A pilot randomized trial of carbamazepine for behavioral symptoms in treatment-resistant outpatients with Alzheimer disease.

The authors performed a 6-week, randomized, double-blind, placebo-controlled, parallel-group trial of carbamazepine (400 mg/day) with 21 agitated subjects (16 completers) who had been treated unsuccessfully with antipsychotics. There was greater improvement for the carbamazepine group on the Clinical Global Impression of Change (P=0.055) and the Brief Psychiatric Rating Scale (BPRS) Hostility item (P=0.009), with a trend toward worsening on the BPRS Hallucination item (P=0.067). Overall, carbamazepine showed modest clinical benefit in these subjects, who had not responded to antipsychotics, and particular benefit for hostility. The effect on global ratings was similar to those found in an earlier report in nursing home residents.

The Spanish Instrument Protocol: design and implementation of a study to evaluate treatment efficacy Instruments for Spanish-speaking patients with Alzheimer's disease. The Alzheimer's Disease Cooperative Study.

Development of improved outcome measures for Alzheimer's disease (AD) clinical trials is a major objective of the Alzheimer's Disease Cooperative Study (ADCS), an NIA-sponsored, multisite clinical trials consortium. The ADCS is committed to recruiting and following minority patients in clinical trials. At present, a serious impediment to recruiting non-English-speaking minorities is the lack of instruments with adequate translation. Because Spanish is the second most commonly spoken language in the United States and because persons of Hispanic origin represent approximately 10% of the population, we conducted an instrument development protocol for Spanish-speaking patients. Evaluating treatment efficacy in Spanish-speaking AD patients requires the development of assessments that are comparable to those used for English-speaking participants in clinical trials. The ADCS Instrument Development Project evaluated the sensitivity, reliability, and validity of new or improved measures in each of five assessment domains: (a) cognition (immediate and delayed memory, praxis, attention, and executive function); (b) clinical global change; (c) activities of daily living; (d) behavioral symptoms (agitation and other noncognitive symptoms); and (e) cognition in severely impaired patients. These new treatment efficacy instruments were translated for Spanish speakers and a Spanish Instrument Study was conducted in parallel with the English version of the study. This report describes instrument translation, entry criteria, and recruitment procedures. In addition, the demographic and clinical characteristics of the cohort at baseline are presented and compared to the English-speaking cohort. Implications for the development of comparably sensitive Spanish language instruments are discussed.

A double-blind crossover pilot study of l-deprenyl (selegiline) combined with cholinesterase inhibitor in Alzheimer's disease.

The potential efficacy of oral l-deprenyl (5 mg b.i.d.) added to the regimen of 10 patients with Alzheimer's disease receiving either tacrine or physostigmine was assessed in a double-blind, placebo-controlled, 4-week, two-period crossover pilot study. l-Deprenyl was associated with significant improvement in scores on the cognitive subscale of the Alzheimer's Disease Assessment Scale, suggesting possible additive effects of l-deprenyl to the effects of cholinesterase inhibitors.

Topographic quantitative EEG amplitude in recovered alcoholics.

Topographic measures of electroencephalographic (EEG) amplitude were used to compare recovered alcoholics (n = 14) with sex- and age-matched control subjects. Delta, alpha, and beta activity did not distinguish the groups, but regional differences in theta distribution did. Recovered alcoholics showed more uniform distributions of theta amplitudes in bilateral anterior and posterior regions compared with controls. Because a minimum of 5 years had elapsed since the recovered alcoholic subjects fulfilled DSM-III-R criteria for alcohol abuse or dependence, it is unlikely these EEG theta differences reflect the effects of withdrawal.

Do blood pressure and age predict response to tacrine (THA) in Alzheimer's disease? A preliminary report.

Recent studies in major depression suggest that a pretreatment systolic orthostatic blood pressure (PSOP) fall of greater than or equal to 10 mm Hg in response to changing from a supine to a standing position may predict response to antidepressant treatment in older depressed patients. Because orthostatic blood pressure response is regulated, in part, by central cholinergic and noradrenergic systems, and both are implicated in Alzheimer's disease, PSOP was assessed as a predictor of initial response in Alzheimer's disease outpatients in a treatment protocol with tacrine, a cholinesterase inhibitor. We found that the magnitude of PSOP fall and increasing age each contributed to the prediction of response to tacrine. These results may suggest a relatively greater involvement of other neurotransmitter systems in younger, nonresponding Alzheimer's disease patients, and the results differ from those of a previous study.

Seizures following triazolam withdrawal despite benzodiazepine treatment.

The authors report a case of a 55-year-old man undergoing a triazolam withdrawal syndrome that was recognized and treated with high doses of benzodiazepines, but the patient nevertheless developed seizures. Reasons for the occurrence of these seizures despite treatment are discussed within the context of the differential potency that exists among benzodiazepines in binding to central and peripheral benzodiazepine receptors.