Serotonin toxicity caused by an interaction between fentanyl and paroxetine

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.

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.

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.