Psychomotor performance in healthy young adult volunteers receiving lormetazepam and placebo: a single-dose, randomized, double-blind, crossover trial.
BACKGROUND
Lormetazepam is a hypnotic benzodiazepine currently used in the treatment of insomnia. When this agent is used appropriately, its pharmacologic properties predict a high therapeutic index with a good tolerability profile.


OBJECTIVE
The primary aim of this study was to compare the effects on psychomotor performance of lormetazepam and placebo in healthy young adult subjects. A secondary objective was to evaluate the clinical tolerability of lormetazepam.


METHODS
This was a randomized, double-blind,placebo-controlled, crossover study in healthy young adult volunteers. All volunteers received single doses of lormetazepam 1 mg and placebo, with a 1-week interval between doses. The primary study variables were visual simple reaction time (VSRT) and visual choice reaction time (VCRT), measured before dosing with lormetazepam or placebo and at 20, 60, 120, 180, 240, and 360 minutes after dosing using a standard computerized apparatus. To increase the sensitivity of the results, visual reaction times were also recorded using a validated mobile computerized device. Secondary variables were the duration and quality of sleep on the night before each study session, rated by subjects using a 100-mm visual analog scale; the Epworth Sleepiness Scale for daytime drowsiness; and the Critical Flicker Fusion Threshold test. Spontaneously reported adverse events were recorded and monitored throughout the study.


RESULTS
The study included 18 healthy young adult volunteers (12 women, 6 men; mean [SD] age, 26.7 [2.8] years [range, 21-30 years]; mean body weight, 58 [9.5] kg). There were no significant differences in either VSRT or VCRT after administration of lormetazepam or placebo. Independent of study drug but consistent with the accepted range of variability between the 2 devices, overall reaction times were significantly shorter with the use of the mobile device compared with the standard apparatus (P < 0.01). Analysis of the results showed no sequence effects or other evidence of learning. There were no changes in the secondary study variables after administration of the test drugs. Administration of lormetazepam was associated with dizziness in 2 subjects, in 1 case occurring in association with somnolence. These adverse events were mild and subsided spontaneously 3 hours after drug intake. After administration of placebo, 1 subject reported slight somnolence 60 minutes after dosing that persisted through 180 minutes.


CONCLUSIONS
In this small, selected group of healthy young adult subjects, a single dose of lormetazepam 1 mg did not affect psychomotor performance, assessed in terms of visual reaction times, compared with placebo.
Fabbrini
Monica
M
Section of Neurology, Department of Neurosciences, University of Pisa, Pisa, Italy.
Frittelli
Cristina
C
Bonanni
Enrica
E
Maestri
Michelangelo
M
Manca
Maria Laura
ML
Iudice
Alfonso
A
D000328:Adult; D018592:Cross-Over Studies; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D006993:Hypnotics and Sedatives / Q000009:adverse effects*; D008140:Lorazepam / Q000009:adverse effects* / Q000031:analogs & derivatives*; D008297:Male; D011597:Psychomotor Performance / Q000187:drug effects*; D011930:Reaction Time / Q000187:drug effects; D013997:Time Factors
D006993:Hypnotics and Sedatives; C023842:lormetazepam; D008140:Lorazepam