A 19-year-old woman is brought to the emergency department by her roommate, who reports the patient is “not acting right.” She has a history of depression for which she is prescribed fluoxetine. Her friend reports that she was well and without complaints until a few hours prior to arrival when she took some ecstasy. Vital signs: temperature 105°F, heart rate 125/min, respiratory rate 20/min, blood pressure 140/80 mm Hg, and pulse oximetry of 99% on room air. Her physical examination is notable for diaphoresis, confusion, and disorientation. She also has lower extremity hypertonicity and clonus. Appropriate treatment includes administration of:
Dantrolene and benzodiazepines.
Cyproheptadine and benzodiazepines.
This is a classic presentation of serotonin syndrome. Serotonin syndrome is caused by an excess of serotonin in the central nervous system (CNS). The list of medications that increase serotonin is large. Selective serotonin reuptake inhibitors (SSRI) and methylenedioxymethamphetamine (MDMA, or Ecstasy) both work by increasing serotonin. Antidepressants such as monoamine oxidase inhibitors (MAOI) and tricyclic antidepressants (TCA), analgesics such as meperidine and fentanyl, serotonin 5-HT blockers (triptans), dextromethorphan, LSD, and lithium can also increase serum serotonin levels. The symptoms are a spectrum beginning with mild tremor and agitation, then increasing in severity to altered mentation, hypertonicity, and hyperthermia. Emergency department management begins with removal of all serotonergic agents and supportive care. There is no role for centrally acting antipyretics such as acetaminophen because the hyperthermia comes from increased muscular activity. Cyproheptadine (Periactin) is a serotonin antagonist and is used to counter the effects of serotonin. It can only be given orally and its efficacy has been questioned by some experts, but it remains the standard of care. Benzodiazepines should be used to decrease muscular tone and agitation. In severe cases, paralytics may be necessary to reduce muscle tone. Activated charcoal is contraindicated in patients with an altered mental status or those who are at risk for aspiration. Given orally, charcoal is very safe; however, when aspirated into the lungs, it can be lethal. Dantrolene is indicated for the treatment of malignant hyperthermia, which is a genetic disorder of calcium reuptake into the sarcoplasmic reticulum of the muscle cell. Dantrolene is a drug that blocks calcium release from the sarcoplasmic reticulum. It has not been proven to be beneficial in serotonin syndrome.