Effectiveness and tolerability of melatonin and zolpidem for the alleviation of jet lag.

BACKGROUND: The aim of this study was to compare the effectiveness and tolerability of a chronobiotic (melatonin) with a hypnotic (zolpidem) and the combination of both substances to alleviate jet lag symptoms associated with eastward travel. METHODS: This double-blind, randomized, placebo-controlled study is based on 137 volunteers flying from Switzerland to the American continent and back (6-9 time zones). The participants either received melatonin 5 mg (n = 35), zolpidem 10 mg (n = 34), a combination thereof (n = 29) or placebo (n = 39) on the eastbound flight back to Switzerland and once daily at bedtime on 4 consecutive days after the flight. The test battery included daily sleep logs, symptoms questionnaires, and the Profile of Mood States (POMS). Also, on the last treatment day, Visual Analog Scales (VAS) were completed to assess overall jet lag ratings and treatment effectiveness. Baseline data were collected on 4 consecutive days 2 wk after the flight. During post-flight treatment and baseline, motor activity was assessed in a subgroup of 49 subjects using wrist-worn ambulatory monitors. RESULTS: The self-rated sleep quality was significantly improved by zolpidem, especially during the night flight. Subjects taking zolpidem reported significantly less jet lag and zolpidem was rated as the most effective jet lag medication. However, zolpidem and the combination melatonin/zolpidem were less well tolerated than melatonin alone; adverse event reports included nausea, vomiting, amnesia and somnambulia to the point of incapacitation. Confusion, morning sleepiness and nausea were highest in the combination group. CONCLUSIONS: All active treatments led to a decrease of jet lag severity with zolpidem being the most effective treatment, particularly in facilitating sleep on night flights. Potential individual adverse reactions to this hypnotic have to be considered.