Clinical meaning
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.