, Volume 89, Issue 1, pp 1–7 | Cite as

Evaluation of l-tryptophan for treatment of insomnia: A review

  • Dietrich Schneider-Helmert
  • Cheryl L. Spinweber
Original Investigations


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.

Key words

l-Tryptophan Insomnia Interval therapy Sleep Human Disorder of Initiating and Maintaining Sleep (DIMS) 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Adam K, Oswald I (1979) One gram of l-tryptophan fails to alter the time taken to fall asleep. Neuropharmacology 18:1025–1027Google Scholar
  2. Association of Sleep Disorders Centers (1979). Diagnostic classification of sleep and arousal disorders (1st ed). Prepared by the Sleep Disorders Classification Committee, H.P. Roffward, Chairman. Sleep 2:1–137Google Scholar
  3. Brezinova V, Loudon J, Oswald I (1972) Tryptophan and sleep. Lancet II:1086–1087Google Scholar
  4. Bridges PK, Bartlett JR, Sepping P, Kantamaneni BD, Curzon G Precursors and metabolites of 5-hydroxytryptamine and dopamine in the ventricular cerebrospinal fluid of psychiatric patients. Psychol Med 6:399–405Google Scholar
  5. Broadhurst AD (1977) l-Tryptophan: a CNS-depressant? Presented at 2nd conference of I.S.T.R.Y., University of Wisconsin, Madison, Wisconsin, August 10–12Google Scholar
  6. Brown CC, Horrom NJ, Wagman AMI (1979) Effects of l-tryptophan on sleep-onset insomniacs. Waking and Sleeping 3:101–108Google Scholar
  7. Cooper AJ (1979) Tryptophan antidepressant ‘physiological sedative’: fact or fancy? Psychopharmacology 61:97–102Google Scholar
  8. Domino EF (1976) Pharmacokinetics of oral tryptophan in drug-free psychiatric patients. In: Gottschalk LA, Merlis E (eds) Pharmacokinetics of psychoactive drugs. Spectrum Publications, New York, pp 117–126Google Scholar
  9. Gnirss F, Schneider-Helmert D, Schenker J (1978) l-Tryptophan + oxprenolol: a new approach to the treatment of insomnia. Pharmakopsychiatr 11:180–185Google Scholar
  10. Gnirss F, Schneider-Helmert D, Schenker J (1980) Chronobiological aspects of normal and disturbed sleep: a longitudinal study with polygraphic recordings. In: Popovicin L, Asgian B, Bodin G (eds) Sleep 1978: Fourth European Congress Sleep Research, Karger, Basel, pp 675–678Google Scholar
  11. Greenwood MH, Friedel J, Bond AJ, Curzon G, Lader MH (1974) The acute effects of intravenous infusion of l-tryptophan in normal subjects. Clin Pharmacol Ther 16:455–464Google Scholar
  12. Griffiths WJ, Lester BK, Coulter JD, Williams HL (1972) Tryptophan and sleep in young adults. Psychophysiology 9:345–356Google Scholar
  13. Hartmann E (1967) The effect of l-tryptophan on the sleep-dream cycle in man. Psychon Sci 8:479–480Google Scholar
  14. Hartmann E (1970) l-Tryptophane and 50H-tryptophane: effects on human sleep. Psychophysiology 7:320–321Google Scholar
  15. Hartmann E (1977) l-Tryptophan: a rational hypnotic with clinical potential. Am J Psychiatry 134:366–370Google Scholar
  16. Hartmann E, Cravens J (1975) Effects of long-term administration of l-tryptophane on human sleep. Sleep Res 4:76Google Scholar
  17. Hartmann E, Elion R (1977) The insomnia of ‘sleeping in a strange place’: effects of l-tryptophane. Psychopharmacology 53:131–133Google Scholar
  18. Hartmann E, Spinweber CL (1979) Sleep induced by l-tryptophan: l-tryptophan: effect of dosages within the normal dietary intake. J Nerv Ment Dis 167:497–499Google Scholar
  19. Hartmann E, Chung R, Chien C (1971) l-Tryptophane and sleep. Psychopharmacologia 19:114–127Google Scholar
  20. Hartmann E, Cravens J, List S (1974) Hypnotic effects of l-tryptophan. Arch Gen Psychiatry 31:394–397Google Scholar
  21. Hartmann E, Olfield M, Carpenter J (1979) Tryptophan, dietary intake: effect on subjective sleepiness. Sleep Res 8:98Google Scholar
  22. Hartmann E, Lindsley JG, Spinweber CL (1983a) Chronic insomnia: effects of tryptophan, flurazepam, secobarbital, and placebo. Psychopharmacology 80:138–142Google Scholar
  23. Hartmann E, Spinweber CL, Ware JC (1983b) Effect of amino acids on quantified sleepiness. Nutr Behav 1:179–183Google Scholar
  24. Herrington RN, Bruce A, Johnston EC, Lader MH (1976) Comparative trial of l-tryptophan and amitriptyline in depressive illness. Psychol Med 6:673–678Google Scholar
  25. Institute of Medicine (1979) Sleeping Pills, Insomnia, and Medical Practice. National Academy of Sciences, Washington DCGoogle Scholar
  26. Koella WP (1977) Beta-blockers and sleep. Kielholz P (ed) Beta-blockers and the central nervous system, Huber, Bern, pp 174–184Google Scholar
  27. Lindberg D, Ahlfors UG, Dencker SJ, Fruensgaard K, Hansten S, Tensen K, Ose E, Kihkanen TA (1979) Symptom reduction in depression after treatment with l-tryptophan or imipramin. Acta Psychiatr Scand 60:287–294Google Scholar
  28. Linnoila M, Viukari M, Numminen A, Auvinen J (1980) Efficacy and side effects of chloral hydrate and tryptophan as sleeping aids in psychogeriatric patients. Int Pharmacopsychiatry 15:124–128Google Scholar
  29. Makipour H, Iber FL, Hartmann E (1972) Effects of l-tryptophan on sleep in hospitalized insomniac patients. Sleep Res 1:65Google Scholar
  30. Moldofsky H, Lue FA (1980) The relationship of alpha and delta EEG frequencies to pain and mood in ‘fibrositis’ patients treated with chlorpromazine and l-tryptophan. Elect Clin Neurophysiol 50:71–80Google Scholar
  31. Nedopil N, Brandl A (1980) Acute effects of l-tryptophan and oxprenolol on the sleep of chronic hyposomnic patients (a double-blind study). Fifth European Congress Sleep Research Society, Abstract # 103 AmsterdamGoogle Scholar
  32. Nicholson AN, Stone BM (1979) l-Tryptophan and sleep in healthy man. Electroencephalogr Clin Neurophysiol 47:539–545Google Scholar
  33. Oswald I, Ashcroft GW, Berger RJ, Eccleston D, Evans JI, Thacore VR (1966) Some experiments in the chemistry of normal sleep. Br J Psychiatry 112:391–399Google Scholar
  34. Schneider-Helmert D (1981) Interval therapy with l-tryptophan in severe chronic insomniacs: a predictive laboratory study. Int Pharmacopsychiatry 16:162–173Google Scholar
  35. Schneider-Helmert D (1982) Heilung chronifizierter Insomnien durch Langzeittherapie mit l-tryptophan. Deutsches Ärzteblatt 79:57–64Google Scholar
  36. Schneider-Helmert D, Bodmer M (1983) Definitive recovery from chronic severe insomnia by long-term interval therapy with l-tryptophan. Sleep Res 12:393Google Scholar
  37. Small JG, Milstein V, Golay S (1979) l-Tryptophan and other agents for sleep EEG. Clinical Electroencephalogr 10:60–68Google Scholar
  38. Spinweber CL (1981) Daytime effects of l-tryptophan. Psychopharmacol Bull 17:81–82Google Scholar
  39. Spinweber CL (1983) l-Tryptophan (3 grams): hypnotic effects in chronic poor sleepers. Sleep Res 12:192Google Scholar
  40. Spinweber CL, Ursin R, Hilbert RP, Hilderbrand RL (1983) l-Tryptophan: effects on daytime sleep latency and the waking EEG. Electroenceph Clin Neurophysiol 55:652–661Google Scholar
  41. Steinberg R, Nedopil N, Ruether E (1981) Long-term effects of l-tryptophan and oxprenolol in hyposomnia. In: Koella WP (ed) Sleep 1980: Fifth European Congress Sleep Research, Karger, Basel, pp 426–428Google Scholar
  42. Wyatt RJ, Engelman K, Kupfer DJ, Fram DH, Sjoerdsma A, Snyder F (1970) Effects of l-tryptophan (a natural sedative) on human sleep. Lancet II:842–846Google Scholar
  43. Yuwiler A, Brammer GL, Morley JE, Raleigh MJ, Flannery JW, Geller E (1981) Short-term and repetitive administration of oral tryptophan in normal men: effects on blood tryptophan, serotonin, and kynurenine concentrations. Arch Gen Psychiatry 38:619–626Google Scholar

Copyright information

© Springer-Verlag 1986

Authors and Affiliations

  • Dietrich Schneider-Helmert
    • 1
  • Cheryl L. Spinweber
    • 1
  1. 1.Naval Health Research CenterSan DiegoUSA

Personalised recommendations