CNS Drugs

, Volume 6, Issue 6, pp 416–425 | Cite as

S-Adenosylmethionine (Ademetionine) in Psychiatric Disorders

Historical Perspective and Current Status
  • Maya Spillmann
  • Maurizio Fava
Leading Article

Summary

S-Adenosylmethionine (SAMe; ademetionine) is a naturally occurring compound that is found in virtually all living organisms. It serves as a major source of methyl groups in the brain, donating these groups to molecules such as hormones, neurotransmitters, nucleic acids, proteins and phospholipids, and is of fundamental importance in a number of intracellular metabolic pathways.

The most commonly reported effect of SAMe is mood elevation in depressed patients. A few, relatively small clinical studies have shown that parenteral SAMe is superior to placebo and at least as effecti ve as standard antidepressants, perhaps with a relatively rapid onset of action. Furthermore, the addition of SAMe to standard antidepressants may shorten the time to treatment response compared with the use of antidepressants alone. There are also additional reports suggesting the usefulness of the compound in dementia. SAMe appears to be remarkably well tolerated and free of severe adverse effects.

Further studies are needed to clearly establish the role that SAMe may play in the treatment of depressive disorders and dementia.

Keywords

Schizophrenia Adis International Limited Methionine Adenosyltransferase BioI Psychiatry Subacute Combine Degeneration 

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References

  1. 1.
    Friedel HA, Goa KL, Benfield P. S—Adenosyl—L—methionine: a review of its pharmacological properties and therapeutic potentialin liver dysfunction and affective disorders in relationto its physiological role in cell metaholism. Drugs 1989; 38 (3): 389–416PubMedCrossRefGoogle Scholar
  2. 2.
    Baldessarini RJ. Neuropharmacology of S—adenosyl—L—methionine. Am J Med 1987; 83 Suppl. 5A: 95–103CrossRefGoogle Scholar
  3. 3.
    Baldessarini RJ, Kopin IJ. S—Adenosylmethionine in brain and other tissues. J Neurochem 1966; 13: 769–77PubMedCrossRefGoogle Scholar
  4. 4.
    Baldessarini RJ. Biological transmethylation involving S—adenosylmethionine: development of assay methods and implications for neuropsychiatry. Int Rev Neurobiol 1975; 18: 41–67PubMedCrossRefGoogle Scholar
  5. 5.
    Stryer L. Biochemistry. New York: Freeman, W H and CompanyGoogle Scholar
  6. 6.
    Cantoni GL. S—adenosylmethionine; a new intermediate formed enzymatically from L—methionine and adenosine triphosphate. J Bio Chern 1953; 204: 403–16Google Scholar
  7. 7.
    Chawla RK, Bonkovsky HL, Galambos JT. Biochemistry and pharmacology of S—adenosyl—L—methionine and rationale forits use in liver disease. Drugs 1990; 40 Suppl. 3: 98–110CrossRefGoogle Scholar
  8. 8.
    Bottiglieri T. Hyland K, Reynolds EH. The clinical potential of ademetionine (S—adenosylmethionine) in neurological disorders.Drugs 1994; 48 (2): 137–52CrossRefGoogle Scholar
  9. 9.
    Cimino M, Vantini G, Algeri S, et al. Age related modification of dopaminergic and β—adrenergic receptor system: restorationto normal activity by modifying membrane fluidity withSAMe. Life Sci 1984; 34: 2029-39Google Scholar
  10. 10.
    Otero-Losada ME, Rubio Me. Acute changes in 5−HT metabolism after S—adenosylmethionine administration. Gen Pharmacol1989; 20: 403–6PubMedCrossRefGoogle Scholar
  11. 11.
    Otero-Losada ME, Rubio Me. Acute effects of S—adenosylmethionine on catecholaminergic central function. Eur J Pharmacol 1990; 163: 353–6CrossRefGoogle Scholar
  12. 12.
    Curcio M, Catto E, Stramentinoli G, et al. Effect of S—adenosyl—L—methionine on serotonin metabolism in rat brain. Prog Neuropsychopharmacol 1978; 2: 65–71PubMedCrossRefGoogle Scholar
  13. 13.
    McKeever MP, Weir DG, Molloy AM, et al. Betaine—homocysteine methyl transferase: organ distribution in man, pig and ratand subcellular distribution in the rat. Clin Sci 1991; 81 (4):551–6PubMedGoogle Scholar
  14. 14.
    Reynolds EH, Stramentinoli G. Folic acid, S—adenosylmethionine and affective disorders. Psychol Med 1983; 13 (4): 705–10PubMedCrossRefGoogle Scholar
  15. 15.
    Shorvon SO, Carney MWP, Chanarin I. et al. The neuropsychiatry of megaloblastic anaemia. BMJ 1980; 281: 1036–8PubMedCrossRefGoogle Scholar
  16. 16.
    Bottiglieri T, Hyland K. S—adenosylmethionine levels in psychiatric and neurological disorders: a review. Acta Neurol Scand1994; Suppl. 154: 19–26CrossRefGoogle Scholar
  17. 17.
    Bottiglieri T, Laundy M, Martin R, et al. S—adenosylmethionine influences monoamine metabolism [letter]. Lancet 1984; IIGoogle Scholar
  18. 18.
    Bottiglieri T, Chary TK, Laundy M, et al. Transmethylation in depression. Ala J Med Sci 1988; 25 (3): 296–301Google Scholar
  19. 19.
    Jacobsen S, Danneskiold-Samsøe B, Bach Andersen R. Oral S—adenosylmethionine in primary tibromyalgia. Double—blindclinical evaluation. Scand L Rheumatol 1991; 20: 294–302CrossRefGoogle Scholar
  20. 20.
    Maes M, Meltzer HY. The serotonin hypothesis of major depression. In: Bloom FE, Kupfer 01, editors. Psychopharmacology,the fourth generation of progress. 4th ed. New York: Raven Press Ltd, 1995: 933–44Google Scholar
  21. 21.
    Schatzberg AF, Schildkraut JJ. Recent studies on norepinephrine in mood disorders. In: Bloom FE, Kupfer OJ, editors. Psychopharmacology, the fourth generation of progress. 4th ed. New York: Raven Press Ltd, 1995: 911–20Google Scholar
  22. 22.
    Willner P. Dopaminergic mechanism in depression and mania. In: Bloom FE, Kupfer OJ, editors. Psychopharmacology, thefourth generation of progress. 4th ed. New York: Raven Press Ltd, 1995: 921–32Google Scholar
  23. 23.
    Baldessarini R, Stramentinoli G, Lipinski LE Methylation in schizophrenia: an old hypothesis revisited. In: Zappia V, editor.Biochemical and pharmacological roles of adenosylmethionineand the central nervous system. Oxford: Pergamon Press, 1979: 127–40Google Scholar
  24. 24.
    Baldessarini RL, Stramentinoli G, Lipinski LE Methylation hypothesis. Arch Gen Psychiatry 1979; 36: 303–7PubMedCrossRefGoogle Scholar
  25. 25.
    Stramentinoli G, Baldessarini RJ. Lack of enhancement of dimethyltryptamine formation in rat brain and rabbit lung invivo by methionine or S—adenosylmethionine. J Neurochem1978; 31: 1015–20PubMedCrossRefGoogle Scholar
  26. 26.
    Bottiglieri T, Godfrey P, Flynn T, et al. Cerebrospinal fluid Sadenosylmethionine in depression and dementia: effects oftreatment with parenteral and oral S—adenosylmethionine. Neurol Neurosurg Psychiatry 1990; 53: 1096–8CrossRefGoogle Scholar
  27. 27.
    Castagna A, Le Grazie C, Accordini P, et al. Cerebrospinal fluid S—adenosylmethionine (SAMe) and glutathionine concentrationsin HIV infection: effect of treatment with parenteralSAMe. Neurology 1995; 45: 1678–83PubMedCrossRefGoogle Scholar
  28. 28.
    Lever EG, Elwes ROC, Williams A, et al. Subacute combined degeneration of the cord due to folate deficiency: response tomethyl folate treatment. J Neurol Neurosurg Psychiatry 1986Oct; 49: 1203–7PubMedCrossRefGoogle Scholar
  29. 29.
    Keating IN, Trimble KC, Mulcahy F, et al. Evidence of brain methyltransferase inhibition and early involvement in HIVpositivepatients. Lancet 1991; 337: 935–9PubMedCrossRefGoogle Scholar
  30. 30.
    Bottiglieri T, Reynolds EH, Toone BK, et al. CSF S—adenosylmethionine in neuropsychiatric disorders [letter]. Lancet1991; 338: 121PubMedCrossRefGoogle Scholar
  31. 31.
    Stramentinoli G. Pharmacologic aspects of S—adenosylmethionine. Pharmacokinetics and pharmacodynamics. Am Med 1987; 83 (5A): 35–42CrossRefGoogle Scholar
  32. 32.
    Carney MWP, Chary TKN, Bottiglieri T, et al. Switch mechanism in affective illness and oral S—adenosylmethionine(SAM). Br J Psychiatry 1987; 150: 724–5PubMedCrossRefGoogle Scholar
  33. 33.
    Bell KM, Potkin SG, Carreon 0, et al. S—adenosylmcthionine blood levels in major depression: changes with drug treatment.Acta Neurol Scand 1994; Suppi. 154: 15–8CrossRefGoogle Scholar
  34. 34.
    Matthysse S, Baldessarini RL. S—adenosylmethionine and catechol—O—methyl—transferase in schizophrenia. Am J Psychiatry1972; 128: 1310–2PubMedGoogle Scholar
  35. 35.
    Tolbert LE. MAT kinetics in affective disorders and schizophrenia: an account. Ala L Med Sci 1988; 25 (3): 291–5Google Scholar
  36. 36.
    Carney MWP. Neuropharmacology of S—adenosyl methionine. Clin Neuropharmacol 1986; 9 (3): 235–43PubMedCrossRefGoogle Scholar
  37. 37.
    Coppen A, Abou-Saleh M. Plasma folate and affective morbidity during long—term lithium therapy. Br L Psychiatry 1982;141: 87–9CrossRefGoogle Scholar
  38. 38.
    Levitt Al, Ioffe RT. Folate, B 12, and life course of depressive illness. BioI Psychiatry 1989; 25: 867–72CrossRefGoogle Scholar
  39. 39.
    Ordonez LA, Wurtman RL. Folic acid deficiency and methyl group metabolism in rat brain: effects of L—dopa. Arch Biochem Biophys 1974; 160 (2): 372–6PubMedCrossRefGoogle Scholar
  40. 40.
    Osmond H, Smythies J. Schizophrenia: a new approach. J Ment Sci 1952; 98: 309–15PubMedGoogle Scholar
  41. 41.
    Smythies lR. Recent advances in the biochemistry of psychosis. Lancet 1960; Jun II: 1287–9CrossRefGoogle Scholar
  42. 42.
    Smythies JR. Recent advances in the biochemistry of schizophrenia. Guy’s Gazette 1966; May 14: 242–7Google Scholar
  43. 43.
    Smythies lR. The transmethylation hypothesis and one—carbon cycle hypothesis of schizophrenia. Psychol Med 1983; 13:711–4PubMedCrossRefGoogle Scholar
  44. 44.
    Cohen SM, Nichols A, Wyatt R, et al. The administration of methionine to chronic schizophrenic patients: a review of tenstudies. Bioi Psychiatry 1974; 8: 209–25Google Scholar
  45. 45.
    Andreoli VM. Maffei F, Tonon Gc. SAMe blood levels in schizophrenia and depression. In: Andreoli VM, Agnoli A, Fazio C, editors. Transmethylations and the central nervoussystem. New York: Springer Verlag, 1978: 147–50Google Scholar
  46. 46.
    American Psychiatric Association. Diagnostic and statistical manual of mental disorders. 2nd ed. Washington, DC: American Psychiatric Association, 1968Google Scholar
  47. 47.
    American Psychiatric Association. Diagnostic and statistical manual of mental disorders. 4th ed. Washington, DC: American Psychiatric Association, 1994Google Scholar
  48. 48.
    Fazio C. Andreoli V, Agnoli A, et al. Therapeutic effects and mechanism of S—adenosylmethionine (SAMe) in depressivedisorders fin Italian]. Minerva Med 1973; 64 (29): 1515–29PubMedGoogle Scholar
  49. 49.
    Bressa GM. S—adenosyl—l—methionine (SAMe) as antidepressant: meta—analysis of clinical studies. Acta Neurol Scand 1994; Suppl. 154: 7–14CrossRefGoogle Scholar
  50. 50.
    Salvadorini F, Galeone F, Saba P, et al. Evaluation of S—adenosylmethionine (SAMe) effectiveness on depression. Curr Ther Res 1980; 27: 908–18Google Scholar
  51. 51.
    Lipinski JF, Cohen BM, Frankenburg F, et al. Open trial of S—adenosylmethionine for treatment of depression. Am J Psychiatry1984; 141 (3): 448–50Google Scholar
  52. 52.
    Agnoli A, Fazio C, Andreoli V, et al. Neuropsychiatric disorders and transmethylation: therapeutic effects of S—adenosyl—Lmethioninefin Italian]. Clin Ter 1975; 75 (6): 567–79PubMedGoogle Scholar
  53. 53.
    Fava M, Giannelli A, Rapisarda V, et al. Rapidity of onset of the antidepressant effect of parenteral S—adenosyl—L—methionine.Psychiatry Res 1995; 56: 295–7PubMedCrossRefGoogle Scholar
  54. 54.
    Barberi A, Pusateri C. Clinical effects of S—adenosyl—L—methionine (SAMe) in depressive disorders [in Italian]. Minerva Psichiatr 1978; 19: 235–43Google Scholar
  55. 55.
    Salmaggi P, Bressa GM, Nicchia G, et al. Double—blind, placebo—controlled study of S—adenosyl—L—methionine in depressedpostmenopausal women. Psychother Psychosom1993; 59: 34–40PubMedCrossRefGoogle Scholar
  56. 56.
    Fava M, Rosenbaum JF, Birnbaum R, et al. The thyrotropin response to thyrotropin—releasing hormone as a predictor ofresponse to treatment in depressed outpatients. Acta Psychiatr Scand 1992; 86: 42–5PubMedCrossRefGoogle Scholar
  57. 57.
    Ianicak PG, Lipinski L, Davis LM, ct al. S—adenosylmethionine in depression. A literature review and preliminary report. Ala J Med Sci 1988; 25 (3): 306–12Google Scholar
  58. 58.
    Agnoli A, Andreoli V, Casacchia M, et al. Effect of S—adenosyl—L—methionine (SAMe) upon depressive symptoms. J Psychiatr Res 1976; 13: 43–54PubMedCrossRefGoogle Scholar
  59. 59.
    Caruso I, Fumagalli M, Boccassini L, et al. Antidepressant activity of S—Adenosyl methionine [letter]. Lancet 1984; 1: 904PubMedCrossRefGoogle Scholar
  60. 60.
    Carney MWP, Edeh J, Bottiglieri T, et al. Affective illness and S—adenosylmethionine: a preliminary report. Clin Neuropharmacol1986; 9 (4): 379–85PubMedCrossRefGoogle Scholar
  61. 61.
    Kagan BL, Sultzer DL, Rosenlicht N, et al. Oral S—adenosylmethionine in depression: a randomized, double—blind,placebo—controlled trial. Am J Psychiatr 1990; 147: 591–5PubMedGoogle Scholar
  62. 62.
    Bell MB, Carreon D, Pion L, et al. Oral s—adenosylmethionine in the treatment of depression: a double—blind comparisonwith desipramine. Study report. BioResearch File. 3rd ed.1990: 53–4Google Scholar
  63. 63.
    De Vanna M, Rigamonti R. Oral S—adenosyl—L—methionine in depression. Curr Ther Res 1992; 52 (3): 478–85CrossRefGoogle Scholar
  64. 64.
    Bell KM, Pion L, Bunney WEL, et al. S—adenosylmethionine treatment of depression: a controlled clinical trial. Am J Psychiatry1988; 145 (9): 1110–4PubMedGoogle Scholar
  65. 65.
    Mantero M, Pastorino P, Carolei A, et al. Controlled doubleblind study (SAMe—imipramine) in depression syndromes finItalian]. Minerva Med 1975; 66: 4098–101PubMedGoogle Scholar
  66. 66.
    Monaco P, Quattrocchi F. Study of the antidepressive effects of a biological transmethylating agent (S—adenosyl—methionineor SAM) lin Italian]. Riv Neurol 1979; 49: 417–39PubMedGoogle Scholar
  67. 67.
    Miccoli L, Porro V, Bertolino A. Comparison between the antidepressant activity of S—adenosylmethionine (SAMe) and that of some tricyclic drugs. Acta Neurol Napoli 1978; 33: 243–55PubMedGoogle Scholar
  68. 68.
    Scarzella R, Appiotti A. A double—blind clinical comparison of SAMe vs. clomipramine in depressive disorders [in Italian]. Riv Sper Freniatr 1978; 102: 359–65Google Scholar
  69. 69.
    Calandra C, Roxas M, Rapisarda V. Antidepressant action of SAM in comparison to chlorimipramine. Hypotheses to interpretthe mechanism of action fin Italian]. Minerva Psichiatr 1979; 20 (2): 147–52PubMedGoogle Scholar
  70. 70.
    Scaggion G, Baldan L, Domanin S. Antidepressive action of S—adenosylmethionine compared to nomifensine maleate finItalian]. Minerva Psichiatr 1982; 23 (2): 93–7PubMedGoogle Scholar
  71. 71.
    De Leo D. S—adenosylmethionine as an antidepressant — a double blind trial versus placebo. CUff Ther Res 1987; 41: 865–70Google Scholar
  72. 72.
    Rosenbaum J, Fava M, Falk WE, et al. The antidepressant potential of oral S—adenosyl—l—methionine. Acta Psychiatr Scand1990; 81: 432–6PubMedCrossRefGoogle Scholar
  73. 73.
    Rocco PL. Major depression complicating medical illness: utility of S—adenosyl—L—methionine. Neuropsychopharmacology1994; 10 Suppl. Pt 2: 99Google Scholar
  74. 74.
    Torta R, Zanalda E, Rocca P, et al. Inhibitory activity of S—adenosyl—L—methionine on serum gamma—glutamyl—transpeptidaseincrease induced by psychodrugs and anticonvulsants.Curr Ther Res 1988; 44: 144–59Google Scholar
  75. 75.
    Alvarez E, Udina C, Guillamat R. Shortening of latency period in depressed patients treated with SAMe and other antidepressantdrugs. Cell Bio Rev 1987; 81: 103–10Google Scholar
  76. 76.
    Berlanga C, Ortega-Soto HA, Ontiveros M, et al. Efficacy of S—adenosyl—L—methionine in speeding the onset of action ofimipramine. Psychiatry Res 1992; 44 (3): 257–62PubMedCrossRefGoogle Scholar
  77. 77.
    Cerutti R, Sichel MP, Perin M, et al. Psychological distress during puerperium: a novel therapeutic approach using S—adenosylmethionine.Curr Ther Res 1993; 53 (6): 707–16CrossRefGoogle Scholar
  78. 78.
    Lo Russo A, Monaco M, Pani A, et al. Efficacy of S—adenosyl—L—methionine in relieving psychologic distress associatedwith detoxification on opiate abusers. Curr Ther Res 1994; 55 (8): 905–13CrossRefGoogle Scholar
  79. 79.
    Agricola R, Dalla Verde G, Urani R, et al. S—adenosyl—L—methionine in the treatment of major depression complicatingchronic alcoholism. CUff Ther Res 1994; 55 (1): 83–92CrossRefGoogle Scholar
  80. 80.
    Crellin R, Bottiglieri T, Reynolds EH. Folates and psychiatric disorders. Drugs 1993; 45: 623–36PubMedCrossRefGoogle Scholar
  81. 81.
    Cohen BM, Satlin A, Zubenko GS. S—adenosyl—L—methionine in the treatment of Alzheimer’s disease. J Clin Psychopharmacol1988; 8 (1): 43–7PubMedCrossRefGoogle Scholar
  82. 82.
    Fontanari D, Di Palma C, Giorgetti G, et al. Effects of S—adenosyl—L—methionine on cognitive and vigilance functions inelderly. CUff Ther Res 1994; 55 (6): 682–9CrossRefGoogle Scholar
  83. 83.
    Reynolds EH, Carney MWP, Toone BK, et al. Transmethylation and neuropsychiatry. Cell Bioi Rev 1987; 2: 93–102Google Scholar
  84. 84.
    Reynolds EH, Godfrey P, Bottiglieri T. S—adenosyl—methionine and Alzheimer’s disease [abstract]. Neurology 1989; 39 Suppl. 1: 397Google Scholar
  85. 85.
    Carney MWP, Martin R, Bottiglieri T, et al. Switch mechanism in affective illness and S—adenosylmethionine. Lancet 1983; 1: 820–1PubMedCrossRefGoogle Scholar

Copyright information

© Adis International Limited 1996

Authors and Affiliations

  • Maya Spillmann
    • 1
  • Maurizio Fava
    • 1
  1. 1.Depression Clinical and Research Program, Clinical Psychopharmacology UnitMassachusetts General HospitalBostonUSA

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