Cause
A large number of medications either alone in high dose or in combination can produce serotonin syndrome.
| Class | Drugs |
|---|---|
| Antidepressants | Monoamine oxidase inhibitors (MAOIs), TCAs, SSRIs, SNRIs, bupropion, nefazodone, trazodone mirtazapine |
| Opioids | tramadol, pethidine, fentanyl, pentazocine, buprenorphine oxycodone, hydrocodone |
| CNS stimulants | MDMA, MDA, phentermine, diethylpropion, amphetamine, sibutramine, methylphenidate, methamphetamine, cocaine dextromethorphan |
| 5-HT1 agonists | triptans |
| Psychedelics | 5-Methoxy-diisopropyltryptamine, LSD |
| Herbs | St John's Wort, Syrian rue, Panax ginseng, Nutmeg, Yohimbe |
| Others | tryptophan, L-Dopa, valproate, buspirone, lithium, linezolid, dextromethorphan, 5-hydroxytryptophan, chlorpheniramine, risperidone, olanzapine, ondansetron, granisetron, metoclopramide, ritonavir |
Many cases of serotonin toxicity occur in patients who have ingested drug combinations that synergistically increase synaptic serotonin. It may also occur in patients following an overdose of a single serotonergic agent. The combination of MAOIs and other serotonin agonists or precursors pose a particularly severe risk of a life-threatening serotonin syndrome. Many MAOIs inhibit monoamine oxidase irreversibly, so that the enzyme cannot function until it has been replaced by the body, which can take at least four weeks.
Many medications may have been incorrectly thought to cause serotonin syndrome. For example, some case reports have implicated atypical antipsychotics in serotonin syndrome, but it appears based on their pharmacology that they are unlikely to cause the syndrome. It has also been suggested that mirtazapine has no significant serotonergic effects, and is therefore not a dual action drug. Bupropion has also been suggested to cause serotonin syndrome, although as there is no evidence that it has any significant serotonergic activity, it is thought unlikely to produce the syndrome. In 2006 the United States Food and Drug Administration issued an alert suggesting that the combined use of SSRIs or SNRIs and triptan medications or sibutramine could potentially lead to severe cases of serotonin syndrome. This has been disputed by other researchers as none of the cases reported by the FDA met the Hunter criteria for serotonin syndrome. The condition has however occurred in surprising clinical situations, and because of phenotypic variations among individuals, it has been associated with unexpected drugs, including mirtazapine.
The relative risk and severity of serotonergic side effects and serotonin toxicity, with individual drugs and combinations, is complex. Serotonin syndrome has been reported in patients of all ages, including the elderly, children, and even newborn infants due to in utero exposure. The serotonergic toxicity of SSRIs increases with dose, but even in over-dose it is insufficient to cause fatalities from serotonin syndrome in healthy adults. Elevations of central nervous system serotonin will typically only reach potentially fatal levels when drugs with different mechanisms of action are mixed together. Various drugs, other than SSRIs, also have clinically significant potency as serotonin reuptake inhibitors, (e.g. tramadol, amphetamine, and MDMA) and are associated with severe cases of the syndrome.
Read more about this topic: Serotonin Syndrome