Serum Carbamazepine Levels Research Articles

P-175 - Concordance of maintenance treatment patterns for bipolar disorders with current practice guidelines in an outpatient setting

Introduction Wide variations in guideline concordance rates for bipolar disorder have been reported. To the authors' knowledge, no studies have been carried out in Spain. Objective To evaluate whether maintenance treatment patterns for outpatients with bipolar disorders in usual practice are concordant with evidence-based prescription guidelines. Methods Cross-sectional data are being collected, starting June 2011, from outpatients diagnosed of bipolar I or II disorders attended at a Mental Health Center in Bilbao (Spain). Information about their maintenance treatment is reviewed, and labelled as “concordant” or “non-concordant”. Medication considered concordant with current guidelines1,3 are lithium (serum levels 0,6–1,2 mEq/L obtained within the previous 6 months), valproate (serum levels 50–100 μg/mL within the previous 6 months), carbamazepine (serum levels 4–12 μg/mL within the previous 6 months), quetiapine (≥300 mg/d), olanzapine (≥10 mg/d), aripiprazole (≥15 mg/d) and, in bipolar II, lamotrigine ≥100 mg/d. Adjunctive use of other medications is also recorded. To assess concordance when various drugs are combined, at least one of them needs to be within therapeutic dose. Results Hitherto, data from 50 patients have been analyzed (66% females; mean age 52,82 ± 13,35; 68% bipolar I). 60% of them present a concordant treatment; 67,64% in the bipolar I subgroup and 43,75% in the bipolar II. Half of the patients are on antidepressants. Conclusions Despite the still small sample size and need of a multicenter assessment, adherence to guidelines seems suboptimal, mainly respecting bipolar II. Implementing interventions that have proven effective for enhancing evidence-based care and therefore improving outcomes should be considered.

Successful treatment of carbamazepine poisoning with hemodialysis: A case report and review of the literature

A 48-year-old man was brought to the emergency room after ingesting an unknown amount of carbamazepine. He was unconscious and not responding to the noxious stimuli. He was intubated and was placed on mechanical ventilation because of respiratory insufficiency. Primary detoxification was performed with a gastric lavage and charcoal instillation. His serum carbamazepine level was 25.6 mcg/mL at the time of admission. His computed tomography of the brain was normal. He was managed conservatively but there was no improvement in his neurological status in the next 24 hours. Serum carbamazepine level was repeated and reported to be 28.3 mcg/mL. As there was no improvement in his sensorium and the serum carbamazepine levels remained persistently high, extracorporeal removal of carbamazepine was attempted. As the facility to carry out hemoperfusion was not available immediately, the decision to initiate hemodialysis was taken. After 3 sessions of hemodialysis, his sensorium improved markedly and the carbamazepine level at this time was within the therapeutic range. He was discharged after psychiatry consultation and counseling. We review the literature regarding extra corporeal techniques for the removal of carbamazepine and discuss them in this article.

小児におけるPhenobarbitalとCarbamazepineの血中濃度, ならびに, 熱性痙攣と全身痙攣型てんかんにおける有効血中濃度の検討

小児におけるPhenobarbitalとCarbamazepineの血中濃度, ならびに, 熱性痙攣と全身痙攣型てんかんにおける有効血中濃度の検討

Discordant carbamazepine values between two immunoassays: carbamazepine values determined by ADVIA centaur correlate better with those determined by LC-MS/MS than PETINIA assay

Discordant carbamazepine values as determined by two different immunoassays may be due to different cross-reactivities with the active metabolite carbamazepine 10, 11-epoxide and may cause confusion in interpreting carbamazepine serum levels. In this study, we compared carbamazepine values in samples containing carbamazepine and the epoxide metabolite, as determined by liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) and by two commercial carbamazepine immunoassays: the PETINIA and the ADVIA Centaur carbamazepine. Clinical specimens were used for the comparative studies wherein we determined carbamazepine concentrations using the PETINIA, ADVIA Centaur, and LC-MS/MS assays. We observed an excellent correlation between carbamazepine concentrations determined by the ADVIA Centaur and LC-MS/MS methods while carbamazepine values were overestimated using the PETINIA assay. When aliquots of drug-free serum were supplemented with clinically relevant concentrations of the carbamazepine epoxide metabolite, we observed negligible cross-reactivity of epoxide with the ADVIA Centaur assay but over 90% cross-reactivity with the PETINIA assay. We conclude that the ADVIA centaur assay accurately measures carbamazepine concentrations in plasma or serum and that the PETINIA assay significantly overestimates true carbamazepine concentration. Such discordance may cause confusion in interpreting serum carbamazepine levels.

Predictability of individualized dosage regimens of carbamazepine and valproate mono- and combination therapy

Many investigators agree that appropriate rational utilization of therapeutic drug monitoring (TDM) with Bayesian feedback dosage adjustment facilitates epilepsy treatment with carbamazepine (CBZ) and/or valproate (VPA) by increasing the seizure control and safety, as well as by reducing treatment costs. In previous works we have developed and used in clinical practice population pharmacokinetic (PK) models of different dosage forms for VPA and post-induction CBZ behaviour, as well as for combined therapy with CBZ plus another 'old' antiepileptic drug (AED). An important step of external validation is to evaluate how well a procedure of Bayesian individualizing AED dosage regimens based on a proposed population PK model and sparse TDM data 'works', and how helpful it is in real practical clinical settings. The aim of this study was to evaluate the predictability of individualized dosage regimens for monotherapy with CBZ in the post-induction period or with VPA, as well as for CBZ and VPA given as combination therapy based on TDM data of epileptic patients and the earlier developed population models. Four groups of TDM data were analysed using the USC*PACK software for PK/PD analysis: 556 predictions for adult epileptic patients on CBZ monotherapy, 662 predictions for VPA monotherapy, 402 predictions of CBZ serum levels and 430 predictions of VPA serum levels for adult epileptic patients on CBZ+VPA combination therapy. Statistical characteristics of the prediction errors (PE) and weighted PE were used to estimate bias and precision of predictions. Intraindividual and interoccasional variability of predictions were also estimated. This study demonstrated that in most cases of CBZ and VPA monotherapy and combination therapy, predictions of future AED concentrations based on the earlier developed population PK models, TDM data and patient-specific maximum a posteriori probability Bayesian posterior parameter values provided clinically acceptable estimates. Statistical analysis of the residuals demonstrated that the distributions of residual and weighted residual were close to the normal distribution (Kolmogorov-Smirnov test, P > 0·05) and their mean values did not differ statistically significant from zero (no statistically significant bias, P > 0·05) for all groups of predictions. The observed decreased quality of predictions of VPA concentrations during VPA+CBZ combination therapy, especially when CBZ dosages were changed, might well be explained by their PK interactions. For all groups, in linear regression analysis, the observed trend of decreasing of the prediction quality over various future prediction time horizons was considered statistically significant (P < 0·05). Prediction of serum levels further in future was less precise than those closer to the present for a 1·5- to 3·5-year observation period. No bias in predictions was associated with the time horizons. Our validation results suggest good predictive performance of the population models developed earlier, and quite acceptable predictions of future AED serum levels for individualized dosage regimens of CBZ and VPA therapy in real clinical settings.

Disinhibition Due to Disruption of the Orbitofrontal Circuit Treated Successfully With Carbamazepine: A Case Series

Disinhibition Due to Disruption of the Orbitofrontal Circuit Treated Successfully With Carbamazepine: A Case Series

Influence of disulfiram on the serum concentration of carbamazepine in patients with epilepsy

Treatment of alcoholics with phenytoin and disulfiram (DI) simultaneously is complicated and inexpedient because of the marked drug interaction. The aim of this study was to investigate whether an interaction exists between DI and carbamazepine (CBZ). The serum levels of CBZ and the metabolite CBZ-10, 11-epoxide were measured by high-pressure liquid chromatography in seven out-patients with epilepsy, on monotherapy with CBZ, before and during two weeks administration of DI. Five patients completed the investigation. None were alcoholics. The changes in the serum levels were insignificant, i.e. without clinical important. Moreover, uncontrolled clinical experience has not indicated any interaction between DI and CBZ. Thus the influence of DI on the metabolism of CBZ is probably negligible. CBZ is suggested, therefore, when anticonvulsive therapy is needed by alcoholics in treatment with DI.

Cerebellar atrophy does not increase susceptibility to carbamazepine toxicity.

Cerebellar atrophy (CA) is a frequent finding in patients with chronic epilepsy. To find out whether the existence of CA has an influence on the tolerance of high-dose monotherapy with carbamazepine, we compared the lowest individual toxic serum levels in patients with complex focal seizures, with CA (n = 27) and without CA (n = 20) in computerized tomography (CT). There was no statistical difference between the groups, even after separating patients with mild CA (n = 20) from those with more severe damage (n = 7). In addition, other clinical, EEG and CT data also seemed to have no influence on the individual toxic threshold serum levels of carbamazepine.

Effect of Carbamazepine Therapy on Serum Lipids in Children With Partial Epilepsy

Alteration in serum lipids leads to atherosclerosis. Antiepileptic drugs alter serum lipids. The effect of carbamazepine therapy on serum lipids of children with partial epilepsy and correlation of changes with carbamazepine level was prospectively studied. The study population of 29 children (16 male, 13 female; age range, 3-12 years) diagnosed with partial epilepsy were enrolled within 14 days of starting carbamazepine. Serum lipids were measured at enrollment and at 3 months. Carbamazepine levels were determined at 3 months of therapy. Mean total cholesterol was 130.2 +/- 27.3 mg/dL at enrollment, and increased significantly to 144.8 +/- 32.9 mg/dL at 3 months (P = 0.018). There was a significant change in mean low and very low density lipoproteins, and in triglycerides (P < 0.05). Both the ratio of total cholesterol to high density lipoprotein and the ratio of low density lipoprotein to high density lipoprotein increased significantly. There was no significant change in levels of high density lipoprotein. At 3 months, mean carbamazepine level was 6.5 +/- 1.8 microg/dL. Changes in serum lipids did not correlate with serum carbamazepine level (P > 0.05). Carbamazepine therapy increases levels of lipids that increase the risk of atherosclerosis.

Value of therapeutic drug level monitoring and unbound (free) levels

Therapeutic drug monitoring (TDM) has declined with newer anti-epileptic drugs (AEDs) having no therapeutic window. Use of unbound (free) fraction has almost completely disappeared. The case reported highlights its importance and offers sound reason for its retention. A 66-year-old Caucasian man with known epilepsy was admitted with vomiting, ataxia and nystagmus presumably due to AED toxicity. Medications included valproate (VPA) 1g bd; phenytoin (PHT) 200mg tds; carbamazepine (CBZ) 400mg mane, 200mg midi, 400mg nocte; levetiracetam (LEV) 250mg bd. Initial AED-TDM revealed total serum levels of CBZ: 27micromol/L; PHT: 37micromol/L; VPA 499micromol/L, therapeutic or subtherapeutic. Free levels were subsequently measured demonstrating CBZ: 8.2micromol/L; PHT: 5micromol/L; VPA 93micromol/L. Consequently, VPA was initially omitted and dosage reduced with cessation of toxicity. AED regimen was greatly simplified and remained efficacious. This case highlights the value of TDM with polypharmacy and suggested AED toxicity. Total AED levels failed to identify the cause, which the unbound, free fraction identified. While total PHT was borderline subtherapeutic (37micromol/L; range: 40-80) the free level was therapeutic (5micromol/L; range: 4-8) and while VPA was therapeutic (VPA 499micromol/L; range: 300-750) the free level was supratherapeutic (93micromol/L; range: 30-75). Acknowledgement of discordance between total and free levels for highly protein-bound AED is highlighted.

Detoxication Treatment for Carbamazepine and Lithium Overdose

This article reports detoxication treatments of a case of combined overdose of carbamazepine and lithium in a 38-year-old female with bipolar disorder. She was brought to the emergency unit after the family found her unresponsive and lying near empty packages for carbamazepine (corresponded to 7.7 g) and lithium carbonate (corresponded to 6.6 g) tablets. On admission, her blood pressure, heart rate and respiratory rate were 80/55 mmHg, 90 per minute and 13 per minute, respectively. Her GCS was 3 (E1, M1, V1). She received gastric lavage after intratracheal intubation, followed by administration of activated charcoal via gastric tube, and a large volume (800 ml/h) of lactate Ringer's solution by intravenous infusion. The serum levels of carbamazepine and lithium approximately 5 h after ingestion were 56.0 mug/ml and 3.56 mEq/l, respectively. The carbamazepine overdose was mainly treated by a 3 h charcoal hemoperfusion (CHP). The CHP treatment decreased serum carbamazepine levels by approximately 30-40% as compared with the levels simulated by Bayesian analysis using 1-point or 2-points serum level(s) (without detoxication treatment). For lithium overdose continuous infusion of Ringer's solution was effective, which increased serum sodium gradually and facilitated the elimination of lithium. In conclusion, the treatments with CHP and continuous infusion of Ringer's solution were considered to be effective for detoxification of carbamazepine and lithium overdose, respectively, when compared with those drug levels without detoxication treatment that simulated by Bayesian analysis method.

The age and dose-related hyponatremia during carbamazepine and oxcarbazepine therapy in epileptic children

Purpose : To assess the prevalence of hyponatremia in epileptic children receiving carbamazepine or oxcarbazpine, we investigate serum sodium changes according to age, serum carbamazepine level, and daily oxcarbazepine dosage, and the prevalence of symptoms of hyponatremia. Methods : We reviewed the clinical data of the 197 children receiving carbamazepine and/or oxcarbazepine with or without antiepileptic therapy. And these were classified into the carbamazepine treated patients (group I), oxcarbazepine treated patients (group II), and carbamzepine or oxcarbazepine with other antiepileptics treated patients (group III). Potentially predictive values for development of hyponatremia were examined in each group: age, plasma level of carbamazepine and daily dosage of oxcarbazepine. We assessed the symptoms of hyponatremia. Results : The overall prevalence of hyponatremia was 20.8% (group I, II and III : 17.9%, 22.6%, and 21.8%, respectively), and the prevalence in groups II and III compared with controls (P

Interference by Carbamazepine and Oxcarbazepine With Serum- and Urine-Screening Assays for Tricyclic Antidepressants

The purpose of this work was to evaluate the potential cross-reactivity of 2 antiepileptic medications containing 3-ringed structures, namely, carbamazepine and oxcarbazepine, with screening assays for tricyclic antidepressants. A cross-sectional study of 52 patients between 3 and 19 years of age who had been prescribed either carbamazepine or oxcarbazepine was conducted. A serum fluorescence-polarized immunoassay and a urine enzyme-linked immunoassay were used. The serum carbamazepine or oxcarbazepine level was measured. Gas chromatography/mass spectrometry, a confirmatory test for tricyclic antidepressant detection, was subsequently performed on the serum specimen. A linear dependency on medication level was observed with the serum fluorescence-polarized immunoassay assay. This relationship was stronger for carbamazepine (4.2 microg/L tricyclic antidepressant detected per microgram/liter of carbamazepine) than for oxcarbazepine (0.7 microg/L tricyclic antidepressant detected per milligram/liter). At higher carbamazepine levels (8.0-11.6 mg/L), 12 of 13 patients had a positive serum fluorescence-polarized immunoassay result; at lower levels (0.1-7.9 mg/L), only 1 of 20 had a positive result. None of the patients who were receiving oxcarbazepine showed significant tricyclic antidepressant activity on either assay. Carbamazepine interferes at a statistically significant level with serum fluorescence-polarized immunoassay assay and in a dose-dependent fashion. Neither carbamazepine nor oxcarbazepine exhibit significant tricyclic antidepressant activity on urine enzyme-linked immunoassay assay.

Relation of blood platelet count during carbamazepine and oxcarbazepine treatment with daily dose, and serum concentrations of carbamazepine, carbamazepine-10, 11-epoxide, and 10-hydroxycarbazepine

Carbamazepine (CBZ) occasionally causes haematological disorders such as thrombocytopenia, and recently a case of oxcarbazepine (OXCBZ)-induced thrombocytopenia has been described. The aim of our study was blood platelet count determination in epileptic patients treated with CBZ and OXCBZ, and its relationship with the dose and serum levels of these drugs and its metabolites. The serum levels of CBZ and its epoxide, and the pharmacologically active monohydroxy derivative of OXCBZ were determined in 137 patients treated with CBZ, and 60 patients treated with OXCBZ. The platelet count, mean platelet volume, and platelet size distribution width were also determined. The difference between the platelet counts of the patient groups treated with CBZ and OXCBZ was not significant. No significant correlations between the platelet count and serum levels of the administered antiepileptic drugs and their metabolites were found. However, significant negative correlations between the platelet count and the daily doses of CBZ and OXCBZ were obtained (p<0.01). In 5 cases (4 treated with CBZ and 1 with OXCBZ) the platelet count was <150 x 10(9)/l. In accordance with the mean platelet volume and platelet distribution width, the thrombocytopenia observed in some of the patients studied was due to a hyper-destruction of peripheral blood platelets. However, the results obtained suggest that the mechanism of CBZ or OXCBZ-induced thrombocytopenia is not due to a direct toxicity of these drugs or their major metabolites on the circulating platelets. Although, the patients treated with OXCBZ shown a lower prevalence for thrombocytopenia (1.7%) than those treated with CBZ (2.9%), the routine platelet count monitoring in patients treated with both drugs may be recommended.

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.

Carbamazepine-Induced Transient Auditory Pitch-Perception Deficit

This report presents six cases of transient auditory disturbance caused by carbamazepine, with a particular focus on pitch-perception deficit. Basic disorders in the six cases included epilepsy (cryptogenic localization-related epilepsy and benign childhood epilepsy) and glossopharyngeal neuralgia. Since 1993, in which we reported the first description of transient pitch-perception deficit associated with carbamazepine, a further 26 cases have been reported. However, this carbamazepine-induced transient pitch-perception deficit may be more frequent than previously suspected. Moreover, because auditory disturbance occurs at therapeutic serum levels of carbamazepine, patient awareness of reversible hearing impairment on initiating carbamazepine therapy is important.

Mania secondary to right-sided stroke — responsive to olanzapine

Mr. G, aged 51 years, presented to the emergency services with a history of abnormal behaviour of 1-week duration. History revealed that patient sustained stroke 1 month ago. He was neither a diabetic nor a hypertensive. He had no history of psychiatric illness. Alcohol dependence and unspecified psychosis were reported in firstdegree relatives. Mental state examination showed irritable mood, inflated self-esteem, increased motor activity and increased amount and rate of speech. He also displayed distractibility and poor judgement. He had no insight into his illness. Neurological examination revealed a mild left-sided facial and limb weakness. His memory was found to be intact. HIV ELISA and VDRL tests reported negative. CT and MRI scan showed a nonhaemorrhagic infarct involving right medial frontal lobe (1.5 2.0 cm) and right parietal lobe (2.5 3.0 cm). Patient was diagnosed as a case of organic manic disorder (F06.30) (according to criteria of the International Classification of Diseases, 10th Revision). When rated on Young mania rating scale (YMRS) [4], he scored 33 out of a total score of 60. The patient was treated with 1200 mg carbamazepine per day, and serum level of carbamazepine was 8 mg/ml. A 6-week trial failed to improve his mood symptoms.

Effect of Plasma Exchange on Carbamazepine Levels in a Patient with Myasthenia Gravis and Epilepsy

Patients taking antiepileptic medications may require plasma exchange (PEX) for treatment of an unrelated condition. We studied total serum levels of carbamazepine (CBZ) serially, before and after five PEX cycles, in an epilepsy patient who underwent PEX for myasthenia gravis. A small but consistent reduction in the CBZ levels was noted immediately after each cycle, and a gradual and cumulative increase in the serum levels was observed over the duration of the PEX cycles. We conclude that alterations in the serum CBZ levels with PEX are not clinically significant to merit adjustment of the CBZ dose.

Carbamazepine enhances the activity of glutamate transporter type 3 via phosphatidylinositol 3-kinase

Glutamate transporters (also called excitatory amino acid transporters, EAAT) participate in maintaining extracellular homeostasis of glutamate, a major excitatory neurotransmitter, and regulating glutamate neurotransmission. EAAT3, the major neuronal EAAT, may also regulate γ-aminobutyric acid-mediated inhibitory neurotransmission. Dysfunction of EAAT3 has been shown to induce seizure in rats. We hypothesize that carbamazepine, a commonly used antiepileptic agent, enhances EAAT3 activity. We tested this hypothesis using oocytes artificially expressing EAAT3 and C6 rat glioma cells expressing endogenous EAAT3. In oocytes, carbamazepine dose-dependently enhanced EAAT3 activity. The EC50 of this carbamazepine effect was 12.2 μM. The concentrations of carbamazepine to significantly enhance EAAT3 activity were within the therapeutic serum levels (17–51 μM) of carbamazepine for the antiepileptic effect. Carbamazepine decreased the Km but did not change the maximal response of EAAT3 to glutamate. Carbamazepine-increased EAAT3 activity was inhibited by wortmannin or LY-294002, phosphatidylinositol 3-kinase (PI3K) inhibitors, but was not affected by staurosporine, chelerythrine or calphostin C, protein kinase C inhibitors. In C6 cells, carbamazepine also enhanced the endogenous EAAT3 activity. However, carbamazepine did not affect the activity of EAAT4 expressed in Cos7 cells. These results suggest that carbamazepine at clinically relevant concentrations specifically enhances the affinity of EAAT3 for glutamate to increase EAAT3 activity via a PI3K-dependent pathway. EAAT3 may be a therapeutic target for carbamazepine in the central nervous system.

Effects of Add‐on Melatonin Administration on Antioxidant Enzymes in Children with Epilepsy Taking Carbamazepine Monotherapy: A Randomized, Double‐blind, Placebo‐controlled Trial

Melatonin has been shown to exhibit antioxidant, antiexcitotoxic, and free radical-scavenging properties in various animal models. The study was designed to assess its effects on the blood levels of antioxidant enzymes in children with epilepsy receiving carbamazepine (CBZ). In a double-blind, randomized, parallel-group, placebo-controlled trial, we assessed the effect of add-on melatonin (6-9 mg/day for 14 days) on the antioxidant enzymes glutathione peroxidase (GPx) and glutathione reductase (GRd) in 31 children with epilepsy receiving CBZ monotherapy, who were seizure free at least for the last 6 months. The interaction of melatonin with CBZ and its active metabolite, carbamazepine-10, 11-epoxide (CBZ-E), also was studied. An increase in GRd activity was noted in the melatonin group as compared with a decrease of the same enzyme in the placebo group. Changes in GPx activity failed to reach statistical significance. No significant changes were found in the serum levels of CBZ and CBZ-E in either group. The study suggests that melatonin exerts antioxidant activity in patients with epilepsy receiving CBZ therapy.