Hypersensitivity to carbamazepine presenting with a leukemoid reaction, eosinophilia, erythroderma, and renal failure

We report a patient in whom hypersensitivity to carbamazepine presented with generalized erythroderma, a severe leukemoid reaction, eosinophilia, hyponatremia, and renal failure. This is the first report of such an unusual reaction to carbamazepine.     

Carbamazepine and hyponatremia in patients with affective disorder

The authors assessed 20 carbamazepine-treated patients for the development of hyponatremia. None of the patients had readings below 135 meg/liter of sodium before carbamazepine therapy, but five (25%) did have such readings after carbamazepine therapy. Three of these patients developed frank symptoms of hyponatremia within 1-3 months of the start of therapy. In one patient, hyponatremia developed after rechallenge with carbamazepine. The authors suggest that caution be used in prescribing carbamazepine to patients with low or borderline low sodium values.     

Hyponatremia during carbamazepine therapy in patients with intellectual disability

Carbamazepine is an anticonvulsant and psychotropic medication commonly used in the treatment of people with intellectual disability (ID). The incidence of hyponatremia during treatment in this population is unclear. The present study aimed to determine the prevalence of hyponatremia during carbamazepine treatment in patients with ID, and to investigate the risk factors and clinical features of this condition. The prevalence of hyponatremia was retrospectively assessed in 53 people receiving carbamazepine (subject group) and 64 people not receiving carbamazepine (control group) who lived in a residential centre for people with ID. The relationship between serum sodium level, sex, age, daily carbamazepine dose and serum carbamazepine levels was examined. The prevalence of the clinical features of hyponatremia was assessed in this population using a checklist. The prevalence of hyponatremia was 41.5% and 9.4% in the subject and control groups, respectively. The mean serum sodium level in the subject group was significantly lower than that in the control group. Hyponatremia correlates significantly with a high daily carbamazepine dose and a high serum carbamazepine level. The checklist of clinical features was not useful in detecting hyponatremia clinically. Hyponatremia is a common occurrence in this population. In the light of the uncertain significance of mild, chronic hyponatremia, the value of routine monitoring of serum electrolytes has yet to be established.     

Acute Cholangitis Induced by Carbamazepine

Summary: We report a case of a patient with fever and intrahepatic cholestasis induced by carbamazepine (CBZ). This adverse reaction has been described in only a single case. We observed complete resolution of the hepatic damage once the agent was discontinued. CBZ rechallenge was followed by recurrence of all symptoms and abnormalities. Hepatic function improved again when CBZ was discontinued.     

Increased Valproate Serum Concentrations Upon Carbamazepine Cessation

Valproate (VPA) serum concentrations (Cp) were followed in six epileptic mentally retarded patients when carbamazepine (CBZ) was discontinued. VPA Cp significantly increased when CBZ was discontinued. A new plateau of VPA Cp was achieved 4 weeks post-CBZ discontinuation. This time factor is analogous to the autoinduction property of CBZ. Careful VPA Cp monitoring is recommended when CBZ or other enzyme inducing agents are discontinued.     

Weight gain, increased appetite, and excessive food intake induced by carbamazepine

Four young patients who developed weight gain induced by carbamazepine therapy are described. The patients received the carbamazepine as anticonvulsant treatment, and soon after starting the drug, abruptly developed an increase in appetite with a concomitant increase in food intake. During a period of 2 months the patients' weights rose by between 7 and 15 kg. Dietary restriction during the carbamazepine treatment was ineffective in promoting weight loss, and loss of the excess weight was achieved only when the drug was discontinued. These patients demonstrate an as yet unpublished adverse effect of carbamazepine. In carbamazepine-induced weight gain, overeating and fat deposition must be taken into consideration as a differential diagnosis to the hitherto described water retention and edema.     

Increased adverse events associated with antiepileptic drugs in anti–leucine‐rich glioma‐inactivated protein 1 encephalitis

Anti–leucine‐rich glioma‐inactivated protein 1 (LGI1) encephalitis is a rare autoimmune condition presenting mainly as altered mental state, cognitive dysfunction, and seizure. Antiepileptic drugs (AEDs) are usually initiated to control seizures despite their limited efficacy; however, accumulating clinical experience suggests a high incidence of adverse reactions to AEDs in anti‐LGI1 encephalitis. We reviewed the medical records of patients who were diagnosed with anti‐LGI1 encephalitis to analyze the adverse effects of AEDs in these patients. Among the 20 patients who were treated with AEDs, 10 (50%) changed their AEDs due to adverse cutaneous drug reaction. Eight of them presented with maculopapular eruption, one with drug rash with eosinophilia and systemic symptoms syndrome, and one with eczema. Causative agents mostly consisted of aromatic AEDs. Oxcarbazepine was discontinued in two additional patients due to hyponatremia. Six patients (30%) discontinued their dose of levetiracetam because of psychiatric manifestations including irritability/aggressive behavior (four patients), insomnia (one patient), and depressive mood (one patient). Clinicians should consider adverse cutaneous drug reaction, psychiatric adverse events, and hyponatremia when selecting AEDs for the treatment of anti‐LGI1 encephalitis.     

Acute intermittent porphyria, seizures, and antiepileptic drugs: a report on a 3-year-old Nigerian boy.

A 3-year-old Nigerian boy was treated with phenobarbitone after having a nonfebrile seizure. Two weeks later his urine was found to contain porphobilinogen, indicating that latent acute intermittent porphyria had been unmasked by phenobarbitone. The drug was discontinued and carbamazepine was substituted. The urine became free of porphobilinogen and the patient remained well. In developing countries phenobarbitone is the most widely used anticonvulsant; it must be avoided in acute intermittent porphyria, and carbamazepine may be tolerated.     

Hyponatremic coma under oxcarbazepine therapy.

Oxcarbazepine (OXC) is considered to be a promising new antiepileptic drug with similar efficacy and better tolerability compared to carbamazepine (CBZ). However, hyponatremia is supposed to occur even more often than with CBZ. We report on a patient who developed hyponatremic coma under OXC with a serum sodium level of 115 mmol/l, the second published case of OXC-induced hyponatremia with serious clinical adverse effects.     

Carbamazepine-viloxazine interaction in patients with epilepsy.

In six depressed epileptic patients stabilised on carbamazepine therapy, addition of the antidepressant agent viloxazine (300 mg/day for three weeks) induced a marked (average 55%) increase in steady-state plasma carbamazepine concentration. The concentration of the active metabolite carbamazepine-10,11-epoxide also increased during viloxazine therapy, but to a lesser extent (16%). In three patients, these effects were associated with symptoms of carbamazepine intoxication, which regressed rapidly when plasma carbamazepine and carbamazepine-10,11-epoxide levels returned to baseline values after discontinuation of viloxazine. In a seventh patient, viloxazine had to be discontinued after only two weeks because of severe side effects associated with a striking elevation of carbamazepine and carbamazepine 10,11-epoxide levels (by 197% and 137% respectively). Although viloxazine appears to be one of the few antidepressants which can be used safely in patients with epilepsy these results indicate that the drug should be prescribed with great caution in subjects treated with carbamazepine. The mechanism of the interaction probably involves inhibition of the metabolism of both carbamazepine and its active epoxide metabolite.     

Syndrome of inappropriate secretion of antidiuretic hormone due to citalopram and venlafaxine

INTRODUCTION: Selective serotonin reuptake inhibitors (SSRIs) and venlafaxine are often used to treat depression in the elderly due to their low incidence of side effects. All five of the SSRIs currently available and venlafaxine have been associated with hyponatremia. CASE REPORT: This article describes the case of an 87-year-old man with depression who presented with hyponatremia after starting treatment with citalopram. After excluding other common causes of hyponatremia, a diagnosis of syndrome of inappropriate secretion of antidiuretic hormone (SIADH) was confirmed. Sodium levels returned to the normal range following discontinuation of citalopram. Subsequently, due to the persistence of depression, treatment with venlafaxine was initiated. Three weeks later, hyponatremia associated with SIADH was once again diagnosed and venlafaxine was discontinued. The hyponatremia resolved in 2 weeks. DISCUSSION: Both SSRIs and venlafaxine have been associated with SIADH in numerous case reports and retrospective studies. Risk factors for developing hyponatremia with these drugs are advanced age and treatment with other medications. To our knowledge, this is the first case report in which SIADH was associated with two different families of antidepressants in the same patient. CONCLUSION: Physicians should be aware of the risk of hyponatremia when prescribing SSRIs and venlafaxine in elderly patients with multiple drug therapies. Sodium levels should be monitored during treatment.     

Valproic acid, unlike other anticonvulsants, has no effect on methadone metabolism: two cases

Two patients who were concomitantly undergoing methadone maintenance treatment and receiving phenytoin suffered continuing opioid withdrawal symptoms as a results of phenytoin's acceleration of methadone metabolism. When anticonvulsant therapy was discontinued, these patients had seizures. One patient was switched to carbamazepine as an alternative anticonvulsant, but this treatment resulted in a similar clinical problem. When both patients received valproic acid instead, the withdrawal symptoms disappeared and their conditions stabilized.     

Protease inhibitor-induced carbamazepine toxicity

Neurologic manifestations of HIV infection are quite diverse and can develop into seizures. Because new drug therapies have been developed, it is important to know the interactions between antiretroviral and antiepileptic agents. A 36-year-old patient with HIV developed a set of progressive left hemiparesis and secondarily generalized partial seizures related to progressive multifocal leukoencephalopathy. Phenytoin and carbamazepine were necessary to control the seizures. Instead of diverse antiretroviral therapies, the viral load was increased. Protease inhibitors (ritonavir and saquinavir) were added to the treatment and the patient developed progressive ataxia related to carbamazepine toxicity. Carbamazepine was discontinued and the patient remained asymptomatic. The patient was diagnosed with carbamazepine toxicity related to the introduction of ritonavir. Ritonavir is a potent inhibitor of hepatic cytochrome P450, mainly the CYP3A4 isoform. Carbamazepine is metabolized by this subsystem. Ritonavir acted as a CYP3A4 inhibitor, diminishing carbamazepine metabolism and provoking an increase in serum levels and clinical toxicity. We present a case of interaction between ritonavir and carbamazepine. Interaction between antiepileptic and antiretroviral agents is an emergent problem caused by the increasing association of the two therapies. We recommend strict monitoring of serum antiepileptic drug (AED) levels to avoid toxicity and inadequate seizure control.     

Cerebral salt-wasting syndrome in a patient with neuroleptic malignant syndrome

BACKGROUND: Hyponatremia associated with neuroleptic malignant syndrome has thus far been described as a syndrome of inappropriate secretion of antidiuretic hormone. OBJECTIVES: To ascertain and describe the role of cerebral salt-wasting syndrome as the cause of hyponatremia in a patient with neuroleptic malignant syndrome. PATIENT: A psychotic patient being treated with olanzapine presenting with sopor, muscle rigidity, polyuria, tachycardia, pyrexia, and severe hyponatremia. METHODS: Serial serological examinations of plasma tonicity (sodium level and osmolality), brain natriuretic peptide, and antidiuretic hormone were performed, and sodium excretion and urine osmolality were determined from 24-hour urine collection. In addition, markers for rhabdomyolysis were monitored. RESULTS: The patient shows clear symptoms of cerebral salt-wasting syndrome in association with neuroleptic malignant syndrome, characterized by severe hyponatremia, volume depletion, and elevated brain natriuretic peptide but normal antidiuretic hormone levels. Cerebral salt-wasting syndrome improved under dantrolene sodium treatment and concomitant fluid and sodium replacement. CONCLUSION: Hyponatremia in patients with neuroleptic malignant syndrome might more likely reflect cerebral salt-wasting syndrome than a syndrome of inappropriate secretion of antidiuretic hormone as an additional aspect of autonomic dysregulation caused by antidopaminergic drugs.     

Oxcarbazepine monotherapy in children and adolescents: a single-center clinical experience

This single-center analysis evaluated the efficacy of oxcarbazepine monotherapy in children and adolescents. A retrospective chart review identified 60 patients (male=33, female=27) aged 6 months to 17.8 years (mean age 8.2+/-4.7 years) with partial onset epilepsy receiving oxcarbazepine monotherapy. The range of oxcarbazepine dose was 6-71 mg/kg/day (mean 26.3+/-11.4 mg/kg/day). The duration of therapy ranged from 3 months to 8 years (mean duration 16.7+/-14.3 months). Fifty-one patients (85%) achieved>or=50% reduction in seizure frequency, and 25 of 60 patients (42%) achieved seizure freedom. Ten patients (16.67%) reported adverse events including drowsiness, aggressive behavior, ataxia, dizziness, diplopia, and leg cramps. No hyponatremia or skin rash was observed. Twenty-four patients were switched from carbamazepine to oxcarbazepine monotherapy. In these patients carbamazepine was discontinued because of incidence of adverse events, poor seizure control, or both. Seventy-nine percent of patients switched from carbamazepine to oxcarbazepine monotherapy had >or=50% reduction in seizure frequency, and 37.5% became seizure-free. These findings suggest that oxcarbazepine monotherapy is effective and well tolerated in children and adolescents with partial epilepsy.     

Oxcarbazepine-induced hyponatremia and the regulation of serum sodium after replacing carbamazepine with oxcarbazepine in children

While severe hyponatremia is reported to be more frequent in adults treated with oxcarbazepine (OXC) than with carbamazepine (CBZ), there is not sufficient data about the incidence of hyponatremia in childhood during treatment with OXC. We evaluated changes in serum electrolyte balance in 75 children with epilepsy before and during treatment with OXC and after replacing carbamazepine (CBZ) therapy with OXC therapy. All patients had normal sodium serum levels at the onset of OXC. During treatment with OXC we found hyponatremia (Na +< 135 mmol/l) without clinical symptoms in 26.6 % of the children (n = 20), sodium levels below 125 mmol/l were observed in 2 children (2.6 %). Clinically relevant hyponatremia occurred in one girl only (1.3 %). In a subgroup of 27 children, in whom CBZ was directly replaced with OXC, hyponatremia without symptoms was found in one child under CBZ (3.7 %) and in six children under OXC (22.2 %). Dosage of OXC, serum levels of the active metabolite of OXC, antiepileptic comedication or patients' age and gender were of no predictive value for the development of hyponatremia. Electrolytes should be measured before establishing OXC and if clinically relevant side effects occur.     

Carbamazepine and cardiac conduction disturbances

Carbamazepine-induced cardiac conduction disturbance is reported in 2 patients suffering from epilepsy. The cardiac defects disappeared in both patients after carbamazepine was discontinued, and reappeared in 1 patient after treatment was resumed.     

神经外科低钠血症的鉴别诊断和处理

目的探讨各型低钠血症的诊断和处理原则。方法回顾性分析562例低钠血症的临床资料,分出不同的类型给以不同的处理。结果562例中因利尿引起430例,补钠不足46例,尿崩症56例,抗利尿激素分泌不当综合征18例,恼性盐耗综合征11例,1例由肾小管损伤引起。结论因补钠不足或利尿引起的补钠即可,尿崩症以补充抗利尿激素为主,抗利尿激素分泌不当综合征应以限水为主,脑性盐耗综合征须采取综合治疗,肾小管损伤低钠血症会随着肾小管功能恢复而纠正。     

Successful mirtazapine treatment of an 81-year-old patient with syndrome of inappropriate antidiuretic hormone secretion

Elderly patients are at a higher risk for inappropriate antidiuretic hormone secretion when treated with antidepressants. In response to severe depressive symptoms, we initiated treatment with citalopram of an 81-year-old female patient with slightly reduced sodium and chloride levels. The sodium and chloride levels decreased continuously during treatment with citalopram; six days after the citalopram was discontinued, sodium and chloride levels returned to normal. We then switched treatment to mirtazapine. Close monitoring revealed that the patient's sodium and chloride levels never decreased and the patient did not relapse for more than two months. This case study indicates that treatment with citalopram may worsen preexisting hyponatremia. Mirtazapine appears to be safe for use in high-risk, elderly patients.