Discontinuation Of Carbamazepine Research Articles

Carbamazepine-induced toxidermia: Case report and a literature review

IntroductionCarbamazepine is effectively used in treatment of bipolar disorder for its thymoregulatory virtues, but it can induce numerous side effects, including skin eruptions that can be severe sometimes.ObjectivesTo study the relationship between toxidermia and treatment with carbamazepine.MethodsWe report the case of a patient who developed a toxidermia following the intake of carbamazepine.ResultsMr. AD, 19 years old, with medical history of diabetes, has been diagnosed with bipolar disorder since the age of 17. He was initially treated with risperidone with an irregular follow-up.He was hospitalized in our department for a manic episode with psychotic features with agitation and refusal of treatment.The patient was put on injectable treatment 15 mg/day of Haloperidol and 20 mg/day of diazepam.After 5 days in hospital, we switched to the oral route, gradually increasing haloperidol doses to 30mg, reducing diazepam doses and introducing carbamazepine for thymoregulatory purposes.Carbamazepine was progressively increased up to a dose of 800mg per day.Fourteen days after the introduction of carbamazepine, the patient presented a generalized rash requiring the discontinuation of this medication. He was treated with an anti-histamine and local corticosteroids, on the advice of dermatologists.In the days following discontinuation of carbamazepine, skin lesions regress and then disappear.Biologically, we observed a rise in eosinophilic polynuclear cells to 580, followed by a gradual decrease after stopping the treatment.A pharmacovigilance opinion was sought, concluding that carbamazepine was responsible for the toxidermia, given the delay in onset and the favorable evolution after discontinuation of the incriminating treatment. Moreover, this undesirable effect is well described in the literature.Hence the contraindication to further use of carbamazepine in Mr. AD.In addition, the patient was put on sodium valproate with good tolerance.ConclusionsEach prescribed drug must be considered as potentially capable of causing cutaneous reactions as an adverse effect. Both the prescriber and the patient must be made aware of this phenomenon. The attitude can be modulated on a case-by-case basis, after specialist advice, depending on the severity of the rash and the disease to be treated.Disclosure of InterestNone Declared

Carbamazepine for Chronic Muscle Pain: A Retrospective Assessment of Indications, Side Effects, and Treatment Response.

Myopathies fall under the umbrella of rare diseases, however, muscle pain is a relevant, under-recognized symptom with limited treatment options. Carbamazepine is an oral sodium channel blocker approved for the treatment of seizures and neuropathic pain. In 54 individuals receiving carbamazepine for muscle pain, we retrospectively assessed the subjective treatment response, side effects, and reasons for carbamazepine discontinuation. The underlying diagnoses leading to muscle pain were diverse, ranging from metabolic (n = 5) and other hereditary (n = 9) to acquired (n = 2) myopathies and myotonia syndromes (n = 22). Under carbamazepine (daily dose 254 ± 138 mg), patients reported a significant reduction of pain, quantified by an 11-point numeric rating scale (-1.9 ± 1.8, p < 0.001). Compared to age- and sex-matched controls, our sensory assessment revealed a significant dysfunction of Aδ-nerve fibers in patients with chronic muscle pain. Neuropathic pain components identified by the painDETECT questionnaire or quantitative sensory testing did not seem to influence the reported treatment response. Side effects (n = 18) such as fatigue, elevated liver enzymes, and diarrhea, as well as lack of pain improvement (n = 6), led to carbamazepine discontinuation in 44.4% (24/54). Mediated by dysfunctional Aδ-nerve fibers, muscle pain is common in a variety of myopathies. Carbamazepine may reduce pain levels, but comes with therapy-limiting side effects.

Simultaneous Use of Carbamazepine and Lithium in the Treatment of Outpatients with Rapid Cycle Bipolar Disorder: Randomized, Double-Blind Placebo-Controlled Study

Purpose:rapid cycle bipolar disorder may be more resistant to treatment than other bipolar disorders. However, the effect of the synergistic use of carbamazepine and lithium in the treatment of outpatients with rapid cycle bipolar disorder without psychiatric comorbidity has not been studied in a double-blind, placebo-controlled design.Patients and methods: participants in a double-blind, placebo-controlled study met DSM-5 criteria for bipolar disorder with a rapid cycle between the ages of 18 and 65 years. The response and side effects of carbamazepine, lithium, and placebo were compared using analysis of variance (ANOVA) and chi-square tests. The respondent underwent F2, demonstrating superiority with respect to carbamazepine and lithium than in the case of placebo. Carbamazepine and lithium were generally well tolerated by the study patients, although a larger number of patients receiving carbamazepine and lithium (n = 2) early discontinued the study due to side effects.Results:twenty-seven of the 36 participants taking the combined carbamazepine and lithium regimen responded at 12 weeks, compared with six of 38 participants who received a placebo (p < 0.001). Two common side effects that led to discontinuation of carbamazepine and the lithium group were allergic reaction and drowsiness. Frequent complaints of sweating and headache during placebo treatment occurred in two out of 38 men. There were no unexpected or serious adverse events.Conclusions: the combined use of carbamazepine and lithium in the treatment of outpatients with rapid cycle bipolar disorder has demonstrated superior use of carbamazepine and lithium than placebo.

Changes in serum perampanel concentration profile after discontinuation of carbamazepine.

To evaluate changes in the pharmacokinetics of perampanel after discontinuation of carbamazepine. We enrolled 13 patients receiving perampanel who discontinued carbamazepine therapy between June 2016 and December 2018. Data on serum concentrations were obtained from the therapeutic drug monitoring database of the National Epilepsy Center (Shizuoka, Japan). To compare the pharmacokinetics of perampanel before and after discontinuation of carbamazepine, we determined the concentration/dose (CD) ratio of perampanel (serum level [ng/mL] divided by the dose [mg/kg]). The follow-up period was set to eight weeks following the discontinuation of carbamazepine therapy. The mean baseline CD ratio of perampanel was 1,247ng/mL/mg/kg which increased markedly over time after discontinuation of carbamazepine, with a mean CD ratio at Weeks 1-2, Weeks 3-4, and Weeks 5-8 of 2,683, 3,914, and 4,220, respectively. At eight weeks, the mean CD ratio of perampanel had increased by 276%. Eleven patients developed adverse events, including dizziness, somnolence, irritability, and ataxia. Five of these 11 patients required perampanel dose reduction within eight weeks after discontinuation of carbamazepine. Two patients achieved seizure-free status at Weeks 5-8. The serum perampanel concentration began to increase from one week after discontinuation of carbamazepine, and continued to rise for eight weeks. Based on these findings, we recommend frequent monitoring of serum perampanel concentration for at least eight weeks after stopping carbamazepine therapy. Monitoring is required as a guide for dose adjustment in order to achieve a safe and effective therapeutic dose of perampanel.

Changes in perampanel levels during de‐induction: Simulations following carbamazepine discontinuation

ObjectiveTo evaluate the time course of changes in perampanel levels when co‐administered with carbamazepine, and following carbamazepine discontinuation, using a physiologically based pharmacokinetic (PBPK) model.MethodsThe PBPK model was developed, verified using clinical PK data, and used to simulate the effect of abrupt discontinuation and down‐titration (75 mg twice daily [bid]/wk) of co‐administered carbamazepine 300 mg bid on the PK of perampanel once daily (qd). Perampanel dose tapering (8‐4 mg) and up‐titration (2‐6 mg) were simulated during abrupt carbamazepine 300 mg bid discontinuation to identify a titration schedule that minimizes changes in perampanel plasma concentrations.ResultsThe PBPK model accurately reproduced perampanel plasma concentration‐time profiles from clinical studies in single‐ and multiple‐dose regimen simulations, including multiple‐dose carbamazepine co‐administration. The time course of return to pre‐induced perampanel levels occurred more slowly following carbamazepine down‐titration (~48 days after first down‐titration) vs abrupt discontinuation (~25 days). Perampanel dose tapering (8‐4 mg) at abrupt carbamazepine discontinuation produced minimal changes in steady‐state concentrations, which returned to the levels observed during carbamazepine co‐administration in ~15 days from the time of carbamazepine discontinuation. When perampanel was up‐titrated in the presence of carbamazepine, return to steady state occurred more slowly when carbamazepine was down‐titrated weekly (~45 days) vs abrupt discontinuation (~24 days).ConclusionThis PBPK model simulated and predicted optimal perampanel dose tapering and up‐titration schedules for maintaining perampanel levels during conversion to monotherapy. These results may guide physicians when managing conversion from perampanel polytherapy with concomitant enzyme‐inducing anti‐seizure medications to monotherapy.

A case of hemodialysis and steroid therapy for carbamazepine-induced eosinophilic granulomatosis with polyangiitis: a case report with literature review

BackgroundCarbamazepine-induced acute kidney injury is mainly caused by acute tubulointerstitial nephritis. Only one case of carbamazepine-induced eosinophilic granulomatosis with polyangiitis (EGPA) with acute kidney injury has been reported. But the patient’s condition improved with the immediate discontinuation of carbamazepine. We present a case requiring hemodialysis and steroid therapy for carbamazepine-induced EGPA with acute kidney injury.Case presentationA 77-year-old man with allergic rhinitis was prescribed carbamazepine for trigeminal neuralgia 1 year ago. He developed rash and itching on the left forearm 1 month ago and was diagnosed with polymorphic exudative erythema and admitted to our hospital. Laboratory data revealed leukocytosis eosinophilia and renal failure (serum creatinine 9.2 mg/dL). Carbamazepine was discontinued, and hemodialysis was initiated because of acute uremia and oliguria. A lymphocyte stimulation test for carbamazepine was positive. Polyneuropathy in the upper and lower extremities was observed by electromyogram, and a renal biopsy indicated EGPA. The main clinical findings were allergic rhinitis, eosinophilia, and vasculitis symptoms, such as multiple mononeuritis and muscle weakness. Renal biopsy showed diffuse cellular infiltration dominated by eosinophils in the interstitium, with granulomatous changes in particular observed around the arteriole. Fibrinoid necrosis was also observed around the arteriole. We therefore made a diagnosis of carbamazepine-induced EGPA. Following steroid therapy after the discontinuation of carbamazepine, the patient was discharged from our hospital without hemodialysis. In contrast with the previous case of EGPA, the present case had the following characteristics: (1) elderly male patient, (2) hemodialysis required for acute kidney injury, and (3) improved renal function following steroid therapy after discontinuation of carbamazepine.ConclusionOur case report indicates that early diagnosis and appropriate therapy can improve acute kidney injury caused by carbamazepine and allow the patient to discontinue dialysis.

Polymorphic erythema associated with mycoplasma pneumoniae.

Image in medicine Male child, 6 and a half years old, followed for psychomotor delay from the age of 2 years with diagnosis of epilepsy put on sodium valproate for 3 years and in the absence of seizure control carbamazepine was added 2 months before admission. The patient had presented 5 days before his consultation a generalized erythematous rash with edemas of two lower limbs, a dry cough and a fever. He was initially treated as a meningococcemia. On skin examination: generalized erythematous lesions with a rosette appearance, vesicular lesions in the lips. On admission to the service, the patient was put on acilovir, josamycin with discontinuation of carbamazepine. HSV 1 and 2 serology returned negative. Mycoplasma serology was positive for IgM and negative for IgG. The chest X-ray was normal. The skin biopsy was in favor of superficial dermatitis. The evolution was favorable with progressive disappearance of the lesions. Aciclovir was discontinued due to the rapid improvement and negativity of serology and josamycin was discontinued after 14 days of treatment. The general condition improved in 48 hours and the skin lesions disappeared in 15 days. Figure 1 polymorphic erythema associated with mycoplasma pneumoniae in a child of six and half years old

Carbamazepine-induced systemic lupus erythematosus: A case-based review.

A case of carbamazepine-induced systemic lupus erythematosus (CBZ-DILE) is presented, along with a literature review, with the aim to define the clinical and serological characteristics of this group, and compare them with systemic lupus erythematosus (SLE) triggered by other drugs (DILE). A 31-year-old woman presented with a 6-month history of hand arthritis and nasal ulcers. She had been diagnosed with epilepsy at 12 years of age and had continued treatment with carbamazepine (CBZ) for the past 18 years with excellent clinical control. Laboratory data revealed antinuclear antibodies (ANA) positive to a titer of 1/1280, and positive anti-nucleosome antibodies. The patients’ clinical symptoms disappeared after the CBZ discontinuation and did not reappear during the 1-year follow-up period. A search was made in the PubMed/Medline database of the (CBZ-DILE) published cases. A total of 26 cases of CBZ-DILE were found in the search. CBZ-DILE cases are characterized by variable latency periods that often last for years and are not related to the dose of CBZ. Most frequent clinical findings of CBZ-DILE in patients are arthralgia/arthritis, mucocutaneous manifestations, constitutional symptoms, and pleuritis or pericarditis. The renal involvement has not been reported in CBZ-DILE. Antihistone antibodies were observed less frequently, and anti-dsDNA antibodies were observed more frequently than in the “classic” DILE. The ANA remained positive in over 60% of cases during the follow-up after withdrawal. The CBZ-DILE has significant clinical and laboratory manifestations that distinguish it from classic DILE or idiopathic SLE.

Discontinuation of carbamazepine due to concerns of long-term consequences of enzyme induction.

SummaryObjectiveTreatment with carbamazepine (CBZ), a potent enzyme inducer, is known to affect the lipid profile, steroid, and vitamin D metabolism. Consequently, it has been postulated that patients on CBZ should be switched to noninducing antiepileptic drugs (AEDs). However, little is known about the seizure outcome following a CBZ switch in seizure‐free patients. We aimed to address this issue using a controlled observational study design.MethodsFifty‐eight patients taking CBZ for focal epilepsy were assessed for discontinuing CBZ treatment due to concerns of long‐term adverse‐effects; 34 discontinued its therapy and 24 continued with CBZ. Six‐month seizure freedom was the primary end point. Furthermore, serum samples (total cholesterol (TC), low‐density lipoprotein (LDL), high‐density lipoprotein (HDL), triglycerides, sex hormone–binding globulin (SHBG), free testosterone, and 25‐hydroxyvitamin D levels from before and at least 3 months after discontinuation or continuation were obtained from all patients.ResultsSeizure‐free patients had a 5‐fold elevated odds of seizure recurrence if CBZ was discontinued (95% confidence interval [CI 0.51–49.3; p = 0.17). A significant decrease in serum levels of TC, LDL, HDL, and SHBG as well as a significant increase in that of free testosterone were found in the discontinuation group compared with those who continued CBZ. Nonsignificant changes in triglycerides and vitamin D levels were detected.SignificanceDiscontinuation of CBZ in seizure‐free patients seems to carry a moderate, but legitimate, risk of relapse. Conversely, our results indicate that CBZ might have unfavorable effects on serum levels of TC, LDL, HDL, SHBG, and free testosterone.

Severe Resistant Hypertension Induced by Carbamazepine in an Elderly Patient

We report a case of a 73-year-old patient with a 17 year-history of well-controlled primary hypertension with a single antihypertensive drug, which became uncontrolled since 9 months ago when he started on oral carbamazepine (CBZ) therapy for syringomyelia. On admission, the patient had a blood pressure of 200‒215/95‒104 mmHg despite an antihypertensive combination therapy with five different drugs. Further investigations ruled out secondary hypertension such as primary aldosteronism, pheochromocytoma and renal artery stenosis. After the discontinuation of CBZ, the blood pressure profile became significantly improved. The rechallenge with CBZ aggravated his blood pressure profile. Therefore, we considered that resistant hypertension was induced by the oral CBZ therapy.

Carbamazepine-induced hypogammaglobulinemia

Carbamazepine is used to control seizures. Its common side effects are sleep disorders, anorexia, nausea, vomiting, polydipsia, irritability, ataxia, and diplopia. Involvement of the immune system is rare, and few cases of decreased immunoglobulin levels have been reported. We describe a patient with low immunoglobulin levels due to carbamazepine use who presented with recurrent urinary tract infection. Intravenous immunoglobulin was administered, and immunoglobulin levels increased to safer levels after discontinuation of carbamazepine. Previous reports describe severe infection after carbamazepine-induced hypogammaglobulinemia. Therefore, in patients using antiepileptics, particularly carbamazepine, serum immunoglobulin levels should be checked in those with recurrent infections.

Antipsychotic Prescribing Practices Following Withdrawal of Concomitant Carbamazepine

The goal of this study was to examine provider prescribing habits following carbamazepine discontinuation and to assess for the presence of antipsychotic-related adverse drug reactions due to the loss of car-bamazepine-related induction of the cytochrome P450 enzyme (CYP) 3A4 and p-glycoprotein. A retrospective chart review of patient records from January 2006 through December 2007 at the Veterans Affairs (VA) San Diego Healthcare System was done, which focused on the co-prescription of carbamazepine and a second-generation (atypical) antipsychotic (aripiprazole, quetiapine, risperidone) that is significantly affected by CYP3A4/p-glycoprotein induction. The cases in which carbamazepine was discontinued while the antipsychotic was continued during the 2-year time frame were then analyzed further. Data were collected concerning documentation of antipsychotic-related adverse drug reactions that occurred after carbamazepine was discontinued and prescribers' responses to carbamazepine discontinuation. Nine patients were identified who had concomitant prescriptions for carbamazepine and a second-generation antipsychotic and who then discontinued carbamazepine. In only one case did the provider initially decrease the dose of the antipsychotic when carbamazepine was discontinued. Two patients experienced akathisia 3 weeks after carbamazepine was discontinued. Many providers are not adjusting the dose of second-generation antipsychotics after discontinuation of a CYP3A4/p-glycoprotein inducer, placing patients at risk for adverse drug reactions. In addition to provider education, mechanisms need to be integrated into the current prescription processing software to alert providers of kinetic changes related to medication discontinuation. In addition, when discontinuing carbamazepine in patients who are being concomitantly treated with a second-generation antipsychotic that is a CYP3A4/p-glycoprotein substrate, providers should arrange for patient follow-up 2-4 weeks after carbamazepine discontinuation to evaluate patients for antipsychotic-related adverse drug reactions.

Drug–drug interactions – a preventable patient safety issue?

Spontaneous reporting systems remain the cornerstone of the early detection of previously unknown adverse drug reactions (ADRs) [1]. However, a large proportion of ADRs are known and preventable and they are often due to the coadministration of drugs known to interact [2]. Spontaneous reports of known ADRs can provide insight into the inappropriate co-prescribing of medications. The World Health Organization (WHO) ADR Database (Vigibase) contains more than 3.8 million suspected ADR reports from 82 countries [3]. We examined the coreporting in Vigibase of all drugs classified as ‘established’ and ‘clinically important’ in the Swedish, Finnish, INteraction X-referencing drug–drug interaction database (SFINX database) [4] used in a Swedish patient record system. Thirty-five ‘established and clinically important’ drug–drug interactions (DDIs) were identified. Co-prescribing of these drugs was then searched for in VigiBase. Subsequently, data were retrieved on the severity and evidence for interactions involving these pairs, and actions recommended in Stockley's Interaction Alert [5]. Of those 35 ‘established and clinically important’ drug pairs, 31 were reported in Vigibase, involving 9547 reports from 50 countries. The reported DDIs are listed in Table 1. The serious nature of many of the ADRs listed in Table 1 makes this a major patient safety issue. Also, seven pairs had had only theoretical evidence previously available, and another four pairs had had no previous evidence. Table 1 Clinically important drug–drug interactions Amongst a wide range of drugs, the majority of reports concerned anticonvulsants and anticoagulants. Many of the most reported drug pairs included drugs with narrow therapeutic indexes, such as warfarin, carbamezepine, phenytoin and theophylline. This was further emphasized by the nature of the adverse events reported for the drug pairs: ‘therapeutic level increased’, ‘drug level increased’, ‘drug level decreased’ and ‘therapeutic level decreased’. Spontaneous reports sometimes lack detail, which makes the analysis difficult. For example, risperidone/carbamezepine and convulsions could be due to underlying disease or an overdose effect of risperidone on discontinuation of carbamazepine. In many reports one drug only was reported as ‘suspected’. For example, only 149/661 cases of decreased prothrombin and 197/408 cases of gastrointestinal haemorrhage with warfarin and acetylsalicylic acid were reported as co-suspected or interacting. Judging by attribution of suspicion, it seems that potential interactions were not recognized, although we should not assume that all reports are necessarily results of inappropriate use. The continuing reporting of seemingly well-established interactions strongly suggests insufficient impact of drug information on routine prescribing practices. For example, the US Food and Drug Administration (FDA) has warned of concurrent therapy of rosiglitazone and insulin [6], as it was associated with increased risk of cardiac failure [7]. Since that FDA warning in May 2004, 402 reports of the pair, 52 reports of cardiac failure and 46 reports of the most common symptom, peripheral oedema, have been entered into VigiBase. Studies have shown that education can improve both doctors' and medical students' prescribing patterns [8], and electronic advice can significantly improve recognition of dangerous drug combinations [9]. This review has focused on an analysis of spontaneous reports, with no estimate of drug use. The raw number of reports of combinations should not be interpreted as an estimate of incidence. For some combinations, increased recent reporting might be explicable by increased drug use. Many of the drug pairs have been marketed for several years, and for two-thirds of thepairs reporting started >10 years ago. Our results illustrate a longstanding international problem of comedication of contraindicated drugs. This is in agreement with national studies that have shown that physicians fail to recognize [9] and continue to prescribe contraindicated drugs [10]. We contend that VigiBase and other available data sources could, and should, be utilized to identify preventable ADRs through active screening for potential DDIs. Also, much more effort is needed to communicate patient safety findings appropriately to healthcare providers and patients.

Intermittent Complete Atrioventricular Block after Long Term Low-Dose Carbamazepine Therapy with a Serum Concentration Less than the Therapeutic Level

After twelve months of low dose carbamazepine therapy (200 mg daily) for temporal lobe epilepsy, a 66-year-old woman presented to the hospital complaining of frequent episodes of sudden dizziness. Because Holter monitoring documented intermittent complete atrioventricular block, the patient was admitted to the hospital when the serum concentration of carbamazepine was 4 microg/mL. After discontinuation of carbamazepine, the patient returned to normal sinus rhythm. The present case suggests that complete atrioventricular block may occur long after initiation of carbamazepine therapy in an older woman even if the daily dosage or the serum concentration of carbamazepine is low.

Hyponatraemia during low-dose carbamazepine therapy

We report the syndrome of inappropriate antidiuresis as a much earlier side-effect of carbamazepine administration in a 29-year Nigerian female patient with generalized tonic-elonic seizures. Although asymptomatic, the biochemical abnormality improved after discontinuation of carbamazepine. Hyponatraemia developed after rechallenge with controlled release carbamazepine. The authors suggest that serum sodium levels be carried out before commencement of carbamazepine and caution be used in prescribing carbamazepine to patients with low or borderline low sodium values.

Putative B-cell Apoptosis as a Cause of Hypogammaglobulinemia in Carbamazepine Hypersensitivity: A Case Report

RATIONALE: Carbamazepine (CBZ) hypersensitivity syndrome develops between one week and three months after starting therapy. Findings include malaise, fever, lymphadenopathy, hypogammaglobulinemia, rash, pharyngitis, and hepatosplenomegaly. A decrease in B-cells and increase in T-suppressor cells have been implicated as mechanisms for transient hypogammaglobulinemia. We report a patient with panhypogammaglobulinemia, multiorgan dysfunction and severely diminished B-cells secondary to CBZ hypersensitivity. METHODS: Case report; literature review. RESULTS: A 15 year-old African-American female with a history of asthma and cryptogenic epilepsy developed fever, diffuse lymphadenopathy, pharyngitis, facial and neck swelling, liver dysfunction and an erythematous maculopapular rash three months after initiating CBZ. Workup revealed hypogammaglobulinemia (IgG 253, IgA 23, IgM 19) with 0.3% CD19+ cells, elevated serum TNF-alpha (60.2 pg/ml) and IL-6 (22.6 pg/ml). Granulomatous inflammation was noted on liver and bone marrow biopsies. Lymph node biopsy showed an absence of normal follicles and germinal centers with only scattered B-lymphocytes. CBZ in vitro lymphoproliferative assays revealed a 3.5-fold stimulation index with CBZ. Three months after CBZ discontinuation, the patient had normalized quantitative immunoglobulins and improved B-cell numbers with resolution of symptoms. Determination of CBZ-induced apoptosis was made by measurements of serum CD95 (Fas/APO-1). Assays revealed a four-fold increase above the mean normal level of CD95 two weeks status-post discontinuation, and a return to near normal levels at the twelve-week follow-up. Since discharge she has done well on an alternative anti-epileptic. CONCLUSIONS: Carbamazepine hypersensitivity is associated with fever, rash, lymphadenopathy, cytokine imbalance, granulomatous inflammation and hypogammaglobulinemia. Fas-mediated apoptosis of B-cells is one mechanism by which hypogammaglobulinemia may occur.

Influence of Major Antiepileptic Drugs on Attention, Reaction Time, and Speed of Information Processing: Results from a Randomized, Double‐blind, Placebo‐controlled Withdrawal Study of Seizure‐free Epilepsy Patients Receiving Monotherapy

All major antiepileptic drugs (AEDs) have been reported to be associated with cognitive side effects. Uncertainty exists regarding the degree of cognitive effects, primarily because many studies do not adhere to basic standards of methodology and design. The aim of this study was to assess the effect of discontinuation of AEDs in patients receiving monotherapy on measures of attention, reaction time, and speed of information processing. The 150 subjects who had been seizure free>2 years on drug monotherapy went through a randomized, double-blind, placebo-controlled study. Each patient was included for 12 months or until seizure relapse. Cognitive function was assessed with the California Computerized Assessment Package at baseline and 7 months after discontinuation. The major finding in this study is that discontinuation of major AEDs significantly improved performance on tests that require complex cognitive processing under time pressure. The difference in speed of cognitive processing between the two groups on these tasks was between 24 to 43 ms. Simple tasks of attention and reaction time revealed no significant differences between the discontinuation group and the nondiscontinuation group. Most of the subjects in the study were medicated with carbamazepine (CBZ) and valproate (VPA). The outcome of discontinuation of CBZ was similar to the outcome for the total study population, whereas withdrawal of VPA revealed only a nonsignificant tendency in the same direction. The results suggest that seizure-free epilepsy patients receiving monotherapy can obtain improvement in cognitive function if they discontinue AED treatment.

Careful Monitoring for Agranulocytosis During Carbamazepine Treatment

Careful Monitoring for Agranulocytosis During Carbamazepine Treatment

Leistungsknick, Thoraxschmerz und Polyserositis bei einem 35-jährigen Patienten mit antikonvulsiver Therapie

We report on a rare case of a late-onset drug-induced lupus erythematosus. A 35 year old male patient complained about dyspnea, chest pain and reduced physical activity for three months. His medical history consisted of epilepsy treated with carbamazepine for 20 years. After diagnosis of a large pericardial effusion and percardiocentesis (1200 ml) the diagnosis of viral perimyocarditis was suspected. Under antiphlogistic treatment the symptoms vanished initially. Four weeks later the pericardial effusion recurred and a livedo reticularis became evident. A structural or infectious heart disease, in particular viral myocarditis, was ruled out invasively. Serologic testing revealed antinuclear antibodies and antibodies against histones without presence of antibody against ds-DNA, thereby confirming the diagnosis of carbamazepine-induced lupus erythematodes. After discontinuation of carbamazepine and immunosuppressive medication the patient recovered completely.

Carbamazepine induced transient monoclonal gammopathy and immunodeficiency

Immune abnormalities have been found in many patients receiving anti-epileptic drugs. However, the effects of carbamazepine are still conflicting. We report the case of a 31-year-old woman who began carbamazepine treatment because of idiopathic epilepsy of adulthood. After three years of treatment she developed arthralgias and malaise. Complete immunologic evaluation showed a total absence of immunoglobulin M with decreased levels of immunoglobulin A, positive antinuclear antibodies and monoclonal paraproteinemia type IgG-kappa. The possibility of B cell lymphoma or myeloma was ruled out. Skin testing was negative. Bone marrow examination was normal. After carbamazepine discontinuation, levels of IgA and IgM increased until reaching normal values over 3 years. The monoclonal gammopathy of undetermined significance also disappeared over this period. During this period of immunodeficiency, the patient did not complain of any infectious complications