Next-day residual effects of hypnotics in DSM-IV primary insomnia: a driving simulator study with simultaneous electroencephalogram monitoring.
BACKGROUND
Most studies that investigated the next-day residual effects of hypnotic drugs on daytime driving performances were performed on healthy subjects and after a single drug administration.


OBJECTIVE
In the present study, we further examine whether the results of these studies could be generalised to insomniac patients and after repeated drug administration.


METHODS
Single and repeated (7 day) doses of zolpidem (10 mg), zopiclone (7.5 mg), lormetazepam (1 mg) or placebo were administered at bedtime in a crossover design to 23 patients (9 men and 14 women aged 38.8+/-2.0 years) with Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) primary insomnia. Driving tests were performed 9-11 h post-dose.


RESULTS
Results showed that treatment effects were evidenced for subjective sleep, for driving abilities, and for electroencephalogram (EEG) recorded before (resting EEG) and during the driving simulation test (driving EEG). Compared to placebo, zopiclone increased the number of collisions and lormetazepam increased deviation from speed limit and deviation from absolute speed, whereas zolpidem did not differentiate from placebo on these analyses. EEG recordings showed that in contrast to zolpidem, lormetazepam and zopiclone induced typical benzodiazepine-like alterations, suggesting that next-day poor driving performance could relate to a prolonged central nervous system effect of these two hypnotics.


CONCLUSIONS
The present results corroborate studies on healthy volunteers showing that residual effects of hypnotics increase with their half-lives. The results further suggest that drugs preserving physiological EEG rhythms before and during the driving simulation test 9-11 h post-dose, such as zolpidem, do not influence next-day driving abilities.
Staner
Luc
L
FORENAP-Institute for Research in Neurosciences, Neuropharmacology and Psychiatry, Centre Hospitalier, Rouffach, France. luc.staner@forenap.asso.fr
Ertlé
Stéphane
S
Boeijinga
Peter
P
Rinaudo
Gilbert
G
Arnal
Marie Agnès
MA
Muzet
Alain
A
Luthringer
Rémy
R
D000328:Adult; D001143:Arousal / Q000187:drug effects; D001334:Automobile Driving / Q000523:psychology; D053961:Azabicyclo Compounds; D002940:Circadian Rhythm / Q000187:drug effects; D003198:Computer Simulation; D039721:Diagnostic and Statistical Manual of Mental Disorders; D004311:Double-Blind Method; D004569:Electroencephalography / Q000187:drug effects*; D005260:Female; D006801:Humans; D006993:Hypnotics and Sedatives / Q000008:administration & dosage / Q000009:adverse effects*; D008140:Lorazepam / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D008297:Male; D010879:Piperazines / Q000008:administration & dosage / Q000009:adverse effects; D011725:Pyridines / Q000008:administration & dosage / Q000009:adverse effects; D007319:Sleep Initiation and Maintenance Disorders / Q000175:diagnosis / Q000188:drug therapy* / Q000523:psychology; D000077334:Zolpidem
D053961:Azabicyclo Compounds; D006993:Hypnotics and Sedatives; D010879:Piperazines; D011725:Pyridines; C515050:zopiclone; D000077334:Zolpidem; C023842:lormetazepam; D008140:Lorazepam