Nous rapportons le cas chez un patient de 66 ans, douloureux chronique car atteint d’un adénocarcinome prostatique métastasé aux os, de la survenue d’un syndrome sérotoninergique résultant de l’interaction entre les différents antalgiques opioïdes (oxycodone libération prolongée [LP] et spray de fentanyl) et l’introduction pour troubles de l’humeur de faibles doses d’escitalopram (5mg/jour). Les manifestations cliniques de cette entité rare, mais parfois aux conséquences redoutables, se traduisent habituellement par une altération de l’état mental avec des troubles cognitifs, la survenue de troubles neuromusculaires et un dysfonctionnement du système neurovégétatif. Sa physiopathologie est en rapport avec une hyperstimulation des récepteurs 5-HT_1A résultant, soit d’une monothérapie, soit de l’association de plusieurs agents pharmacologiques qui vont augmenter la transmission sérotoninergique au niveau cérébral. Les psychiatres devant un patient dépressif et algique dans un contexte de pathologies somatiques se doivent de rester vigilants sur les interactions médicamenteuses favorisant la survenue d’un syndrome sérotoninergique. Une meilleure information tant aux patients qu’aux autres intervenants (spécialistes d’organes, algologues, généralistes) pourrait permettre d’en réduire sa survenue.

We report a case of serotonin syndrome caused by interaction between nasal fentanyl, oxycodone and escitalopram. Due to chronic painful episodes with paroxistic level of pain, a 66-year-old patient, treated for prostate adenocarcinoma and bone metastases received an association of major opiate analgesics (oxycodone 120mg/day for 6 months and fentanyl nasal spray four puff of 200μg/puff). After the addition, for mood disorders, of a small dose of escitalopram (5mg/day), he developed severe serotoninergic features including diaphoresis, night sweating, tremor, diarrhea, visual disorders with mydriasis and weight loss of 8.8 lbs (4kg). Discontinuation of escitalopram resulted in complete resolution of his symptoms within 48h except for persistent blurred vision.

The clinical manifestations of this case meet Sternbach’s criteria of serotonin syndrome. Its possible etiologic factors include adverse drug reaction and pharmacodynamic interaction between selective serotonin reuptake inhibitor (SSRI) antidepressant and opioid analgesics. The Naranjo probability scale suggested a probable causality of escitalopram, oxycodone and fentanyl treatment on the serotonin syndrome. Serotonin syndrome occurrence is estimated around 0.04% in the literature with incidence rates between 14 to 16% in voluntary overdose with serotoninergic agents. It is an infrequent syndrome with, most of the time, a mild to moderate clinical expression. Nevertheless, lethal evolution might occur resulting from either monotherapy with serotoninergic agents (eg: SSRI antidepressants) or the combination of several medications that will increase serotoninergic transmission and therefore intra cerebral serotonin levels. Its physiopathology is related to a hyperstimulation of 5-HT_1A receptors. Its clinical manifestations involve mental status impairment and cognitive disorders, neuromuscular disorders and neurovegetative impairment. The prescription of SSRI antidepressants among patients depressed, and in pain, exhibiting somatic diseases, and who require regimens of major opiate or related analgesics, is not without risk.

Clinicians and especially psychiatrists should be aware of possible interaction and the risk of serotonin syndrome when a patient receives a combination of different opioid analgesics and serotonin reuptake inhibitor antidepressants. Improved information and collaboration with somatic and pain specialists and the general practitioners could help reduce the occurrence of this syndrome which can have dreadful consequences. Patients must be informed of such complications, which means that patients should be asked for a history of such events and monitored for serotoninergic adverse events, in order to avoid delays in this diagnosis.