴奋性神经递质-谷氨酸来发挥作用。吡仑帕奈是第一个选择性α-氨基-3-羟基-5-甲基-4-异噁唑(α-amino-3-hydroxy-5-methyl-4-isoxazole-propionate,AMPA)受体拮抗剂,也是第一个选择性抑制兴奋性突触后功能的ASMs,由于其独特的作用靶点及机制,已被世界上许多国家批准用于局灶性及全面性癫痫患者的辅助添加治疗与单药治疗。另外,随着对吡仑帕奈神经保护、抗氧化、神经...     

吡仑帕奈治疗儿童难治性癫痫的疗效和安全性研究

目的评估吡仑帕奈在儿童难治性癫痫患者中的有效性、安全性与耐受性。方法回顾性分析2020年1月—2021年1月在苏州大学附属儿童医院就诊的34例难治性癫痫患儿的病历资料,通过对比患儿的基线情况与吡仑帕奈添加治疗后第4、8、12、24、36、48周的癫痫发作情况,来评估吡仑帕奈的疗效与不良反应。结果患儿添加吡仑帕奈治疗时的平均年龄为(8.1±4.1)岁,男女性别比为1∶1。吡仑帕奈添加治疗后,第4、8、12、24、36、48周的有效率分别为37.5%、46.7%、50.0%、47.4%、53.8%、42.9%,不良反应发生率为32.4%,药物保留率为88.2%。结论吡仑帕奈治疗难治性癫痫具有良好的有效性、安全性与耐受性。个性化治疗和较好的基线发作控制水平或许可以提高吡仑帕奈治疗的有效性和药物保留率。     

第三代新型抗癫痫药吡仑帕奈在癫痫治疗中的研究进展

吡仑帕奈是第三代新型抗癫痫药物(AEDs),也是首个治疗癫痫的高度选择性非竞争性α-氨基-3-羟基-5-甲基-4-异喃恶唑丙酸(a-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid,AMPA)型谷氨酸受体拮抗剂.现已在许多国家广泛用于治疗各种癫痫,并取得较好疗效.文章...     

吡仑帕奈治疗儿童难治性癫痫的研究进展

吡仑帕奈是第三代新型抗癫痫药,自其上市,已经在许多国家广泛用于治疗各种儿童癫痫,并取得较好疗效。本文综述了吡仑帕奈在儿童难治性癫痫治疗方面的临床疗效、不良反应、认知功能影响等,有助于临床医生更全面地了解吡仑帕奈在儿童癫痫治疗方面的临床特点,尽可能大地在控制发作和降低不良反应间取得平衡,以更好地治疗癫痫患儿。     

托吡酯添加治疗转换为单药治疗癫痫56例疗效观察

目的 观察添加托吡酯(TPM)治疗有效的癫痫患者转换为TPM单药治疗的疗效。方法 对56例添加TPM治疗有效并持续6个月以上的患者，逐渐减、停合用的抗癫痫药，转换为TPM单药治疗。结果 转换成功32例(57．1％)，完全控制13例，显效15例，有效4例，恶化4例，中途退出20例；不良反应减少14例次(35．8％)。结论 添加TPM治疗有效且稳定的非难治性癫痫患者大多数可成功转换为TPM单药治疗，而难治性癫痫患者转换为TPM单药治疗的成功率较低。     

Efficacy and safety of perampanel oral loading in postanoxic super‐refractory status epilepticus: A pilot study

Refractory nonconvulsive status epilepticus (NCSE) occurs in 10%‐30% of patients following resuscitation after cardiac arrest. Both the optimal treatment and prognosis of postanoxic status epilepticus remain uncertain. We analyzed acute electroencephalographic changes, neurological outcome at 3 months, and adverse effects in consecutive postanoxic patients with super‐refractory NCSE treated with add‐on oral loading of perampanel. Eight postanoxic patients with super‐refractory NCSE were treated with perampanel (dose range = 6‐12 mg). All patients had continuous electroencephalographic monitoring showing definite generalized NCSE and favorable multimodal prognostic indicators (presence of brainstem reflexes, presence of bilateral N20 responses, absence of periodic discharges/generalized epileptic periodic discharges). In six patients (75%), status epilepticus resolved within 72 hours after administration of perampanel, without changing the comedication. Neurological outcomes at 3 months were return to normal or minimal disability in four patients (50%). A mild cholestatic liver injury, which required no specific treatment, was observed in five patients (62.5%). Perampanel 6‐12 mg oral loading appeared to be an effective option in selected patients with postanoxic super‐refractory NCSE with good prognostic indicators. In this patient population, our safety data indicate a risk of cholestasis.     

Efficacy,safety, and tolerability of perampanel in Asian and non‐Asian patients with epilepsy

People of different ethnic or racial backgrounds may experience variations in pharmacokinetic and pharmacodynamic responses to drug therapies. Our post hoc analysis evaluated the efficacy, safety, and tolerability of perampanel in Asian and non‐Asian populations with refractory focal seizures with or without focal to bilateral tonic‐clonic (FBTC) seizures. This analysis pooled data from 4 randomized, placebo‐controlled, phase‐3 studies involving patients aged ≥12 years who have focal seizures with or without FBTC seizures. Patients were receiving 2, 4, 8, or 12 mg perampanel (or placebo) by the end of a 6‐week titration period and for a further 13 weeks during the maintenance phase. Efficacy endpoints included median percent change in seizure frequency per 28 days, and 50% and seizure‐freedom responder rates relative to baseline. The median percent change in seizure frequency per 28 days from baseline was significantly greater than placebo for perampanel 8 and 12 mg (?31.1% and ?38.1% change, respectively; each P < 0.0001) in the Asian population, and for perampanel 4, 8, and 12 mg (?21.1% [P = 0.0001], ?26.3% [P < 0.0001], and ?27.7% [P = 0.0001] change, respectively) in the non‐Asian population. The 50% responder rate relative to baseline was significantly greater than placebo for perampanel 8 and 12 mg (40.1% and 43.8%, respectively; each P < 0.0001) in the Asian population, and for perampanel 4, 8, and 12 mg (29.4% [P = 0.0002], 32.8% [P < 0.0001] and 34.5% [P = 0.0001]), respectively, in the non‐Asian population. Seizure‐freedom rate among all patients was 4.9%‐11.7% for perampanel 2, 4, 8, and 12 mg. The most frequently reported treatment‐emergent adverse events (TEAEs) across both populations were dizziness, somnolence, irritability, headache, and fatigue. The most common psychiatric TEAEs were aggression and irritability. Perampanel demonstrated a favorable and similar risk‐benefit profile in both Asian and non‐Asian populations with refractory focal seizures.     

A post hoc analysis of the long‐term safety and efficacy of perampanel in Asian patients with epilepsy

This post hoc analysis assessed the long‐term safety, tolerability, and efficacy of perampanel in Asian patients with refractory focal seizures; an additional analysis assessed the effect of perampanel on focal impaired awareness seizures (FIAS) with focal to bilateral tonic‐clonic (FBTC) seizures. In this subanalysis, data from Asian patients ≥12 years of age who had focal seizures with FBTC seizures despite taking one to 3 concomitant antiepileptic drugs at baseline, and who had entered either the long‐term extension phase of 3 phase‐3 perampanel trials (study 307) or the 10‐week extension phase of study 335, were analyzed for the effect of perampanel on duration of exposure, safety, and seizure outcomes. Of 874 Asian patients included in the analysis, 205 had previously received placebo during the double‐blind phase‐3 trials and 669 had previously received perampanel 2‐12 mg/day; 313 had FIAS with FBTC seizures at core study baseline. The median duration of exposure to perampanel was 385.0 days, and the retention rate at one year was 62.6%. Overall, during the first 52 weeks of perampanel treatment, 777 patients (88.9%) had treatment‐emergent adverse events (TEAEs), most of which were mild to moderate in severity. The most frequent TEAEs were dizziness (47.1%), somnolence (22.3%), and nasopharyngitis (17.4%). During the first 52 weeks of perampanel treatment, median percent change in seizure frequency per 28 days from pre‐perampanel baseline for all focal seizures was ?28.1%, and ?51.7% for FIAS with FBTC seizures. The 50% responder rate relative to pre‐perampanel baseline for all focal seizures was 33.8%, and 51.1% for FIAS with FBTC seizures. Long‐term treatment with perampanel in Asian patients had safety, tolerability, and efficacy similar to that of the global population in the phase‐3 trials and extension study 307. The safety profile and response rate suggest benefit for an Asian population of patients with refractory epilepsy.     

One‐year clinical experience of perampanel in Spain: a multicentre study of efficacy and tolerability

Perampanel, a non‐competitive antagonist of the α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazole‐propionic acid receptors, is the most recent antiepileptic drug available in Spain, marketed in January 2014. It was initially approved by the European Medicines Agency as adjunctive treatment for partial‐onset seizures in patients 12 years and older, but recently also for primary generalized tonic‐clonic seizures. Although clinical trials provide essential information about the drug, they do not reflect daily clinical practice. This retrospective study shows the initial experience with perampanel in 11 Spanish hospitals during its first year post‐commercialisation. All patients who started perampanel treatment were included, but efficacy and tolerability were only assessed in those patients with a minimum follow‐up period of six months. In total, 256 patients were treated with perampanel before September 2014, and 253 had an observational period of one year. After six months, 216/256 patients (84%) continued on perampanel and 180/253 (71.1%) completed one year of treatment. The mean number of previous antiepileptic drugs used was 6.83 and the median number of concomitant antiepileptic drugs was 2. The mean perampanel dose was 7.06 mg and 8.26 mg at six and 12 months, respectively. The responder rate was 39.5% and 35.9% at both follow‐up points, respectively. Adverse events were experienced by 91/253 (35.5%) and resulted in withdrawal in 37 (14.6%). The most common adverse events were somnolence, dizziness, and irritability. We found no significant differences between concomitant use of enzyme‐inducing and non‐inducing antiepileptic drugs, regarding efficacy, adverse effects, or withdrawals. Irritability was not influenced by concomitant use of levetiracetam, relative to other drugs, but was more frequently observed in patients with a history of psychiatric problems or learning disabilities.     

Losigamone add-on therapy in partial epilepsy: a placebo-controlled study

OBJECTIVES: To evaluate the efficacy and tolerability of losigamone (LSG). PATIENTS AND METHODS: Double-blind, placebo-controlled add-on study with 3x500 mg LSG/die for the treatment of chronic partial seizures in 203 patients (99 treated with LSG, 104 on placebo). RESULTS: The median percent change of seizures was 14.9% (LSG) versus 6.7% (placebo) (P=0.004). Seizure frequency was decreased by more than 50% in 22.3% (LSG) and 14.6% (placebo) of patients (P=0.13). Mean percent change of seizures was best in patients with only one additional anticonvulsant drug (LSG versus placebo, P=0.004). Adverse events (usually CNS-related side effects of mild to moderate intensity) were reported in 59.6% (LSG) and 37.5% (placebo) of patients. CONCLUSIONS: LSG proved to be an effective and well tolerated anticonvulsant drug for the treatment of chronic partial seizures.     

托吡酯添加治疗难治性癫癎的临床观察

目的　观察添加托吡酯对难治性癫的临床效果与副作用。方法　对 18例难治性癫患者 ,加用TPM后观察其发作频率并与加用前进行比较 ,计算总有效率。同时进行临床疗效和副作用观察。结果　病人加用托吡酯后总有效率为 5 0 % ,其中显效率达 2 2 2 % (3例未再发作 )。副反应以胃肠道反应及神经系统症状为主 ,发生率为 5 2 6%。结论　加用TPM治疗难治性癫安全有效。