Annals of Emergency Medicine
Volume 28, Issue 5 , Pages 520-526 , November 1996

Serotonin Syndrome

Received 24 January 1995 ,Revised 21 March 1996 ,Accepted 27 March 1996.

References 

  1. Borys DJ, Setzer SC, Ling LJ, et al.  Acute fluoxetine overdose: A report of 234 cases. Am J Emerg Med. 1992;10:115–120
  2. Simonsen LLP. Top 200 Drugs: Rx prices still moderating as managed care grows. Pharm Times. April 1995;17–23
  3. Hess SM, Doepfner W. Behavioral effects and brain amine contents in rats. Arch Int Pharmacodyn Ther. 1961;134:89–99
  4. Grahame-Smith DC. Studies in vivo on the relationship between brain tryptophan, brain 5-HT synthesis and hyperactivity in rats treated with a monoamine oxidase inhibitor and L-tryptophan. J Neurochem. 1971;18:1053–1066
  5. Sinclair JG. Dextromethorphan-monoamine oxidase inhibitor interaction in rabbits. J Pharm Pharmacol. 1973;25:803–808
  6. Oates JA, Sjoerdsma A. Neurologic effects of tryptophan in patients receiving monoamine oxidase inhibitor. Neurology. 1960;10:1076–1078
  7. Smith B, Prockop DJ. Central-nervous system effects of ingestion of L-tryptophan by normal subjects. N Engl J Med. 1962;267:1338–1341
  8. Cohen RM, Pickar D, Murphy DL. Myoclonus-associated hypomania during MAO-inhibitor treatment. Am J Psychiatry. 1980;137:105–106
  9. Insel TR, Roy BF, Cohen RM, et al.  Possible development of the serotonin syndrome in man. Am J Psychiatry. 1982;139:945–955
  10. Mitchell RS. Fatal toxic encephalitis occurring during iproniazid therapy in pulmonary tuberculosis. Ann Intern Med. 1955;42:417–424
  11. Sternbach H. The serotonin syndrome. Am J Psychiatry. 1991;148:705–713
  12. Nierenberg DW, Semprebon M. The central nervous system serotonin syndrome. Clin Pharmacol Ther. 1993;53:84–88
  13. Sporer KA. The serotonin syndrome. Drug Safety. 1995;13:94–104
  14. Bodner RA, Lynch T, Lewis L, et al.  Serotonin syndrome. Neurology. 1995;45:219–223
  15. Ohman R, Spigset O. Serotonin syndrome induced by fluvoxamine-lithium interaction. Pharmacopsychiatry. 1993;26:263–264
  16. Kojima H, Terao T, Yoshimura R. Serotonin syndrome during clomipramine and lithium therapy [letter]. Am J Psychiatry. 1993;150:1897
  17. Tackley RM, Tregaskis B. Fatal disseminated intravascular coagulation following a monoamine oxidase inhibitor/tricyclic interaction. Anaesthesia. 1987;42:760–763
  18. Miller F, Friedman R, Tanenbaum J, et al.  Disseminated intravascular coagulation and acute myoglobinuric renal failure: A consequence of the serotonin syndrome. J Clin Psychopharmacol. 1991;11:277–279
  19. Goodwin GM, De Souza RJ, Green AR, et al.  The pharmacology of the behavioral and hyperthermic responses of rats to 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT). Psychopharmacology. 1987;91:506–511
  20. Yamada J, Sugimoto Y, Horisaka K. The behavioral effects of 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) in mice. Eur J Pharmacol. 1988;154:299–304
  21. Risch SC, Nemeroff CB. Neurochemical alterations of serotonergic neuronal systems in depression. J Clin Psychiatry. 1992;53:3–7
  22. Glennon RA, Darmani NA, Martin BR. Multiple populations of serotonin receptors may modulate the behavioral effects of serotonergic agents. Life Sci. 1991;48:2493–2498
  23. Sleight AJ, Marsden CA, Martin KF, et al.  Relationship between extracellular 5-hydroxytryptamine and behavior following monoamine oxidase inhibition and L-tryptophan. Br J Pharmacol. 1988;93:303–310
  24. Tricklebank MD, Forler C, Fozard JR. The involvement of subtypes of the 5-HT receptor and of catecholaminergic systems in the behavioral response to 8-hydroxy-2(di-n-propylamino) tetralin in the rat. Eur J Pharmacol. 1984;106:271–282
  25. Green AR, Grahame-Smith DG. The role of brain dopamine in the hyperactivity syndrome produced by increased 5-HT synthesis in rats. Neuropharmacology. 1974;13:949–959
  26. Heal DJ, Green AR, Boullin DJ, et al.  Single and repeated administration of neuroleptic drugs to rats: Effects on striatal dopamine-sensitive adenylate cyclase and locomotor activity produced by tranylcypromine and L-tryptophan or L-dopa. Psychopharmacology. 1976;49:287–300
  27. Silbergeld EK, Hurska RE. Lisuride and LSD: Dopaminergic and serotonergic interactions in the serotonin syndrome. Psychopharmacology. 1979;65:233–257
  28. Lieberman JA, Kane JM, Reife R. Neuromuscular effects of monoamine oxidase inhibitors. J Clin Psychopharmacol. 1985;5:221–228
  29. Marsden CA, Curson G. The contributions of tryptamine to the behavioural effects of L-tryptophan in tranylcypromine-treated rats. Psychopharmacology. 1978;57:71–76
  30. Marsden CA, Curson G. The role of tryptamine in the behavioural effects of tranylcypromine + L-tryptophan. Neuropharmacology. 1979;18:159–164
  31. Green AR, Youdim MBH. Effects of monoamine oxidase inhibition by clorgyline, deprenyl or tranylcypromine on 5-hydroxytryptamine concentration in rat brain and hyperactivity following subsequent tryptophan administration. Br J Pharmacol. 1975;55:415–422
  32. Price LH, Charney DS, Heninger GR. Serotonin syndrome [letter]. Am J Psychiatry. 1992;149:1116–1117
  33. Muly EC, McDonald W, Steffens D, et al.  Serotonin syndrome produced by a combination of fluoxetine and lithium [letter]. Am J Psychiatry. 1993;150:1565
  34. Sandyk R. L-Dopa induced "serotonin syndrome" in a parkinsonian patient on bromocriptine [letter]. J Clin Psychopharmacol. 1986;6:194–195
  35. Goldberg RJ, Huk M. Serotonin syndrome from trazodone and buspirone [letter]. Psychosomatics. 1992;33:235–236
  36. Kaskey GB. Possible interaction between MAOI and "ecstasy.". Am J Psychiatry. 1992;149:411–412
  37. Smilkstein MJ, Smolinske SC, Rumack BH. A case of MAO inhibitor/MDMA interaction: Agony after ecstasy. Clin Toxicol. 1987;25:149–159
  38. Lejoyeux M, Fineyre F, Andes J. The serotonin syndrome [letter]. Am J Psychiatry. 1992;149:1410–1411
  39. Lenzi A, Raffaelli S, Marazziti D. Serotonin syndrome-like symptoms in a patient with obsessive-compulsive disorder, following inappropriate increase in fluvoxamine dosage. Pharmacopsychiatry. 1993;26:100–101
  40. Kaskey GB. Possible interaction between MAOI and "ecstasy.". Am J Psychiatry. 1992;149:411–412
  41. Spigset O, Mjorndal T, Loveheim O. Serotonin syndrome caused by a moclobemide-clomipramine interaction. BMJ. 1993;306:248
  42. Brodribb TR, Downey M, Gilbar PJ. Efficacy and adverse effects of moclobemide [letter]. Lancet. 1994;343:475
  43. Rivers N, Horner B. Possible lethal interaction between Nardil and dextromethorphan. Can Med Assoc J. 1970;103:85
  44. Skop BP, Finkelstein JA, Mareth TR, et al.  The serotonin syndrome associated with paroxetine, an over-the-counter cold remedy, and vascular disease. Am J Emerg Med. 1994;12:642–644
  45. Meyer D, Halfin V. Toxicity secondary to meperidine in patients on monoamine oxidase inhibitors: A case report and critical review. J Clin Psychpharmacol. 1981;1:319–321
  46. Zornberg GL, Bodkin JA, Cohen BM. Severe adverse interaction between pethidine and selegiline [letter]. Lancet. 1991;337:264
  47. Hansen TE, Dieter K, Keepers GA. Interaction of fluoxetine and pentazocine. Am J Psychiatry. 1990;147:949–950
  48. Kalsner S, Nickerson M. Mechanisms of cocaine potentiation of responses to amines. Br J Pharmacol. 1969;35:428–439
  49. Tordoff SG, Stubbing JF, Linter SPK. Delayed excitatory reaction following interaction of cocaine and monoamine oxidase inhibitor (Phenelzine). Br J Anaesth. 1991;66:516–518
  50. Feighner JP, Boyer WF, Tyler DL, et al.  Adverse consequences of fluoxetine-MAOI combination therapy. J Clin Psychiatry. 1990;51:222–225
  51. Pato MT, Murphy DL, DeVane CL. Sustained plasma concentrations of fluoxetine and/or norfluoxetine four and eight weeks after fluoxetine discontinuation [letter]. J Clin Pharmacol. 1991;11:224–225
  52. Coplan JD, Gorman JM. Detectable levels of fluoxetine metabolites after discontinuation: An unexpected serotonin syndrome [letter]. Am J Psychiatry. 1993;150:837
  53. Yang HYT, Neff NH. The monoamine oxidases of brain: Selective inhibition with drugs and the consequences for the metabolism of the biogenic amines. J Pharmacol Exp Ther. 1974;189:733–740
  54. Wells DG, Bjorksten AR. Monoamine oxidase inhibitors revisited. Can J Anaesth. 1989;36:66–74
  55. Ciocatto E, Fagiano G, Bava GL. Clinical features and treatment of overdosage of monoamine oxidase inhibitors and their interaction with other psychotropic drugs. Resuscitation. 1972;1:69–72
  56. Mendis N, Pare CMB, Sandler M, et al.  Is the failure of L-deprenyl, a selective monoamine oxidase B inhibitor, to alleviate depression related to freedom from the cheese effect?. Psychopharmacology. 1981;73:87–90
  57. Elsworth JD, Glover V, Reynolds GP, et al.  Deprenyl administration in man: A selective monoamine oxidase B inhibitor without the "cheese effect.". Psychopharmacology. 1978;57:33–38
  58. Neuvonen PJ, Pohjola-Sintonen S, Tacke U, et al.  Five fatal cases of serotonin syndrome after moclobemide-citalopram or moclobemide-clomipramine overdoses [letter]. Lancet. 1993;342:1419
  59. Mendlewicz J, Youdim MBH. Anti-depressant potentiation of 5-hydroxytryptophan by L-deprenyl, an MAO "type B" inhibitor. J Neural Transm. 1978;43:279–286
  60. Fowler CJ, Ross SB. Selective inhibitors of monoamine oxidase A and B: Biochemical, pharmalogical and clinical properties. Med Res Rev. 1984;4:323–358
  61. Blackwell B. Monoamine oxidase inhibitor interactions with other drugs. J Clin Psychopharmacol. 1991;11:55–59
  62. Murphy DL, Lipper S, Slater S, et al.  Selectivity of clorgyline and pargyline as inhibitors of monamine oxidases A and B in vivo in man. Psychopharmacology. 1979;69:129–132
  63. Suchowersky O, deVries J. Possible interactions between deprenyl and prozac [letter]. Can J Neurol Sci. 1990;17:352–353
  64. "Dear Doctor" Letter Regarding Eldepryl. Tampa, Florida: Somerset Pharmaceuticals; November 14, 1994;
  65. Graham PM, Potter JM, Paterson JW. Combination monoamine oxidase inhibitor/tricyclic antidepressant interaction [letter]. Lancet. 1982;2:440
  66. Kuhn WF, Light PJ, Kuhn SC. Stiff-man syndrome: Case report. Acad Emerg Med. 1995;2:735–738
  67. Rosenberg J, Pentel P, Pond S, et al.  Hyperthermia associated with drug intoxication. Crit Care Med. 1986;14:964–969
  68. Levenson SL. Neuroleptic malignant syndrome. Am J Psychiatry. 1985;142:1137–1142
  69. Heyland D, Sauve M. Neuroleptic malignant syndrome without the use of neuroleptics. Can Med Assoc J. 1991;145:817–819
  70. Halman M, Goldbloom DS. Fluoxetine and neuroleptic malignant syndrome. Biol Psychiatry. 1990;28:518–521
  71. Lazarus A. Therapy of neuroleptic malignant syndrome. Psychiatric Dev. 1986;1:19–30
  72. Rosenberg MR, Green M. Neuroleptic malignant syndrome: Review of response to therapy. Arch Intern Med. 1989;149:1927–1937
  73. Nierenberg D, Disch M, Manheimer E, et al.  Facilitating prompt diagnosis and treatment of the neuroleptic malignant syndrome. Clin Pharmacol Therap. 1991;50:580–586
  74. Brennan D, MacManus M, Howe J, et al.  "Neuroleptic malignant syndrome" without neuroleptics [letter]. Br J Psychiatry. 1988;152:578–579
  75. Kline SS, Mauro LS, Scala-Barnett DM, et al.  Serotonin syndrome versus neuroleptic malignant syndrome as a cause of death. Clin Pharmacol. 1989;8:510–514
  76. Singh AN, Maguire J. Neuroleptic malignant syndrome: A misnomer? [letter]. Br J Psychiatry. 1987;151:863–865
  77. Beaumont G. Drug interactions with clomipramine (Anafranil). J Int Med Res. 1973;1:480–484
  78. Kuisma MJ. Fatal serotonin syndrome with trismus [letter]. Ann Emerg Med. 1995;26:108
  79. Asch DA, Parker RM. The Libby Zion case: One step forward or two steps backward?. N Engl J Med. 1988;318:771–775
  80. Henry JA. Serotonin syndrome [letter]. Lancet. 1994;343:607
  81. Braitberg G. Serotonin syndrome [letter]. 1994;160:527–528
  82. Lucki I, Nobler MS, Frazer A. Differential actions of serotonin antagonists on two behavioral models of serotonin receptor activation in the rat. J Pharmacol Exp Ther. 1984;1:133–139
  83. Stewart RM, Campbell A, Sperk G, et al.  Receptor mechanisms in increased sensitivity to serotonin agonists after dihydroxytryptamine shown by electronic monitoring of muscle twitches in the rat. Psychopharmacology. 1979;60:281–289
  84. Klawans HL, Goetz C, Weiner WJ. 5-Hydroxytryptophan induced myoclonus in guinea pigs and the possible role of serotonin in infantile myoclonus. Neurology. 1973;23:1234–1240
  85. Deakin JFW, Green AR. The effects of putative 5-hydroxytryptamine antagonists on the behavior produced by administration of tranylcypromine and L-tryptophan or tranylcypromine and L-DOPA to rats. Br J Pharmacol. 1978;64:201–209
  86. Weinstock M, Weiss C, Gitter S. Blockade of 5-hydroxytryptamine receptors in the central nervous system by beta-adrenoreceptor antagonists. Neuropharmacology. 1977;16:273–276
  87. Sprouse JS, Aghajanian GK. (-)-Propranolol blocks the inhibition of serotonergic dorsal raphe cell firing by 5-HT1A selective agonists. Eur J Pharmacol. 1986;128:295–298
  88. Shepherd JT, Whiting B. Beta-adrenergic blockade in the treatment of M.A.O.I. self-poisoning [letter]. Lancet. 1974;2:1021
  89. Guze BH, Baster LR. Serotonin syndrome: Case responsive to propranolol [letter]. J Clin Psychopharmacol. 1986;6:119–120
  90. Klee B, Kronig MH. Case report of probable sertraline-induced akathisia. Am J Psychiatry. 1993;150:986–987
  91. Lappin R, Auchincloss E. Treatment of serotonin syndrome with cyproheptadine. N Engl J Med. 1994;331:1021–1022
  92. Jenner P, Pratt JA, Marsden DC. Mechanisms of action of clonazepam in myoclonus in relation to effects of GABA and 5-HT. Adv Neurol. 1986;43:629–643
  93. Gimenez-Roldan S, Mateo D, Yebenes JG. Clinical, biochemical and pharmacological observation in a patient with postasphyxic myoclonus: Association to serotonin hyperactivity. Clin Neuropharmacol. 1988;11:151–160
  94. Snider SR, Hutt CS, Stein B, et al.  Increase in brain serotonin produced by bromocriptine. Neurosci Lett. 1975;1:237–241
  95. Snider SR, Hutt C, Stein B, et al.  Correlation of behavioural inhibition or excitation produced by bromocriptine with changes in brain catecholamine turnover. J Pharm Pharmacol. 1976;28:563–566
  96. Hutt CS, Snider SR, Fahn S. Interaction between bromocriptine and levodopa. Neurology. 1977;27:505–510
  97. Coons DJ, Hillman FJ, Marshall RW. Treatment of neuroleptic malignant syndrome with dantrolene sodium: A case report. Am J Psychiatry. 1982;139:944–945
  98. Meredith TJ, Jacobsen D, Haines JA, et al.  Naloxone, Flumazenil and Dantrolene as Antidotes, vol I, IPCS/CEC Evaluation of Antidotes Series. Cambridge, England: University Press; 1991;
  99. Kaplan R, Feinglass N, Webster W, et al.  Phenelzine overdose treated with dantrolene sodium. JAMA. 1986;255:642–644
  100. Nisijima K, Ishiguro T. Does dantrolene influence central dopamine and serotonin metabolism in the neuroleptic malignant syndrome? A retrospective study. Biol Psychiatry. 1993;33:45–48

☆ From the Toxicology Treatment Program, Department of Emergency Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania.

☆☆ Reprints not available from the author.

★ Reprint no. 47/1/75652

PII: S0196-0644(96)70116-6

Annals of Emergency Medicine
Volume 28, Issue 5 , Pages 520-526 , November 1996

Article Tools

* Image Usage & Resolution