Carbamazepine in the treatment of aggression: a case report and a review of the literature

Aggressive behaviour is an inescapable clinical problem confronting practitioners of medicine, neurology and psychiatry. Several drugs have been used to treat it, with limited success. Successful use of carbamazepine in the treatment of aggressive behaviour in a patient with limbic dysfunction is reported, and varieties of aggressive behaviour that respond to carbamazepine are examined. The authors suggest that carbamazepine may have a specific anti-aggressive effect perhaps due to an anti-kindling effect, but caution that double-blind studies are needed before firm conclusions are drawn.     

同时测定血清中苯巴比妥、苯妥英及卡马西平的反相高效液相色谱法

为了探讨高效液相色谱法同时测定苯巴比妥（ＰＢ）、苯妥英（ＰＨＴ）、卡马西平（ＣＢＺ）血药浓度的最佳实验条件，将标本在ｐＨ７．６条件下用二氯甲烷提取后经高纯度氮气在５０℃水浴中吹干，再用甲醇重溶后进行色谱分析。色谱条件：ＹＷＧ－Ｃ１８柱（２５０ｍｍ×４．６ｍｍ，１０μｍ），流动相甲醇：水为６０∶４０，流速１ｍｌ／ｍｉｎ，柱温４０℃，波长２５４ｎｍ。结果ＰＢ、ＰＨＴ、ＣＢＺ的最低检出浓度各为０．６７μｇ／ｍｌ、０．９４μｇ／ｍｌ和０．３１μｇ／ｍｌ。在三个不同水平下，ＰＢ、ＰＨＴ、ＣＢＺ的平均回收率各为９８．１４％、９６．７２％和９９．３６％，日内和日间变异均低于６．２５％，内源性物质及１０种常用药物未见干扰，在分析范围内具有良好的线性关系。该方法操作简便、快捷、准确，可满足临床和科研的需要。     

Dose dependent enzyme induction by oxcarbazepine?

Summary Antipyrine half life and clearance was compared in four patients with classical idiopathic trigeminal neuralgia during carbamazepine (CBZ) or CBZ/phenytoin (PHT) and after substitution with oxcarbazepine (OXC) monotherapy.OXC is observed to be less of a hepatic enzyme inducer than CBZ or CBZ/PHT in combination, however induction by OXC may be dose related.     

Dose-Dependent Pharmacokinetics of Carbamazepine in Rats: Determination of the Formation Clearance of Carbamazepine-10,11-epoxide

The dose dependency of carbamazepine pharmacokinetics was characterized in rats, a common test animal for antiepileptic drug efficacy. With a randomized Latin square schedule, 5, 10, and 20 mg/kg doses of carbamazepine were injected intravenously into six Sprague-Dawley rats followed by the administration of a 5 or 10 mg/kg i.v. dose of CBZ-E to each rat. Following administration, the concentrations of CBZ and Carbamazepine-10,11-epoxide (CBZ-E) in whole blood were determined by a reverse-phase HPLC assay. Plasma protein binding of both carbamazepine and CBZ-E was linear over the concentration range observed in this study. Carbamazepine concentration–time plots were log-linear, but the slopes were not parallel. Carbamazepine total-body clearances were 15.1 ± 3.26, 13.4 ± 5.66, and 10.0 ± 3.11 ml/min/kg at the 5, 10, and 20 mg/kg doses, respectively (significance of difference between the 5 and the 20 mg/kg dose = 0.06 < P < 0.05; Kruskal–Wallis test, Dunn's procedure). However, the formation clearance to CBZ-E did not change, suggesting that metabolism via other pathways was decreased at higher carbamazepine doses.     

A case of organic brain syndrome following head injury successfully treated with carbamazepine

A case of organic brain syndrome occurring in relation to psychological stress 2 years after a severe head injury is described. Treatment with haloperidol resulted only in slight improvement. A dramatic improvement was achieved with carbamazepine.     

CSF somatostatin in affective illness and normal volunteers

Somatostatin is a hypothalamic tetradecapeptide with many central nervous system actions. We investigated a potential role for altered somatostatin activity in affective disorder by measuring somatostatin in the cerebrospinal fluid (CSF) of 47 patients with affective disorder and of 39 normal volunteers. Medication-free depressed patients showed significantly lower levels of CSF somatostatin than normal volunteers (p less than .001) or patients during the improved state (p less than .01). Somatostatin levels were significantly and inversely correlated with duration of sleep on the night of the lumbar puncture (p less than .05). Treatment with carbamazepine reduced CSF somatostatin (p less than .01) in contrast to the absence of effect of imipramine, desmethylimipramine, and lithium carbonate and the significant increase in CSF somatostatin seen in a small group of patients treated with zimelidine. The implications of these findings with respect to attempts to explore the neurobiology of depression are discussed.     

Changes in circulating thyroid hormones during short-term hepatic enzyme induction with carbamazepine

Summary The effect of short-term hepatic enzyme induction with carbamazepine (CBZ) on circulating thyroid hormone concentrations was studied in 10 healthy male subjects. CBZ 400 mg per day was given for 21 days in 6 subjects and for 14 days in a further 4. In the former group the effect of therapy on the pituitary/thyroid axis was also assessed by measuring thyroid stimulating hormone (TSH) response to thyrotrophin-releasing hormone. CBZ therapy resulted in induction of hepatic monooxygenase activity, evidenced by a fall in antipyrine half-life (11.1±0.7 to 7.6±0.7 h; p<0.001), and a rise in antipyrine clearance (0.72±0.06 to 0.98±0.1 ml min^–1 kg^–1; p<0.001). A significant fall in total serum thyroxine (T4) (81.9±2.9 to 75.1±2.9 nmol l^–1), and triiodothyronine (T3); (1.59±0.07 to 1.37±0.05 nmol l^–1) and free T4 (16.03±0.82 to 14.2±0.8 pmol l^–1) was seen after CBZ therapy. (all p<0.05). No significant change in reverse T3 or thyroid binding globulin occurred. In the 6 subjects studied for 21 days, maximal changes were found following 14 days' treatment. Basal and stimulated TSH remained unaltered. These effects on circulating thyroid hormone concentrations are likely to be secondary to hepatic enzyme induction leading to accelerated nondeiodinative hepatic hormone disposal. The reason for the failure of pituitary TSH secretion to rise in response to the fall in circulating T4 and T3 is unclear but may have implications for chronic treatment with CBZ in epileptic patients.     

The comparative cognitive side-effects of lithium,carbamazepine and combined lithium--carbamazepine in patients treated for affective disorders

The cognitive side-effects of lithium, carbamazepine (CBZ) and combination CBZ and lithium were compared in a crossover double-blind study. The CBZ range was 17–26 Mmol/1 and the lithium range 0·41–1·10 mmol/1. Twelve subjects (seven females, five males), five with bipolar and seven with unipolar affective disorders, were randomly distributed to one of three group; the order of the conditions was different for each group, whereby each condition was tested in each of the three time phases of the study. The group varied according to the order of the three drug conditions. From measures of memory, attention and perceptuomotor functioning two measures showed significant differences between drug conditions. A tracking task showed impairment in the combined CBZ--lithium condition compared to the single administration of either drug. A memory task testing cued recall for prose was performed better in the CBZ group; results were not confounded by correlations with self-ratings of mood.     

Treatment of periodic depression with carbamazepine

A case of periodic depression treated prophylactically with carbamazepine for over 10 years is reported. Recurrence of depressive episode was completely inhibited during the carbamazepine treatment and depressive relapses occurred 2 to 4 months after the discontinuation of carbamazepine treatment. No notable side effect was found during the treatment.     

Effect of activated charcoal on absorption and elimination of phenobarbitone,carbamazepine and phenylbutazone in man

Summary The effect of activated charcoal, given as a water suspension, on the absorption and elimination of phenobarbitone 200 mg, carbamazepine 400 mg and phenylbutazone 200 mg, was studied in five healthy volunteers, using a randomized crossover design. Absorption of the drugs was almost completely prevented (more than 95%) when charcoal 50 g was ingested within five minutes of taking the drugs. When activated charcoal was taken one hour after the drugs, the mean inhibition of drug absorption was considerably less and the inhibition was greatly dependent on the individual rate of absorption. The half-life of phenobarbitone was markedly shortened from a control value of 110±23 h to 19.8±1.0 h (P<0.05), with a corresponding increase in plasma clearance from 4.6 ml/min to 23 ml/min, when activated charcoal 118 g, in five divided doses was given between 10 and 48 h after ingestion of the drug. The half-life of carbamazepine was shortened by 45% (P<0.05) and the reduction in the half-life of phenylbutazone (30%) by charcoal, too, was statistically significant. The only side effect from use of the charcoal suspension was constipation, which occured in three subjects after repeated doses, and which was easily treated with lactulose if required. Although activated charcoal should be given as soon as possible, even its delayed use may be indicated, due to the slow absorption often seen in acute intoxication. The use of multiple doses of charcoal appears to be indicated as an additional treatment of certain severe intoxications to prevent the release of drugs from charcoal, and to increase their rate of elimination if they are secreted into the gut with subsequent reabsorption.