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Molecular Pain 2020The trigeminal nerve (V) is the fifth and largest of all cranial nerves, and it is responsible for detecting sensory stimuli that arise from the craniofacial area. The... (Review)
Review
The trigeminal nerve (V) is the fifth and largest of all cranial nerves, and it is responsible for detecting sensory stimuli that arise from the craniofacial area. The nerve is divided into three branches: ophthalmic (V1), maxillary (V2), and mandibular (V3); their cell bodies are located in the trigeminal ganglia and they make connections with second-order neurons in the trigeminal brainstem sensory nuclear complex. Ascending projections via the trigeminothalamic tract transmit information to the thalamus and other brain regions responsible for interpreting sensory information. One of the most common forms of craniofacial pain is trigeminal neuralgia. Trigeminal neuralgia is characterized by sudden, brief, and excruciating facial pain attacks in one or more of the V branches, leading to a severe reduction in the quality of life of affected patients. Trigeminal neuralgia etiology can be classified into idiopathic, classic, and secondary. Classic trigeminal neuralgia is associated with neurovascular compression in the trigeminal root entry zone, which can lead to demyelination and a dysregulation of voltage-gated sodium channel expression in the membrane. These alterations may be responsible for pain attacks in trigeminal neuralgia patients. The antiepileptic drugs carbamazepine and oxcarbazepine are the first-line pharmacological treatment for trigeminal neuralgia. Their mechanism of action is a modulation of voltage-gated sodium channels, leading to a decrease in neuronal activity. Although carbamazepine and oxcarbazepine are the first-line treatment, other drugs may be useful for pain control in trigeminal neuralgia. Among them, the anticonvulsants gabapentin, pregabalin, lamotrigine and phenytoin, baclofen, and botulinum toxin type A can be coadministered with carbamazepine or oxcarbazepine for a synergistic approach. New pharmacological alternatives are being explored such as the active metabolite of oxcarbazepine, eslicarbazepine, and the new Nav1.7 blocker vixotrigine. The pharmacological profiles of these drugs are addressed in this review.
Topics: Animals; Anticonvulsants; Baclofen; Botulinum Toxins, Type A; Carbamazepine; Facial Pain; Gabapentin; Humans; Lamotrigine; Oxcarbazepine; Pain Management; Phenytoin; Pregabalin; Quality of Life; Trigeminal Neuralgia
PubMed: 31908187
DOI: 10.1177/1744806920901890 -
The Primary Care Companion For CNS... Dec 2018
Topics: Humans; Male; Mental Disorders; Oxcarbazepine; Psychotropic Drugs; Stevens-Johnson Syndrome; Young Adult
PubMed: 30605267
DOI: 10.4088/PCC.18l02304 -
The Cochrane Database of Systematic... Dec 2011Oxcarbazepine, a keto derivative of the 'mood stabiliser' carbamazepine, may have efficacy in the treatment of acute episodes of bipolar disorder. Potentially, it may... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Oxcarbazepine, a keto derivative of the 'mood stabiliser' carbamazepine, may have efficacy in the treatment of acute episodes of bipolar disorder. Potentially, it may offer pharmacokinetic advantages over carbamazepine.
OBJECTIVES
To review the efficacy and acceptability of oxcarbazepine compared to placebo and other agents in the treatment of acute bipolar episodes including mania, mixed episodes and depression.
SEARCH METHODS
Electronic databases were searched up to 2 September 2011. Specialist journals and conference proceedings were handsearched. Authors, experts in the field and pharmaceutical companies were contacted requesting information on published and unpublished trials.
SELECTION CRITERIA
Randomised controlled trials (RCTs) which compared oxcarbazepine with placebo or alternative agents, where the stated intent of intervention was the acute treatment of bipolar affective disorder were sought. Participants with bipolar disorder of either sex and of all ages were included.
DATA COLLECTION AND ANALYSIS
Data were extracted from the original reports individually by two review authors. For dichotomous data, odds ratios (ORs) were calculated with 95% confidence intervals (CI). Continuous data were analysed using standardised mean differences (with 95% CI).
MAIN RESULTS
Seven studies were included in the analysis (368 participants in total). All were on mania, hypomania, mixed episodes or rapid-cycling disorder. Overall, their methodological quality was relatively low.There was no difference in the primary outcome analysis - a fall of 50% or more on the Young Mania Rating Scale (YMRS) - between oxcarbazepine and placebo (N=1, n=110, OR =2.10, 95% CI 0.94 to 4.73) in one study, conducted in children; no studies were available in adult participants.In comparison with other mood stabilisers, there was no difference between oxcarbazepine and valproate as an antimanic agent using the primary outcome (50% or more fall in YMRS, OR=0.44, 95% CI 0.10 to 1.97, 1 study, n=60, P=0.273) or the secondary outcome measure (differences in YMRS between the two groups, SMD=0.18, 95% CI -0.24 to 0.59, 2 studies, n=90, P=0.40). No primary or secondary efficacy outcome measures were found comparing oxcarbazepine with lithium monotherapy.As an adjunctive treatment to lithium, oxcarbazepine reduced depression rating scale scores more than carbamazepine in a group of manic participants on the Montgomery-Åsberg Depression Rating Scale (MADRS) (SMD=- 1.12, 95% CI -1.71 to -0.53, 1 study, n=52, P=0.0002) and on the Hamilton Depression Rating Scale (HDRS) (SMD=- 0.77, 95% CI -1.35 to -0.20, 1 study, n=52, P=0.008).There was a higher incidence of adverse effects, particularly neuropsychiatric, in participants randomised to oxcarbazepine compared to those on placebo (1 study, n=115, 17% to 39% of participants on oxcarbazepine had at least one such event compared to 7% to 10% on placebo).There was no difference in adverse events rates between oxcarbazepine and other mood stabilisers or haloperidol.
AUTHORS' CONCLUSIONS
Currently, there are insufficient trials of adequate methodological quality on oxcarbazepine in the acute treatment of bipolar disorder to inform us on its efficacy and acceptability. Studies predominantly examine the treatment of mania: there are data from subgroup analysis on mixed affective, hypomania and rapid-cycling states.From the few studies included in this review, oxcarbazepine did not differ in efficacy compared to placebo in children and adolescents. It did not differ from other active agents in adults. It may have a poorer tolerability profile compared to placebo. No data were found on outcomes relevant to patients and clinicians, such as length of hospital admission. There is a need for adequately powered randomised controlled trials of good methodological quality to inform us of the therapeutic potential of oxcarbazepine across the spectrum of acute episodes in bipolar disorder.
Topics: Acute Disease; Adolescent; Adult; Antimanic Agents; Bipolar Disorder; Carbamazepine; Child; Humans; Lithium Compounds; Oxcarbazepine; Randomized Controlled Trials as Topic; Valproic Acid
PubMed: 22161387
DOI: 10.1002/14651858.CD004857.pub2 -
Canadian Journal of Psychiatry. Revue... Jul 2006To review the data on the efficacy of oxcarbazepine (OXC) in bipolar disorder (BD) and to provide recommendations for clinicians on the use of this medication in... (Review)
Review
OBJECTIVE
To review the data on the efficacy of oxcarbazepine (OXC) in bipolar disorder (BD) and to provide recommendations for clinicians on the use of this medication in treating BD.
METHOD
Using the terms oxcarbazepine and bipolar disorder, oxcarbazepine and mania, or oxcarbazepine and bipolar depression, we conducted a computer-aided search of MEDLINE for the years 1950 to 2005.
RESULTS
Case reports, retrospective chart reviews, open prospective studies, and double-blind studies reported the efficacy and effectiveness of OXC in treating BD. The data indicate that OXC has efficacy in treating acute mania and may be a useful add-on in treating acute bipolar depression and in BD prophylaxis. OXC is generally well-tolerated.
CONCLUSION
We recommend using OXC as monotherapy or as add-on therapy in refractory mania, but we recommend it be used predominantly as an add-on treatment for other phases of BD in patients who have not improved with well-established treatments or in patients who have difficulty tolerating adequate dosages.
Topics: Antipsychotic Agents; Bipolar Disorder; Carbamazepine; Double-Blind Method; Guidelines as Topic; Humans; Oxcarbazepine; Randomized Controlled Trials as Topic
PubMed: 16933591
DOI: 10.1177/070674370605100809 -
Drugs Jun 1992Oxcarbazepine is the 10-keto analogue of carbamazepine but has a distinct pharmacokinetic profile. In contrast to the oxidative metabolism of carbamazepine,... (Review)
Review
Oxcarbazepine is the 10-keto analogue of carbamazepine but has a distinct pharmacokinetic profile. In contrast to the oxidative metabolism of carbamazepine, oxcarbazepine is rapidly reduced to its active metabolite, 10,11-dihydro-10-hydroxy-carbamazepine. With the possible exception of the P450IIIA isozyme of the cytochrome P450 family, neither oxcarbazepine nor its monohydroxy derivative induce hepatic oxidative metabolism. Direct comparison of oxcarbazepine and carbamazepine has shown no difference in efficacy between these 2 agents in terms of reducing seizure frequency in patients with partial epilepsy with or without secondary generalisation, or with tonic-clonic seizures. Substitution of oxcarbazepine for carbamazepine in multiple antiepileptic drug regimens improved seizure control in some patients with refractory epilepsy; however, the rise in serum concentrations of concurrent antiepileptic agents secondary to elimination of carbamazepine-associated hepatic enzyme induction may have also played a role. Substitution of oxcarbazepine for carbamazepine was associated with improved cognition and alertness in some patients with epilepsy. Limited data indicate that oxcarbazepine may be a useful alternative to carbamazepine in the management of trigeminal neuralgia. Experience in patients with acute mania is promising, but the value of oxcarbazepine in managing affective disorders, particularly as a prophylactic agent, is not established. Oxcarbazepine may be better tolerated than carbamazepine; however, the current published database is small and the potential for oxcarbazepine to induce the type of serious idiosyncratic reactions occasionally associated with carbamazepine is unknown. Hyponatraemia has been reported in patients treated with oxcarbazepine. Although apparently asymptomatic, fluid restriction may be deemed necessary in some patients to reduce the risk of precipitating seizures secondary to low serum sodium. Thus, oxcarbazepine appears to be an effective substitute for carbamazepine in those patients intolerant of this agent, or experiencing significant drug interactions. Wider clinical experience should help clarify the long term efficacy and tolerability of oxcarbazepine. Pharmacokinetic advantages over current antiepileptic drugs, carbamazepine in particular, may then favour oxcarbazepine for consideration as a first-line agent in the management of partial and tonic-clonic epilepsy.
Topics: Affective Disorders, Psychotic; Anticonvulsants; Carbamazepine; Drug Interactions; Epilepsy; Humans; Oxcarbazepine; Trigeminal Neuralgia
PubMed: 1379159
DOI: 10.2165/00003495-199243060-00007 -
The Cochrane Database of Systematic... Mar 2020Epilepsy is a common neurological disorder. In approximately 30% of epilepsy cases, seizures are uncontrolled by one antiepileptic drug (AED). These people require... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Epilepsy is a common neurological disorder. In approximately 30% of epilepsy cases, seizures are uncontrolled by one antiepileptic drug (AED). These people require treatment with a combination of multiple AEDs and are described as having drug-resistant epilepsy. Oxcarbazepine is a keto-analogue of carbamazepine, an established AED, and can be used as an add-on treatment for drug-resistant epilepsy.
OBJECTIVES
To assess the efficacy and tolerability of oxcarbazepine as an add-on treatment for people with drug-resistant focal epilepsy.
SEARCH METHODS
The following databases were searched on 24 September 2018: Cochrane Register of Studies (CRS Web), which includes the Cochrane Epilepsy Group Specialized Register and the Cochrane Central Register of Controlled Trials (CENTRAL); Medline (Ovid) 1946 to 21 September 2018; ClinicalTrials.gov; and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP). Originally, we also searched SCOPUS as a substitute for Embase, but this is no longer necessary, because randomised and quasi-randomised controlled trials in Embase are now included in CENTRAL.
SELECTION CRITERIA
Randomised controlled trials with parallel-group or cross-over design, recruiting people of any age with drug-resistant focal epilepsy. We accepted any level of blinding and trials could be placebo- or active-controlled.
DATA COLLECTION AND ANALYSIS
In accordance with the methodological procedures expected by the Cochrane Collaboration, two review authors independently assessed trial eligibility before extracting data and assessing risk of bias. We assessed the primary outcomes: median percentage seizure reduction per 28 days; 50% or greater reduction in seizure frequency; and adverse effects including ataxia, hyponatraemia, and somnolence. We assessed the secondary outcomes: seizure freedom; treatment withdrawal; cognitive effects; and quality of life. We used an intention-to-treat population for all primary analyses. We present results as risk ratios (RR) with 95% confidence intervals (CI), with the exception of adverse effects which we present with 99% CI.
MAIN RESULTS
We identified six eligible studies, involving 1593 participants. We judged that three studies were at unclear risk of bias and three were at high risk of bias. Bias mainly arose from lack of methodological details and from high attrition rates. Participants were aged 1 month to 65 years, with a diagnosis of drug-resistant focal epilepsy. All studies were either placebo- or alternative-dose-controlled with parallel-group design. The treatment period varied from 9 days to 26 weeks. The median percentage seizure reduction per 28 days (3 studies; moderate-certainty evidence) ranged from 26% to 83.3% for participants randomised to experimental oxcarbazepine compared to 7.6% to 28.7% for participants randomised to control treatment. Oxcarbazepine may increase the responder rate for 50% or greater reduction in seizure frequency compared to control treatment (RR 1.80, 95% CI 1.27 to 2.56; random-effects model; 6 studies; low-certainty evidence). For seizure freedom, the RR was 2.86 (95% CI 1.19 to 6.87; random-effects model; 5 studies; low-certainty evidence), suggesting an advantageous effectiveness of oxcarbazepine over control treatment. Treatment with oxcarbazepine was associated with an increased treatment withdrawal rate compared to control (RR 1.75, 95% CI 1.44 to 2.13; fixed-effect model; 6 studies; moderate-certainty evidence). The largest oxcarbazepine dose used, 2400 mg/d, was associated with a higher treatment withdrawal rate (RR 2.38, 95% CI 1.92 to 2.94; fixed-effect model; 2 studies) compared to control, than 1200 mg/d (RR 1.54, 95% CI 1.21 to 1.95; fixed-effect model; 3 studies) or 600 mg/d oxcarbazepine (RR 0.79, 95% CI 0.55 to 1.15; fixed-effect model; 1 study). Treatment with oxcarbazepine was associated with an increased incidence of multiple adverse effects including: ataxia (RR 2.54, 99% CI 0.86 to 7.54; random-effects model; 5 studies; moderate-certainty evidence); and somnolence (RR 2.03, 99% CI 1.17 to 3.54; random-effects model; 6 studies; low-certainty evidence). Hyponatraemia occurred more frequently with oxcarbazepine treatment but not significantly so (RR 2.53, 99% CI 0.27 to 23.85; fixed-effect model; 6 studies; moderate-certainty evidence).
AUTHORS' CONCLUSIONS
Oxcarbazepine might be effective at reducing seizure frequency when used as an add-on for drug-resistant focal epilepsy. The efficacy outcomes - 50% or greater seizure reduction and seizure freedom - were derived from low-certainty evidence. We are, therefore, uncertain whether the estimated effect size is representative of the true effect. In contrast, the evidence for median percentage seizure reduction and treatment withdrawal were of moderate certainty: thus, we are fairly certain of the effect estimates' reliability. Overall, we are unsure of the true efficacy of oxcarbazepine, but have concerns about its tolerability.
Topics: Anticonvulsants; Drug Resistant Epilepsy; Drug Therapy, Combination; Humans; Intention to Treat Analysis; Oxcarbazepine; Quality of Life; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 32129501
DOI: 10.1002/14651858.CD012433.pub2 -
The Cochrane Database of Systematic... Apr 2006Worldwide, phenytoin is a commonly used antiepileptic drug. Oxcarbazepine is one of the newer antiepileptic drugs and has similar chemical properties to its parent... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Worldwide, phenytoin is a commonly used antiepileptic drug. Oxcarbazepine is one of the newer antiepileptic drugs and has similar chemical properties to its parent compound carbamazepine. For the new drugs such as oxcarbazepine, it is important to know how they compare with standard treatments.
OBJECTIVES
To review the best evidence comparing oxcarbazepine and phenytoin when used as monotherapy in patients with epilepsy.
SEARCH STRATEGY
We searched the Cochrane Epilepsy Group's Specialized Register (December 2005), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 3, 2005), and MEDLINE (1966 to November 2005). No language restrictions were imposed. We checked the reference lists of retrieved studies for additional reports of relevant studies. We also contacted pharmaceutical companies to try and identify any unpublished studies.
SELECTION CRITERIA
Randomized controlled trials in children or adults with epilepsy. Trials must have included a comparison of oxcarbazepine monotherapy with phenytoin monotherapy.
DATA COLLECTION AND ANALYSIS
This was an individual patient data review. Two review authors independently assessed trial quality and extracted data. Study authors were contacted for additional information. Outcomes were (a) time on allocated treatment; (b) time to achieve 6, 12 and 24-month remission; (c) time to first seizure post randomization; (d) quality of life measures if available. Clinical heterogeneity was assessed by reviewing differences across trials in characteristics of randomized patients, dosing protocols and trial design. Data were analysed on an intention to treat basis. Stratified logrank tests were used to obtain study-specific and overall estimates of hazard ratios (with 95% confidence intervals), where a HR > 1 indicates that an event is more likely on phenytoin.
MAIN RESULTS
Individual patient data were available for 480 patients from two trials, representing 100% of the patients recruited into the two trials that met our inclusion criteria. By convention, for the outcomes time to withdrawal of allocated treatment and time to first seizure a hazards ratio (HR) > 1 indicates a clinical advantage for oxcarbazepine and for time to 6 and 12-month remission a HR > 1 indicates a clinical advantage for phenytoin. The main overall results (HR, 95% confidence interval (CI)) were: (i) time to withdrawal of allocated treatment 1.64 (1.09 to 2.47), (ii) time to 6-month remission 0.89 (0.66 to 1.22), (iii) time to 12-month remission 0.92 (0.62 to 1.37), (iv) time to first seizure 1.07 (0.83 to 1.39). The overall results indicate that oxcarbazepine is significantly better than phenytoin for time to treatment withdrawal, but suggest no overall difference between oxcarbazepine and phenytoin for other outcomes. Results stratified by seizure type indicate no significant advantage for either drug for patients with generalized onset seizures, but a potentially important advantage in time to withdrawal for oxcarbazepine for patients with partial onset seizures: HR 1.92 (95% CI 1.17 to 3.16). The age distribution of adults classified as having generalized epilepsy suggests a significant number of patients may have had their epilepsy misclassified.
AUTHORS' CONCLUSIONS
For patients with partial onset seizures oxcarbazepine is significantly less likely to be withdrawn, but current data do not allow a statement as to whether oxcarbazepine is equivalent, superior or inferior to phenytoin in terms of seizure control. Guidelines recommend carbamazepine as a first line treatment for patients with partial onset seizures and more evidence is needed regarding the comparative effects of oxcarbazepine and carbamazepine to further inform policy. For patients with generalized onset tonic-clonic seizures, valproate is considered the first line standard treatment and the results of this review do not inform current treatment policy. Misclassification of patients' epilepsy type may have confounded the results of this review.
Topics: Anticonvulsants; Carbamazepine; Epilepsies, Partial; Epilepsy; Humans; Oxcarbazepine; Phenytoin; Randomized Controlled Trials as Topic; Remission Induction
PubMed: 16625587
DOI: 10.1002/14651858.CD003615.pub2 -
Pediatric Neurology Sep 2022There are no prior cases in the literature that report immunoglobulins dropping secondary to oxcarbazepine use in an adolescent patient.
BACKGROUND
There are no prior cases in the literature that report immunoglobulins dropping secondary to oxcarbazepine use in an adolescent patient.
CASE
This patient was an adolescent female taking buspirone, mirtazapine, and oxcarbazepine for mood stabilization. She was admitted to an inpatient disordered eating program for malnutrition. During her malnutrition evaluation, the patient was found to have low serum IgA, low IgM, and low-normal IgG. A slow wean of oxcarbazepine was initiated, and all immunoglobulins showed an increasing trend after stopping oxcarbazepine.
DISCUSSION
Gabapentin was an added medication during hospitalization but is not known to affect immunoglobulins. Malnutrition is the only other significant factor that changed during the patient's hospital stay. With malnutrition alone, immunoglobulins are normal and IgA could be increased; this essentially rules out malnutrition and disordered eating as the cause of this patient's hypogammaglobulinemia, implicating oxcarbazepine as the cause.
CONCLUSION
Chronic oxcarbazepine use was the most likely cause of the hypogammaglobulinemia seen in this patient; this is not currently a reported side effect of oxcarbazepine. This case highlights the importance of judicious use of all medications given the risk of even rare potential side effects.
Topics: Adolescent; Agammaglobulinemia; Anticonvulsants; Carbamazepine; Female; Humans; Immunoglobulin A; Immunoglobulins; Malnutrition; Oxcarbazepine
PubMed: 35839527
DOI: 10.1016/j.pediatrneurol.2022.06.009 -
Expert Opinion on Pharmacotherapy Apr 2007Oxcarbazepine (OXC) is a keto-congener of carbamazepine, which has fewer side effects and drug interactions. However, the efficacy of OXC in treating bipolar disorder is... (Review)
Review
Oxcarbazepine (OXC) is a keto-congener of carbamazepine, which has fewer side effects and drug interactions. However, the efficacy of OXC in treating bipolar disorder is not as well established as that of carbamazepine. This article is a systematic literature review of all studies regarding OXC and bipolar disorders, with particular attention to papers published in the last 6 years. Using the terms 'oxcarbazepine and bipolar disorder', 'oxcarbazepine and mania' or 'oxcarbazepine and bipolar depression', a computer-aided search of MEDLINE for the years 2000-2006 has been conducted. Since its introduction as an antiepileptic drug in early 2000, clinical research regarding the potential role of OXC in the treatment of bipolar disorder remains limited. There is a lack of double-blind, placebo-controlled studies. Studies recently published have small samples of patients, with insufficient follow-up periods and other methodological weaknesses. The efficacy of OXC in bipolar disorder has not been widely studied. Some authors recommend using OXC as monotherapy or as add-on therapy in refractory mania, although results are not conclusive. It is unknown whether OXC has efficacy in the maintenance treatment of bipolar disorder. OXC can be particularly useful as an add-on treatment in bipolar disorder patients for whom previous treatments have failed, or in patients who have difficulty tolerating adequate dosages of standard approved treatments.
Topics: Anticonvulsants; Bipolar Disorder; Carbamazepine; Clinical Trials as Topic; Humans; Oxcarbazepine; Practice Guidelines as Topic
PubMed: 17376019
DOI: 10.1517/14656566.8.5.649 -
Seizure Jan 2002
Comparative Study
Topics: Anticonvulsants; Carbamazepine; Dose-Response Relationship, Drug; Drug Administration Schedule; Epilepsy; Humans; Oxcarbazepine
PubMed: 11888266
DOI: 10.1053/seiz.2002.0673