serotonin syndrome


Summary: An adverse drug interaction characterized by altered mental status, autonomic dysfunction, and neuromuscular abnormalities. It is most frequently caused by use of both serotonin reuptake inhibitors and monoamine oxidase inhibitors, leading to excess serotonin availability in the CNS at the serotonin 1A receptor.

Top Publications

  1. Strouse T, Kerrihard T, Forscher C, Zakowski P. Serotonin syndrome precipitated by linezolid in a medically ill patient on duloxetine. J Clin Psychopharmacol. 2006;26:681-3 pubmed
  2. Shioda K, Nisijima K, Nishida S, Kato S. Possible serotonin syndrome arising from an interaction between caffeine and serotonergic antidepressants. Hum Psychopharmacol. 2004;19:353-4 pubmed
  3. Packer S, Berman S. Serotonin syndrome precipitated by the monoamine oxidase inhibitor linezolid. Am J Psychiatry. 2007;164:346-7 pubmed
  4. Ng B, Cameron A, Liang R, Rahman H. [Serotonin syndrome following methylene blue infusion during parathyroidectomy: a case report and literature review]. Can J Anaesth. 2008;55:36-41 pubmed publisher
    ..following methylene blue infusion for parathyroidectomy; to advance the argument for a diagnosis of serotonin syndrome; and to consider this diagnosis in previous, unexplained reports of adverse reactions amongst patients ..
  5. Wigen C, Goetz M. Serotonin syndrome and linezolid. Clin Infect Dis. 2002;34:1651-2 pubmed
    We present a case of serotonin syndrome in a patient who initiated linezolid therapy shortly after discontinuation of therapy with a selective serotonin reuptake inhibitor (paroxetine).
  6. Wong E, Chan N, Sze K, Or K. Serotonin syndrome in a renal transplant patient. J R Soc Med. 2002;95:304-5 pubmed
  7. Houlihan D. Serotonin syndrome resulting from coadministration of tramadol, venlafaxine, and mirtazapine. Ann Pharmacother. 2004;38:411-3 pubmed
    To report a case of serotonin syndrome (SS) resulting from the addition of tramadol to a medication regimen of venlafaxine and mirtazapine.
  8. Eadie M. Convulsive ergotism: epidemics of the serotonin syndrome?. Lancet Neurol. 2003;2:429-34 pubmed
    ..sweating, and fever lasting for several weeks--suggest serotonergic overstimulation of the CNS (ie, the serotonin syndrome). The ergot alkaloids are serotonin agonists...
  9. Stewart A, Cachat J, Gaikwad S, Robinson K, Gebhardt M, Kalueff A. Perspectives on experimental models of serotonin syndrome in zebrafish. Neurochem Int. 2013;62:893-902 pubmed publisher
    b>Serotonin syndrome (SS) is a serious life-threatening disorder associated with elevated brain serotonergic function...

More Information


  1. Giannini A, Giannini J, Melemis S, Giannini J. Treatment of acute mania with ambient air anionization: variants of climactic heat stress and serotonin syndrome. Psychol Rep. 2007;100:157-63 pubmed
    ..3 and 31.6, respectively. Pretreatment and posttreatment total scores were 31.6 and 26.3, respectively. Previous research indicates a role for serotonin in producing this antimanic effect...
  2. Ailawadhi S, Sung K, Carlson L, Baer M. Serotonin syndrome caused by interaction between citalopram and fentanyl. J Clin Pharm Ther. 2007;32:199-202 pubmed
    To report a case of serotonin syndrome associated with interaction between fentanyl and citalopram, as evidenced by medication history, clinical features and reversal following discontinuation of fentanyl.
  3. Bonetto N, Santelli L, Battistin L, Cagnin A. Serotonin syndrome and rhabdomyolysis induced by concomitant use of triptans, fluoxetine and hypericum. Cephalalgia. 2007;27:1421-3 pubmed
  4. Kalueff A, Fox M, Gallagher P, Murphy D. Hypolocomotion, anxiety and serotonin syndrome-like behavior contribute to the complex phenotype of serotonin transporter knockout mice. Genes Brain Behav. 2007;6:389-400 pubmed
    ..displayed spontaneous Straub tail, tics, tremor and backward gait - a phenotype generally consistent with 'serotonin syndrome'-like behavior...
  5. Kan R, Endou M, Unno Y. [A case of serotonin syndrome following minimum doses of sertraline]. Seishin Shinkeigaku Zasshi. 2009;111:1041-6 pubmed
    We report a 75-year-old woman developing serotonin syndrome following minimum doses of sertraline. She showed a depressed mood, insomnia, and general fatigue and was taking sulpiride at 300 mg/day, alprazolam at 1.2 mg/day, zopiclone at 7...
  6. Birmes P, Coppin D, Schmitt L, Lauque D. Serotonin syndrome: a brief review. CMAJ. 2003;168:1439-42 pubmed
  7. Sahiner V, Erden Aki S. [Serotonin syndrome associated with linezolid use: a case report]. Turk Psikiyatri Derg. 2009;20:398-402 pubmed
    The serotonin syndrome is a toxic state largely attributable to changes in sensitivity of serotonin receptor system in the brainstem and spinal cord resulting from increased serotonergic activity in central neurologic system, due to use ..
  8. Dvir Y, Smallwood P. Serotonin syndrome: a complex but easily avoidable condition. Gen Hosp Psychiatry. 2008;30:284-7 pubmed publisher
    b>Serotonin syndrome is a potentially life-threatening adverse drug reaction caused by excessive serotonergic agonism in central and peripheral nervous system serotonergic receptors (Boyer EW, Shannon M. The serotonin syndrome...
  9. Mestres J, Seifert S, Oprea T. Linking pharmacology to clinical reports: cyclobenzaprine and its possible association with serotonin syndrome. Clin Pharmacol Ther. 2011;90:662-5 pubmed publisher
    The link between cyclobenzaprine (Flexeril) administration and serotonin syndrome (SS) is subject to debate...
  10. Parrott A. Recreational Ecstasy/MDMA, the serotonin syndrome, and serotonergic neurotoxicity. Pharmacol Biochem Behav. 2002;71:837-44 pubmed
    ..In the hot and crowded conditions of raves/dances, mild versions of the serotonin syndrome often develop, when hyperthermia, mental confusion, and hyperkinesia predominate...
  11. Mittino D, Mula M, Monaco F. Serotonin syndrome associated with tramadol-sertraline coadministration. Clin Neuropharmacol. 2004;27:150-1 pubmed
  12. Lawyer T, Jensen J, Welton R. Serotonin syndrome in the deployed setting. Mil Med. 2010;175:950-2 pubmed
    b>Serotonin syndrome is a potential side effect of some psychotropic medications in common use today. With over 8000 adverse events related to this condition in 2004 alone, this risk warrants further attention...
  13. Day L, Jeanmonod R. Serotonin syndrome in a patient taking Lexapro and Flexeril: a case report. Am J Emerg Med. 2008;26:1069.e1-3 pubmed publisher
    The serotonin syndrome is a rare toxicological emergency increasingly seen in emergency practice, secondary to increased use of proserotinergic drugs...
  14. Tahir N. Serotonin syndrome as a consequence of drug-resistant infections: an interaction between linezolid and citalopram. J Am Med Dir Assoc. 2004;5:111-3 pubmed
  15. Kirschner R, Donovan J. Serotonin syndrome precipitated by fentanyl during procedural sedation. J Emerg Med. 2010;38:477-80 pubmed publisher
    ..Both developed neuromuscular examinations consistent with serotonin syndrome, a diagnosis that must be established on the basis of clinical criteria...
  16. Evans R, Tepper S, Shapiro R, Sun Edelstein C, Tietjen G. The FDA alert on serotonin syndrome with use of triptans combined with selective serotonin reuptake inhibitors or selective serotonin-norepinephrine reuptake inhibitors: American Headache Society position paper. Headache. 2010;50:1089-99 pubmed publisher
    In 2006, a US Food and Drug Administration (FDA) alert warned about the potential life-threatening risk of serotonin syndrome when triptans are used in combination with selective serotonin reuptake inhibitors (SSRIs) or selective ..
  17. Gillman P. Serotonin syndrome: history and risk. Fundam Clin Pharmacol. 1998;12:482-91 pubmed
    ..The various serotonergic drugs that may be implicated in serotonin syndrome are tabulated and discussed in relation to the relative risk...
  18. Fisher A, Davis M. Serotonin syndrome caused by selective serotonin reuptake-inhibitors-metoclopramide interaction. Ann Pharmacother. 2002;36:67-71 pubmed
    To report 2 cases of serotonin syndrome with serious extrapyramidal movement disorders occurring when metoclopramide was coadministered with sertraline or venlafaxine.
  19. Jaber B, Lobon L, Madias N. The serotonin syndrome complicating co-prescription of paroxetine and clarithromycin. Am J Med. 2006;119:e3 pubmed
  20. Poeschla B, Bartle P, Hansen K. Serotonin syndrome associated with polypharmacy in the elderly. Gen Hosp Psychiatry. 2011;33:301.e9-11 pubmed publisher
    ..agents, alone and in combination, across multiple disciplines, makes it likely that the prevalence of serotonin syndrome will rise...
  21. Demers J, Malone M. Serotonin syndrome induced by fluvoxamine and mirtazapine. Ann Pharmacother. 2001;35:1217-20 pubmed
    To document a case of serotonin syndrome associated with the combined use of fluvoxamine and mirtazapine, and to discuss the pharmacodynamic and pharmacokinetic interactions that were the likely causes of this potentially serious adverse ..
  22. Sclar D, Robison L, Skaer T. Concomitant triptan and SSRI or SNRI use: a risk for serotonin syndrome. Headache. 2008;48:126-9 pubmed
    ..To discern the prevalence of concomitant use of a triptan and a selective serotonin reuptake inhibitor (SSRI) or a selective serotonin/norepinephrine reuptake inhibitor (SNRI) in the USA...
  23. Nisijima K, Shioda K, Yoshino T, Takano K, Kato S. Memantine, an NMDA antagonist, prevents the development of hyperthermia in an animal model for serotonin syndrome. Pharmacopsychiatry. 2004;37:57-62 pubmed
    ..In the present study, the efficacy of NMDA antagonists, including memantine and MK-801, and potent 5-HT (2A) antagonists, including risperidone and ketanserin, was evaluated in a 5-HT syndrome animal model...
  24. Smalla K, Sahin J, Putzke J, Tischmeyer W, Gundelfinger E, Kreutz M. Altered postsynaptic-density-levels of caldendrin in the para-chloroamphetamine-induced serotonin syndrome but not in the rat ketamine model of psychosis. Neurochem Res. 2009;34:1405-9 pubmed publisher
    ..These results underscore the dynamic association of caldendrin with the PSD and suggest a role of this synaptic calcium sensor in the PCA-induced serotonin syndrome.
  25. Ozkardesler S, Gurpinar T, Akan M, Koca U, Sarikaya H, Olmez T, et al. A possible perianesthetic serotonin syndrome related to intrathecal fentanyl. J Clin Anesth. 2008;20:143-5 pubmed publisher
    b>Serotonin syndrome occurs with selective serotonin reuptake inhibitors, opioids, and other serotonergic agents...
  26. Boban Blagaic A, Blagaic V, Mirt M, Jelovac N, Dodig G, Rucman R, et al. Gastric pentadecapeptide BPC 157 effective against serotonin syndrome in rats. Eur J Pharmacol. 2005;512:173-9 pubmed
    b>Serotonin syndrome commonly follows irreversible monoamine oxidase (MAO)-inhibition and subsequent serotonin (5-HT) substrate (in rats with fore paw treading, hind limbs abduction, wet dog shake, hypothermia followed by hyperthermia)...
  27. Vizcaychipi M, Walker S, Palazzo M. Serotonin syndrome triggered by tramadol. Br J Anaesth. 2007;99:919 pubmed
  28. Frank C. Recognition and treatment of serotonin syndrome. Can Fam Physician. 2008;54:988-92 pubmed
  29. Huang V, Gortney J. Risk of serotonin syndrome with concomitant administration of linezolid and serotonin agonists. Pharmacotherapy. 2006;26:1784-93 pubmed
    ..Inhibition of this enzyme can predispose patients who are concomitantly taking serotonin agonists to serotonin syndrome. Because of the potential of linezolid to inhibit monoamine oxidase, premarketing studies were conducted ..
  30. Gillman P. The serotonin syndrome and its treatment. J Psychopharmacol. 1999;13:100-9 pubmed
    b>Serotonin syndrome is caused by drug induced excess of intrasynaptic 5-hydroxytryptamine. The clinical manifestations are mediated by the action of 5-hydroxytryptamine on various subtypes of serotonin receptors...
  31. Ubogu E, Katirji B. Mirtazapine-induced serotonin syndrome. Clin Neuropharmacol. 2003;26:54-7 pubmed
    ..This is a rare report of serotonin syndrome induced by mirtazapine monotherapy...
  32. Dannawi M. Possible serotonin syndrome after combination of buspirone and St John's Wort. J Psychopharmacol. 2002;16:401 pubmed
  33. Baigel G. Cyproheptadine and the treatment of an unconscious patient with the serotonin syndrome. Eur J Anaesthesiol. 2003;20:586-8 pubmed
  34. Mason P, Morris V, Balcezak T. Serotonin syndrome. Presentation of 2 cases and review of the literature. Medicine (Baltimore). 2000;79:201-9 pubmed
    b>Serotonin syndrome is an underreported complication of pharmacotherapy that has been relatively ignored in the medical literature...
  35. Debellis R, Schaefer O, Liquori M, Volturo G. Linezolid-associated serotonin syndrome after concomitant treatment with citalopram and mirtazepine in a critically ill bone marrow transplant recipient. J Intensive Care Med. 2005;20:351-3 pubmed
    ..A case report involving linezolid with citalopram and mirtazepine in the precipitation of serotonin syndrome in a critically ill bone marrow transplant patient is described in this article.
  36. Jones D, Story D. Serotonin syndrome and the anaesthetist. Anaesth Intensive Care. 2005;33:181-7 pubmed
    b>Serotonin syndrome results from excessive activation of serotonin (5-hydroxytryptamine; 5-HT) receptors in the nervous system, on the surface of platelets, and on the vascular endothelium...
  37. Miller D, Lovell E. Antibiotic-induced serotonin syndrome. J Emerg Med. 2011;40:25-7 pubmed publisher
    ..its broad spectrum of clinical presentations and to the large number of available serotonergic medications, serotonin syndrome (SS) remains an elusive diagnosis to many clinicians...
  38. Sokoro A, Zivot J, Ariano R. Neuroleptic malignant syndrome versus serotonin syndrome: the search for a diagnostic tool. Ann Pharmacother. 2011;45:e50 pubmed publisher
    ..To evaluate the use of urine dopamine and catecholamine concentrations as diagnostic aids in a patient with neuroleptic malignant syndrome (NMS) in the emergency department setting...
  39. Kaufman K, Levitt M, Schiltz J, Sunderram J. Neuroleptic malignant syndrome and serotonin syndrome in the critical care setting: case analysis. Ann Clin Psychiatry. 2006;18:201-4 pubmed
    b>Serotonin syndrome (SS) and neuroleptic malignant syndrome (NMS) are medical emergencies associated with psychotropic administration...
  40. Sclar D, Robison L, Castillo L, Schmidt J, Bowen K, Oganov A, et al. Concomitant use of triptan, and SSRI or SNRI after the US Food and Drug Administration alert on serotonin syndrome. Headache. 2012;52:198-203 pubmed publisher
    ..or a selective serotonin/norepinephrine reuptake inhibitor (SNRI) after the US Food and Drug Administration issued an alert regarding serotonin syndrome in 2006 and to contrast findings with data published prior to the federal warning.
  41. Steinberg M, Morin A. Mild serotonin syndrome associated with concurrent linezolid and fluoxetine. Am J Health Syst Pharm. 2007;64:59-62 pubmed
    A case of serotonin syndrome that developed during concurrent linezolid and fluoxetine is presented.
  42. Karunatilake H, Buckley N. Serotonin syndrome induced by fluvoxamine and oxycodone. Ann Pharmacother. 2006;40:155-7 pubmed
    ..To report a case of severe serotonergic symptoms following the addition of oxycodone to fluvoxamine...
  43. Chambost M, Liron L, Peillon D, Combe C. [Serotonin syndrome during fluoxetine poisoning in a patient taking moclobemide]. Can J Anaesth. 2000;47:246-50 pubmed
    ..To present a case of delayed serotonin syndome (SS), a less well-known adverse effect of fluoxetine intoxication...
  44. Jones S, Athan E, O BRIEN D. Serotonin syndrome due to co-administration of linezolid and venlafaxine. J Antimicrob Chemother. 2004;54:289-90 pubmed
  45. Huska M, Catalano G, Catalano M. Serotonin syndrome associated with the use of escitalopram. CNS Spectr. 2007;12:270-4 pubmed
    ..escitalopram therapy, such as insomnia, nausea, and increased sweating, there are no reported cases of serotonin syndrome associated with escitalopram therapy to date...
  46. Salazar M, Eiland L. Intrathecal baclofen withdrawal resembling serotonin syndrome in an adolescent boy with cerebral palsy. Pediatr Emerg Care. 2008;24:691-3 pubmed publisher differentiated with autonomic dysreflexia, malignant hyperthermia, neuroleptic malignant syndrome, and serotonin syndrome. We report a case of ITB withdrawal secondary to low residual volume in the pump reservoir and resembling ..
  47. Montane E, Barriocanal A, Isern I, Parajon T, Costa J. Multiple drug interactions - induced serotonin syndrome: a case report. J Clin Pharm Ther. 2009;34:485-7 pubmed publisher
    b>Serotonin syndrome is a potentially life-threatening disorder of excessive serotoninergic activity often due to drug interactions...
  48. Velez L, Shepherd G, Roth B, Benitez F. Serotonin syndrome with elevated paroxetine concentrations. Ann Pharmacother. 2004;38:269-72 pubmed
    To describe a case of serotonin syndrome due to paroxetine and ethanol.
  49. Ables A, Nagubilli R. Prevention, recognition, and management of serotonin syndrome. Am Fam Physician. 2010;81:1139-42 pubmed
    b>Serotonin syndrome is a potentially life-threatening condition caused by excessive serotonergic activity in the nervous system. It is characterized by mental status changes, autonomic instability, and neuromuscular hyperactivity...
  50. Hachem R, Hicks K, Huen A, Raad I. Myelosuppression and serotonin syndrome associated with concurrent use of linezolid and selective serotonin reuptake inhibitors in bone marrow transplant recipients. Clin Infect Dis. 2003;37:e8-11 pubmed
    We report 2 cases of serotonin syndrome and myelosuppression in bone marrow transplant recipients who received linezolid in combination with a selective serotonin reuptake inhibitor (SSRI)...
  51. Ghanizadeh A, Ghanizadeh M, Seifoori M. Can fluoxetine alone cause serotonin syndrome in adolescents?. Psychopharmacol Bull. 2008;41:76-9 pubmed
    b>Serotonin syndrome is usually reported by the use of a combination of drugs. This is a possible case of serotonin syndrome after using Fluoxetine.
  52. Bijl D. The serotonin syndrome. Neth J Med. 2004;62:309-13 pubmed
    The serotonin syndrome is a complex of symptoms that are thought to be largely attributable to changes in sensitivity in the serotonin receptor systems in the brainstem and the spinal cord due to drugs...
  53. Narita M, Tsuji B, Yu V. Linezolid-associated peripheral and optic neuropathy, lactic acidosis, and serotonin syndrome. Pharmacotherapy. 2007;27:1189-97 pubmed
    ..reported after commercial release, including cases of lactic acidosis, peripheral and optic neuropathy, and serotonin syndrome. Peripheral and optic neuropathy was usually seen after several months of linezolid therapy (median 5 mo), ..