Effects of risperidone on psychometric and cognitive functions in healthy elderly volunteers

• Published in: Psychopharmacologia Vol. 165; no. 4; pp. 419 - 429
• Main Authors: ALLAIN, H, TESSIER, C, BENTUE-FERRER, D, TARRAL, A, LE BRETON, S, GANDON, J. M, BOUHOURS, P
• Format: Journal Article
• Language: English
• Published: Berlin Springer 01.02.2003; Springer Nature B.V
• Subjects: Aged; Anti-Anxiety Agents - blood; Anti-Anxiety Agents - pharmacology; Antipsychotic Agents - blood; Antipsychotic Agents - pharmacology; Biological and medical sciences; Cognition - drug effects; Cognition - physiology; Cross-Over Studies; Dose-Response Relationship, Drug; Double-Blind Method; Drug Evaluation; Electrooculography; Female; Humans; Lorazepam - blood; Lorazepam - pharmacology; Male; Medical sciences; Memory - drug effects; Neuropharmacology; Pharmacology. Drug treatments; Psycholeptics: tranquillizer, neuroleptic; Psychology. Psychoanalysis. Psychiatry; Psychomotor Performance - drug effects; Psychomotor Performance - physiology; Psychopharmacology; Risperidone - blood; Risperidone - pharmacology; Pharmacokinetic pharmacodynamic relationship; Neuroleptic; Toxicity; Psychomotor response; Cognition; Electroencephalography; Serotonine receptor; Healthy elderly volunteers; Benzodiazepine derivatives; Lorazepam; Antagonist; Risperidone; Human; Healthy subject; Dopamine receptor; Dopamine antagonist; Serotonin antagonist; Single dose; Oral administration; Controlled therapeutic trial; Biological activity; Bridging study; Cognitive functions; Performance; Pharmacokinetics; Elderly
• ISSN: 0033-3158; 1432-2072
• DOI: 10.1007/s00213-002-1272-2

Dementia includes not only cognitive deficit but may also include psychiatric and behavioral symptoms. These psychological symptoms of dementia require specific treatment without deleterious effects on cognitive functions. The aim of the present study was to assess the effects of a single dose of risperidone (0.25 or 0.5 mg) on psychomotor performances and cognitive functions compared to a placebo and to a positive control, lorazepam 1 mg, in 12 healthy elderly subjects. This study was a randomized, double-blind, four-way crossover clinical trial involving four 8-h long treatment periods. The pharmacodynamic assessment criteria included a battery of psychomotor tests, a subjective evaluation and an electroencephalogram. Safety was evaluated by clinical laboratory tests, electrocardiogram and recording of adverse events. Concentrations of risperidone, 9-hydroxy-risperidone and lorazepam were determined before and 2 h after dosing. RESULTS. Few significant effects were observed on psychomotor tests with risperidone at all dosages. Risperidone was devoid of any deleterious effects on speed of reaction, vigilance and sustained attention, working and long-term memory and increased cortical arousal. Risperidone demonstrated minor impairment on motor activity (decreased finger taping), postural stability, and information processing (impaired digit symbol substitution). Contentedness subjective evaluation was decreased with risperidone 0.5 mg, 6 h after dosing. No significant difference was observed on EEG frequencies and no sedative activity was detected with risperidone. At 2 h after dosing, risperidone plasma concentrations were 1.54+/-0.99 ng/ml and 2.80+/-1.41 ng/ml; 9-hydroxy-risperidone concentrations were 0.77+/-0.46 ng/ml and 1.54+/-0.85 ng/ml after intake of 0.25 mg and 0.5 mg doses, respectively. Well-known detrimental effects of lorazepam on psychomotor performances were observed and sedative effects were confirmed by the EEG findings. At 2 h following lorazepam 1 mg administration, plasma concentrations were 13.40+/-2.17 ng/ml. None of both compounds induced serious adverse events. The results of this clinical trial conducted on healthy subjects demonstrated that low doses of risperidone, but not low doses of lorazepam, did not disturb the cognitive functions in the elderly.