An Unusual Case of Serotonin Syndrome with Oxycodone and Citalopram

Abstract

<jats:p>A 77-year-old female with recurrent non-small-cell lung cancer presented to a hospital outpatient clinic with tremor, weakness, inability to coordinate motor movements, and confusion. It was suspected that the symptoms were due to possible central nervous system metastases; however, a CT scan of her head was unremarkable. The lung clinic liaison pharmacist took a medication history from the patient, complimented by extra information from the patient’s community pharmacy. The pharmacist suspected the rare side effect of serotonin syndrome was responsible for the patient’s presenting symptoms caused by the combination of oxycodone and citalopram. The patient’s symptoms resolved soon after oxycodone was changed to morphine.</jats:p>

Impact of a specialist clinical cancer pharmacist at a multidisciplinary lung cancer clinic

“…The most comparable study was a survey of 405 solid tumor patients attending outpatient clinics at the Princess Margaret Hospital, Toronto, Canada, where 27% of the patients were exposed to potential drug interactions . Our study shows that drug interactions accounted for only 4.2% of all interventions; however, they were responsible for six of the seven interventions classified as “extreme risk.” The majority of identified drug interactions were clinically significant (including a previously published case report of drug‐induced serotonin syndrome) and required alteration of the patient's medications or additional follow‐up, such as further hospital appointments and/or laboratory tests.…”

Opioid‐induced inhibition of the human 5‐HT and noradrenaline transporters in vitro: link to clinical reports of serotonin syndrome

“…However, a more severe manifestation of 5‐HT toxicity is the potentially fatal serotonin syndrome, which includes a triad of effects: mental state changes (delirium, agitation, confusion and coma), autonomic stimulation (hyperthermia, tachycardia and diaphoresis) and neuromuscular excitation (tremor, hyperreflexia and rigidity; Gillman, ). The serotonin syndrome has been associated with several opioids or combinations of opioids with other serotonergic drugs in numerous case reports (Schwartz et al, ; Guo et al, ; Monte et al, ; Rastogi et al, ; Walter et al, ; Shakoor et al, ; Abadie et al, ). In a small analysis of pharmacovigilance data from a single country, tramadol was the opioid that was most frequently associated with the serotonin syndrome (Chassot et al, ).…”

Serotonin Syndrome Probably Triggered by a Morphine–Phenelzine Interaction

“…To our knowledge, only a handful of reports exist in the case of oxycodone and none in the case of morphine. Some authors have proposed alternative mechanisms to explain a hypothetical oxycodone‐triggered serotonin syndrome, such as the action of oxymorphone (a minor metabolite) on κ‐receptors (which ultimately led to a transient increase in serotonin levels), an oxycodone‐mediated increased in the concentration of drugs with known serotonin activity, or even an oxycodone‐mimicked serotonin syndrome . These explanations cannot be simply extrapolated to morphine because important pharmacodynamic and pharmacokinetic differences between both drugs exist.…”

“…There is, however, some theoretical basis to support a direct morphine‐mediated serotonin increase in animal models . In addition, chemically related opioids such as oxycodone, oxymorphone, buprenorphine, hydromorphone (a minor metabolite of morphine), and, to a lesser extent, codeine, were associated with previous reports of serotonin toxicity . The involvement of these morphine‐derived opioids (that share the same phenanthrene structure despite different affinities for opioid receptors) in the cases of serotonin syndrome argues in favor of a morphine‐mediated toxicity through an interaction with phenelzine.…”

“…Conversely, the evidence available in the case of nonserotonergic opiates, such as oxycodone or morphine, being associated with serotonin toxicity is at best heterogeneous, and alternative explanations have been suggested . To our knowledge, morphine has never been implicated in reports of serotonin toxicity.…”