Impact of melatonin, zaleplon, zopiclone, and temazepam on psychomotor performance.
BACKGROUND
Modern military operations may require pharmaceutical methods to sustain alertness and facilitate sleep in order to maintain operational readiness. In operations with very limited sleep windows, hypnotics with very short half-lives (e.g., zaleplon, t(1/2) 1 h) are of interest, while with longer sleep opportunities, longer acting agents (e.g., zopiclone, temazepam (t(1/2) 4-6 hours) may be used. This study was designed to compare the effect of a single dose of zaleplon, zopiclone, temazepam, and melatonin on psychomotor performance and to quantify the post-ingestion time required for return to normal performance.


METHODS
There were 23 subjects (9 men, 14 women), 21-53 yr of age, assessed for psychomotor performance on 2 test batteries (4 tasks) that included a sleepiness questionnaire. Psychomotor testing was conducted prior to, and for 7 h after, ingestion of a single dose of each of placebo, zaleplon 10 mg, zopiclone 7.5 mg, temazepam 15 mg, and time-released melatonin 6 mg. The experimental design was a double-blind cross-over with counter-balanced treatment order.


RESULTS
Zaleplon, zopiclone, and temazepam impaired performance on all four tasks: serial reaction time (SRT), logical reasoning (LRT), serial subtraction (SST), and multitask (MT). Melatonin did not impair performance on any task. The time to recovery of normal performance for SRT during the zaleplon, zopiclone and temazepam conditions were 3.25, 6.25, and 5.25 h respectively; for LRT were 3.25, >6.25, and 4.25 h; for SST were 2.25, >6.25, and 4.25 h, and for MT were 2.25, 4.25, and 3.25 h. The recovery time to baseline subjective sleepiness levels for zaleplon, zopiclone, temazepam, and melatonin were 4.25, >6.25, 5.25, and >4.25 h, respectively.


CONCLUSIONS
In spite of a prolonged period of perceived sleepiness, melatonin was superior to zaleplon in causing no impact on performance. The remaining drugs listed in increasing order of performance impact duration are zaleplon, temazepam, and zopiclone.
Paul
Michel A
MA
Toronto laboratories of Defence Research and Development Canada, Toronto, Ontario, Canada. michel.paul@drdc-rddc.gc.ca
Gray
Gary
G
Kenny
Gord
G
Pigeau
Ross A
RA
D000081:Acetamides / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics; D000284:Administration, Oral; D000328:Adult; D014151:Anti-Anxiety Agents / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics; D000975:Antioxidants / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D053961:Azabicyclo Compounds; D018592:Cross-Over Studies; D004311:Double-Blind Method; D005221:Fatigue; D005260:Female; D006207:Half-Life; D006801:Humans; D006993:Hypnotics and Sedatives / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics; D008297:Male; D008550:Melatonin / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D008875:Middle Aged; D008889:Military Personnel; D010879:Piperazines / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics; D010919:Placebos; D011597:Psychomotor Performance / Q000187:drug effects*; D011743:Pyrimidines / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics; D012890:Sleep; D013647:Task Performance and Analysis; D013693:Temazepam / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics
D000081:Acetamides; D014151:Anti-Anxiety Agents; D000975:Antioxidants; D053961:Azabicyclo Compounds; D006993:Hypnotics and Sedatives; D010879:Piperazines; D010919:Placebos; D011743:Pyrimidines; C515050:zopiclone; D013693:Temazepam; D008550:Melatonin; C085665:zaleplon