Serotonin Syndrome Following Combined Administration of Dopaminergic and Noradrenergic Agents in a Patient With Akinetic Mutism After Frontal Intracerebral Hemorrhage: A Case Report

Clin Neuropharmacol. 2017 Jul/Aug;40(4):180-182. doi: 10.1097/WNF.0000000000000220.

Abstract

Background: Serotonin syndrome (SS) is a potentially life-threatening condition that can be caused by use of proserotonergic drugs. Several studies have reported that combined administration of various medications may induce SS. We report a case of SS in a patient who was being treated with dopaminergic and noradrenergic drugs.

Case presentation: A 55-year-old man with a right frontal intracerebral hemorrhage extending to the left cerebral hemisphere presented with clinical features of akinetic mutism. Three months after onset, dopaminergic (methylphenidate, levodopa/benserazide) and noradrenergic (atomoxetine) drugs were administered to enhance his cognitive function. His cognitive function gradually improved during 8 weeks of dose escalation. One day after the dose of atomoxetine was increased from 40 mg/d to 60 mg/d, the patient developed inducible clonus, rigidity, diarrhea, tachycardia, and hyperthermia, in keeping with a diagnosis of SS. The symptoms and signs suggestive of SS resolved on the day following cessation of all dopaminergic and noradrenergic drugs.

Conclusions: This case demonstrates that medications generally known as dopaminergic or noradrenergic agents could have serotonergic effects via a mechanism that is yet to be fully elucidated. The clinical manifestations of SS can be diverse, ranging from mild to severe and potentially fatal symptoms. When administering a combination of catecholaminergic agents, clinicians should carefully monitor the patient's neurologic status for unexpected adverse reactions.

Publication types

  • Case Reports

MeSH terms

  • Adrenergic Uptake Inhibitors / administration & dosage
  • Adrenergic Uptake Inhibitors / adverse effects*
  • Akinetic Mutism / diagnostic imaging*
  • Akinetic Mutism / drug therapy
  • Akinetic Mutism / etiology
  • Atomoxetine Hydrochloride / administration & dosage
  • Atomoxetine Hydrochloride / adverse effects
  • Benserazide / administration & dosage
  • Benserazide / adverse effects
  • Cerebral Hemorrhage / complications
  • Cerebral Hemorrhage / diagnostic imaging*
  • Cerebral Hemorrhage / drug therapy
  • Dopamine Agents / administration & dosage
  • Dopamine Agents / adverse effects
  • Dopamine Uptake Inhibitors / administration & dosage
  • Dopamine Uptake Inhibitors / adverse effects*
  • Drug Combinations
  • Drug Therapy, Combination
  • Humans
  • Levodopa / administration & dosage
  • Levodopa / adverse effects
  • Male
  • Methylphenidate / administration & dosage
  • Methylphenidate / adverse effects
  • Middle Aged
  • Serotonin Syndrome / chemically induced
  • Serotonin Syndrome / complications
  • Serotonin Syndrome / diagnostic imaging*

Substances

  • Adrenergic Uptake Inhibitors
  • Dopamine Agents
  • Dopamine Uptake Inhibitors
  • Drug Combinations
  • benserazide, levodopa drug combination
  • Methylphenidate
  • Levodopa
  • Atomoxetine Hydrochloride
  • Benserazide