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Key Features

  • Potential food or drug interactions can occur during therapeutic use

  • Ingestion of tyramine-containing foods (eg, aged cheese and red wines) or any sympathomimetic drug may cause a severe hypertensive reaction

  • Severe or fatal hyperthermia (serotonin syndrome)

    • May occur when monoamine oxidase inhibitors (MAOIs) are given with serotonin-enhancing drugs (eg, meperidine, fluoxetine, paroxetine, fluvoxamine, venlafaxine, tryptophan, dextromethorphan, tramadol)

    • Can also occur with moclobemide (an MAOI not available in the United States) and linezolid, which has MAOI properties

    • Can also occur with selective serotonin reuptake inhibitors (SSRIs) in large doses or in combination with other SSRIs, even in the absence of an MAOI or meperidine

Clinical Findings

  • Acute overdose

    • Ataxia, excitement, hypertension, and tachycardia

    • Several hours later: hypotension, convulsions, and hyperthermia

  • Food or drug hypertensive reaction

    • Hypertension

    • Tachycardia

    • Headache

    • Possible intracranial hemorrhage

  • Serotonin syndrome

    • Fever

    • Agitation

    • Delirium

    • Diaphoresis

    • Hyperreflexia

    • Clonus (spontaneous, inducible, ocular)

    • Hyperthermia (can be life-threatening)

Diagnosis

  • Serum drug levels are not available nor useful

  • Generally not detected on urine toxicology screens

Treatment

  • Acute overdose

    • Administer activated charcoal, 60–100 g orally or via gastric tube, mixed in aqueous slurry if ingestion is within 1

    • Treat hypotension with fluids and positioning, but avoid use of pressor agents if possible

    • Treat severe hypertension with nitroprusside, phentolamine, or other rapid-acting vasodilators

  • Serotonin syndrome

    • Cyproheptadine, 4 mg orally (or by gastric tube) every hour for three or four doses, or chlorpromazine 25 mg intravenously, can be effective

  • Observe patients for at least 24 h because hyperthermia may be delayed (see Hyperthermia)

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