Pregabalin as add-on therapy induces REM sleep enhancement in partial epilepsy: a polysomnographic study

Background and purpose:  To evaluate the effects of pregabalin (PGB) adjunctive therapy on sleepwake cycle and daytime somnolence in adult patients affected by partial epilepsy.
Methods:  Twelve patients affected by partial epilepsy underwent a 24-h ambulatory polysomnography and a subjective evaluation of daytime somnolence by means of the Epworth Sleepiness Scale (ESS), before and after 3 months treatment with PGB.
Results:  Pregabalin therapy reduced seizures by >50% in 8 out of 12 patients. It induced a significant increase of REM sleep and a decrease of stage 2 NREM sleep (S2). A significant increase of the ESS score was observed without reaching the pathological cut-off value (mean ESS score <10). No statistical correlation between REM sleep and seizure frequency was observed.
Discussion:  Pregabalin seems to be effective and safe in partial epilepsy. The increase of REM sleep may be indicative of an improvement of nocturnal sleep quality considering the involvement of REM sleep in learning and memory processes. REM sleep enhancement may be the result of both a direct effect of PGB on sleep generators and an indirect effect due to its clinical efficacy. The increase of ESS score within normal range suggests that daytime somnolence is a minor adverse effect of PGB.     

妥泰治疗难治性癫痫的临床疗效观察

目的 :观察妥泰 (TPM)单药对难治性癫痫 (RE)的临床疗效和安全性。方法 :RE4 1例 ,添加TPM治疗后逐渐撤去原服用的抗癫痫药物 ,而用TPM单药治疗。以添加TPM前 12周平均每 4周发作频率为基线 ,与评价前12周平均每 4周发作频率进行个体自身比较。按常规计算完全控制率和有效率。并进行临床观察和实验室检查。结果 :完全控制率 34 1% ,有效率 6 5 9%。不良反应 2 5例次 ,但绝大部分轻微 ,可自行消失。结论 :TPM对RE疗效显著 ,安全性好     

Pregabalin for the management of partial epilepsy

Pregabalin is one of the latest antiepileptic drugs introduced for the treatment of partial epilepsy. Its efficacy and safety as adjunctive therapy in refractory partial epilepsy have been established in four double-blind placebo-controlled trials (n = 1396) and 4 long-term open-label studies (n = 1480). In 3 fixed-dose trials, the proportion of patients with a ≥50% reduction in seizure frequency across the effective dose-range (150–600 mg/day) ranged between 14% and 51%, with a clear dose-response relationship. Suppression of seizure activity could be demonstrated as early as day 2. The most frequently reported CNS-related adverse events included dizziness, somnolence, ataxia and fatigue, were usually mild or moderate, and tended to be dose related. In long-term studies, weight gain was reported as an adverse event by 24% of patients. When pregabalin dose was individualized to according to response within the 150 to 600 mg/day dose range, tolerability was considerably improved compared with use of a high-dose, fixed-dose regimen (600 mg/day) without titration. In long-term studies up to 4 years, no evidence of loss efficacy was identified. During the last year on pregabalin, 3.7% of patients were seizure-free. Pregabalin appears to be a useful addition to the therapeutic armamentariun for the management of refractory partial epilepsy.     

妥泰加用治疗成人难治性部分性癫痫的疗效观察

目的：观察妥泰（TPM）加用治疗成人难治性部分性伴或不伴随继发身性发作（GTCS）的疗效,安全性及耐受性。方法：56例在不动原用抗癫痫药（AEDs)的基础上加用TPM治疗20周、前8周为加量期,后12周为维持治疗的稳定期,治疗前（基础期）记录好作频率,用药情况。体重等作为自身对照。TPM自25mg/d开始,逐渐加量,目标剂量为200mg/d,治疗及治疗结束各查基础AEDs血药浓度进行比较,治疗结束行全面疗效分析。结果：TPM加用治疗20周后,与基础期发作频率比较,64．29％患者发作频率降低≥50％;25．00％,患者发生频率降低≥75％＜100％;16．07％完全不发。不良反应轻至中度,但与合AEDs的多少有关。50％患者体重可有不同程度的下降。TPM对止痛民西平及丙戊酸钠血药浓度影响不大。结论：TMP是治疗难治性部分性伴或不伴继发GTCS的表效的药物。     

托吡酯添加治疗儿童难治性癫痫的开放性自身对照临床研究

目的 评价托吡酯添加治疗儿童难治性癫痫的疗效及安全性。方法 应用托吡酯对44例难治性癫痫患儿进行开放性自身对照临床研究,其中单纯部分性发作患儿14例次,复杂部分性发作患儿23例次,部分性发作继发全面性发作患儿16例次。于服药后6个月评价托吡酯的疗效和安全性,以及临床疗效与药物剂量关系。结果 托吡酯治疗总有效率为58.14％(25/43例次),以发作次数减少≥50％为界,单纯部分性发作患儿治疗总有效率为57.14％(8/14例次),复杂部分性发作63.64％(14/22例次),部分性发作继发全面性发作68.75％(11/16例次)。6例Lennox-Gastaut综合征患儿中仅2例有效。托吡酯治疗后的不良反应发生率为46.51％(20/43例次),主要为厌食(37.21％)和体重下降(27.91％)。托吡酯所致不良反应较轻微,部分患儿继续接受治疗可自行缓解。结论 尽管在服用托吡酯期间须行不良反应监测,但其作为添加剂治疗儿童难治性癫痫安全有效,且对患儿血尿常规、肝肾功能均无明显影响。     

Lacosamide as an adjunctive therapy in pediatric patients with refractory focal epilepsy

Purpose: To evaluate the efficacy and safety of lacosamide in pediatric patients with refractory focal epilepsy. Methods: We reviewed retrospectively the medical records of children younger than 18 years of age treated at Seoul National University Bundang Hospital, in whom oral lacosamide was used as an adjunctive treatment for refractory focal epilepsy. Clinical information regarding the patients’ epilepsy and the outcome of lacosamide treatment was gathered and analyzed. Results: Twenty-one patients (16 boys, 5 girls) were included, with a median age of 13.9 (range, 1.2–17.9) years. The mean number of concomitant antiepileptic drugs was 3.0 (range, 1–6) and the mean duration of follow-up was 10.1 (range, 6.1–13.0) months. The mean maintenance dose of lacosamide was 5.4 (range, 1.4–9.8) mg/kg/day. Fourteen patients (67%) were responders; four of these were seizure free at the last follow-up. Seven patients (33%) were nonresponders: two of these presented with <50% seizure reduction and five showed no change in seizure frequency. Two patients (10%) discontinued oral lacosamide because of adverse events (aggressive behavior and depression). Mild transient treatment-related adverse events were observed in eight of the 21 patients (38%). Conclusions: Lacosamide represents a useful drug that is effective for a wide range of pediatric refractory focal epilepsy and is well tolerated.     

Lamotrigine as adjunctive therapy in patients with refractory epilepsy and mental retardation

This study evaluated the effects of lamotrigine as adjunctive therapy for refractory epilepsy in patients with mental retardation. Patients with epilepsy and mental retardation having uncontrolled seizures despite treatment with other antiepileptic drugs were eligible (n=67). The open-label study comprised a Baseline Phase, an Escalation Phase during which lamotrigine was titrated to a target dose, an 8-week Maintenance Phase during which doses of lamotrigine and concomitant antiepileptic drugs were maintained, and a 12-week Optimization Phase during which doses of lamotrigine and other antiepileptic drugs could be adjusted. Almost half (44%) of patients experienced a 50% reduction in seizure frequency during the Maintenance Phase after addition of lamotrigine; 15% of patients became seizure-free. A similar pattern of results was reported for the Optimization Phase. Investigator-rated clinical status was improved relative to baseline in 66 and 74% of patients at the end of the Maintenance and Optimization Phases, respectively. Most patients experienced improvements in seizure frequency, duration, and intensity during the Maintenance Phase (62 to 72%) and the Optimization Phase (65 to 74%). Many patients were rated as having improved social functioning during the Maintenance Phase (42%) and the Optimization Phase (46%). The Aberrant Behavior Checklist score for lethargy and the mean Habilitative Improvement Scale score were improved at the ends of the Maintenance and Optimization Phases relative to baseline (P< or =0.04). One limitation of this study is its open-label design, which limits the ability definitively to attribute the clinical improvements to lamotrigine. Adjunctive lamotrigine in patients with refractory epilepsy and mental retardation appears to decrease seizure frequency and improve behavior while permitting a reduction in dose of concomitant antiepileptic drugs.     

Long-term efficacy and tolerability of topiramate as add-on therapy in refractory partial epilepsy: An observational study

Purpose:   To evaluate the long-term efficacy and tolerability of topiramate (TPM) as add-on therapy in patients with refractory partial epilepsy.
Methods:   This is a retrospective, single-center, long-term observational study. Patients fulfilling the criteria of medical intractability proposed by Berg et al. were entered into the study if they were newly prescribed TPM as add-on therapy between January 2000 and June 2002. The usual starting dosage of TPM was 50 mg/day and optimal-dose adjustments were made according to individual clinical responses. Efficacy and tolerability were analyzed every year during 5-year follow-up in the "intention-to-treat (ITT) population." Retention rate was estimated by Kaplan-Meyer analysis.
Results:   A total of 125 patients were included in the study and 107 patients (85.6%) were followed for 5 years. Retention rate was 87.2% at 1 year and 64% at 5 years. At the end of 5 years, the median seizure frequency reduction rate was 69.0% and responder rate was 43.2% in the ITT population. Cumulative seizure-free rate (SFR) was 30.4% and the terminal 1-year SFR was 12.8% in the ITT population (20.0% in completers) at 5-year follow-up. Adverse events (AEs) occurred in 39.2% of patients, including significant AEs leading to antiepileptic drug (AED) withdrawal in 14.4%. The most common AEs were anorexia (16.0%), weight loss (10.4%), and gastrointestinal symptoms (8.8%). Concomitant AEDs were reduced in 25.0% of the completers.
Discussion:   Low-dose and slow-dose escalation of TPM in add-on therapy for patients with refractory partial epilepsy is effective and well tolerated in long-term, individualized clinical practice.     

The long-term effect of clobazam as adjunctive therapy in epilepsy

Thirty drug-resistant epilepsy patients were given 20-30 mg of clobazam in addition to their other anticonvulsants and followed up for 2-3 years in an open-ended study. Fit frequency was markedly reduced in 43% of patients, few side effects occurred and psychological parameters including the Crown-Crisp questionnaire, showed improvement. It therefore seems that clobazam is a useful additional drug added to conventional anticonvulsant regimes.     

Measurement of seizure freedom in adjunctive therapy studies in refractory partial epilepsy: the levetiracetam experience.

PURPOSE: To assess the advantages and disadvantages of six methodologies used in calculating seizure freedom rates in placebo-controlled, adjunctive therapy trials of new antiepileptic drugs (AEDs) in partial epilepsy, and two methodologies for long-term follow-up studies. METHODS: Data from levetiracetam trials were used to illustrate the impact of different methodologies on seizure freedom rates. Seizure-freedom data for several new AEDs were identified from the published medical literature using MEDLINE and from a recent comprehensive textbook. RESULTS: Most randomized, placebo-controlled add-on clinical trials of new AEDs contain little or no information about seizure freedom. Importantly, the methodology used can profoundly affect results when calculating seizure-free rates. Seizure freedom data should be reported as well as the methodology used. The minimum duration for assessing seizure freedom should be the entire stable dose period in short-term trials and at least six months for long-term follow-up studies. It is proposed that the seizure freedom rates be calculated and reported with at least two different methodologies, one that considers patients withdrawing from treatment without having had a seizure as successes, and one that considers the same patients as failures. For an effective and well-tolerated AED, seizure freedom rates will be consistent across the two methodologies. CONCLUSIONS: Seizure freedom is the ultimate goal of AED therapy and should be reported for all clinical trials. Methodological differences among the few clinical studies reporting seizure freedom rates make it difficult to compare results across trials. Improved reporting of methodologies and seizure-free rates is warranted.     

Pregabalin as add-on therapy for refractory partial seizures in every day clinical practice

We retrospectively reviewed our clinical experience with PGB when used as add-on therapy in 101 patients (56 women and 45 men) with refractory partial epilepsy, who have been followed up for at least 1 year. Mean age was 40 years (16-64); mean number of concomitant AEDs was 2.8. Most patients (43) had temporal lobe epilepsy. Median number of seizures per month was 16 (3-240). Mean PGB dose used was 412.5 mg. Responder rate (percentage of patients with >or=50% seizure reduction) at 6 and 12 months was 52% and 39.6%, respectively. Seizure freedom for at least 6 and 12 months has been achieved by 12 patients (11.8%) and 6 patients (5.9%) respectively. At 1 year, 61 patients (60.4%) are still taking PGB. Forty patients have discontinued PGB, because of inefficacy (16 patients, 15.8%), adverse effects (15 patients, 14.8%) or both (9 patients, 8.9%). Sixty per cent of patients reported adverse events, being weight gain (>10% body weight) the most frequent, seen in 26 patients (25.7%). Dizziness/ataxia was seen in 20 (19.8%). Adverse effects were generally mild to moderate.     

Minocycline as adjunctive therapy for schizophrenia: an open-label study

Minocycline is a caspase inhibitor, decreases inducible nitric oxide synthase, and has been shown to delay disease in a mouse model of neuropsychiatric disorders. Recently, we reported the antipsychotic effects of minocycline in patients with schizophrenia. In a pilot investigation, we administered minocycline (150 mg/d) for 4 weeks as an open-label adjunct to antipsychotic medication to 22 patients with schizophrenia. The Positive and Negative Syndrome Scale for schizophrenia showed statistically significant and robust clinical improvements with minocycline treatment, which were maintained at follow-up evaluation 4 weeks after the end of minocycline treatment. There were no adverse events. These results suggest that minocycline may be a safe and effective adjunct to antipsychotic medications, and that augmentation with minocycline may prove to be a viable strategy for "boosting" antipsychotic efficacy and for treating schizophrenia.     

Two-year efficacy of lacosamide as adjunctive therapy for generalized tonic-clonic seizures in patients with juvenile myoclonic epilepsy

ObjectiveTo report the long-term efficacy of adjunctive lacosamide therapy in patients with juvenile myoclonic epilepsy whose generalized tonic-clonic seizures were significantly reduced by treatment.MethodsA retrospective study was conducted in patients who visited the Department of Child Neurology, National Hospital Organization Nishiniigata Chuo Hospital and the Department of Pediatrics, National Hospital Organization Nagasaki Medical Center. Among patients who had been diagnosed with juvenile myoclonic epilepsy, those who received lacosamide as adjunctive therapy for refractory generalized tonic-clonic seizures for at least 2 years from January 2017 to December 2022, and who achieved seizure freedom or >50% seizure reduction in tonic-clonic seizures were included. The medical records and neurophysiological data of the patients were reviewed retrospectively.ResultsFour patients met the inclusion criteria. The mean age at the onset of epilepsy was 11.3 years (range 10–12), and the mean age of starting lacosamide was 17.5 years (range 16–21). All patients received two or more antiseizure medications prior to lacosamide. Three of four patients had seizure freedom for more than 2 years, and the one remaining patient had >50% seizure reduction for more than one year. Only one patient had recurrent myoclonic seizures after starting lacosamide. The mean lacosamide dose at the last visit was 425 mg/day (range 300–600).ConclusionAdjunctive lacosamide therapy might be a treatment option for juvenile myoclonic epilepsy with generalized tonic-clonic seizures, which are not responsive to standard antiseizure medications.     

Minocycline as adjunctive therapy for patients with unipolar psychotic depression: an open-label study

Background

Approximately 25% of patients admitted to a hospital as a result of depression are actually suffering from psychotic depression. Psychotic symptoms can be present in patients with either unipolar depression or bipolar depression and can be difficult to treat. It was reported the second-generation tetracycline may exert potential antidepressant effects through its robust neuroprotective activities, which include neurogenesis, antioxidation, and anti-glutamate excitotoxicity, and may direct regulation of pro-inflammatory agents.

Methods

This was a 6-week, open-label study to evaluate the efficacy and safety of minocycline in combination with antidepressants in adult inpatients (n = 25) diagnosed with major depression with psychotic features (psychotic depression) according to DSM-IV-TR. The primary endpoint was the change from baseline in the Hamilton Depression Rating Scale (HAM-D-21) score from baseline to week 6. Secondary endpoints were changes in the Brief Psychiatric Rating Scale (BPRS) and the Clinical Global Impression (CGI) Scale scores from baseline to week 6. Spontaneously reported adverse events were recorded.

Results

The patients' average age was 46.9 ± 10.2 years. Minocyline (150 mg/day) in combination with antidepressants (fulvoxamine, paroxetine, and sertraline) provided significant improvement in depression. Mean (± SD) HAM-D-21 was reduced to 6.7 ± 1.9 at week 6 from a baseline value of 40.4 ± 2.5. Significant improvement of psychotic symptoms (mean ± SD) was indicated by the decrease in BPRS scores from baseline (63.3 ± 8.7) to week 6 (4.6 ± 2.4). No serious adverse events occurred.

Conclusions

These preliminary data suggest that minocycline in combination with antidepressants is effective and well tolerated in the treatment of unipolar psychotic depression. Further studies using larger, double-blind, parallel-group design are warranted to confirm these findings.     

Efficacy and safety of lacosamide as an adjunctive therapy for refractory focal epilepsy in paediatric patients: a retrospective single‐centre study

Aim. Lacosamide is an antiepileptic drug approved for the treatment of focal epilepsy in adult patients. The aim of this observational study was to review our centre's experience with lacosamide and to characterize its effectiveness and tolerability as an adjunctive antiepileptic drug in a retrospective cohort of children with refractory focal epilepsy. Methods. We retrospectively reviewed the medical records of 22 patients who received lacosamide from November 2009 to April 2014 at the CHU Ste‐Justine, University of Montreal. Treatment responders were defined as children with a ≥50% reduction in seizure frequency compared to baseline, and this was determined three months after the initiation of treatment and at the last follow‐up visit. Results. We included 14 boys and eight girls with a mean age of 12.9 years (SD: 5.2; range: 5.2–20.7 years) at the initiation of treatment. The average length of follow‐up was 11.9 months. Patients had previously received an average of 7.5 antiepileptic drugs. The mean number of concomitant antiepileptic drugs was 2.3. The mean initial and maintenance doses were 2.9 and 8.4 mg/kg/d, respectively. Thirteen (59%) and ten (45%) patients were responders after three months of treatment and at the last follow‐up visit, respectively. One became seizure‐free. Adverse effects were reported in 11 patients and none were severe. Responders and non‐responders were identical with respect to all studied parameters except gender, with the proportion of responders being greater in girls than in boys (75% vs 29%; p=0.035). Conclusion. Our study adds evidence that lacosamide appears to be a safe and effective adjunctive therapy for children with refractory focal epilepsy.     

Clinical experience with oral lacosamide as adjunctive therapy in adult patients with uncontrolled epilepsy: a multicentre study in epilepsy clinics in the United Kingdom (UK)

IntroductionLacosamide (LCS) is a new antiepileptic drug (AED) licensed in the European Union (EU) and United States (US) in 2008.AimsTo evaluate the efficacy and tolerability of add-on LCS in an out-patient epilepsy clinic setting to obtain useful information for everyday practice.MethodsWe pooled data retrospectively from the case note of patients with refractory epilepsy in whom LCS had been prescribed in 19 hospitals across the United Kingdom.ResultsFour hundred and three patients were included (mean age 41.9 years, 50.6% women, 18.1% with learning disabilities (LD)). Mean follow-up (FU) was 11.6 months (range one day to 42 months). Most patients (86.9%) presented with symptomatic partial epilepsy (SPE) and 80% were taking two or more antiepileptic drugs (AEDs) when LCS was added (mean 2, range 0–4). Retention rates were 80% at six months, 68% at one year and 45% at two years. The efficacy of LCS was evaluated at three months and at the final FU. At three months one hundred and eight patients (31.1%) reported ≥50% seizure reduction and 32 (9.2%) were seizure free. At the final FU 102 (37.5%) reported ≥50% seizures reduction and 28 (9.8%) were seizure free.One hundred and ninety three patients (48.7%) reported adverse effects (AEs). The most frequent were sedation and dizziness, followed by nausea. Lacosamide was discontinued in 150 patients (38%), 60 due to AEs alone.ConclusionLCS appears to be an effective and safe AED when used as adjunctive therapy in patients with refractory partial epilepsy.     

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.     

别嘌醇添加治疗难治性癫痫58例疗效观察

目的 :研究别嘌醇作为添加剂治疗难治性癫痫 (IE)的临床疗效与安全性。方法 :选自 1992～ 2 0 0 0年IE 5 8例 ,加用别嘌醇进行开放性自身对照研究 ,原服用的抗癫痫药 (AEDs)种类和剂量不变 ,以加用别嘌醇前 6个月的月发作频率为基线与治疗后 6个月的发作频率进行比较 ,常规计算发作改变百分率、有效率和脑电图好转率。结果 :发作改变百分数较加用前减少 6 7% (P <0 0 1) ,总有效率 5 8 6 2 % ,反应率为 5 0 % ,脑电图总有效率 6 8% (38/ 5 6 )。其临床疗效为全身强直———阵挛发作 (GTCs) >强直性发作 (Ts) >复杂部分性发作 (CPs) >单纯部分性发作 (SPs)。结论 :加用别嘌醇是治疗难治性癫痫的有效方法之一