Signs and symptoms of carbamazepine overdose

Carbamazepine (CBZ) has been successfully employed in a variety of neurological and psychiatric disorders. The side-effects of CBZ treatment have been extensively studied. As little is known about the symptoms and prognosis of CBZ overdose, our objective was to identify the factors relevant to its prognosis. In a retrospective study of 427 cases, we analysed the distribution of age, sex, total CBZ dose, CBZ plasma level, frequency of symptoms and their association with outcome. In those patients who recovered, coma, somnolence, cerebellar syndrome and epileptic seizures were the most common manifestations of CBZ overdose. In fatal courses coma, epileptic seizures, respiratory depression and respiratory arrest ranked highest. Cardiac arrhythmias and other cardiovascular complications were rare. In 41 of 307 patients (13%) in whom outcome was reported, intoxication was fatal. The occurrence of seizures and CBZ doses exceeding 24g proved to be important indicators of a fatal outcome. The course of intoxication seems to be more benign in patients aged below 15 years.     

Olanzapine plus carbamazepine v. carbamazepine alone in treating manic episodes

BACKGROUND: Combinations of olanzapine and carbamazepine are often used in clinical practice in the management of mania. AIMS: To assess the efficacy and safety of olanzapine plus carbamazepine in mixed and manic bipolar episodes. METHOD: Randomised, double-blind, 6-week trial of olanzapine (10-30 mg/day) plus carbamazepine (400-1200 mg/day; n=58) v. placebo plus carbamazepine (n=60) followed by open-label, 20-week olanzapine (10-30 mg/day) plus carbamazepine (400-1200 mg/day, n=86), with change in manic symptoms as main outcome measure. Safety and pharmacokinetics were also evaluated. RESULTS: There were no significant differences (baseline to endpoint) in efficacy measures between treatment groups, but at 6 weeks triglyceride levels were significantly higher (P=0.008) and potentially clinically significant weight gain (>or=7%) occurred more frequently (24.6% v. 3.4%, P=0.002) in the combined olanzapine and carbamazepine group. Carbamazepine reduced olanzapine concentrations but olanzapine had no effect on carbamazepine concentrations. CONCLUSIONS: The combination of olanzapine and carbamazepine did not have superior efficacy to carbamazepine alone. The increases in weight and triglycerides observed during combination treatment are a matter of concern.     

Phencyclidine: pharmacologic and clinical review

Phencyclidine (PCP), discovered in Germany during the 1920s, has become over the past four decades the number one drug of abuse in the United States. While briefly showing promise as being the "ultimate" anasthetic agent during the late 1950s, it very quickly fell into disfavor because of untoward side-effects during post-anesthetic emergence (1960s). Some few years later (1970s), PCP began its ascent in the illicit drug market. PCP is a drug with a broad range of pharmacological activity. It has been implicated as a major cause of psychiatric decompensation and has a number of clinical syndromes described in the literature. In addition, PCP has been shown to cause significant medical morbidity and mortality.     

Stimulus-induced focal motor seizure in a pediatric patient with carbamazepine overdose

IntroductionCarbamazepine (CBZ) is a common antiepileptic drug that may cause overdoses with seizures as a common neurological manifestation. In previous reports, patients with CBZ overdose exhibited stimulus-induced generalized clinical or electrical seizures. To date, no previous cases of focal motor seizures have been reported.Case reportWe report the case of an 11-year-old girl with spontaneous and stimulus-induced clustering of focal motor seizures following CBZ overdose. The patient had been treated with CBZ (150 mg daily) for focal epilepsy since the age of six years. At the age of 11, she forgot to take a morning dose, took ten CBZ pills (CBZ 1000 mg) as compensation, and presented with generalized seizures. The patient arrived at the hospital in a coma. She demonstrated clustering of focal-to-bilateral tonic-clonic seizures induced by pain stimulus or spontaneously, with focal epileptiform discharges observed on EEG. Her CBZ blood concentration measured 40.4 μg/mL and she was diagnosed with CBZ overdose. The patient showed improvement without any specific treatment, and was later discharged without neurological sequelae.ConclusionPrevious cases of CBZ overdose with stimulus-induced generalized seizures resulted in death or required intensive care. Stimulus-induced focal seizures may indicate a favorable prognosis for CBZ overdose.     

Neuroleptic-induced supersensitivity psychosis: clinical and pharmacologic characteristics

Tardive dyskinesia is thought to result from neostriatal dopaminergic receptor supersensitivity induced by chronic treatment with neuroleptics. The authors suggest that dopaminergic supersensitivity also occurs in the mesolimbic region after chronic neuroleptic exposure, resulting in the development of a supersensitivity psychosis. Neuroleptic-induced supersensitivity psychosis is illustrated by data from 10 patients that demonstrate the syndrome's clinical and pharmacologic characteristics. An implication of neuroleptic-induced mesolimbic supersensitivity is that the tenaency toward psychotic relapse in such patients is determined by more than just the normal course of the illness.     

Dopamine overdose hypothesis: Evidence and clinical implications

About a half a century has passed since dopamine was identified as a neurotransmitter, and it has been several decades since it was established that people with Parkinson's disease receive motor symptom relief from oral levodopa. Despite the evidence that levodopa can reduce motor symptoms, there has been a developing body of literature that dopaminergic therapy can improve cognitive functions in some patients but make them worse in others. Over the past two decades, several laboratories have shown that dopaminergic medications can impair the action of intact neural structures and impair the behaviors associated with these structures. In this review, we consider the evidence that has accumulated in the areas of reversal learning, motor sequence learning, and other cognitive tasks. The purported inverted‐U shaped relationship between dopamine levels and performance is complex and includes many contributory factors. The regional striatal topography of nigrostriatal denervation is a critical factor, as supported by multimodal neuroimaging studies. A patient's individual genotype will determine the relative baseline position on this inverted‐U curve. Dopaminergic pharmacotherapy and individual gene polymorphisms can affect the mesolimbic and prefrontal cortical dopaminergic functions in a comparable, inverted‐U dose‐response relationship. Depending on these factors, a patient can respond positively or negatively to levodopa when performing reversal learning and motor sequence learning tasks. These tasks may continue to be relevant as our society moves to increased technological demands of a digital world that requires newly learned motor sequences and adaptive behaviors to manage daily life activities. © 2013 International Parkinson and Movement Disorder Society     

Phenacemide: A New clinical pharmacologic perspective

Phenacemide (Phenurone®) is an older antiepileptic agent about which little modern clinical pharmacologic information has been available. As assay was developed to measure serum phenacemide levels, and kinetic parameters were studied. In the course of therapy of maximally severe epilepsy in 21 patients, clinical and pharmacologic data were gathered. The therapeutic range for phenacemide is 50–100 μg/ml. Mean dose to reach these levels is 56 mg/kg/day. It is not strongly bound to serum proteins (76% unbound in serum). Phenacemide clearance was significantly lower in the presence of valproic acid but was not changed by any other antiepileptic drug. Elimination T/2 in one patient was 15 h. Seizures were consistently better in 10 of 21 patients (4 with complex partial seizures, 5 with atypical absences with minor motor phenomena, and 1 with generalized convulsions). No idiosyncratic side effects were seen to affect marrow, liver, skin, kidney, etc. Mood-altering side effects were seen in seven patients: five showed a withdrawn syndrome and two showed a restless syndrome. This drug is not frequently useful, but the availability of modern pharmacologic information will maximize the success when it is used.     

丙戊酸钠与卡马西平治疗躁狂发作临床观察

目的：评价丙戊酸钠与卡马西平对锂盐治疗无效的躁狂发作的疗效和副反应。方法：将符合CCMD－2－R躁狂发作诊断标准的5例患者随机分为丙戊酸钠组和卡马西平组,治疗6周。使用Bech-Rafaelsen躁狂量表及临床疗效总评量表的疗效总评评定疗效,用副反应量表及有关实验室检查评定副反应。结果：丙戊酸钠与卡马西平均能有效减轻躁狂症状,疗效相近,丙戊酸钠起效时间迟于卡马西平。丙戊酸钠的副反应主要为肠道反应、震颤等、而卡马西平以共济失调、头晕、嗜睡等多见。结论：丙戊酸钠与卡马西平均可用于锂盐治疗无效的躁狂发作。     

Alprazolam overdose: clinical findings and serum concentrations in two cases

Two patients who attempted suicide with alprazolam had markedly elevated serum concentrations but manifested only mild toxicity. Overdose with alprazolam appears much less likely to be life-threatening than overdose with the tricyclic antidepressants.     

Stroke-like episodes in familial mitochondrial encephalomyopathy: clinical and biochemical aspects

Summary Acute episodes of focal neurological dysfunction are a well-recognized complication of the mitochondrial encephalomyopathies. Because of rapid remission, biochemical tests and other diagnostic procedures are mostly performed after the acute phase. We report the case of a patient suffering from mitochondrial disease manifesting primarily with seizures, progressive deafness and dementia, who experienced multiple stroke-like episodes. Other members of the family with evidence of mitochondrial dysfunction are presented briefly. EEG and biochemical findings in the acute stage are correlated with clinical symptoms, showing characteristics distinct from the chronic illness. The possible involvement of dietary factors in the provocation of stroke-like episodes is discussed and regulation of glucose intake suggested as a strategy in the prevention of stroke-like episodes.     

Inflammation in epilepsy: clinical observations

Over the past decade, an increasing number of observations indicate that activation of inflammatory processes occurs in variety of focal epilepsies. Understanding the feature and consequences of neuroinflammation, including the contribution to development and perpetuation of seizures, as well as to mood or cognitive dysfunction, is a major requisite for delineating its role in epilepsy. The present article discusses the most recent observations supporting the involvement of the inflammatory response in human focal epilepsy. It also evaluates emerging evidence concerning the possibility to identify epilepsy-associated inflammatory biomarkers in cerebrospinal fluid and serum, as well as the potential application of neuroimaging approaches to study the inflammatory reactions in chronic epilepsy patients in vivo, aiming to improve the recognition of appropriate patient populations who might benefit from antiinflammatory or immunomodulatory therapies.     

Interictal psychotic episodes in epilepsy: duration and associated clinical factors

Purpose: There have been few reports showing the distribution of the duration of interictal psychosis (IIP) episodes and their association with clinical characteristics. To clarify the nature of IIP, we studied the duration of IIP episodes and their related factors. Methods: One hundred fifty‐five patients with epilepsy exhibited 320 IIP episodes during our follow‐up period (mean 16.9 years). The duration of all the episodes and the longest episode in each patient during the follow‐up periods were studied. Characteristics of the patients (e.g., epilepsy type, age of onset, and family history of psychosis) and episode‐specific factors (e.g., age of the episode, seizure frequency, administrations of antiepileptic drugs [AEDs] and antipsychotic drugs [APDs]) were analyzed in association with the duration of the episodes. Key Findings: Mean duration of the 320 IIP episodes was 82.7 weeks and that of the longest IIP episodes was 150.1 weeks. During the follow‐up period, 17 patients (11.0%) showed all episodes remitting within a month and 54 (34.8%) showed all episodes lasting for 6 months or longer. The IIP episodes that occurred at a younger age were often prolonged. Patients with a family history of psychosis or with early onset of psychosis tended to have more prolonged IIP episodes. Among the episodes treated with APDs, early administration of APDs was significantly associated with shorter IIP duration. Significance: The distribution of the duration of IIP episodes indicated the broad spectrum and heterogeneity of the IIP phenomena. The individual vulnerability to psychosis may be associated with prolonged episodes. Administration of APDs soon after onset of the episodes appeared to be effective in controlling them. These findings support empirical treatment principles for IIP to administer APDs at an early stage of its development.     

Levodopa-induced dyskinesia: clinical observations

Summary In 144 patients receiving prolonged treatment with levodopa for Parkinson's disease, an attempt was made to establish possible correlations between the incidence of levodopa-induced dyskinesias and the age of the patient at the onset of the disease, the clinical form of the disease, the duration of symptoms before initiation of the levodopa therapy, the duration of the levodopa therapy and the influence of the concomitant treatment. Levodopa-induced dyskinesia was observed in 92 patients (64%). The age at onset of the disease of patients with dyskinesia was significantly different from the age at onset of those without dyskinesia, the means being 54.8 and 68.9 years respectively. Levodopa-induced dyskinesia occurred less often in the group with preponderant tremor than in those with preponderant bradykinesia (29% vs. 69%). The patients treated with levodopa from the very beginning of their disease were less susceptible to dyskinesia than those who had parkinsonism for some time before receiving levodopa. The influence of the duration of levodopa treatment on the manifestation of dyskinesia could not be confirmed because this side-effect usually appeared during the first year of treatment. The concomitant anti-parkinsonian treatment appeared to have no influence on the incidence of dyskinesia. Biochemical and practical implications of these observations are discussed.     

Free level monitoring of carbamazepine and valproic acid: clinical significance

The recently available ultrafiltration technique facilitates determination of the free drug serum concentration of several antiepileptic drugs. For this reason a reappraisal of the clinical significance of free level monitoring was thought necessary. In this study on 203 patients receiving carbamazepine monotherapy and 101 patients receiving valproic acid monotherapy, the total and free drug levels were correlated with therapeutic outcome and side effects. Our investigations indicated no closer correlation between free concentration and seizure reduction or side effects than between total concentration and effectiveness or side effects. However, we found a close correlation between total and free concentrations.