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. 1991 Dec;16(5):241–246.

Use of tryptophan in combination with other antidepressant treatments: a review.

S N Young 1
PMCID: PMC1188360  PMID: 1797098

Abstract

In four studies, all carried out more than 20 years ago, the combination of tryptophan plus a monoamine oxidase inhibitor was significantly better than tryptophan plus placebo in the treatment of depression. However, there is no evidence that tryptophan has any clinically significant effect on other treatments such as tricyclic antidepressants and ECT. Side effects of the combination of tryptophan and a monoamine oxidase inhibitors have limited the use of this combination. The risk of the serotonin syndrome is small, but it can occur. However, rapid cessation of tryptophan seems to avoid any long lasting adverse effects of the serotonin syndrome. In situations where enhancement of the therapeutic effect of monamine oxidase inhibitors outweighs the risk of adverse effects, the combination of tryptophan and a monoamine oxidase inhibitor is clinically useful. As the studies to date have looked at regular depressed patients, what is needed now is studies of this combination in therapy resistant depression.

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Selected References

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  1. Ashcroft G. W., Eccleston D., Crawford T. B. 5-hydroxyindole metabolism in rat brain. A study of intermediate metabolism using the technique of tryptophan loading. I. Methods. J Neurochem. 1965 Jun;12(6):483–492. doi: 10.1111/j.1471-4159.1965.tb06775.x. [DOI] [PubMed] [Google Scholar]
  2. Ayuso Gutierrez J. L., Aliño J. J. Tryptophan and an MAOI (nialamide) in the treatment of depression. A double-blind study. Int Pharmacopsychiatry. 1971;6(2):92–97. doi: 10.1159/000468258. [DOI] [PubMed] [Google Scholar]
  3. Baldessarini R. J. Treatment of depression by altering monoamine metabolism: precursors and metabolic inhibitors. Psychopharmacol Bull. 1984 Spring;20(2):224–239. [PubMed] [Google Scholar]
  4. Belongia E. A., Hedberg C. W., Gleich G. J., White K. E., Mayeno A. N., Loegering D. A., Dunnette S. L., Pirie P. L., MacDonald K. L., Osterholm M. T. An investigation of the cause of the eosinophilia-myalgia syndrome associated with tryptophan use. N Engl J Med. 1990 Aug 9;323(6):357–365. doi: 10.1056/NEJM199008093230601. [DOI] [PubMed] [Google Scholar]
  5. Bender D. A., Totoe L. High doses of vitamin B6 in the rat are associated with inhibition of hepatic tryptophan metabolism and increased uptake of tryptophan into the brain. J Neurochem. 1984 Sep;43(3):733–736. doi: 10.1111/j.1471-4159.1984.tb12793.x. [DOI] [PubMed] [Google Scholar]
  6. Blauvelt A., Falanga V. Idiopathic and L-tryptophan-associated eosinophilic fasciitis before and after L-tryptophan contamination. Arch Dermatol. 1991 Aug;127(8):1159–1166. [PubMed] [Google Scholar]
  7. Boman B. L-tryptophan: a rational anti-depressant and a natural hypnotic? Aust N Z J Psychiatry. 1988 Mar;22(1):83–97. doi: 10.1080/00048678809158946. [DOI] [PubMed] [Google Scholar]
  8. Brewerton T. D., Reus V. I. Lithium carbonate and L-tryptophan in the treatment of bipolar and schizoaffective disorders. Am J Psychiatry. 1983 Jun;140(6):757–760. doi: 10.1176/ajp.140.6.757. [DOI] [PubMed] [Google Scholar]
  9. COPPEN A., SHAW D. M., FARRELL J. P. Potentiation of the antidepressive effect of a monoamine-oxidase inhibitor by tryptophan. Lancet. 1963 Jan 12;1(7272):79–81. doi: 10.1016/s0140-6736(63)91084-5. [DOI] [PubMed] [Google Scholar]
  10. Chouinard G., Young S. N., Annable L., Sourkes T. L. Tryptophan-nicotinamide, imipramine and their combination in depression. A controlled study. Acta Psychiatr Scand. 1979 Apr;59(4):395–414. doi: 10.1111/j.1600-0447.1979.tb04482.x. [DOI] [PubMed] [Google Scholar]
  11. Coppen A., Shaw D. M., Herzberg B., Maggs R. Tryptophan in the treatment of depression. Lancet. 1967 Dec 2;2(7527):1178–1180. doi: 10.1016/s0140-6736(67)91894-6. [DOI] [PubMed] [Google Scholar]
  12. Coppen A., Wood K. Total and non-bound plasma-tryptophan in depressive illness. Lancet. 1977 Jan 8;1(8002):94–94. doi: 10.1016/s0140-6736(77)91105-9. [DOI] [PubMed] [Google Scholar]
  13. D'Elia G., Lehmann J., Raotma H. Evaluation of the combination of tryptophan and ECT in the treatment of depression. I. Clinical analysis. Acta Psychiatr Scand. 1977 Oct;56(4):303–318. doi: 10.1111/j.1600-0447.1977.tb00231.x. [DOI] [PubMed] [Google Scholar]
  14. Eccleston D., Ashcroft G. W., Crawford T. B. Effect of tryptophan administration on 5HIAA in cerebrospinal fluid in man. J Neurol Neurosurg Psychiatry. 1970 Apr;33(2):269–272. doi: 10.1136/jnnp.33.2.269. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Gelenberg A. J., Wojcik J. D., Falk W. E., Baldessarini R. J., Zeisel S. H., Schoenfeld D., Mok G. S. Tyrosine for depression: a double-blind trial. J Affect Disord. 1990 Jun;19(2):125–132. doi: 10.1016/0165-0327(90)90017-3. [DOI] [PubMed] [Google Scholar]
  16. Gerson S. C., Baldessarini R. J. Motor effects of serotonin in the central nervous system. Life Sci. 1980 Oct 20;27(16):1435–1451. doi: 10.1016/0024-3205(80)90368-9. [DOI] [PubMed] [Google Scholar]
  17. Glassman A. H., Platman S. R. Potentiation of a monoamine oxidase inhibitor by tryptophan. J Psychiatr Res. 1969 Dec;7(2):83–88. doi: 10.1016/0022-3956(69)90013-2. [DOI] [PubMed] [Google Scholar]
  18. Green A. R., Aronson J. K., Curzon G., Woods H. F. Metabolism of an oral tryptophan load. I: Effects of dose and pretreatment with tryptophan. Br J Clin Pharmacol. 1980 Dec;10(6):603–610. doi: 10.1111/j.1365-2125.1980.tb00516.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Green A. R., Aronson J. K., Curzon G., Woods H. F. Metabolism of an oral tryptophan load. II: Effect of pretreatment with the putative tryptophan pyrrolase inhibitors nicotinamide or allopurinol. Br J Clin Pharmacol. 1980 Dec;10(6):611–615. doi: 10.1111/j.1365-2125.1980.tb00517.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Green A. R., Aronson J. K. Metabolism of an oral tryptophan load III: effect of a pyridoxine supplement. Br J Clin Pharmacol. 1980 Dec;10(6):617–619. doi: 10.1111/j.1365-2125.1980.tb00518.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. HESS S. M., DOEPFNER W. Behavioral effects and brain amine content in rats. Arch Int Pharmacodyn Ther. 1961 Nov 1;134:89–99. [PubMed] [Google Scholar]
  22. Hale A. S., Procter A. W., Bridges P. K. Clomipramine, tryptophan and lithium in combination for resistant endogenous depression: seven case studies. Br J Psychiatry. 1987 Aug;151:213–217. doi: 10.1192/bjp.151.2.213. [DOI] [PubMed] [Google Scholar]
  23. Honoré P., Møller S. E., Jørgensen A. Lithium + L-tryptophan compared with amitriptyline in endogenous depression. J Affect Disord. 1982 Mar;4(1):79–82. doi: 10.1016/0165-0327(82)90022-2. [DOI] [PubMed] [Google Scholar]
  24. Kirkegaard C., Møller S. E., Bjørum N. Addition of L-tryptophan to electroconvulsive treatment in endogenous depression. A double-blind study. Acta Psychiatr Scand. 1978 Nov;58(5):457–462. doi: 10.1111/j.1600-0447.1978.tb03576.x. [DOI] [PubMed] [Google Scholar]
  25. LAUER J. W., INSKIP W. M., BERNSOHN J., ZELLER E. A. Observations of schizophrenic patients after iproniazid and tryptophan. AMA Arch Neurol Psychiatry. 1958 Jul;80(1):122–130. doi: 10.1001/archneurpsyc.1958.02340070140021. [DOI] [PubMed] [Google Scholar]
  26. Murphy D. L., Baker M., Goodwin F. K., Miller H., Kotin J., Bunney W. E., Jr L-tryptophan in affective disorders: indoleamine changes and differential clinical effects. Psychopharmacologia. 1974 Jan 9;34(1):11–20. doi: 10.1007/BF00421216. [DOI] [PubMed] [Google Scholar]
  27. Møller S. E., Kirk L. The effect of allopurinol on the kynurenine formation in humans following a tryptophan load. Acta Vitaminol Enzymol. 1978;32(5-6):159–162. [PubMed] [Google Scholar]
  28. Møller S. E. Pharmacokinetics of tryptophan, renal handling of kynurenine and the effect of nicotinamide on its appearance in plasma and urine following L-tryptophan loading of healthy subjects. Eur J Clin Pharmacol. 1981;21(2):137–142. doi: 10.1007/BF00637514. [DOI] [PubMed] [Google Scholar]
  29. Oldendorf W. H., Szabo J. Amino acid assignment to one of three blood-brain barrier amino acid carriers. Am J Physiol. 1976 Jan;230(1):94–98. doi: 10.1152/ajplegacy.1976.230.1.94. [DOI] [PubMed] [Google Scholar]
  30. PARE C. M. POTENTIATION OF MONOAMINE-OXIDASE INHIBITORS BY TRYPTOPHAN. Lancet. 1963 Sep 7;2(7306):527–528. doi: 10.1016/s0140-6736(63)90271-x. [DOI] [PubMed] [Google Scholar]
  31. Raphals P. Disease puzzle nears solution. Science. 1990 Aug 10;249(4969):619–619. doi: 10.1126/science.2166338. [DOI] [PubMed] [Google Scholar]
  32. Riley G. J., Shaw D. M. Total and non-bound tryptophan in unipolar illness. Lancet. 1976 Dec 4;2(7997):1249–1249. doi: 10.1016/s0140-6736(76)91180-6. [DOI] [PubMed] [Google Scholar]
  33. Shaw D. M., Macsweeney D. A., Hewland R., Johnson A. L. Tricyclic antidepressants and tryptophan in unipolar depression. Psychol Med. 1975 Aug;5(3):276–278. doi: 10.1017/s0033291700056646. [DOI] [PubMed] [Google Scholar]
  34. Steiner W., Fontaine R. Toxic reaction following the combined administration of fluoxetine and L-tryptophan: five case reports. Biol Psychiatry. 1986 Sep;21(11):1067–1071. doi: 10.1016/0006-3223(86)90287-8. [DOI] [PubMed] [Google Scholar]
  35. Sternbach H. The serotonin syndrome. Am J Psychiatry. 1991 Jun;148(6):705–713. doi: 10.1176/ajp.148.6.705. [DOI] [PubMed] [Google Scholar]
  36. Teff K. L., Young S. N., Marchand L., Botez M. I. Acute effect of protein or carbohydrate breakfasts on human cerebrospinal fluid monoamine precursor and metabolite levels. J Neurochem. 1989 Jan;52(1):235–241. doi: 10.1111/j.1471-4159.1989.tb10922.x. [DOI] [PubMed] [Google Scholar]
  37. Thomson J., Rankin H., Ashcroft G. W., Yates C. M., McQueen J. K., Cummings S. W. The treatment of depression in general practice: a comparison of L-tryptophan, amitriptyline, and a combination of L-tryptophan and amitriptyline with placebo. Psychol Med. 1982 Nov;12(4):741–751. doi: 10.1017/s0033291700049047. [DOI] [PubMed] [Google Scholar]
  38. Toyo'oka T., Yamazaki T., Tanimoto T., Sato K., Sato M., Toyoda M., Ishibashi M., Yoshihira K., Uchiyama M. Characterization of contaminants in EMS-associated L-tryptophan samples by high-performance liquid chromatography. Chem Pharm Bull (Tokyo) 1991 Mar;39(3):820–822. doi: 10.1248/cpb.39.820. [DOI] [PubMed] [Google Scholar]
  39. Walinder J., Skott A., Carlsson A., Nagy A., Bjorn-Erik R. Potentiation of the antidepressant action of clomipramine by tryptophan. Arch Gen Psychiatry. 1976 Nov;33(11):1384–1389. doi: 10.1001/archpsyc.1976.01770110112012. [DOI] [PubMed] [Google Scholar]
  40. Wilkins K., Wigle D. Eosinophilia-myalgia syndrome. CMAJ. 1990 Jun 1;142(11):1265–1266. [PMC free article] [PubMed] [Google Scholar]
  41. Worrall E. P., Moody J. P., Peet M., Dick P., Smith A., Chambers C., Adams M., Naylor G. J. Controlled studies of the acute antidepressant effects of lithium. Br J Psychiatry. 1979 Sep;135:255–262. doi: 10.1192/bjp.135.3.255. [DOI] [PubMed] [Google Scholar]
  42. Wurtman R. J., Hefti F., Melamed E. Precursor control of neurotransmitter synthesis. Pharmacol Rev. 1980 Dec;32(4):315–335. [PubMed] [Google Scholar]
  43. Wålinder J., Carlsson A., Persson R. 5-HT reuptake inhibitors plus tryptophan in endogenous depression. Acta Psychiatr Scand Suppl. 1981;290:179–190. doi: 10.1111/j.1600-0447.1981.tb00719.x. [DOI] [PubMed] [Google Scholar]
  44. Young S. N., Gauthier S. Effect of tryptophan administration on tryptophan, 5-hydroxyindoleacetic acid and indoleacetic acid in human lumbar and cisternal cerebrospinal fluid. J Neurol Neurosurg Psychiatry. 1981 Apr;44(4):323–328. doi: 10.1136/jnnp.44.4.323. [DOI] [PMC free article] [PubMed] [Google Scholar]
  45. Young S. N., Oravec M. The effect of growth hormone on the metabolism of a tryptophan load in the liver and brain of hypophysectomized rats. Can J Biochem. 1979 Jun;57(6):517–522. doi: 10.1139/o79-065. [DOI] [PubMed] [Google Scholar]

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