Overview
Clinical Meaning
Serotonin syndrome risk assessment requires understanding the multiple pharmacological mechanisms that increase serotonergic activity.
WHNP
WHNP
Serotonin syndrome risk assessment requires understanding the multiple pharmacological mechanisms that increase serotonergic activity. Drugs are categorized by mechanism: (1) Increased serotonin synthesis: L-tryptophan supplements. (2) Increased serotonin release: amphetamines, MDMA (ecstasy), mirtazapine, fenfluramine. (3) Decreased serotonin reuptake: SSRIs (fluoxetine, sertraline, paroxetine, citalopram, escitalopram), SNRIs (venlafaxine, duloxetine, desvenlafaxine), TCAs (clomipramine, imipramine), opioids (tramadol, meperidine, fentanyl, methadone), others (dextromethorphan, St. John's Wort, trazodone). (4) Decreased serotonin metabolism: MAOIs (phenelzine, tranylcypromine, selegiline, rasagiline), and drugs with MAOI activity (linezolid, methylene blue, procarbazine). (5) Direct receptor agonists: triptans (sumatriptan), buspirone, LSD, ergotamine. Risk is ADDITIVE — combining drugs from different mechanism categories is particularly dangerous. The risk hierarchy: MAOI + reuptake inhibitor > two reuptake inhibitors > reuptake inhibitor + releaser > reuptake inhibitor + direct agonist. The NP must screen all new prescriptions against the patient's current medication list for serotonergic interactions, including OTC drugs and supplements.
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