Skip to main content
Log in

l -5-Hydroxytryptophan treatment of sleep terrors in children

  • Original Paper
  • Published:
European Journal of Pediatrics Aims and scope Submit manuscript

Abstract

To test the hypothesis that the administration of l -5-hydroxytryptophan ( l -5-HTP) might exert beneficial effects on sleep terrors, we carried out an open pharmacological trial in a group of children with sleep terrors compared to a group of children with the same disorder but without l -5-HTP treatment. Participants in the trial were 45 children (34 males and 11 females; age range 3.2–10.6 years), referred to the Sleep Centre of the Department of Developmental Neurology and Psychiatry of the University of Rome “La Sapienza”, affected by sleep terrors. All subjects underwent: (1) complete medical and sleep history; (2) complete neurological examination and EEG recording whilst awake and sleeping, (3) a structured sleep diary for 2 months, (4) after 1 month, all subjects were examined again from the clinical and EEG points of view and (5) after 6 months, a structured interview in order to evaluate the clinical outcome. After the first visit, l -5-HTP was administered (2 mg/kg per day) at bedtime to 31 randomly selected patients for a single period of 20 consecutive days. After 1 month of treatment, 29/31 (93.5%) of patients showed a positive response. In the comparison group without drug therapy, after 1 month, the episodes disappeared only in four children (28.6%) while ten children (71.4%) showed the persistence of episodes with the same frequency as before. After 6 months, 26/31 (83.9%) of children treated with l -5HTP were sleep terror-free, while in five children (16.1%) sleep terror episodes persisted. Of the children in the comparison group, ten (71.4%) continued to show sleep terrors at 6-month follow-up. Conclusion:to our knowledge, this is the first study demonstrating the efficacy of a new drug treatment for sleep terrors. These results confirm our initial hypothesis and represent evidence that treatment with l -5-hydroxytryptophan is able to modulate the arousal level in children and to induce a long-term improvement of sleep terrors.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Subscribe and save

Springer+ Basic
EUR 32.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or Ebook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

Abbreviations

EMS :

eosinophilia-myalgia syndrome

HSDWA :

hypersynchronous high voltage delta waves arousal

HVMD :

high voltage monomorphic delta

l -5-HTP :

l -5-hydroxytryptophan

NREM :

non rapid eye movement

PLMs :

periodic limb movements during sleep

SDB :

sleep-disordered breathing

References

  1. Adrien J (1995) The serotoninergic system and sleep-wakefulness regulation. In: Kales A (ed) The pharmacology of sleep. Springer, Berlin Heidelberg New York, pp 91–116

  2. American Sleep Disorders Association (1997) International classification of sleep disorders, revised: diagnostic and coding manual. American Sleep Disorders Association, Rochester, Minnesota

  3. Balon R (1994) Sleep terror disorder and insomnia treated with trazodone: a case report. Ann Clin Psychiatry 6: 161–163

    CAS  PubMed  Google Scholar 

  4. Bastuji H, De Villard R, Garde P, Challamel MJ (1991) High voltage monomorphic delta activity during sleep in children with pavor nocturnus or somnambulism, and in normal controls. Sleep Res 20A: 285

    Google Scholar 

  5. Cameron OG, Thyer BA (1985) Treatment of pavor nocturnus with alprazolam. J Clin Psychiatry 46: 504

    CAS  Google Scholar 

  6. Dahl RE (1992) The pharmacologic treatment of sleep disorders. Psychiatric Clin North Am 15: 161–178

    CAS  Google Scholar 

  7. Daniels SR, Hudson JI, Horwitz RI (1995) Epidemiology of potential association between l -tryptophan ingestion and eosinophilia-myalgia syndrome. J Clin Epidemiol 48: 1413–1427

    Article  CAS  PubMed  Google Scholar 

  8. De Giorgis G, Miletto R, Iannuccelli M, Camuffo M, Scerni S (1987) Headache in association with sleep disorders in children: a psychodiagnostic evaluation and controlled clinical study - l -5-HTP versus placebo. Drugs Exp Clin Res 13: 425–433

    PubMed  Google Scholar 

  9. DiMario FJ Jr, Emery ES III (1987) The natural history of sleep terrors. Clin Pediatr 26: 505–511

    Google Scholar 

  10. Driver H, Shapiro C (1993) Parasomnias. BMJ 306: 921–924

    CAS  PubMed  Google Scholar 

  11. Espa F, Ondze B, Deglise P, Billiard M, Besset A (2000) Sleep architecture, slow wave activity, and sleep spindles in adult patients with sleepwalking and sleep terrors. Clin Neurophysiol 111: 929–939

    Article  CAS  PubMed  Google Scholar 

  12. Farinelli S, Mariani A, Grimaldi A, Mariani M, Iannessi A, De Rosa F (1991) Eosinophilia-myalgia syndrome associated with 5-OH-tryptophan. Description of a case. Recenti Prog Med 82: 381–384

    CAS  PubMed  Google Scholar 

  13. Gijsman HJ, van Gerven JM, de Kam ML, Schoemaker RC, Pieters MS, Weemaes M, de Rijk R, van der Post J, Cohen AF (2002) Placebo-controlled comparison of three dose-regimens of 5-hydroxytryptophan challenge test in healthy volunteers. J Clin Psychopharmacol 22: 183–189

    Article  CAS  PubMed  Google Scholar 

  14. Guilleminault C, Palombini L, Pelayo R, Chervin RD (2003) Sleepwalking and sleep terrors in prepubertal children: what triggers them? Pediatrics 111: e17–e25

    PubMed  Google Scholar 

  15. Imeri L, Mancia M, Bianchi S, Opp MR (2000) 5-hydroxytryptophan, but not l -tryptophan, alters sleep and brain temperature in rats. Neuroscience 95: 445–452

    Article  CAS  PubMed  Google Scholar 

  16. Jacos BL, Azmitia EC (1992) Structure and function of the brain serotonin system. Physiol Rev 72: 165–229

    CAS  PubMed  Google Scholar 

  17. Kaufman J, Birmaher B, Perel J, Dahl RE, Stull S, Brent D, Trubnick L, Al-Shabbout M, Ryan ND (1998) Serotonergic functioning in depressed abused children: clinical and familial correlates. Biol Psychiatry 44: 973–981

    Article  CAS  PubMed  Google Scholar 

  18. Klarskov K, Johnson KL, Benson LM, Cragun JD, Gleich GJ, Wrona M, Jiang X-R, Dryhurst G, Naylor S (2003) Structural characterization of a case-implicated contaminant, “peak x,” in commercial preparations of 5-hydroxytryptophan. J Rheumatol 30: 89–95

    CAS  PubMed  Google Scholar 

  19. Kohen DP, Mahowald MW, Rosen GM (1992) Sleep-terror disorder in children: the role of self-hypnosis in management. Am J Clin Hypn 34:233–244

    CAS  PubMed  Google Scholar 

  20. Lask B (1988) A novel and non-toxic treatment for sleep terrors. BMJ 297: 592

    CAS  Google Scholar 

  21. Michelson D, Page SW, Casey R, Trucksess MW, Love LA, Milstien S, Wilson C, Massaquoi SG, Crofford LJ, Hallett M et al (1994) An eosinophilia-myalgia syndrome related disorder associated with exposure to l -5-hydroxytryptophan. J Rheumatol 21: 2261–2265

    CAS  PubMed  Google Scholar 

  22. Philen RM, Hill RH Jr, Flanders WD, Caudill SP, Needham L, Sewell L, Sampson EJ, Falk H, Kilbourne EM (1993) Tryptophan contaminants associated with eosinophilia-myalgia syndrome. The Eosinophilia-Myalgia Studies of Oregon, New York and New Mexico. Am J Epidemiol 138: 154–159

    CAS  PubMed  Google Scholar 

  23. Popoviciu L, Corfariu O (1983) Efficacy and safety of midazolam in the treatment of night terrors in children. Br J Clin Pharmacol 16[Suppl 1]: 97S–102S

  24. Ramaekers VT, Senderek J, Haeusler M, Haering M, Abeling N, Zerres K, Bergmann C, Heimann G, Blau N (2001) A novel neurodevelopmental syndrome responsive to 5-hydroxytryptophan and carbidopa. Mol Genet Metab 73: 179–187

    Article  CAS  PubMed  Google Scholar 

  25. Reimao R, Lefevre AB (1982) Evaluation of flurazepam and placebo on sleep disorders in childhood. Arq Neuropsiquiatr 40: 1-13

    CAS  PubMed  Google Scholar 

  26. Ribeiro CA (2000) l -5-Hydroxytryptophan in the prophylaxis of chronic tension-type headache: a double-blind, randomized, placebo-controlled study. For the Portuguese Head Society. Headache 40: 451–456

    Article  CAS  PubMed  Google Scholar 

  27. Riemann D, Vorderholzer U (1998) Treatment of depression and sleep disorders. Significance of serotonin and l -tryptophan in pathophysiology and therapy. Fortschr Med 116: 40–42

    CAS  Google Scholar 

  28. Ryan ND, Birmaher B, Perel JM, Dahl RE, Meyer V, Al-Shabbout M, Iyengar S, Puig-Antich J (1992) Neuroendocrine response to l -5-hydroxytryptophan challenge in prepubertal major depression. Depressed vs normal children. Arch Gen Psychiatry 49: 843–851

    CAS  PubMed  Google Scholar 

  29. Schneider-Helmert D, Spinweber CL (1986) Evaluation of l -tryptophan for treatment of insomnia: a review. Psychopharmacology 89: 1–7

    CAS  PubMed  Google Scholar 

  30. Schruers K, van Diest R, Nicolson N, Griez E (2002) l -5-Hydroxytryptophan induced increase in salivary cortisol in panic disorder patients and healthy volunteers. Psychopharmacology 161: 365–369

    PubMed  Google Scholar 

  31. Shapiro S (1996) Epidemiologic studies of the association of l -tryptophan with the eosinophilia-myalgia syndrome: a critique [see comments]. J Rheumatol Suppl 46: 44–58

    CAS  PubMed  Google Scholar 

  32. Weissbluth M (1984) Is drug treatment of sleep terrors warranted? Am J Dis Child 138: 1086

    CAS  Google Scholar 

  33. Williamson BL, Klarskov K, Tomlinson AJ, Gleich GJ, Naylor S (1998) Problems with over-the-counter 5-hydroxy- l -tryptophan. Nat Med 4: 983

    Article  CAS  PubMed  Google Scholar 

  34. Wyatt RJ, Engelamn K, Kupfer DJ, Fram DH, Sjoerdsma A and Snyder F (1970) Effects of l -tryptophan (a natural sedative) on human sleep. Lancet 7678: 842–845

    Google Scholar 

  35. Zucconi M, Oldani A, Ferini-Strambi L, Smirne S (1995) Arousal fluctuations in non-rapid eye movement parasomnias: the role of cyclic alternating pattern as a measure of sleep instability. J Clin Neurophysiol 12: 147–154

    CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Oliviero Bruni.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Bruni, O., Ferri, R., Miano, S. et al. l -5-Hydroxytryptophan treatment of sleep terrors in children. Eur J Pediatr 163, 402–407 (2004). https://doi.org/10.1007/s00431-004-1444-7

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00431-004-1444-7

Keywords

Navigation