The role of sedation tests in identifying sedative drug effects in healthy volunteers and their power to dissociate sedative-related impairments from memory dysfunctions

Abstract

The study investigated whether four specified drugs would show similar patterns on tests considered to measure sedation. In addition, their drug-effect patterns on sedation and memory performance were compared to determine whether the sedative effects could be differentiated from the memory effects. Two double-blind, placebo-controlled, crossover studies, each with 16 healthy volunteers, were performed, one testing lorazepam (2.5 mg) and mirtazapine (15 mg) and the other olanzapine (10 mg) and haloperidol (2.5 mg). Subjective sedation was assessed by means of visual analogue scales (VAS) and objective sedation using a simple-reaction-time (SRT) task and a choice-reaction-time (CRT) task, code substitution (symbol digit substitution test (SDST)) and the peak velocity of saccadic eye movements (SEM). A verbal memory test (VMT) was administered to evaluate memory capacity. Apart from haloperidol, all drugs proved to impair performance on all five sedation indices. Contrary to the VAS, the objective measures yielded different response profiles. Two types of drug-effect patterns emerged: one for greater impairments in response speed (SRT, SEM) and one for greater impairments in information processing (CRT, SDST). Lorazepam and olanzapine impeded memory performance, whereas mirtazapine did not. With the use of standardized scores it proved possible to differentiate between the size of the effects of the drugs on the sedation and memory tests. To accurately assess the level and nature of sedation and to differentiate sedation from memory impairments different types of sedation measures are required. Besides studying the subjective effects, it is recommended to also test psychomotor responses and information processing speed.