Sleep laboratory and outpatient studies of the hypnotic efficacy of the amino acid L-tryptophan are reviewed, with particular emphasis on evaluation of therapeutic effectiveness in the treatment of insomnia. In younger situational insomniacs, whose sleep problem consists solely of longer than usual sleep latencies, L-tryptophan is effective in reducing sleep onset time on the first night of administration in doses ranging from 1 to 15 g. In more chronic, well-established sleep-onset insomnia or in more severe insomnias characterized by both sleep onset and sleep maintenance problems, repeated administration of low doses of L-tryptophan over time may be required for therapeutic improvement. In these patients, hypnotic effects appear late in the treatment period or, as shown in some studies, even after discontinuation of treatment. The improvement in sleep measures post-treatment has given rise to use of a treatment regimen known as "interval therapy", in which L-tryptophan treatment alternates with an L-tryptophan-free interval until improvement occurs. The absence of side effects and lack of development of tolerance in long-term use are important factors in the decision to embark upon a trial of L-tryptophan treatment. In addition, L-tryptophan administration is not associated with impairment of visuomotor, cognitive, or memory performance, nor does it elevate threshold for arousal from sleep.

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In a double-blind parallel group design, 80 young adult males were divided into eight treatment groups. Subjects received 15 or 30 mg flurazepam, 0.25 or 0.50 mg triazolam, or placebo at bedtime, and 250 mg caffeine or placebo in the morning for 2 treatment days. Two objective (Multiple Sleep Latency Test and lapses) and two subjective (Stanford Sleepiness Scale and Visual Analog Scale) measures of sleepiness, five performance tests, and two mood measures (Profile of Mood Scale and Visual Analog Mood Scale) were administered repeatedly on both days. Significant treatment effects were found for sleepiness but not for performance or mood. Early morning caffeine significantly antagonized next day hypnotic-induced drowsiness and enhanced alertness in the subjects who received bed-time placebo. Flurazepam, 30 mg, subjects were more sleepy than all other groups. Although not significantly different, the flurazepam, 30 mg, group demonstrated a trend toward poorer performance and a more negative mood than all other groups. Caffeine most improved performance of this group. In all groups, sleepiness was greatest and performance and mood poorest in early morning trials and caffeine was most effective at this time.

The present study was part of a larger 3-day, 2-night double-blind parallel group design in which 80 young adult men were divided into eight treatment groups to examine the effects of benzodiazepines and caffeine on nocturnal sleep and daytime sleepiness, performance, and mood. The present study was done to examine further the relationship among daytime sleepiness, performance, mood, and nocturnal sleep and to determine if and how these relationships were affected by the nighttime use of benzodiazepine and the ingestion of caffeine in the morning. Subjects received 15 or 30 mg of flurazepam, 0.25 or 0.50 mg of triazolam, or placebo at bedtime and 250 mg of caffeine or placebo in the morning for two treatment days. Two objective (Multiple Sleep Latency Test and lapses) and two subjective (Stanford Sleepiness Scale and Visual Analog Scale) measures of sleepiness, five performance tests, and two mood measures (Profile of Mood Scale and Visual Analog Scale) were administered repeatedly on both days. Electroencephalogram sleep was recorded on both nights. Objective sleep measures of daytime sleepiness were not significantly related to either performance or mood, but subjects with greater daytime sleepiness had significantly longer and more efficient nocturnal sleep. Neither benzodiazepine or caffeine influenced these relationships. In contrast, higher estimates of subjective sleepiness were significantly associated with poorer mood and tended to be related to poorer performance. Caffeine significantly reduced these relationships. Nocturnal sleep measures were not related to subjective estimates of daytime sleepiness.

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