title: A method for determining the magnitude of change across different cognitive functions in clinical trials: the effects of acute administration of two different doses alprazolam.
abstract: While there is no doubt that benzodiazepine administration leads to transient cognitive impairment in healthy adults, the nature and magnitude of such impairment has not been well described. The cognitive effects of a single dose of alprazolam 0.5 and 1 mg were therefore assessed in 36 healthy adults on measures of psychomotor function, visual attention, working memory, planning and learning in a double-blind parallel-groups study. Measures of these different cognitive functions were selected on the basis of their brevity and because they yielded distributions of performance data that were without skew, floor or ceiling effects of range restriction (i.e. normal distributions). With data satisfying the assumptions for parametric analysis, measures of effect size could be computed in addition to significance testing, thus allowing for direct and meaningful comparison between the different performance measures used. Alprazolam 0.5 mg reduced only the speed of attentional performance although the magnitude of this reduction was large (d = 0.8). At 1.0 mg, impairments in psychomotor function, equivalent to that seen for attentional function at the lower dose, were observed. In addition, moderate (d approx = 0.5) impairments in working memory, and learning also became obvious. When considered together, these results suggest that low-dose alprazolam primarily alters visual attentional function. At the higher dose psychomotor functions also become impaired, and it is likely that the combination of these led to the observed moderate impairments in higher level executive and memory processes. The current study also illustrates a method for directly comparing the magnitude of change in cognitive function between measures with different performance metrics.
authors.affiliation: CNS Early Development, Pfizer Global Research and Development Groton, CT, USA.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Snyder
authors.forename: John
authors.initials: J
authors.lastname: Werth
authors.forename: Bruno
authors.initials: B
authors.lastname: Giordani
authors.forename: Angela F
authors.initials: AF
authors.lastname: Caveney
authors.forename: Douglas
authors.initials: D
authors.lastname: Feltner
authors.forename: Paul
authors.initials: P
authors.lastname: Maruff
mesh_terms: D000328:Adult; D000525:Alprazolam / Q000008:administration & dosage / Q000494:pharmacology*; D014151:Anti-Anxiety Agents / Q000008:administration & dosage / Q000494:pharmacology*; D001245:Association Learning / Q000187:drug effects; D001288:Attention / Q000187:drug effects; D003072:Cognition Disorders / Q000139:chemically induced* / Q000523:psychology; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008568:Memory / Q000187:drug effects; D008570:Memory, Short-Term / Q000187:drug effects; D009483:Neuropsychological Tests; D011340:Problem Solving / Q000187:drug effects; D011597:Psychomotor Performance / Q000187:drug effects; D012107:Research Design; D013028:Space Perception / Q000187:drug effects
chemical_list: D014151:Anti-Anxiety Agents; D000525:Alprazolam