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Electronic Letters to:

Case Reports:
S.-L. Guo, T.-J. Wu, C.-C. Liu, C.-C. Ng, C.-C. Chien, and H.-L. Sun
Meperidine-induced serotonin syndrome in a susceptible patient
Br. J. Anaesth. 2009; 0: aep167v1-167 [Abstract] [Full text] [PDF]
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Electronic letters published:

[Read E-letter] Meperidine induced serotonin syndrome
David M Christmas, Tracey R. Christmas   (6 November 2009)

Meperidine induced serotonin syndrome 6 November 2009
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David M Christmas,
Academic Specialist Registrar
Psychopharmacology Unit, Univeristy of Bristol,
Tracey R. Christmas

Send letter to journal:
Re: Meperidine induced serotonin syndrome

Dear Editor,

We read with interest the recent case report by Guo and colleagues on meperidine induced serotonin syndrome.1 It provides a useful reminder that the drugs we prescribe may cause rare and serious side effects of which it is our duty to be aware. In the case of serotonin syndrome, up to 85% of physicians may be unaware of its existence.2 Meperidine has a long history of association with serotonin syndrome, being implicated in a high profile case more than 20 years ago 3, and numerous other reports since.4-6

Serotonin syndrome is probably not an idiopathic drug reaction; it is likely a direct result of excessive serotonin action at post-synaptic 5HT receptors.7 As such it commonly occurs after an overdose of serotonergic medication (it has been reported in up to 14% of SSRI overdoses 8), but combining serotonergic medications will also increase the risk. Indeed, preclinical studies suggest that serotonin levels are higher, and the incidence of serotonin syndrome greater, with combinations rather than individual agents. 9

This appears to have been the case in this report, where two serotonergic medications have been combined. The authors did not report the potential of the prescribed fentanyl as a contributor to this case of serotonin syndrome.10-13 This unwittingly emphasises their concluding point that a greater awareness of serotonin syndrome is required due to the wide range of serotonergic drugs available.

In a hospital setting there are many common medications with lesser known serotonergic actions which, when combined together or with an antidepressant, can precipitate serotonin syndrome. One group of importance is the phenylpiperidine group of opioids, which includes meperidine and fentanyl mentioned here, as well as tramadol (a synthetic analogue) which also has numerous reports linking it to serotonin syndrome.14-17 Methadone is another common opioid which has been implicated.18 19 Other groups of medications associated with serotonin syndrome include non-antidepressant MAOIs such as selegiline 20 and linezolid 21, some antiemetics (e.g. metoclopramide 22) and tryptan antimigraine medication 23 (although this latter group has been debated 24). Thorough reviews on the serotonin syndrome and the medications implicated in causing it are available.9 25 We agree with the authors sentiments that a greater awareness of the syndrome and the medications involved is required.

Dr T.R. Christmas, Anaesthetic SpR, Bristol Royal Infirmary

*Dr D.M. Christmas Academic Specialist Registrar, Psychopharmacology Unit, University of Bristol *david.christmas@bristol.ac.uk

Reference List

(1) Guo SL, Wu TJ, Liu CC, Ng CC, Chien CC, Sun HL. Meperidine- induced serotonin syndrome in a susceptible patient. Br J Anaesth 2009 September;103(3):369-70.

(2) Mackay FJ, Dunn NR, Mann RD. Antidepressants and the serotonin syndrome in general practice. Br J Gen Pract 1999 November;49(448):871-4.

(3) Asch DA, Parker RM. The Libby Zion case. One step forward or two steps backward? N Engl J Med 1988 March 24;318(12):771-5.

(4) Altman EM, Manos GH. Serotonin syndrome associated with citalopram and meperidine. Psychosomatics 2007 July;48(4):361-3.

(5) Das PK, Warkentin DI, Hewko R, Forrest DL. Serotonin syndrome after concomitant treatment with linezolid and meperidine. Clin Infect Dis 2008 January 15;46(2):264-5.

(6) Tissot TA. Probable meperidine-induced serotonin syndrome in a patient with a history of fluoxetine use. Anesthesiology 2003 June;98(6):1511-2.

(7) Gillman PK. A review of serotonin toxicity data: implications for the mechanisms of antidepressant drug action. Biol Psychiatry 2006 June 1;59(11):1046-51.

(8) Isbister GK, Bowe SJ, Dawson A, Whyte IM. Relative toxicity of selective serotonin reuptake inhibitors (SSRIs) in overdose. J Toxicol Clin Toxicol 2004;42(3):277-85.

(9) Sun-Edelstein C, Tepper SJ, Shapiro RE. Drug-induced serotonin syndrome: a review. Expert Opin Drug Saf 2008 September;7(5):587-96.

(10) Ailawadhi S, Sung KW, Carlson LA, Baer MR. Serotonin syndrome caused by interaction between citalopram and fentanyl. J Clin Pharm Ther 2007 April;32(2):199-202.

(11) Kirschner R, Donovan JW. Serotonin Syndrome Precipitated by Fentanyl during Procedural Sedation. J Emerg Med 2008 August 30.

(12) Ozkardesler S, Gurpinar T, Akan M, Koca U, Sarikaya H, Olmez T, Elar Z. A possible perianesthetic serotonin syndrome related to intrathecal fentanyl. J Clin Anesth 2008 March;20(2):143-5.

(13) Noble WH, Baker A. MAO inhibitors and coronary artery surgery: a patient death. Can J Anaesth 1992 December;39(10):1061-6.

(14) Garrett PM. Tramadol overdose and serotonin syndrome manifesting as acute right heart dysfunction. Anaesth Intensive Care 2004 August;32(4):575-7.

(15) Houlihan DJ. Serotonin syndrome resulting from coadministration of tramadol, venlafaxine, and mirtazapine. Ann Pharmacother 2004 March;38(3):411-3.

(16) Mason BJ, Blackburn KH. Possible serotonin syndrome associated with tramadol and sertraline coadministration. Ann Pharmacother 1997 February;31(2):175-7.

(17) Sansone RA, Sansone LA. Tramadol: seizures, serotonin syndrome, and coadministered antidepressants. Psychiatry (Edgmont ) 2009 April;6(4):17-21.

(18) Martinez TT, Martinez DN. A case of serotonin syndrome associated with methadone overdose. Proc West Pharmacol Soc 2008;51:42-4.

(19) Bush E, Miller C, Friedman I. A case of serotonin syndrome and mutism associated with methadone. J Palliat Med 2006 December;9(6):1257-9.

(20) Hinds NP, Hillier CE, Wiles CM. Possible serotonin syndrome arising from an interaction between nortriptyline and selegiline in a lady with parkinsonism. J Neurol 2000 October;247(10):811.

(21) Taylor JJ, Wilson JW, Estes LL. Linezolid and serotonergic drug interactions: a retrospective survey. Clin Infect Dis 2006 July 15;43(2):180-7.

(22) Fisher AA, Davis MW. Serotonin syndrome caused by selective serotonin reuptake-inhibitors-metoclopramide interaction. Ann Pharmacother 2002 January;36(1):67-71.

(23) Soldin OP, Tonning JM. Serotonin syndrome associated with triptan monotherapy. N Engl J Med 2008 May 15;358(20):2185-6.

(24) Evans RW. More on serotonin syndrome associated with triptan monotherapy. N Engl J Med 2008 August 21;359(8):870-1.

(25) Boyer EW, Shannon M. The serotonin syndrome. N Engl J Med 2005 March 17;352(11):1112-20.

Conflict of Interest:

DC has been the recipient of a educational grant from Schering-Plough 2007.