Psychosomatics 48:361-a-363, July-August 2007
doi: 10.1176/appi.psy.48.4.361-a
© 2007 Academy of Psychosomatic Medicine
Serotonin Syndrome Associated With Citalopram and Meperidine
Evan M. Altman, D.O., Chief Resident, and
Gail H. Manos, M.D., Training Director, Dept. of Psychiatry, Naval Medical Center, Portsmouth, VA
TO THE EDITOR: Serotonin syndrome (SS) is serious and poses a potentially life-threatening risk, resulting when two or more serotonin reuptake-inhibiting medications are used together. Although some agents are quickly recognized as serotonergic, others are less well-known. We describe a unique case of SS in a hospitalized patient when meperidine was added to a medication regimen that included citalopram.
Case Report
"Ms. C," a 44-year-old woman who had had surgical resection of rectal cancer, was diagnosed with depression shortly after her cancer diagnosis. She was started on citalopram 20 mg by mouth (po) daily. Nine months later, she was admitted to surgery for debridement of the rectal wound. She was on the surgery ward when her depression significantly worsened. Psychiatry helped with the patient’s symptoms as per the requesting ward team; we provided psychotherapy and increased citalopram to 40 mg po daily.
Her depression steadily improved over several weeks. Thus, it was a surprise when Ms. C. was found to be "behaving very oddly" one night. She was experiencing acute agitation, disorientation, paranoia, perceptual disturbances, and nausea. Simultaneously, she spiked a temperature of 39.1°C. Her systolic blood pressure was 161 mmHg, and her diastolic blood pressure was 86 mmHg. Respirations were 22 per minute, and heart rate was 112 beats per minute.
The Psychiatry Dept. was not contacted that night because these symptoms were believed a typical part of her "psychiatric condition." Her medical work-up included computed tomography (CT), ECG, and chest X-ray, all of which were normal. Physical examination uncovered a localized wound infection, and blood cultures revealed no growth after 5 days. Laboratory results included an elevated total white blood-cell count of 14,500 µ/L, platelet count of 531,000 µ/L, and hemoglobin and hematocrit of 13 g/dl and 39%, respectively. A complete metabolic panel was within normal limits.
Review of her as-needed (prn) medications revealed hydromorphone 50 mg intravenously (IV) every 6 hours (q 6 hr.) for pain, hydrocodone bitartrate-acetaminophen 5 mg/500 mg po q 6 hr. for pain, and promethazine 12.5 mg IV q 6 hr. for nausea. For breakthrough pain, patient-controlled anesthesia with meperidine had been added before onset of the symptoms. The total parenteral dose of meperidine, over 8 hours, was 230 mg.
Ms. C’s symptoms began within 10 hours of starting meperidine, and then stopped 12 hours after discontinuation. Once meperidine was stopped, no episodes occurred during the next 3 months. Gatifloxacin, for treatment of the wound infection, had been initiated 5 days before symptom onset and then continued for 5 more days, for a total 10-day course. Other medications included zolpidem tartrate 10 mg before bedtime (hs), lansoprazole 30 mg twice daily (bid), subcutaneous enoxaparin sodium 30 mg twice daily (bid), and a fentanyl patch 50 mcg/hour every 72 hours.
Discussion
SS is a serious, potentially life-threatening condition resulting from hyperstimulation of 5-hydroxytriptamine (5-HT) receptors. The diagnosis is based on Sternbach’s criteria.1 Three of the following must be satisfied: mental status changes, agitation, myoclonus, hyperreflexia, diaphoresis, shivering, tremor, diarrhea, incoordination, or fever. Symptoms coincide with initiation of, addition of, or increase in dosage of a serotomimetic agent. Other etiologies are excluded. Finally, a neuroleptic agent should not have been initiated or increased in dosage before onset of signs and symptoms.1,2
Ms. C was on citalopram for 9 months, with a dose increase 5 weeks before symptom onset. Her symptoms began within 24 hours of meperidine administration, and she was confused, agitated, febrile, hypertensive, tachycardic, and tachypneic. These symptoms resolved 12 hours after meperidine was discontinued.
A careful MEDLINE search, using keywords, "serotonin syndrome," "citalopram," "meperidine," and "SSRI" found no reported cases of SS with citalopram and meperidine together. The literature did reveal reports with citalopram and other serotonergic agents,3 and serotonergic agents and meperidine,4 as well as meperidine and monoamine oxidase inhibitors.5 There was one case with fluoxetine and meperidine.6 Evidence suggests that fentanyl may possibly block serotonin reuptake.4,7 The patient’s other medications have negligible affinity for the 5-HT receptor.7
Potential dangers, including SS, may occur when medically ill patients are prescribed serotonergic agents. Sometimes, medications like meperidine are not immediately identified as serotonergic, and are added to a patient’s regimen. There currently is no contraindication to their coadministration, and prescribers may not receive warnings about their simultaneous use. Because of their overall safety compared with older antidepressants, clinicians may underestimate the potential for SSRIs and newer serotonergic medications to cause serious morbidity. Serotonergic agents should only be used with meperidine-type analgesics when the benefits to the patient’s health outweigh the potential consequences.
REFERENCES
- Sternbach H: The serotonin syndrome. Am J Psychiatry 1991; 148:705–713[Abstract/Free Full Text]
- Boyer EW, Shannon M: The serotonin syndrome. N Engl J Med 2005; 352:1112–1120[Free Full Text]
- Mahlberg R, Kunz D, Sasse J, et al: Serotonin syndrome with tramadol and citalopram. Am J Psychiatry 2004; 161:1129[Free Full Text]
- Giese SY: Serotonin syndrome: potential consequences of Meridia combined with Demerol or fentanyl. Plast Reconstr Surg 2001; 107:293–294[Medline]
- Latta KS, Ginsberg B, Barkin RL: Meperidine: a critical review. Am J Therapeut 2002; 9:53–68[CrossRef][Medline]
- Tissot TA: Probable meperidine-induced serotonin syndrome in a patient with a history of fluoxetine use. Anesthesiology. 2003; 98:1511-1512
- Baldessarini RJ: Drugs and the treatment of psychiatric disorders: depression and anxiety disorders, in Goodman and Gilman’s The Pharmacological Basis of Therapeutics, 10th Ed. Edited by Hardman JG, Limbird LE. New York, McGraw-Hill, 2001, pp 456-460
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