Table 3

Medications causing serotonin syndrome

MECHANISMDRUGS CAUSING SEROTONIN TOXICITY WITHOUT DRUG INTERACTIONDRUG COMBINATIONS CAUSING MODERATE TO SEVERE TOXICITY
Increased production of serotonin

  • L-tryptophan

  • L-tryptophan with MAOI

Increased serotonin release from neurons11

  • Amphetamines

  • NMDA

  • Amphetamines and MAOI

  • NMDA and MAOI

  • NMDA and SSRI (lower risk)

5-HT1A antagonism11

  • Buspirone

  • LSD

  • Paroxetine and buspirone

Decreased serotonin reuptake9,11–13,15

  • SSRIs

  • Venlafaxine

  • Clomipramine, imipramine

  • Tramadol, meperidine, methadone, fentanyl

  • Dextromethorphan

  • St John’s wort

  • Analgesics with MAOI or SSRI

  • Clomipramine with MAOI

  • SSRIs, venlafaxine with MAOI

  • SSRIs, venlafaxine, buproprion

MAO inhibition11,14

  • MAOIs

  • Selegiline

  • Linezolid

  • Moclobemide and SSRIs or venlafaxine

  • Irreversible MAOIs with all serotonergic drugs

  • Linezolid and SSRIs

Uncertain

  • Lithium9

  • 5-HT1a —serotonin 1A receptor, LSD—lysergic acid diethylamide, MAO— monoamine oxidase, MAOI—monoamine oxidase inhibitor, NMDA—N-methyl-D-aspartate, SSRI—selective serotonin reuptake inhibitor.