Serotonin Syndrome Probably Triggered by a Morphine–Phenelzine Interaction

Abstract

Serotonin syndrome is a potentially life-threatening condition caused by excessive central and peripheral stimulation of serotonin brainstem receptors, usually triggered by inadvertent interactions between agents with serotonergic activity. Evidence supporting an association between nonserotonergic opiates, such as oxycodone or morphine, and serotonin syndrome is very limited and even contradictory. In this case report, we describe a patient who developed serotonergic-adverse effects likely precipitated by an interaction between morphine and phenelzine. A 57-year-old woman presented to the emergency department with complaints of increasing visual hallucinations, restlessness, photophobia, dizziness, neck stiffness, occipital headache, confusion, sweating, tachycardia, and nausea over the previous week. On admission, her blood pressure was 185/65 mm Hg, and clonus was noted in the lower extremities. The patient was hospitalized 10 days earlier for cellulitis of the left breast secondary to a left mastectomy 5 months earlier, and a short course of oral morphine was prescribed for pain control. Her routine medications consisted of aspirin, atorvastatin, bisoprolol, clopidogrel, gabapentin, omeprazole, phenelzine, and ramipril. Supportive measures were initiated on admission. Phenelzine and morphine were discontinued immediately, leading to a progressive resolution of symptoms over the next 48 hours. Phenelzine was restarted on discharge without further complications. Use of the Drug Interaction Probability Scale indicated a probable relationship (score of 6) between the patient's development of serotonin syndrome and the combination of morphine and phenelzine. The mechanism underlying this interaction, however, remains unclear and warrants further investigation. Clinicians should carefully weigh the risk and benefits of initiating morphine in patients taking monoamine oxidase inhibitors or any other serotonin-enhancing drugs.

Neuroleptic malignant syndrome and serotonin syndrome: a comparative bibliometric analysis

“…Serious drug-drug interactions leading to NMS were mentioned in a limited number of articles and involved the administration of two dopamine antagonists [87] or two atypical antipsychotic drugs [88]. However, there were many articles discussing potential SS caused by drug-drug interactions, which included SSRI-methylene blue [89], SSRI-metoclopramide [89], sertraline-phenelzine [90], anti-depressants-opioids [91], citalopramfentanyl [92], a combination of two anti-depressants [93], SSRI-linezolid [94][95][96][97][98][99][100][101][102], sertraline-phenelzine [90], citalopram-buspirone [103], venlafaxine-tranylcypromine [104], and many others [92,[105][106][107][108][109].…”

The anaesthetist, opioid analgesic drugs, and serotonin toxicity: a mechanistic and clinical review

“…A likely case of ST involving morphine was reported in a 57-yrold patient with symptoms, including restlessness, hallucinations, confusion, sweating, nausea, high blood pressure, and clonus in the lower extremities. 122 Progressive resolution of symptoms occurred over 48 h after discontinuation of phenelzine, which was part of the patient's routine medications. ST has been reported after the co-administration of hydrocodone and escitalopram, 118 and a case of ST involving hydromorphone was recently diagnosed in an adult patient taking duloxetine and oxycodone.…”

A Metric Space Approach on the Molecular vs. Chemical Similarity of Some Analgesic and Euphoric Compounds

“…After a careful reading of the values listed in Table 4, where nicotine, caffeine and sucrose have been left out of the computations, one can easily see the proximity among morphine, codeine and heroine (S 10,2 = 0.87 and S 10,3 = 0.87). The matchings that are also of interest are these of morphine to serotonin S 10,7 = 0.80 and to adrenaline S 10,8 = 0.79, which have been studied in the frame of the opioids association with serotonin syndrome ( [68,69]). Speaking about serotonin its proximity to adrenaline (S 7,8 = 0.96) seems fair due to the fact that are both neurotransmitters that contribute to how exercise affects brain function [70].…”