Monoamine oxidase inhibitors, opioid analgesics and serotonin toxicity

Abstract

Toxicity resulting from excessive intra-synaptic serotonin, historically referred to as serotonin syndrome, is now understood to be an intra-synaptic serotonin concentration-related phenomenon. Recent research more clearly delineates serotonin toxicity as a discreet toxidrome characterized by clonus, hyper-reflexia, hyperthermia and agitation. Serotonergic side-effects occur with serotonergic drugs, and overdoses of serotonin re-uptake inhibitors (SRIs) frequently produce marked serotonergic side-effects, and in 15% of cases, moderate serotonergic toxicity, but not to a severe degree, which produces hyperthermia and risk of death. It is only combinations of serotonergic drugs acting by different mechanisms that are capable of raising intra-synaptic serotonin to a level that is life threatening. The combination that most commonly does this is a monoamine oxidase inhibitor (MAOI) drug combined with any SRI. There are a number of lesser-known drugs that are MAOIs, such as linezolid and moclobemide; and some opioid analgesics have serotonergic activity. These properties when combined can precipitate life threatening serotonin toxicity. Possibly preventable deaths are still occurring. Knowledge of the properties of these drugs will therefore help to ensure that problems can be avoided in most clinical situations, and treated appropriately (with 5-HT(2A) antagonists for severe cases) if they occur. The phenylpiperidine series opioids, pethidine (meperidine), tramadol, methadone and dextromethorphan and propoxyphene, appear to be weak serotonin re-uptake inhibitors and have all been involved in serotonin toxicity reactions with MAOIs (including some fatalities). Morphine, codeine, oxycodone and buprenorphine are known not to be SRIs, and do not precipitate serotonin toxicity with MAOIs.

Toxicité sérotoninergique provoquée par une interaction entre le fentanyl et la paroxétine

“…11 The authors attributed these symptoms to opioid-induced rigidity due to their rapid reversibility with naloxone, but this may have been an atypical presentation of serotonin toxicity. 10 We believe that the case presented in our report is unique, by demonstrating definitive features of serotonin toxicity in the postoperative period following an interaction between an SSri (paroxetine) and perioperative fentanyl.…”

“…Serotonin toxicity, caused by pharmacological stimulation of serotonergic pathways, is thought to be dose-related. 10 The combination of SSris and fentanyl, administered for perioperative analgesia, has not previously been reported to precipitate serotonin toxicity. However, one case report has described postoperative muscular rigidity, hyper-reflexia, and inducible clonus, following intraoperative fentanyl (500 µg) with chronic exposure to venlafexine.…”

El síndrome serotoninérgico

“…Fármacos involucrados en el síndrome serotoninérgico según su mecanismo de serotonina y no han sido involucrados en el SS [25]. Esto hay que tomarlo con cierta prudencia, pues estos mismos autores indican que la oxicodona no inhibe la recaptura de serotonina y por tanto una interacción con ella es poco probable, pero otros han descrito lo que podría ser una interacción con oxicodona [26,27].…”

“…Se ha mencionado también que los antihistamínicos de primera generación tipo clorfeniramina y bromofeniramina pueden inhibir la recaptura de serotonina, por lo que hay que estar pendientes de las combinaciones de medicamentos que involucren estas sustancias [25,43]. …”

Êxtase (MDMA): efeitos farmacológicos e tóxicos, mecanismo de ação e abordagem clínica

“…O MDMA também está relacionado com o aparecimento da síndrome da serotonina, caracterizada por confusão, diaforese, diarréia e instabilidade cardiovascular, bem como aumento do tônus e rigidez muscular, tremores e mioclonia 68 . A excessiva contração muscular pode acarretar hipertermia, com uma taxa de mortalidade de 10% a 15% 69 .…”