EFFECTS OF NOCTURNAL DOSES OF MIRTAZAPINE AND MIANSERIN ON SLEEP AND ON DAYTIME PSYCHOMOTOR AND DRIVING PERFORMANCE IN YOUNG, HEALTHY-VOLUNTEERS

Eighteen healthy volunteers participated in a randomized, double blind , cross-over trial. They received mirtazapine, mianserin or placebo du ring separate periods of 15 days. Mirtazapine and mianserin were respe ctively administered in doses of 15 mg and 30 mg nocte for the first 7 days and doses of 30 mg and 60 mg nocte for the remaining 8 days. Ass essments were made at baseline and on days 2, 8, 9 and 16 of each peri od to compare effects of drugs and placebo on mood, psychomotor (CTT, CRT, CFF and Vigilance) and 'actual' driving performance. Sleep qualit y and duration and side-effects were assessed at baseline and every tr eatment day. Mirtazapine 15 mg and mianserin 30 mg slightly impaired p sychomotor and driving performance on day 2 of treatment. On day 8, th e effects were virtually gone, although some driving impairment could still be observed in the mianserin condition. No drug effects on perfo rmance were found on day 9 despite the dose escalation. On day 16 of t reatment, driving performance and vigilance slightly decreased in, res pectively, the mirtazapine and the mianserin conditions. These effects indicate that tolerance to the drugs' adverse effects was not complet e. This observation was also supported by subjective data. Similar inc rements in sleep duration and feelings of lethargy, drowsiness and wea kness were observed throughout treatment with both drugs. Alertness an d contentedness was always lower during both drug treatments than with placebo. Spontaneously reported adverse events were similar to self-r ated side-effects and more of both were recorded during mianserin trea tment. It is concluded that the acute and subchronic effects of noctur nal doses of both drugs were similar and equally low in magnitude. Eff ects on performance were much less than those seen in other studies af ter administration during the day. Full daily doses of both drugs shou ld be prescribed in nocturnal dosing regimens, and not in divided dose s over the day, for avoiding excessive sedation and performance impair ment. (C) 1998 John Wiley & Sons, Ltd.