Mechanism | Agent involved |
Increases serotonin formation | Tryptophan, oxitriptan* |
Increases release of serotonin | Amphetamines (including dextroamphetamine, methamphetamine) |
MDMA (ecstasy) | |
Amphetamine derivatives (including fenfluramine, dexfenfluramine, phentermine) | |
Cocaine | |
Mirtazapine | |
Impairs serotonin reuptake from the synaptic cleft into the presynaptic neuron | Cocaine |
MDMA (ecstasy) | |
Meperidine | |
Tramadol | |
Pentazocine | |
Dextromethorphan | |
Selective serotonin reuptake inhibitors (SSRIs; citalopram, escitalopram, fluoxetine, fluvoxamine, paroxetine, and sertraline) | |
Serotonin-norepinephrine reuptake inhibitors (SNRIs; desvenlafaxine, duloxetine, levomilnacipran, milnacipran, and venlafaxine) | |
Sibutramine | |
Bupropion¶ | |
Serotonin modulators (nefazodone, trazodone, vilazodone, and vortioxetine) | |
Cyclic antidepressants (amitriptyline, amoxapine, clomipramine, desipramine, doxepin, imipramine, maprotiline, nortriptyline, protriptyline, trimipramine) | |
St. John's wort (Hypericum perforatum) | |
5-HT3 receptor antagonists (dolasetron, granisetron, ondansetron, palonosetron) | |
Cyclobenzaprine | |
Methylphenidate, dexmethylphenidate | |
Lamotrigine | |
Inhibits serotonin metabolism by inhibition of MAO | MAO inhibitors, nonselective (isocarboxazid, linezolid, phenelzine, Syrian rue [Peganum harmala, harmine], and tranylcypromine) |
MAO-A inhibitorsΔ (methylene blue, moclobemide) | |
MAO-B inhibitorsΔ (rasagiline, safinamide, and selegiline) | |
Direct serotonin receptor agonist | Buspirone |
Triptans (almotriptan, eletriptan, frovatriptan, naratriptan, rizatriptan, sumatriptan, zolmitriptan) | |
Ergot derivatives (including dihydroergotamine, ergotamine, methylergonovine) | |
Fentanyl | |
Lysergic acid diethylamide (LSD) | |
Lasmiditan | |
Lorcaserin◊ | |
Metaxalone | |
Increases sensitivity of postsynaptic serotonin receptor | Lithium |
CNS: central nervous system; MAO: monoamine oxidase; OTC: over-the-counter.
* Within the United States, tryptophan (L-tryptophan) and oxitriptan are available as OTC supplements. In other areas, these agents may be available OTC or by prescription.
¶ Bupropion inhibits neuronal uptake of dopamine and norepinephrine without known effects on serotonin; however, there have been case reports of serotonin syndrome when co-administered with other serotonergic drugs (eg, SSRIs); in some cases this may have been due to bupropion's inhibition of SSRI metabolism by CYP2D6.
Δ MAO selectivity is lost at higher doses and with drug interactions that increase serum drug concentrations. Inhibition of MAO-A is more likely to result in increased levels of serotonin within the CNS (ie, increased risk of serotonin syndrome) relative to MAO-B inhibition.
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