Integrity of central cholinergic neurotransmission is essential for adequate cognitive functioning. Many psychotherapeutic medications have anticholinergic side-effects. In order to determine the impact of circulating anticholinergic activity on cognitive performance, 28 geropsychiatric inpatients underwent cognitive testing at different levels of anticholinergic serum activity. In 10 subjects with a diagnosis of probable Alzheimer's disease, significant deterioration of selected cognitive functions was observed at anticholinergic serum levels that caused no dysfunction in the 18 non-demented subjects. The data suggest that non-demented elderly patients with psychiatric problems tolerate psychotropic pharmacotherapy without significant negative impact on their cognitive competency. By contrast, patients with Alzheimer's disease are at risk of additional impairment. The introduction of anticholinergic serum activity as a monitoring technique for safe psychopharmacotherapy in geriatric patients is discussed.

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Evidence from earlier studies indicates that the antimanic action of valproate becomes most apparent within 1-4 days of achieving serum concentrations 50 µg/ml, that valproate can be orally loaded with achievement of therapeutic serum concentrations within the first several days of treatment, there is a rapid onset of response, and minimal side effects. To provide further data on the safety and efficacy of valproate oral loading in the treatment of acute mania, we evaluated 13 consecutive patients with acute manic syndromes who received valproate initiated at a dosage of 20 mg/kg/day. In most cases, valproate was added to other psychotropics. All 13 patients received at least 5 full days of valproate maintained at or above 20 mg/kg/day, and valproate serum concentrations were 50 µg/ml (mean ± SD = 88 + 25) by the second or third day of treatment. Ten (77%) patients displayed a moderate or marked response. Side effects were infrequent and minor. Consistent with our earlier study, these findings suggest that valproate can be safely administered via a loading dose of 20 mg/kg/day to patients with acute mania, including those on other psychotropics, and that it may produce a rapid response with minimal side effects.

The rapid and safe reduction of manic symptoms is an important initial goal of the pharmacologic treatment of acute mania. The pharmacokinetics and studies of pharmacologic loading of lithium, valproate, and carbamazepine were reviewed. In addition, the feasibility of administering other agents with potential efficacy in mania, e.g., atypical antipsychotics and new anticonvulsants, was discussed. Further double-blind, controlled studies with adequate sample sizes comparing loading strategies with more gradual titration schedules of candidate antimanic agents are needed.