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“Add-On”-therapy with an individualized preparation consisting of free amino acids for patients with a major depression

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Abstract

The efficacy of a deficit oriented add-on therapy with free amino acids in depressive patients treated with the antidepressant Remeron® was evaluated. About 40 in-patients were investigated by a randomised double-blind placebo-controlled study during 4 weeks. Plasma levels of 20 amino acids and measures of depression, suicidal behaviour and aggression were surveyed on admission and after a 4 weeks’ therapy with Remeron® plus an individualized amino acid mixture or placebo. The preparation of the amino acid mixture was based on an aminogram and consisted of essential amino acids plus vitamins and trace elements as co-factors for the amino acid metabolism. Patients of the experimental group showed a significantly better improvement of depression and a higher responder rate than those of the placebo group. The results suggest that oral application of a deficit oriented amino acid mixture can improve the therapeutic outcome of an antidepressant. Furthermore, lacking side effects of the amino acids resulting also in a better patient compliance may improve the benefit/risk ratio.

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References

  1. Adam D, Kasper S, Moller HJ, Singer EA (2005) Placebo-controlled trials in major depression are necessary and ethically justifiable: how to improve the communication between researchers and ethical committees. Eur Arch Psychiatry Clin Neurosci 255:258–260

    Article  PubMed  Google Scholar 

  2. Altamura C, Maes M, Dai J, Meltzer HY (1995) Plasma concentrations of excitatory amino acids, serine, glycine, taurine and histidine in major depression. Eur Neuropsychopharm 5:71–75

    Article  CAS  Google Scholar 

  3. Beck AT, Ward CH, Medelson M, Mock F, Erbaugh F (1961) An inventory for measuring depression. Arch Gen Psychiat 4:561–571

    PubMed  CAS  Google Scholar 

  4. Beckman H, Athen D, Olteanu M, Zimmer R (1979) dl-Phenylalanine versus imipramine: a double-blind controlled study. Arch Psychiatr Nervenkr 227:49–58

    Article  Google Scholar 

  5. Beckman H, Strauss MA, Ludolp E (1977) dl-Phenylalanine in depressed patients: an open study. J Neural Transm 41:123–124

    Article  Google Scholar 

  6. Booij L, Van der Does W, Benkelfat C, Bremner JD, Cowen PJ, Fava M, Gillin C, Leyton M, Moore P, Smith KA, Van der Kloot WA (2002) Predictors of mood response to acute tryptophan depletion. A reanalysis. Neuropsychopharmacol 27:852–861

    Article  CAS  Google Scholar 

  7. Bortz J, Döring N (2002) Forschungsmethoden und Evaluation für Human- und Sozialwissenschaftler. Springer, Berlin

  8. Bralley JA, Lord RS (1994) Treatment of chronic fatigue syndrome with specific amino acid supplementation. J Appl Nutrition 46:74–78

    Google Scholar 

  9. Braverman ER (2003) The healing nutrients within. Basic Health Publications, North Bergen

    Google Scholar 

  10. Charney DS (1998) Monoamine dysfunction and the pathophysiology and treatment of depression. J Clin Psychiat 59:11–14

    CAS  Google Scholar 

  11. Cowen PJ, Parry-Billings M, Newsholme EA (1989) Decreased plasma tryptophan levels in major depression. J Affect Disord 16:27–31

    Article  PubMed  CAS  Google Scholar 

  12. De Boer T (1996) The pharmacologic profile of mirtazapine. J Clin Psychiatry 57:19–25

    PubMed  Google Scholar 

  13. Delgado PL, Miller HL, Salomon RM, Licinio J, Krystal JH, Moreno FA, Heninger GR, Charney DS (1999) Tryptophan-depletion challenge in depressed patients treated with desipramine or fluoxetine: implications for the role of serotonin in the mechanism of antidepressant action. Biol Psychiat 46:212–220

    Article  PubMed  CAS  Google Scholar 

  14. Demyttenaere K, Haddad P (2000) Compliance with antidepressant therapy and antidepressant discontinuation symptoms. Acta Psychiatr Scand 403:50–56

    CAS  Google Scholar 

  15. Dougherty DM, Moeller FG, Bjork JM, Marsh DM (1999) Plasma l-tryptophan depletion and aggression. Adv Exp Med Biol 467:57–65

    PubMed  CAS  Google Scholar 

  16. Evans L, Golshan S, Kelsoe J, Rapaport M, Resovsky K, Sutton L, Gillin JC (2002) Effects of rapid tryptophan depletion on sleep electroencephalogram and mood in subjects with partially remitted depression on bupropion. Neuropsychopharmacol 27:1016–1026

    Article  CAS  Google Scholar 

  17. Farkas T, Dunner DL, Fieve RR (1976) l-Tryptophan in depression. Biol Psychiat 11:295–302

    PubMed  CAS  Google Scholar 

  18. Fernstrom JD, Wurtman RJ (1972) Brain serotonin content: physiological regulation by plasma neutral amino acids. Science 178:414–416

    Article  PubMed  CAS  Google Scholar 

  19. Goldberg I (1980) l-Tyrosine in depression. Lancet 16:364

    Article  Google Scholar 

  20. Gronier B, Azorin JM, Dassa D, Jeanningros R (1993) Evidence for a defective platelet l-tryptophan transport in depressed patients. Int Clin Psychopharmacol 8:87–93

    Article  PubMed  CAS  Google Scholar 

  21. Hamilton M (1976) Hamilton depressions scale. In: Guy W (ed) ECDEU Assessment Manual for Psychopharmacology. Rev. Ed. Rockville, Maryland, pp 179–192

  22. Hampel R, Selg H (1975) FAF. Fragebogen zur Erfassung von Aggressivitätsfaktoren. Hogrefe, Göttingen

    Google Scholar 

  23. Huber H, Ille R, Zapotoczky HG (2000) Suicidal ideation, suicidal risk and aggressiveness: a comparative study of clinical and non-clinical subjects. Eur Arch Psychiatry Clin Neurosci 250:23

    Google Scholar 

  24. Keller MB, Hirschfeld RM, Demyttenaere K, Baldwin DS (2002) Optimizing outcomes in depression: focus on antidepressant compliance. Int Clin Psychopharmacol 17(6):265–271

    Article  PubMed  CAS  Google Scholar 

  25. Kessler RC, McGonagle KA, Zhao S, et al. (1994) Life time and 12-month prevalence of DSM-III-R psychiatric disorders in the United States. Arch Gen Psychiatry 51:8–19

    PubMed  CAS  Google Scholar 

  26. Kishimoto H, Hama Y (1976) The level and diurnal rhythm of plasma tryptophan and tyrosine in manic-depressive patients. Yokohama Med Bull 27:89–97

    CAS  Google Scholar 

  27. Klaassen T, Riedel WJ, Deutz NE, Van Someren A, Van Praag HM (1999) Specificity of the tryptophan depletion method. Psychopharmacol Berlin 141:279–286

    Article  CAS  Google Scholar 

  28. Laidlaw SA, Berg RL, Kopple JD, Naito H, Walker WG, Walser M (1994) Patterns of fasting plasma amino acid levels in chronic renal insufficiency: results from the feasibility phase of the modification of diet in renal disease study. Am J Kidney Dis 23:504–513

    PubMed  CAS  Google Scholar 

  29. Levitan RD, Shen JH, Jindal R, Driver HS, Kennedy SH, Shapiro CM (2000) Preliminary randomized double-blind placebo-controlled trial of tryptophan combined with fluoxetine to treat major depressive disorder: antidepressant and hypnotic effects. J Psychiatry Neurosci 25:337–346

    PubMed  CAS  Google Scholar 

  30. Lucca A, Lucini V, Piatti E, Ronchi P, Smeraldi E (1992) Plasma tryptophan levels and plasma tryptophan/neutral amino acids ratio in patients with mood disorder, patients with obsessive-compulsive disorder, and normal subjects. Psychiat Res 44:85–91

    Article  CAS  Google Scholar 

  31. Maes M, Ombelet W, Verkerk R, Bosmans E, Scharpé S (2001) Effects of pregnancy and delivery on the availability of plasma tryptophan to the brain: relationship to delivery-induced immune activation and early post-partum anxiety and depression. Psychological Medicine 31:847–858

    Article  PubMed  CAS  Google Scholar 

  32. Mathis P, Schmitt L, Benatia M, Granier F, Ghisolfi J, Moron P (1988) Plasma amino acid disturbances and depression. Encephale 14:77–82

    PubMed  CAS  Google Scholar 

  33. Mauri MC, Ferrara A, Boscati L, Bravin S, Zamberlan F, Alecci M, Invernizzi G (1998): Plasma and platelet amino acid concentrations in patients affected by major depression and under fluvoxamine treatment. Neuropsychobiology 37:124–129

    Article  PubMed  CAS  Google Scholar 

  34. Molina JA, Jimenez FJ, Vargas C, Gomez P, De Bustos F, Orti-Pareja M, Tallon-Barranco A, Benito-Leon J, Arenas J, Enriquez-de-Salamanca R (1998) Cerebrospinal fluid levels of non-neurotransmitter amino acids in patients with Alzheimer’s disease. J Neural Transm 105:279–286

    Article  PubMed  CAS  Google Scholar 

  35. Moller HJ (2001) Methodological aspects in the assessment of severity of depression by the Hamilton Depression Scale. Eur Arch Psychiatry Clin Neurosci 251:13–20

    Article  Google Scholar 

  36. Moller SE, De Beurs P, Timmerman L, Tan BK, Leijnse-Ybema HJ, Stuart MH, Petersen HE (1986) Plasma tryptophan and tyrosine ratios to competing amino acids in relation to antidepressant response to citalopram and maprotiline. A preliminary study. Psychopharmacology 88:96–100

    Article  PubMed  CAS  Google Scholar 

  37. Möller HJ, Laux G, Kapfhammer HP (2003) Psychiatrie und Psychotherapie. Springer, Berlin

    Google Scholar 

  38. National Institute of Mental Health (1976) 12-CGI. Clinical global impressions. In: Guy W (ed) ECDEU Assessment Manual for Psychopharmacology. Rockville, Maryland, pp 217–222

    Google Scholar 

  39. Oldendorf WH, Szabo J (1976) Amino acid assignment to one of three blood–brain barrier amino acid carriers. Am J Phys 230:94–98

    CAS  Google Scholar 

  40. Pangborn JB (1986) Nutritionally correct amino acid ranges: urine and plasma. Technical Memorandum 1, Biostatistics

  41. Sabelli HC, Fawcett J, Gusovsky F, Javaid JI, Wynn P, Edwards J, Jeffries H, Kravitz H (1986) Clinical studies on the phenylethylamine hypothesis of affective disorder: urine and blood phenylacetic acid and phenylalanine dietary supplements. J Clin Psychiat 47:66–70

    CAS  Google Scholar 

  42. Saß H, Wittchen HU, Zaudig M (1996) Diagnostisches Manual psychischer Störungen DSM-IV. Hogrefe, Göttingen

  43. Schuster R (1988) Determination of amino acids in biological pharmaceutical plant and food samples by automatic pre-column derivatisation and HPLC. J Chromatogr 431:271–284

    Article  PubMed  CAS  Google Scholar 

  44. Shaw DM, Tidmarsh SF, Johnson AL, Michalakeas AC, Riley GJ, Blazek R, Francis AF (1978) Multicompartmental analysis of amino acids: II. Tryptophan in affective disorder. Psychol Med 8:487–494

    Article  PubMed  CAS  Google Scholar 

  45. Shaw K, Turner J, Del Mar C (2002) Are tryptophan and 5-hydroxytryptophan effective treatments for depression? A meta-analysis. Aust NZ J Psychiat 36:488–491

    Article  Google Scholar 

  46. Shaw K, Turner J, Del Mar C (2002) Tryptophan and 5-hydroxytryptophan for depression. Cochrane Database Syst Rev 2002:CD003198

  47. Smith KA, Fairburn CG, Cowen PJ (1997) Relapse of depression after rapid depletion of tryptophan. Lancet 349:915–919

    Article  PubMed  CAS  Google Scholar 

  48. Spona J (1998) Substituieren—aber individuell. J Geriatr Gerontol 4:18–19

    Google Scholar 

  49. Stieler W, Stadler R (1991) Eosinophilie-Myalgie-Syndrom nach Einnahme von l-Tryptophan. Z Hautkr 66:808–811

    Google Scholar 

  50. Tachiki KH, Hendrie HC, Kellams J, Aprison MH (1977) A rapid column chromatographic procedure for the routine measurement of taurine in plasma of normals and depressed patients. Clin Chim Acta 75:455–465

    Article  PubMed  CAS  Google Scholar 

  51. Young SN (1993) The use of diet and dietary components in the study of factors controlling affect in humans: a review. J Psychiatr Neurosci 18:235–244

    CAS  Google Scholar 

  52. Young SN, Pihl RO, Ervin FR (1988) The effect of altered tryptophan levels on mood and behaviour in normal human males. Clin Neuropharmacol 11:207–215

    Google Scholar 

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Authors and Affiliations

  1. Ludwig Boltzmann Institute for Experimental Endocrinology, Vienna, Austria

    Rottraut Ille,  Jürgen Spona &  Michaela Zickl

  2. University Hospital of Psychiatry, Auenbrugger Platz 31, Graz, 8036, Austria

    Rottraut Ille,  Peter Hofmann,  Theresa Lahousen,  Nina Dittrich,  Götz Bertha,  Karin Hasiba,  Franz Alfons Mahnert &  Hans-Peter Kapfhammer

Authors
  1. Rottraut Ille
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  2. Jürgen Spona
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  3. Michaela Zickl
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  4. Peter Hofmann
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  5. Theresa Lahousen
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  6. Nina Dittrich
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Correspondence to Rottraut Ille.

Additional information

This study was supported by the Ludwig Boltzmann Gesellschaft and the “Amt der Steiermärkischen Landesregierung”.

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Ille, R., Spona, J., Zickl, M. et al. “Add-On”-therapy with an individualized preparation consisting of free amino acids for patients with a major depression. Eur Arch Psychiatry Clin Neurosci 257, 222–229 (2007). https://doi.org/10.1007/s00406-007-0711-9

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  • DOI: https://doi.org/10.1007/s00406-007-0711-9

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