Fifty-four patients (mean age, 46.1 years; range, 18-65) with severe insomnia and a major complaint of sleep maintenance difficulties were studied. The mean duration of insomnia was 12.7 years and the mean sleep onset latency was 67 minutes. Patients were randomly assigned to receive, in double-blind fashion, 1) L-tryptophan (Trp; 1 g), 2) secobarbital (100 mg), 3) flurazepam (30 mg), or 4) placebo for one week. The treatment was taken 30 minutes before bedtime and at least 2 hours after the last food intake. The patients were classified into three groups, based on the type of sleep maintenance complaint. The response to treatment was rated on a 1-5 scale: 1 = worse, 2 = the same, 3 = moderate improvement, 4 = good improvement, 5 = excellent improvement. When all 16 patients receiving Trp were analyzed as a group, there was no significant improvement in insomnia relative to baseline. However, when patients were classified according to the type of insomnia, clear differences in response to Trp were seen. Of 4 patients who reported clear awakenings 1-2 times during the night, none improved. Of 8 patients who reported clear awakenings 3-6 times during the night, 100% improved, with a mean score of 4.0. Of 4 patients who reported dozing on and off throughout the night, twilight sleep, and a blurring between sleep and wakefulness, none improved.

Comment: L-Tryptophan is a precursor to serotonin, which plays a role in normal sleep function. While some studies have shown that L-tryptophan is an effective “sleeping pill”, other studies have not found this amino acid to be beneficial. The results of the present study suggest that L-tryptophan is an effective hypnotic agent only for people with a particular type of sleep maintenance disturbance: that characterized by 3-6 discrete awakenings during the night. Questioning patients about the pattern of their insomnia may aid in the search for an effective treatment.

Lindsley JG, et al. Selectivity in response to L-tryptophan among insomniac subjects: a preliminary report. Sleep 1983;6:247-256.