We report on a patient with schizoaffective disorder who was on combination therapy of lithium, carbamazepine, and the neuroleptic trifluperidol. He experienced a lobar pneumonia and developed an acute and persistent cerebellar deterioration which was most likely due to lithium toxicity, while the serum lithium level was within the therapeutic range. The combination of lithium, carbamazepine, and neuroleptics is common, and is generally considered to be safe. The reported case suggests that this regimen might increase the risk of intoxication with potentially disabling side-effects.

We herein report a case of new-onset epileptic seizures induced by carbamazepine in an individual with autism spectrum disorders (ASD). We clinicians should bear in mind the possibility that epileptic seizures may possibly be either precipitated or exacerbated by carbamazepine especially in individuals with ASD.

In an open prospective study, the stabilizing effects of carbamazepine on agitation, impulsivity and affective lability were investigated in 15 severely demented patients, who had failed to respond to prior neuroleptic medication. Because of leukopenia and allergic reactions in two subjects, carbamazepine treatment was discontinued. In nine patients a clinically relevant improvement was observed.

Indications for lithium in the treatment of bipolar disorders are acute mania, depression and preventive treatment. In the case of insufficient efficacy or adverse effects the first alternative for lithium in acute mania is carbamazepine. However, the role of carbamazepine in preventive treatment is still uncertain. Well designed prospective research is hardly done. Clearly positive reports on the efficacy of carbamazepine concern specific lithium-resistant groups such as the ‘rapid-cyclers’. Valproic acid has been found effective in a few studies in bipolar disorders, especially in acute mania. Clonazepam is sometimes mentioned as a possible alternative, however recent research seriously questions the efficacy of clonazepam in bipolar disorders. Calcium-antagonists, especially verapamil, may have some efficacy in the treatment of acute mania, their role is still very uncertain.

Lithium is considered first choice in the prevention of prospective episodes in patients with bipolar disorder. However, efficacy is not satisfactory in all patients and side effects sometimes prevent the use of lithium. It is argued that efficacy in clinical practice may be less impressive than anticipated from clinical trials, and alternative treatments are beinu advocated increasingly for that reason, such as the anticonvulsants, carbamazepine and valproate.

We report the results of an acute-phase and continuation-phase study of the pharmacological treatment of children and adolescents with bipolar disorders. The acute phase study, with a duration of 6-8 weeks, aimed at developing effect sizes (ES) for lithium, divalproex sodium, and carbamazepine, in the acute phase treatment of Bipolar I or II children and adolescents during a mixed or manic episode. During the acute-phase of treatment, 42 outpatients with a mean age of 11.4 yr. (20 with Bipolar I Disorder and 22 with Bipolar II Disorder) were randomly assigned to 6-8 weeks of open treatment with either lithium, divalproex sodium, or carbamazepine. The primary efficacy measures were the weekly CGI Improvement scores and the Young Mania Rating Scale. Using a ≥ 50% change from baseline to exit in the Y-MRS scores to define response, the effect size for divalproex sodium was 1.63,1.06 for lithium, and 1.00 for carbamazepine. Using this same response measure with the intent-to-treat sample, the response rates were: sodium divalproex 53%; lithium 38%; and carbamazepine 38% (x 2=0.85, 2 d.f., p=0.60). Thirty-five subjects continued in open, treatment for another 16-18 weeks, for a total of 24 weeks of prospective treatment. Overall, of the thirty-five continuation phase subjects, thirty (85%) were categorized as responders at the end of the continuation phase of treatment. Of these thirty-five subjects, 13 (37%) were only on a single mood stabilizer and no other psychotropic agents at the end of the continuation phase. Thirty-one percent of subjects in continuation were also treated with a stimulant medication in addition to mood stabilizers.

The object was to perform simultaneous quantitative analyses of complex pharmaceutical solid mixtures by the Rietveld method. Mixtures consisting of anhydrous β-carbamazepine, anhydrous α-carbamazepine, and carbamazepine dihydrate were chosen as the model system. Lithium fluoride was used as the internal standard. Mixtures of various compositions were prepared and subjected to X-ray powder diffractometry (XRD). The XRD pattern of each mixture was analyzed by the Rietveld method and at the end of the refinement, the goodness of fit was evaluated. When the analyte concentration was high (≥20%), the relative error in the determination was <±5%. The detection of analyte was possible even when its concentration was low (<1% w/w). A unique advantage of the method is that it enables simultaneous quantitative analyses of multiple phases without the requirement of “standard curves.” © 2001 International Centre for Diffraction Data.

Objective: This study investigates attitudes to the prescription of mood stabilizer drugs for older patients by old age psychiatrists.

Methods: From a sample of 508 members of the Old Age Faculty of the Royal College of Psychiatrists practicing in England and Wales, 188 (37%) took part in a postal questionnaire survey. A proforma questionnaire investigating opinions about potential indications for, and current concerns about, mood stabilizer drugs was sent to all participants.

Results: Nearly all respondents initiated prescriptions for mood stabilizer drugs and a large majority agreed that they are therapeutically appropriate for prophylaxis of affective disorder (95%), treatment resistant depression (95%), acute mania (91%) and for behavioral symptoms in dementia (75%). Concerns about safety (77%), drug interactions (68%) and lack of scientific evidence (53%) were common.

Conclusions: Old age psychiatrists are frequent prescribers of mood stabilizer drugs for a variety of indications but have understandable concerns arising from a relative lack of scientific evidence of efficacy and effectiveness in older patients.

ABSTRACT

Background: Anti-epileptic drugs (AEDs) are associated with cognitive side effects. Doubt exists regarding the degree of cognitive effects primarily related to problems with design and methodology in many studies. The aim of the reported study was to assess the effect of AED withdrawal in patients on monotherapy using computerised measures of attention, reaction time and speed of information processing. Methods: One hundred and fifty patients seizure free >2 years on drug monotherapy went through a randomised, double blind, placebo controlled study. All patients were included for 12 months or until seizure relapse. Cognitive function was assessed with the California Computerized Assessment Package at baseline and 7 months after withdrawal. Results: The major finding was 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 withdrawal and non-withdrawal groups was between 24 and 43 ms. No significant difference emerged between the groups on simple tasks of attention and reaction time. Most of the patients in the study were treated with carbamazepine and valproate. The outcome of carbamazepine withdrawal was similar to the outcome for the total study population while discontinuation of valproate only revealed a non-significant tendency in the same direction. Interpretation: The results suggest that seizure-free epilepsy patients on monotherapy can obtain improvement in speeded cognitive processing if they withdraw anti-epileptic treatment.

Objective: To review and summarize the currently available data on the use of anticonvulsant mood stabilizers (carbamazepine, valproic acid, gabapentin, lamotrigine, topiramate) in the treatment of behavioral and psychological symptoms of dementia (BPSD); to determine whether these medications can be recommended for routine clinical use.

Methods: Literature search in five databases (PubMed, MEDLINE, EMBASE, PsychINFO and COCHRANE collaboration) and analysis of the randomized controlled double-blinded clinical trials found therein.

Results: A total of seven RCTs were identified (two for carbamazepine and five for valproate). One study showed statistically significant improvement of BPSD in the medication group in comparison to the placebo group; five studies showed no significant differences; one study showed statistically significant worsening of the symptoms in the medication group vs. placebo. The majority of the studies reported significantly more frequent adverse effects in the medication group.

Conclusion: Although clearly beneficial in some patients, anticonvulsant mood stabilizers cannot be recommended for routine use in the treatment of BPSD at the present time.

The aim of this study was to assess cognitive effects of anticonvulsants in a way that would yield results that are most directly applicable to epilepsy populations. This was done with a placebo-controlled, prospective, randomized, double-blind, parallel group study of anticonvulsant withdrawal in a population of subjects taking a single anticonvulsant with completely controlled seizures. Outcomes of this study on cognitive measures from the California Computerized Assessment Package have recently been reported. To aid comparison with results of prior studies, we report outcomes here on several more standard measures of neuropsychological function. The major findings were that, in subjects with therapeutic drug levels at baseline, drug withdrawal was associated with significant improvement in performance on the Controlled Oral Word Association Test and the Stroop Color–Word Interference Test. Comparable results were achieved in the subgroup taking carbamazepine. (JINS, 2007, 13, 393–400.)