Cognitive, psychomotor and actual driving performance in healthy volunteers after immediate and extended release formulations of alprazolam 1 mg.
BACKGROUND
Alprazolam extended-release (XR) is approved for the treatment of panic disorder. This sustained formulation is absorbed in a delayed manner and is therefore expected to produce fewer and less severe side effects than its immediate release equivalent (alprazolam IR). The effect of alprazolam XR on potentially dangerous daily activities, such as driving a car, is expected to be less as compared to alprazolam IR.


OBJECTIVE
The present study was designed to compare the effects of alprazolam XR (1 mg) and alprazolam IR (1 mg) on actual driving ability and cognitive function.


METHODS
Eighteen healthy volunteers (aged 20-45 years) participated in a double-blind, placebo-controlled, three-way crossover study. At 4 h post-dose, subjects performed a standardized driving test on a primary highway in normal traffic. Cognitive and psychomotor tests were assessed 1, 2.5, and 5.5 h post-dose. Memory functioning was measured only 1 h after administration.


RESULTS
Both formulations severely impaired driving performance between 4 and 5 h after administration. The magnitude of impairment in the driving test observed with alprazolam XR was about half that observed with alprazolam IR. Laboratory test results were in line with the driving data.


CONCLUSIONS
The acute impairing effects of alprazolam XR 1 mg on driving and psychomotor functions were generally less, as compared to its immediate-release equivalent, but still of sufficient magnitude to increase the risk of becoming involved in traffic accidents.
Leufkens
Tim R M
TR
Experimental Psychopharmacology Unit, Brain and Behavior Institute, Faculty of Psychology, Maastricht University, Maastricht, The Netherlands. t.leufkens@psychology.unimaas.nl
Vermeeren
Annemiek
A
Smink
Beitske E
BE
van Ruitenbeek
Peter
P
Ramaekers
Johannes G
JG
D000328:Adult; D000525:Alprazolam / Q000009:adverse effects* / Q000097:blood / Q000737:chemistry; D014151:Anti-Anxiety Agents / Q000009:adverse effects* / Q000097:blood / Q000737:chemistry; D001288:Attention / Q000187:drug effects; D001334:Automobile Driving; D002626:Chemistry, Pharmaceutical; D003071:Cognition / Q000187:drug effects*; D018592:Cross-Over Studies; D003692:Delayed-Action Preparations; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008568:Memory / Q000187:drug effects; D011597:Psychomotor Performance / Q000187:drug effects*; D011930:Reaction Time / Q000187:drug effects; D012016:Reference Values; D013997:Time Factors
D014151:Anti-Anxiety Agents; D003692:Delayed-Action Preparations; D000525:Alprazolam