Controlled-release Carbamazepine Research Articles

Efficacy and tolerability of lacosamide and controlled-release carbamazepine monotherapy in patients with newly diagnosed temporal lobe epilepsy: Post hoc analysis of a randomized, double-blind trial.

Temporal lobe epilepsy (TLE) is often associated with drug-resistant seizures. We evaluated the efficacy and tolerability of lacosamide (LCM) versus controlled-release carbamazepine (CBZ-CR) monotherapy in adults with newly diagnosed TLE. Exploratory post hoc analysis of patients with temporal focus of localization (indicated as the only localization focus) in a double-blind, noninferiority, phase 3 trial (SP0993; NCT01243177) in patients aged ≥16 years with newly diagnosed epilepsy randomized 1:1 to LCM or CBZ-CR monotherapy. Of 886 treated patients in this trial, temporal lobe focus of localization (TLE) was reported as the single focus for 287 (32.4%) patients (LCM 134, CBZ-CR 153). A similar proportion of patients with TLE on LCM (82 [61.2%]) and CBZ-CR (99 [64.7%]) completed the trial. Kaplan-Meier estimates for 6- and 12-month seizure freedom at the last evaluated dose level (stratified by number of seizures in the 3 months before screening [≤2 or >2 seizures]) were similar with LCM and CBZ-CR (6 months overall: 88.7% and 89.7%; 12 months overall: 78.3% and 81.7%). Treatment-emergent adverse events (TEAEs) were reported by fewer patients on LCM (73.9%) than CBZ-CR (81.0%). Drug-related TEAEs (assessed by the investigator) were reported in 41.8% of patients on LCM and 52.3% of patients on CBZ-CR; 11.2% of patients on LCM and 15.0% on CBZ-CR discontinued due to TEAEs. Lacosamide was efficacious and generally well tolerated as monotherapy in patients with TLE with efficacy outcomes comparable with CBZ-CR, and fewer patients on LCM reported any TEAEs, drug-related TEAEs, or discontinued due to TEAEs.

Monotherapy with oxcarbazepine and controlled-release carbamazepine in newly diagnosed adult focal epilepsy (open comparative study)

Introduction. Oxcarbazepine is the first-line therapy for newly diagnosed focal epilepsy in children, but data on its use in adult patients in the Russian population are limited.Aim. Improvement of the efficacy of initial therapy with oxcarbazepine and controlled-release carbamazepine for newly diagnosed focal epilepsy in adults.Patients and methods. The study included 74 adult patients, 39 of them were included in the oxcarbazepine group and 35 in the controlledrelease carbamazepine group. During the 6-month follow-up period, patients completed 5 visits, during which adverse events and effectiveness were assessed, as well as video-EEG monitoring with an assessment of the epileptiform activity index. Results. The proportion of patients with a reduction in seizure frequency of more than 50 % was comparable in both groups, constituting 82.4 % (n = 28) and 85.2 % (n = 23) in the oxcarbazepine and carbamazepine group, respectively. Adverse events developed in 20 % (n = 7) of patients taking carbamazepine, and in the oxcarbazepine group in 12.8 % (n = 5) of patients. The 6-month initial monotherapy retention rate was higher in oxcarbazepine group (71.8 %) compared to carbamazepine group (65.7 %). In both groups, a 2.0–3.5-fold decrease in the average and total epileptiform activity index and epileptiform activity index during sleep was registered.Conclusions. The obtained results indicate similar effectiveness of oxcarbazepine and controlled-release carbamazepine in the treatment of newly diagnosed focal epilepsy in adults and better tolerability of oxcarbazepine in terms of both adverse events rate and lower frequency of drug discontinuation due to adverse events. A decrease in the epileptiform activity index by 2.0–3.5 times is evidence of possible use of the epileptiform activity index as an objective marker of the disease dynamics

Lipid profile with eslicarbazepine acetate and carbamazepine monotherapy in adult patients with newly diagnosed focal seizures: post hoc analysis of a phase III trial and open-label extension study.

Antiseizure medications can have negative effects on plasma lipid levels. To evaluate plasma lipid changes in patients with newly diagnosed focal epilepsy treated with eslicarbazepine acetate (ESL) or controlled-release carbamazepine (CBZ-CR) monotherapy during a phase III, randomized, double-blind (DB) trial and 2 years of ESL treatment in an open-label extension (OLE). Post hoc analysis of a phase III trial and OLE study. Proportions of patients with elevated levels of total cholesterol and low-density lipoprotein (LDL) cholesterol were assessed at DB baseline, OLE baseline (last visit of DB trial), and end of OLE. A total of 184 patients received ESL monotherapy during the OLE: 96 received ESL monotherapy in the DB trial and 88 patients received CBZ-CR monotherapy. The proportions of patients with elevated total cholesterol and LDL cholesterol increased significantly during the DB trial in those treated with CBZ-CR monotherapy [total cholesterol, +14.9% (p < 0.001); LDL cholesterol, +11.5% (p = 0.012)] but decreased significantly after switching to ESL monotherapy in the OLE [total cholesterol, -15.3% (p = 0.008); LDL cholesterol, -11.1% (p = 0.021)]. No significant changes were observed in those treated with ESL monotherapy during the DB trial and OLE. At the end of the DB trial, between-group differences (ESL-CBZ-CR) in the proportions of patients with elevated total and LDL cholesterol were -13.6% (p = 0.037) and -12.3% (p = 0.061), respectively; at the end of the OLE, these between-group differences were -6.0% (p = 0.360) and -0.6% (p = 1.000), respectively. A lower proportion of patients with newly diagnosed focal epilepsy had increased levels of total and LDL cholesterol, compared to baseline, following monotherapy with ESL versus CBZ-CR; after switching from CBZ-CR to ESL, the proportions of patients with increased levels decreased significantly. ClinicalTrials.gov NCT01162460/NCT02484001; EudraCT 2009-011135-13/2015-001243-36.

Severe Carbamazepine Toxicity Treated with Continuous Venovenous Hemofiltration at Palestine Medical Complex: Two Case Reports

Carbamazepine intoxication is not uncommon and accounts for many cases of poisoning among anticonvulsive medications users. Since there is no specific antidote for carbamazepine overdose, management is limited to gastric decontamination and supportive therapy. With its high protein binding, the role of extracorporeal elimination in carbamazepine intoxication is still questionable. Here two cases of severe carbamazepine intoxication are presented; the cases were brought to the emergency department after the ingestion of 12,000 mg of controlled release carbamazepine for the first case, and unknown amounts of the same drug for the second case. Both cases were presented with altered mental status, convulsion, and high serum carbamazepine levels of more than 20 mcg/mL. They were intubated and treated with continuous venovenous hemofiltration, after which carbamazepine levels declined significantly along with subsequent clinical improvement and complete neurological recovery. Both cases were discharged home for further psychiatric care.

Carbamazepine induced central hypothyroidism in a patient of focal seizures due to underlying porencephaly left frontal lobe and hippocampal atrophy

A case of central hypothyroidism, following controlled-release carbamazepine (CBZ-CR) monotherapy for focal seizure prophylaxis. A 19 years old woman, presented to the neurology department with history of three episodes of sudden onset, abnormal body movements during sleep. Patient was diagnosed as a case of focal seizures with secondary generalization and was prescribed tablet CBZ-CR 300 mg twice a day for seizure prophylaxis. 3 months later patient presented with complaints of facial hair growth and menstrual irregularities. The patient was seizure free and was continuing with the treatment. Blood biochemistry parameters indicated central hypothyroidism. According toWorld Health Organization Uppsala monitoring Centre (WHO-UMC) causality assessment, she was classified as ‘possible’ for carbamazepine-induced central hypothyroidism. Carbamazepine was discontinued. She was switched to tablet levetiracetam 500 mg twice daily, thyroxine 25 microgram once daily and clobazam 10 mg at bedtime. Conclusion: Thyroid function tests should be monitored in patients receiving carbamazepine therapy. Keywords: Carbamazepine, Drug induced hypothyroidism, Focal seizure, Thyroid function tests, Porencephaly.

A comparative study of the safety, efficacy, quality of life and pharmacoeconomics of levetiracetam with controlled-release carbamazepine in patients of new onset focal seizures: A randomized controlled academic trial

Background: Carbamazepine is used widely in focal seizures but has the disadvantage of frequent drug interactions. Levetiracetam is a novel antiseizure drug with better pharmacokinetic profile with less drug interactions and having broader therapeutic range. Aims: The aim of our study was to generate more evidence for better management of focal seizures with available anti-seizure monotherapy. Materials and Methods: It was a randomized, prospective, open label, comparative interventional study, conducted at Dr. R.P.G.M.C, Kangra at Tanda. 38 participants received tablet levetiracetam (LEV) 1000 mg/day and 36 participants received tablet controlled-release carbamazepine (CBZ-CR) 600 mg/day. Results: CBZ-CR group had significantly higher CNS depression as compared to LEV (p=0.027). Hematological adverse effects with CBZ-CR were reversible. Both the drugs were safe on kidney and liver. 22 (66.7%) patients in LEV group and 26 (78.8%) in CBZ-CR group remained seizure free. QOL: Both the drugs significantly improved QOL. Pharmacoeconomics: CBZ-CR costed significantly lower than LEV (p Conclusion: Both the drugs are well tolerated and equally efficacious in controlling focal seizures. Quality of- life has improved significantly in both the groups. CBZ-CR is pharmacoeconomically better than LEV for treatment of new onset focal seizures in adult patients. Keywords: Controlled release carbamazepine, Epilepsy, Focal seizure, Levetiracetam, Pharmacoeconomics.

Carbamazepine induced leukopenia: A case series

This is a case series of 4 patients who developed leukopenia on, controlled-release carbamazepine (CBZCR) monotherapy for focal seizure prophylaxis. All 4 cases (2 males and 2 females), presented to the neurology department with history of episodes of sudden onset, abnormal body movements. Patients were diagnosed as cases of focal seizures and were prescribed tablet CBZ-CR 300 mg twice a day for seizure prophylaxis. One month later patients presented for follow-up and were continuing with the treatment. Blood biochemistry parameters indicated leukopenia with total leukocyte count less than 4000 per mm3. According to World Health Organization Uppsala monitoring Centre (WHO-UMC) causality assessment, all 4 cases were classified as ‘probable/likely’ for carbamazepine-induced leukopenia. Carbamazepine was continued and total leukocyte count gradually recovered on 3-months follow-up. Conclusion: Total leukocyte count should be documented before initiating carbamazepine therapy. Patients with pre-existing leukopenia should not receive carbamazepine. All patients receiving carbamazepine should be monitored for leukocyte count in addition to other blood biochemistry parameters. Keywords: Carbamazepine,Drug induced leukopenia, Focal-seizure, Total leukocyte count.

Eslicarbazepine Acetate: A Review in Focal-Onset Seizures

Eslicarbazepine acetate (Zebinix®), a voltage-gated sodium channel blocker, is a once-daily, orally administered anti-seizure medication available in the EU for use as monotherapy in adults with newly diagnosed focal-onset seizures and as adjunctive therapy in adults, adolescents and children aged > 6 years with focal-onset seizures. In adult patients, adjunctive eslicarbazepine acetate was generally associated with a significant decrease in seizure frequency and an increase in responder rate compared with placebo. The drug was also an effective monotherapy agent in adult patients, demonstrating noninferiority to controlled-release carbamazepine, in terms of seizure freedom rates. In paediatric patients, eslicarbazepine acetate provided seizure control when administered as adjunctive therapy, with the benefits appearing to be dependent on age and dose. The antiepileptic efficacy of eslicarbazepine acetate as adjunctive therapy or as monotherapy was maintained during longer-term extension studies, with each extension study period being up to 2 years. Oral eslicarbazepine acetate was generally well tolerated when administered as adjunctive therapy or monotherapy in adult patients and when administered as adjunctive therapy in paediatric patients, with most adverse events being of mild or moderate intensity. In conclusion, with the convenience of once-daily administration, eslicarbazepine acetate is an effective and generally well-tolerated treatment option for adults, adolescents and children aged > 6 years with focal-onset seizures.

What has been the impact of new drug treatments on epilepsy?

Nearly two dozen antiseizure medications (ASMs) with different mechanisms of action have been introduced over the past three decades with the aim of providing better efficacy or safety profile than the previous drugs. Several new ASMs with improvement on a classic drug family or have novel mechanisms of action have been recently approved for epilepsy. The present review explored recent studies or guidelines on new agents and discussed the potential impact of these novel treatments on epilepsy management and future directions of research. Long-term cohort studies showed that, collectively, the second-generation did not improve the overall prognosis of epilepsy. Individual monotherapy studies showed similar efficacy of second-generation (levetiracetam and zonisamide) and third-generation (eslicarbazepine acetate and lacosamide) ASMs compared to controlled-release carbamazepine for the treatment of focal epilepsy. However, there appears to be no evidence to support any second-generation or third-generation ASMs to be as efficacious as valproate monotherapy for generalized and unclassified epilepsies. Cannabidiol adjunctive treatments were found to be efficacious for Dravet syndrome and Lennox-Gastaut syndrome. Although most newer generation ASMs are less prone to drug-drug interactions, stiripentol and cannabidiol can elevate the plasma concentration of N-desmethylclobazam, the active metabolite of clobazam. Generally speaking, the second-generation ASMs have lower teratogenic risk than the older drugs but there is scant study on neurodevelopmental effect of third-generation ASMs. Although the newer generation ASMs may not have improved the overall seizure control they have advantages in terms of drug-drug interactions and teratogenicity, and thus offer valuable individualized options in the treatment of epilepsy.

Tolerability and efficacy of lacosamide and controlled-release carbamazepine monotherapy in patients with newly diagnosed epilepsy and concomitant psychiatric conditions: Post hoc analysis of a prospective, randomized, double-blind trial

Psychiatric comorbidities are common in patients with epilepsy. A double-blind noninferiority monotherapy trial (SP0993; NCT01243177) enrolled newly diagnosed patients (≥16 years) with focal or generalized tonic-clonic seizures. Patients were randomized 1:1 to lacosamide or carbamazepine controlled-release (carbamazepine-CR). Here, we report data from an exploratory post hoc analysis of patients who reported ongoing psychiatric conditions (Medical Dictionary for Regulatory Activities System Organ Class). Of 886 treated patients in the trial, 126 (14.2%; 64 on lacosamide; 62 on carbamazepine-CR) reported at least one ongoing psychiatric condition at screening, most commonly depression (38.1%), insomnia (27.8%), and anxiety (26.2%). In this subgroup, 32/64 (50.0%) patients on lacosamide and 22/62 (35.5%) on carbamazepine-CR completed the trial. The most common reasons for discontinuation in patients on lacosamide and carbamazepine-CR were adverse events (10.9%, 24.2%) and lack of efficacy (18.8%, 11.3%). Treatment-emergent adverse events (TEAEs) were reported in 52 (81.3%) of patients on lacosamide and 56 (90.3%) of patients on carbamazepine-CR, most commonly (≥10% patients in either treatment group; lacosamide, carbamazepine-CR) dizziness (12.5%, 16.1%), headache (12.5%, 14.5%), nasopharyngitis (12.5%, 9.7%), fatigue (7.8%, 14.5%), nausea (7.8%, 11.3%), somnolence (1.6%, 12.9%), and gamma-glutamyltransferase increase (1.6%, 12.9%). Overall, 15 (23.4%) lacosamide-treated and 10 (16.1%) carbamazepine-CR treated patients reported psychiatric TEAEs, most commonly (≥3 patients in either treatment group; lacosamide, carbamazepine-CR) depression (4.7%, 0) and anxiety (3.1%, 6.5%). There were no reports of psychotic disorder, epileptic psychosis, acute psychosis, or serious psychiatric TEAEs. Stratified Kaplan–Meier estimates for 6- and 12-month seizure freedom at the last evaluated dose were similar with lacosamide and carbamazepine-CR (6 months 81.0%, 75.6%; 12 months 62.5%, 66.6%). A higher proportion of patients on lacosamide than carbamazepine-CR completed 6 (67.2%, 45.2%) and 12 months (50.0%, 37.1%) of treatment at the last evaluated dose without a seizure. This exploratory post hoc analysis indicated that lacosamide monotherapy was efficacious and generally well tolerated in patients with newly diagnosed epilepsy and concomitant psychiatric conditions. In this subpopulation, lacosamide showed similar efficacy and numerically better effectiveness than carbamazepine-CR.

Long-term Tolerability of Lacosamide and Controlled-release Carbamazepine Monotherapy by Number of Additional Medical Conditions: A Post Hoc Analysis (S3.008)

Long-term Tolerability of Lacosamide and Controlled-release Carbamazepine Monotherapy by Number of Additional Medical Conditions: A Post Hoc Analysis (S3.008)

Antiepileptic monotherapy in newly diagnosed focal epilepsy. A network meta-analysis.

Second and third generation AEDs have been directly compared to controlled-release carbamazepine (CBZ-CR) as initial monotherapy for new-onset focal epilepsy. Conversely, no head-to-head trials have been performed. The aim of this study was to estimate the comparative efficacy and tolerability of the antiepileptic monotherapies in adults with newly diagnosed focal epilepsy through a network meta-analysis (NMA). Randomized, double-blinded, parallel group, monotherapy studies comparing any AED to CBZ-CR in adults with newly diagnosed untreated epilepsy with focal-onset seizures was identified. The outcome measures were the seizure freedom for 6 and 12months, the occurrence of treatment-emergent adverse events (TEAEs), and the treatment withdrawal due to TEAEs. Mixed treatment comparisons were conducted by a Bayesian NMA using the Markov chain Monte Carlo methods. Effect sizes were calculated as odds ratios (ORs) with 95% credible intervals (CrIs). Four trials were included involving 2856 participants, 1445 for CBZ-CR and 1411 for the comparative AEDs. Monotherapy AEDs compared to CBR-CR were levetiracetam (LEV), zonisamide (ZNS), lacosamide (LCM), and eslicarbazepine acetate (ESL). There were no statistical differences in the 6- and 12-month seizure freedom and TEAEs occurrence between LEV, ZNS, LCM, ESL, and CBZ-CR In the analysis of drug withdrawal due to TEAEs, LCM treatment was associated with a significantly lower discontinuation rate than CBZ-CR (OR 0.659, 95% CrI 0.428-0.950). LEV, ZNS, LCM, and ESL are effective initial monotherapy treatments in adult patients with newly diagnosed focal epilepsy and represent suitable alternatives to CBZ-CR.

Unblinded, randomized multicenter trial comparing lamotrigine and valproate combination with controlled-release carbamazepine monotherapy as initial drug regimen in untreated epilepsy

PurposeTo compare controlled-release carbamazepine monotherapy (CBZ-CR) with lamotrigine and valproate combination therapy (LTG + VPA) in equivalent total drug load, as initial drug regimen in untreated patients with partial and/or generalized tonic-clonic seizures (GTCS). MethodsThis unblinded, randomized, 60-week superiority trial recruited patients having two or more unprovoked seizures with at least one seizure during previous three months. After randomization into CBZ-CR or LTG + VPA, patients entered into eight-week titration phase (TP), followed by 52-week maintenance phase (MP). Median doses of CBZ-CR and LTG + VPA were 600 mg/day and 75 mg/day + 500 mg/day, respectively. Primary outcome measure was completion rate (CR), a proportion of patients who have completed the 60-week study as planned. Secondary efficacy measures included seizure-free rate (SFR) for 52-week of MP and time to first seizure (TTFS) during MP. ResultsAmong 207 randomized patients, 202 underwent outcome analysis (104 in CBZ-CR, 98 in LTG + VPA). CR was 62.5% in CBZ-CR and 65.3% in LTG + VPA (p = 0.678). SFR during MP was higher in LTG + VPA (64.1%) than CBZ-CR (47.8%) (P = 0.034). TTFS was shorter with CBZ-CR (p = 0.041). Incidence of adverse effects (AEs) were 57.7% in CBZ-CR and 60.2% in LTG + VPA and premature drug withdrawal rates due to AEs were 12.5% and 7.1%, respectively, which were not significantly different. ConclusionCR was comparable between LTG + VPA and CBZ-CR, however, both SFR for 52-week MP and TTFS during MP were in favor of LTG + VPA than CBZ-CR. The study suggested that LTG + VPA can be an option as initial drug regimen for untreated patients with partial seizures and/or GTCS except for women of reproductive age.

Randomized double-blind non-inferiority trial of lacosamide versus controlled-release carbamazepine monotherapy – subgroup analysis of unclassified patients with initial generalized tonic-clonic seizures only (P4.110)

Randomized double-blind non-inferiority trial of lacosamide versus controlled-release carbamazepine monotherapy – subgroup analysis of unclassified patients with initial generalized tonic-clonic seizures only (P4.110)

Efficacy of lacosamide monotherapy in patients with newly diagnosed epilepsy stratified by baseline disease severity: sub-analysis of data from a prospective non-inferiority trial versus controlled-release carbamazepine (P5.227)

Efficacy of lacosamide monotherapy in patients with newly diagnosed epilepsy stratified by baseline disease severity: sub-analysis of data from a prospective non-inferiority trial versus controlled-release carbamazepine (P5.227)

Efficacy and tolerability of lacosamide monotherapy in elderly patients with newly diagnosed epilepsy: subgroup analysis of a non-inferiority trial versus controlled-release carbamazepine (P5.232)

Efficacy and tolerability of lacosamide monotherapy in elderly patients with newly diagnosed epilepsy: subgroup analysis of a non-inferiority trial versus controlled-release carbamazepine (P5.232)

Efficacy and tolerability of lacosamide monotherapy in patients with newly diagnosed epilepsy: A prospective randomized double-blind non-inferiority trial versus controlled-release carbamazepine (P5.228)

Efficacy and tolerability of lacosamide monotherapy in patients with newly diagnosed epilepsy: A prospective randomized double-blind non-inferiority trial versus controlled-release carbamazepine (P5.228)

Lacosamide vs. Controlled-Release Carbamazepine Monotherapy as Initial Epilepsy Treatment

Nearly all new antiepilepsy medications (AEDs) obtain initial indications as adjunctive (add-on) therapy in patients with medically uncontrolled

Immediate-release versus controlled-release carbamazepine in the treatment of epilepsy.

Carbamazepine (CBZ) is a commonly used drug for epilepsy that is associated with troublesome adverse events including dizziness, double vision, drowsiness, poor co-ordination and unsteadiness. These adverse events often occur during peaks in drug plasma concentration. These adverse events may limit the daily dose of CBZ that can be tolerated and reduce the chances of seizure control in patients who require high doses. A controlled-release formulation of CBZ delivers the same dose over a longer period of time when compared to a standard immediate-release formulation, thereby reducing post-dose peaks in CBZ plasma concentration and potentially reducing adverse events.This is an updated version of the original Cochrane review published in Issue 12, 2014. To determine the efficacy of immediate-release CBZ (IR CBZ) versus controlled-release CBZ (CR CBZ) in patients diagnosed with epilepsy.The following review questions were investigated.(1) For newly diagnosed patients commencing CBZ, how do IR and CR formulations compare for efficacy and tolerability?(2) For patients on established treatment with IR CBZ but experiencing unacceptable adverse events, what is the effect on seizure control and the tolerability of a switch to a CR formulation versus remaining on the IR formulation? We searched the Cochrane Epilepsy Group Specialized Register, CENTRAL, and MEDLINE (Ovid) from inception to 30 August 2016. Randomised controlled trials comparing IR CBZ to CR CBZ in patients commencing monotherapy and patients presently treated with IR CBZ but experiencing unacceptable adverse events.Primary outcome measures included measures of seizure frequency, incidence of adverse events, proportion of patients with treatment failure and quality of life measures. Two review authors independently assessed trials for inclusion, extracted the data and recorded relevant information on a standardised data extraction form. We used the Cochrane risk of bias tool to assess the methodological quality of included studies.The heterogeneity of the included trials with respect to the reporting of outcomes resulted in only a narrative, descriptive analysis being possible for both the categorical and time-to-event data. Ten trials (296 participants) fulfilled the criteria for inclusion in this review. Only one study had a low risk of bias. Two studies had a high risk of bias and the rest of the studies were rated as unclear risk of bias. One trial included patients with newly diagnosed epilepsy and nine included patients on treatment with IR CBZ.Eight trials reported heterogeneous measures of seizure frequency with conflicting results. A statistically significant difference was observed in only one trial, with patients prescribed CR CBZ experiencing fewer seizures than patients prescribed IR CBZ.Nine trials reported measures of adverse events. There was a trend in favour of CR CBZ with four trials reporting a statistically significant reduction in adverse events compared to IR CBZ. A further two trials reported fewer adverse events with CR CBZ but the reduction was not statistically significant. One trial found no difference in adverse events, and another trial reported more adverse events in the CR CBZ group than the IR CBZ group, although the increase was not statistically significant. For this update no new eligible studies were identified and the conclusions drawn from the initial review remain unchanged.At present, data from trials do not confirm or refute an advantage for CR CBZ over IR CBZ for seizure frequency or adverse events in patients with newly diagnosed epilepsy.For trials involving epilepsy patients already prescribed IR CBZ, no conclusions can be drawn concerning the superiority of CR CBZ with respect to seizure frequency.There is a trend for CR CBZ to be associated with fewer adverse events when compared to IR CBZ. A change to CR CBZ may therefore be a worthwhile strategy in patients with acceptable seizure control on IR CBZ but experiencing unacceptable adverse events. The included trials were of small size and of poor methodological quality limiting the validity of this conclusion.Randomised controlled trials comparing CR CBZ to IR CBZ and using clinically relevant outcomes are required to inform the choice of CBZ preparation for patients with newly diagnosed epilepsy.

Efficacy, safety, and tolerability of lacosamide monotherapy versus controlled-release carbamazepine in patients with newly diagnosed epilepsy: a phase 3, randomised, double-blind, non-inferiority trial

Further options for monotherapy are needed to treat newly diagnosed epilepsy in adults. We assessed the efficacy, safety, and tolerability of lacosamide as a first-line monotherapy option for these patients. In this phase 3, randomised, double-blind, non-inferiority trial, patients from 185 epilepsy or general neurology centres in Europe, North America, and the Asia Pacific region, aged 16 years or older and with newly diagnosed epilepsy were randomly assigned in a 1:1 ratio, via a computer-generated code, to receive lacosamide monotherapy or controlled-release carbamazepine (carbamazepine-CR) twice daily. Patients, investigators, and trial personnel were masked to treatment allocation. From starting doses of 100 mg/day lacosamide or 200 mg/day carbamazepine-CR, uptitration to the first target level of 200 mg/day and 400 mg/day, respectively, took place over 2 weeks. After a 1-week stabilisation period, patients entered a 6-month assessment period. If a seizure occurred, the dose was titrated to the next target level (400 or 600 mg/day for lacosamide and 800 or 1200 mg/day for carbamazepine-CR) over 2 weeks with a 1-week stabilisation period, and the 6-month assessment period began again. Patients who completed 6 months of treatment and remained seizure-free entered a 6-month maintenance period on the same dose. The primary efficacy outcome was the proportion of patients remaining free from seizures for 6 consecutive months after stabilisation at the last assessed dose. The predefined non-inferiority criteria were -12% absolute and -20% relative difference between treatment groups. This trial is registered with ClinicalTrials.gov, number NCT01243177. The trial was done between April 27, 2011, and Aug 7, 2015. 888 patients were randomly assigned treatment. 444 patients taking lacosamide and 442 taking carbamazepine-CR were included in the full analysis set (took at least one dose of study treatment), and 408 and 397, respectively, were included in the per-protocol set. In the full analysis set, 327 (74%) patients in the lacosamide group and 308 (70%) in the carbamazepine-CR group completed 6 months of treatment without seizures. The proportion of patients in the full analysis set predicted by the Kaplan-Meier method to be seizure-free at 6 months was 90% taking lacosamide and 91% taking carbamazepine-CR (absolute treatment-difference: -1·3%, 95% CI -5·5 to 2·8 relative treatment difference: -6·0%). Kaplan-Meier estimates results were similar in the per-protocol set (92% and 93%; -1·3%, -5·3 to 2·7; -5·7%). Treatment-emergent adverse events were reported in 328 (74%) patients receiving lacosamide and 332 (75%) receiving carbamazepine-CR. 32 (7%) patients taking lacosamide and 43 (10%) taking carbamazepine-CR had serious treatment-emergent adverse events, and 47 (11%) and 69 (16%), respectively, had treatment-emergent adverse events that led to withdrawal. Treatment with lacosamide met the predefined non-inferiority criteria when compared with carbamazepine-CR. Therefore, it might be useful as first-line monotherapy for adults with newly diagnosed epilepsy. UCB Pharma.