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Serotonin toxicity caused by an interaction between fentanyl and paroxetine

[Toxicité sérotoninergique provoquée par une interaction entre le fentanyl et la paroxétine]

From the Royal Marsden Hospital, London, United Kingdom.

Address correspondence to: Dr. Simon Rang, Specialist Registrar in Anaesthesia, Department of Anaesthesia, Royal Marsden Hospital, Fulham Road, London, SW3 6JJ, United Kingdom. Phone: +44 207 352 8171; E-mail: simonrang{at}gmail.com

Purpose: To report a case of serotonin toxicity, presenting in the postoperative period, caused by an interaction between paroxetine (a selective serotonin reuptake inhibitor, SSRI) and fentanyl (a phenylpiperidine opioid). Serotonin toxicity precipitated by fentanyl is unusual and has not previously been described in combination with SSRIs in the perioperative setting.

Clinical features: A 60-yr-old woman, established on paroxetine for depression, underwent excision of a chest wall myxofibrosarcoma and chest wall reconstruction. Fentanyl was administered for intraoperative and postoperative analgesia (1 mg intraoperatively, and 2.5 mg by infusion in the first 36 hr, postoperatively). She developed a vague affectation, intermittent agitation, bilateral hyper-reflexia, inducible clonus, and a period of hypertension, suggestive of serotonin toxicity. There was complete resolution after cessation of fentanyl and paroxetine.

Conclusion: The co-administration of SSRIs and fentanyl may precipitate serotonin toxicity. There must be consideration of this unusual interaction when administering fentanyl to patients established on SSRIs. Physicians should be vigilant of the features of serotonin toxicity developing in such patients.

1 Stahl S. Essential Psychopharmacology: Neuroscientific Basis and Practical Applications, 2nd ed. Cambridge University Press; 2000.

2 Sternbach H. The serotonin syndrome. Am J Psychiatry 1991; 148: 705–13.[Abstract/Free Full Text]

3 Insler SR, Kraenzler EJ, Licina MG, Savage RM, Starr NJ. Cardiac surgery in a patient taking monoamine oxidase inhibitors: an adverse fentanyl reaction. Anesth Analg 1994; 78: 593–7.[Free Full Text]

4 Ailawadhi S, Sung KW, Carlson LA, Baer MR. Serotonin syndrome caused by interaction between citalopram and fentanyl. J Clin Pharm Ther 2007; 32: 199–202.[Medline]

5 Noble WH, Baker A. MAO inhibitors and coronary artery surgery: a patient death. Can J Anaesth 1992; 39: 1061–6.[Abstract/Free Full Text]

6 Fraser J, South M. Life-threatening fluvoxamine overdose in a 4-year-old child. Intensive Care Med 1999; 25: 548.[Medline]

7 Dunkley EJ, Isbister GK, Sibbritt D, Dawson AH, Whyte IM. The Hunter Serotonin Toxicity Criteria: simple and accurate diagnostic decision rules for serotonin toxicity. QJM 2003; 96: 635–42.[Abstract/Free Full Text]

8 Codd EE, Shank RP, Schupsky JJ, Raffa RB. Serotonin and norepinephrine uptake inhibiting activity of centrally acting analgesics: structural determinants and role in antinociception. J Pharmacol Exp Ther 1995; 274: 1263–70.[Abstract/Free Full Text]

9 el-Ganzouri AR, Ivankovich AD, Braverman B, McCarthy R. Monoamine oxidase inhibitors: should they be discontinued preoperatively? Anesth Analg 1985; 64: 592–6.[Abstract/Free Full Text]

10 Gillman PK. Monoamine oxidase inhibitors, opioid analgesics and serotonin toxicity. Br J Anaesth 2005; 95: 434–41.[Abstract/Free Full Text]

11 Roy S, Fortier LP. Fentanyl-induced rigidity during emergence from general anesthesia potentiated by venlafexine. Can J Anesth 2003; 50: 32–5.[Abstract/Free Full Text]

12 Hegerl U, Bottlender R, Gallinat J, Kuss HJ, Ackenheil M, Moller HJ. The serotonin syndrome scale: first results on validity. Eur Arch Psychiatry Clin Neurosci 1998; 248: 96–103.[Medline]

13 Bodner RA, Lynch T, Lewis L, Kahn D. Serotonin syndrome. Neurology 1995; 45: 219–23.[Abstract]

14 Lane R, Baldwin D. Selective serotonin reuptake inhibitor-induced serotonin syndrome: review. J Clin Psychopharmacol 1997; 17: 208–21.[Medline]

15 Nisijima K, Shioda K, Yoshino T, Takano K, Kato S. Diazepam and chlormethiazole attenuate the development of hyperthermia in an animal model of the serotonin syndrome. Neurochem Int 2003; 43: 155–64.[Medline]

16 Gillman PK. The serotonin syndrome and its treatment. J Psychopharmacol 1999; 13: 100–9.[Abstract]

17 Graudins A, Stearman A, Chan B. Treatment of the serotonin syndrome with cyproheptadine. J Emerg Med 1998; 16: 615–9.[Medline]

18 Gillman P. PsychoTropical Research [cited 30/3 2008]. Available from URL; http://www.psychotropical.com.