Tolerability Of Carbamazepine Research Articles

Real-world effectiveness and tolerability of carbamazepine and oxcarbazepine in 354 patients with trigeminal neuralgia.

It is widely agreed that carbamazepine and oxcarbazepine are highly effective in the long-term treatment of trigeminal neuralgia. However, the tolerability of these drugs across the different aetiologies of trigeminal neuralgia is still undetermined. In this retrospective, real-world study, we assessed the effectiveness and tolerability of carbamazepine and oxcarbazepine in a large cohort of patients with classical (254 patients), secondary (60 patients) and idiopathic (40 patients) trigeminal neuralgia. We analysed data using a propensity score analysis to account for selection bias; frequencies of side effects associated with carbamazepine and oxcarbazepine were calculated by adjusting data with the inverse probability of treatment weighting. The initial proportion of responders was 88.3% with carbamazepine, and 90.9% with oxcarbazepine. The number of refractory patients was significantly higher in idiopathic (15%) and secondary forms (27%) than in classical trigeminal neuralgia (6%; p<.05). In 53 patients treated with carbamazepine (29.6%) and in 22 treated with oxcarbazepine (12.6%), major side effects caused treatment interruption or dosage reduction to an unsatisfactory level. Side effects occurred more frequently in patients treated with carbamazepine (43.6%) than with oxcarbazepine (30.3%, p<.0001). The frequency of treatment discontinuation was higher in patients with secondary and idiopathic forms than in those with classical trigeminal neuralgia (p<.05). Our real-world study shows that carbamazepine and oxcarbazepine are effective in most patients with trigeminal neuralgia; nevertheless, side effects are still a major issue, particularly in patients with secondary and idiopathic trigeminal neuralgia. Although carbamazepine and oxcarbazepine are effective in most patients with trigeminal neuralgia, their side effects are still a major issue, thus necessitating the development of better-tolerated drugs.

CARBAMAZEPINE AS A PAIN TREATMENT OF TRIGEMINAL NEURALGIA

Pain and fear of pain continue to be the commonest and strongest motivation for the patients to seek medical help. Pain is a personal experience of the sufferer that cannot be shared and wholly belongs to the sufferer. Trigeminal neuralgia (NT) is a notable facial pain disorder resulting in periodic severe pain that produces one of the most severe kinds of pain known to mankind. Treatment of this debilitating condition may be varied, ranging from medical to surgical interventions. Anticonvulsant are commonly used for its treatment. One of anticonvulsant drug is carbamazepine (CBZ). This paper will discuss about the efficacy and tolerability of CBZ for the treatment of NT.

The pharmacokinetics of oral carbamazepine in rats dosed using an automated drug delivery system.

Pharmacokinetics (PK) of antiseizure drugs differ considerably between rats and humans. Rodents require larger and more frequent doses to maintain therapeutic drug levels. This study uses the antiseizure drug (ASD) carbamazepine (CBZ) to validate the application of a previously described automated drug delivery system for delivering chronic oral medication to rats. Treatment-naive, male Sprague-Dawley rats were treated with oral CBZ, 75mg/kg every 6hours for 10days, via the automated feeder. Blood samples were collected on day 0 (acute), day 2 (steady-state), and day 9 (chronic) and used to measure plasma CBZ and carbamazepine-10,11-epoxide (CBZ-E) concentrations via high-performance liquid chromatography. The PK of CBZ and CBZ-E were modeled using Monolix v2018R1. The acute and chronic tolerability of CBZ was evaluated using the open field test. CBZ and CBZ-E concentrations were best described by a one-compartment parent-metabolite model with first-order absorption and elimination kinetics. Observed and predicted CBZ concentrations were maintained within the therapeutic window (4-12μg/mL) for the duration of the study. There was no change in open-field test activity following acute or chronic oral dosing of 75mg/kg CBZ compared to a pretreatment baseline (P>0.4). Oral administration of CBZ dosed q.i.d. in rats using an automated drug delivery system results in therapeutic concentrations of CBZ and its active metabolite. This study represents the first PK validation for this previously described preclinical drug delivery system.

Effect of Levetiracetam Monotherapy in Nonlesional Focal Childhood Epilepsy

This article compares the efficacy and tolerability of carbamazepine (CBZ) and levetiracetam (LEV) when used as initial monotherapy in children with nonlesional focal epilepsy. Patients with nonlesional focal epilepsy were subdivided into two groups according to the initial monotherapy: a LEV group administered LEV at an initial dose of 5 mg/kg/day and a CBZ group. Seizure response, adverse events, medication dose, reasons for discontinuing medication, adherence, and random serum levels were recorded. The overall percentage of patients who failed initial treatment and reasons for each treatment failure were determined. Data were analyzed from 183 children who received CBZ monotherapy and 46 children who received LEV monotherapy for ≥12 months. Overall, 126 patients (68.9%) became seizure-free with CBZ, compared with 37 patients (80.4%) with LEV. Moreover, four patients in CBZ and four patients in LEV groups showed a >50% reduction in seizure frequency. The efficacy rate was significantly higher and the adverse event rate was significantly lower in the LEV group than in the CBZ group (p = 0.0129 and p = 0.0039, respectively). LEV may offer superior efficacy and a lower risk of adverse effects compared with CBZ. LEV as initial monotherapy may represent a valuable treatment option for children with nonlesional focal childhood epilepsy.

Efficacy and tolerability of anti-epileptic drugs-an internet study.

To ascertain efficacy and tolerability of carbamazepine (CBZ), sodium valproate (VPA), lamotrigine (LTG) and levetiracetam (LEV) using the UKAED register (www.ukaed.info). Patients on CBZ (n=91), VPA (n=61), LTG (n=105), LEV (n=72) and healthy control subjects (CTR) on no medication (n=51) were extracted. All patients had anonymously provided information on seizure type and frequency and completed the Liverpool Adverse Event Profile (LAEP). The number of seizure-free patients in the last 4weeks was overall CBZ/VPA/LTG/LEV=60%/79%/67%/67%, for generalized epilepsy was CBZ/VPA/LTG/LEV=67%/89%/65%/94%, and for localization-related epilepsy was CBZ/VPA/LTG/LEV=59%/71%/67%/57%. Mean LAEP scores were CBZ/VPA/LTG/LEV/CTR=42.21/39.66/39.86/43.01/29.69. The mean LAEP was significantly higher in patients reporting depression and in patients with active epilepsy than in patients without depression and remission. Central nervous system (CNS) adverse effects including memory problems, difficulty concentrating, depression, unsteadiness, restlessness, feelings of anger, shaky hands and dizziness were significantly more frequent in CBZ, VPA, LTG and LEV than in CTR. The feeling of anger was significantly more frequent in LEV, and depression was significantly more frequent in CBZ compared to the other drugs. In this Internet-based register of self-reported efficacy and tolerability, CBZ, VPA, LTG and LEV were similar. Self-reported CNS adverse effects were significantly more frequent than in controls. In addition, anger was associated with LEV and depression with CBZ. Confounding factors were depression and uncontrolled epilepsy.

P.2.e.005 Korean medication algorithm for bipolar disorder

Our previous study has shown the beneficial effects of the herbal medicine called Free and Easy Wanderer Plus (FEWP) as adjunctive therapy with carbamazepine (CBZ) in the 12-week treatment of bipolar disorders (Zhang ZJ, Kang WH, Tan QR, Li Q, Gao CG, Zhang FG, et al., Adjunctive herbal medicine with carbamazepine for bipolar disorders: a double-blind, randomized, placebo-controlled study. J Psychiatr Res; 2005). Here, we present follow-up data obtained from a continuation of the previously reported study. Treatment and clinical evaluation of bipolar patients (n = 188) who had randomly received 12-week CBZ plus placebo (n = 92) or CBZ plus FEWP (n = 96) were extended to 26 weeks under double-blind condition. Patients in adjunctive FEWP showed a significantly lower overall discontinuation rate (31%) at endpoint compared to placebo (51%, p = 0.009), and of 15% in adjunctive FEWP discontinued due to intolerable side effects, markedly lower than those in placebo (28%, p = 0.019). No difference in discontinuation for lack of efficacy and exacerbation was observed in the two groups. Patients receiving adjunctive FEWP had significantly fewer adverse side effects and lower serum levels of CBZ than those in placebo. A separate study was further conducted to evaluate the effectiveness of FEWP as monotherapy in depressed patients. A total of 87 unipolar and 62 bipolar depressed patients were randomly assigned to treatment with 36 g/day FEWP (n = 86) or placebo (n = 63) for 12 weeks under double-blind condition. Efficacy was measured using the Hamilton Rating Scale for Depression (HAMD), Montgomery–Asberg Depression Rating Scale (MADRS), and Clinical Global Impression-Severity (CGI-S). Both unipolar and bipolar patients assigned to FEWP displayed significantly greater improvement on the three efficacy indices and significantly higher clinical response rate (74%) than those treated with placebo (42%, p < 0.001) at endpoint. These results suggest that adjunctive FEWP improves tolerability of CBZ in the long-term use, which may be associated with the suppression of blood CBZ concentrations via herb-drug interactions. FEWP monotherapy may be also an effective alternative treatment for depressed conditions.

Effects of SCN1A and GABA Receptor Genetic Polymorphisms on Carbamazepine Tolerability and Efficacy in Chinese Patients with Partial Seizures: 2‐Year Longitudinal Clinical Follow‐Up

To investigate the tolerability and efficacy of carbamazepine treatment in patients with partial-onset seizures and the association with polymorphisms in the sodium channel α-subunit type 1 (SCN1A), and gamma-aminobutyric acid (GABA) receptor genes among the Chinese Han population. 448 patients were genotyped for single nucleotide polymorphisms selected of the SCN1A and GABA-receptor genes. Monotherapy with carbamazepine (CBZ) was administered to the patients. The effectiveness of CBZ treatment was evaluated with regard to efficacy by the decrease in seizures and tolerability by retention rates. SCN1A rs3812718 A/G with CBZ tolerability (P= 0.038) throughout 24 months of clinical follow-up and the GABRA1 rs2290732 A/G were significantly associated with CBZ tolerability (P= 0.001). The maintenance dose and serum level of CBZ in AA genotype carriers of rs3812718 A/G were significantly higher than those of GG genotype carriers between 3 and 12 months of follow-up. The proportion of AA genotype carriers of rs2298771 A/G with seizure free was significantly higher than that of AG+GG genotype carriers from 3 months to 15 months of follow-up (P < 0.05). rs3812718 A/G and rs2290732 A/G polymorphisms affected the tolerability of CBZ. rs2298771 A/G was associated with efficacy of CBZ treatment.

Oxcarbazepine versus carbamazepine monotherapy for partial onset seizures

Partial onset seizures are often treated with the standard antiepileptic drug carbamazepine. Oxcarbazepine is a newer antiepileptic drug related to carbamazepine that is claimed to be better tolerated. To compare efficacy and tolerability of carbamazepine and oxcarbazepine monotherapy for partial onset seizures. We searched the Cochrane Epilepsy Group Specialised Register (4 August 2009), the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library issue 3, 2009), MEDLINE (January 1966 to May 2008), reference lists of relevant articles and conference proceedings. We also contacted manufacturers and researchers in the field for published or unpublished data. Blinded and unblinded randomised controlled trials of carbamazepine versus oxcarbazepine monotherapy for partial onset seizures. Both authors independently assessed trial quality, according to the guidelines in the Cochrane Reviewer's Handbook, and extracted information about study population, type of intervention, outcome measures and study design. All analyses in this review are by intention-to-treat. We tested for statistical heterogeneity among the identified studies using the chi-squared test. Three trials (723 participants) were included. Only one trial used adequate outcome measures of efficacy; therefore, the results pertaining to efficacy are based on a single trial, whereas the results pertaining to adverse events are based on all three included trials. There was no overall difference in time to treatment withdrawal between the two drugs (hazard ratio (HR) of oxcarbazepine (OXC) versus carbamazepine (CBZ): 1.04, 95% confidence interval (CI) 0.78 to 1.39). Further analyses showed no significant difference in treatment withdrawal for unacceptable side effects (HR of OXC versus CBZ: 0.85, 95% CI 0.59 to 1.24) and in treatment withdrawal for inadequate seizure control (HR of OXC versus CBZ: 1.33, 95% CI 0.82 to 2.15). Oxcarbazepine and carbamazepine appeared to be similarly effective and well tolerated although the confidence intervals around estimates were wide and do not rule out the possibility of important differences existing. Significantly fewer patients on carbamazepine treatment developed nausea or vomiting, or both (odds ratio of OXC versus CBZ: 3.15, 95% CI 1.39 to 7.14). Oxcarbazepine and carbamazepine appear to be similarly effective and well tolerated. However, the possibility of important differences existing between these drugs cannot be ruled out.

The beneficial effects of the herbal medicine Free and Easy Wanderer Plus (FEWP) for mood disorders: Double-blind, placebo-controlled studies

Our previous study has shown the beneficial effects of the herbal medicine called Free and Easy Wanderer Plus (FEWP) as adjunctive therapy with carbamazepine (CBZ) in the 12-week treatment of bipolar disorders (Zhang ZJ, Kang WH, Tan QR, Li Q, Gao CG, Zhang FG, et al., Adjunctive herbal medicine with carbamazepine for bipolar disorders: a double-blind, randomized, placebo-controlled study. J Psychiatr Res; 2005). Here, we present follow-up data obtained from a continuation of the previously reported study. Treatment and clinical evaluation of bipolar patients ( n = 188) who had randomly received 12-week CBZ plus placebo ( n = 92) or CBZ plus FEWP ( n = 96) were extended to 26 weeks under double-blind condition. Patients in adjunctive FEWP showed a significantly lower overall discontinuation rate (31%) at endpoint compared to placebo (51%, p = 0.009), and of 15% in adjunctive FEWP discontinued due to intolerable side effects, markedly lower than those in placebo (28%, p = 0.019). No difference in discontinuation for lack of efficacy and exacerbation was observed in the two groups. Patients receiving adjunctive FEWP had significantly fewer adverse side effects and lower serum levels of CBZ than those in placebo. A separate study was further conducted to evaluate the effectiveness of FEWP as monotherapy in depressed patients. A total of 87 unipolar and 62 bipolar depressed patients were randomly assigned to treatment with 36 g/day FEWP ( n = 86) or placebo ( n = 63) for 12 weeks under double-blind condition. Efficacy was measured using the Hamilton Rating Scale for Depression (HAMD), Montgomery–Asberg Depression Rating Scale (MADRS), and Clinical Global Impression-Severity (CGI-S). Both unipolar and bipolar patients assigned to FEWP displayed significantly greater improvement on the three efficacy indices and significantly higher clinical response rate (74%) than those treated with placebo (42%, p < 0.001) at endpoint. These results suggest that adjunctive FEWP improves tolerability of CBZ in the long-term use, which may be associated with the suppression of blood CBZ concentrations via herb-drug interactions. FEWP monotherapy may be also an effective alternative treatment for depressed conditions.

Effectiveness and Tolerability of Carbamazepine vs. Oxcarbazepine as Mood Stabilizers

AbstractBackground. Patients with bipolar illness or maniac-type schizoaffective disorder often present a variety of symptoms and mixed responses to treatment. Several anticonvulsants have been found effective in the treatment of mood disorders. In the early 70's, the clinical efficacy of carbamazepine in the treatment of acute mania was reported. Oxcarbazepine has been available in the United States since 2000. Both drugs display a different spectrum of properties and side effect profiles. Objective. To compare the effectiveness and tolerability of carbamazepine and oxcarbazepine in a naturalistic setting. Methods. A retrospective and concurrent chart review of all patients treated with carbamazepine or oxcarbazepine (n = 33) as mood stabilizers between 01 and 12 2002. The effectiveness was evaluated using the Positive And Negative Syndrome Scale (PANSS). Tolerability was assessed according to side effects recorded on charts. Patients with charts that were not complete were excluded from this study. Resu...

Pharmacokinetics of Anti-epileptic Drugs and their Clinical Significance.

The serum concentration achieved and maintained following the administration of a fixed drug dosage is a direct consequence of the interactions of a wide variety of interrelated processes, including drug absorption, distribution, metabolism, and excretion, and the physiological status of the patient. These interrelationships are reviewed with specific reference to the major anti-epileptic drugs, phenobarbitone, phenytoin, sodium valproate, and carbamazepine, as well as a new first-line antiepileptic, oxcarbazepine.Both older drugs, such as phenobarbitone and phenytoin, and newer drugs, such as carbamazepine (CBZ) and sodium valproate, have been studied extensively over the past years giving valuable information for drug treatment. An important feature of oxcarbazepine (OXC) , which was developed through minimal changes in the structure of CBZ in order to improve on the tolerability of CBZ without sacrificing efficacy, is that its metabolites do not include the 11-epoxide which has been implicated in the side-effects of CBZ. In man, OXC is metabolized to a monohydroxy derivative which has independent anti-epileptic properties. OXC seems to lack several disadavantageous pharmacokinetic properties common to other major anti-epileptic drugs. OXC does not influence its own metabolism after repeated administration, in contrast to the auto-induction displayed by CBZ. The metabolism of OXC is not influenced by anti-epileptic co-medication and does not influence the kinetics of other anti-epileptic drugs - or if it does, then to a lesser extent than CBZ.

Pharmacokinetics of Anti-Epileptic Drugs and their Clinical Significance

The serum concentration achieved and maintained following the administration of a fixed drug dosage is a direct consequence of the interactions of a wide variety of interrelated processes, including drug absorption, distribution, metabolism, and excretion, and the physiological status of the patient. These interrelationships are reviewed with specific reference to the major anti-epileptic drugs, phenobarbitone, phenytoin, sodium valproate, and carbamazepine, as well as a new first-line antiepileptic, oxcarbazepine. Both older drugs, such as phenobarbitone and phenytoin, and newer drugs, such as carbamazepine (CBZ) and sodium valproate, have been studied extensively over the past years giving valuable information for drug treatment. An important feature of oxcarbazepine (OXC) , which was developed through minimal changes in the structure of CBZ in order to improve on the tolerability of CBZ without sacrificing efficacy, is that its metabolites do not include the 11-epoxide which has been implicated in the side-effects of CBZ. In man, OXC is metabolized to a monohydroxy derivative which has independent anti-epileptic properties. OXC seems to lack several disadavantageous pharmacokinetic properties common to other major anti-epileptic drugs. OXC does not influence its own metabolism after repeated administration, in contrast to the auto-induction displayed by CBZ. The metabolism of OXC is not influenced by anti-epileptic co-medication and does not influence the kinetics of other anti-epileptic drugs – or if it does, then to a lesser extent than CBZ.

Low tolerability of carbamazepine in psychiatric patients may restrict its clinical usefulness

There are reports of prophylactic efficacy of carbamazepine (CBZ) in manic depres sives when compared with placebo and chlorpromazine. Following a successful open pilot study by one of the authors, an attempt was made to compare carbamazepine and lithium carbonate in a double-blind, crossover trial, each patient being assigned to take each drug for 9 months in random order. However, of the first 14 patients to take carbamazepine four were withdrawn because of drug rashes and another two because of other adverse effects. The trial was discontinued, and a casenotes survey of 50 consecutive psychiatric patients who had been prescribed carbamazepine for mood disorders was then carried out, to establish the tolerability of the drug in clinical practice. Of these, 22 per cent had suffered dizziness, nausea or unsteadiness despite slow introduction of doses. Drug rashes occurred in 16 per cent of patients within the two weeks of starting treatment. A further 14 per cent had other unwanted effects. In total, 36 per cent of the patients had the drug stopped because of adverse effects. With regard to efficacy, in those taking the drug for more than 4 weeks, clinicians reported a definite or probable advantageous effect in 62 per cent of the sample, definite or probable lack of effect in 19 per cent and no opinion in 19 per cent. This low tolerability is not in accordance with previous reports of 2-6 per cent incidence of drug rashes and 10 per cent overall intolerance in neurological patients. We conclude that tolerability is a major drawback to the use of carbamazepine in some groups of psychiatric patients, although all the side- effects were reversible. However, clinical impressions suggested that in a number of patients no other therapeutic strategy was as effective in preventing mood swings.