Repurposing Valproate, Enteral Clonidine, and Phenobarbital for Comfort in Adult ICU Patients: A Literature Review with Practical Considerations

Pharmacotherapy. 2017 Oct;37(10):1309-1321. doi: 10.1002/phar.2017.


Provision of adequate sedation is a fundamental part of caring for critically ill patients. Propofol, dexmedetomidine, and benzodiazepines are the most commonly administered sedative medications for adult patients in the intensive care unit (ICU). These agents are limited by adverse effects, need for a monitored environment for safe administration, and lack of universal effectiveness. Increased interest has recently been expressed about repurposing older pharmacologic agents for patient comfort in the ICU. Valproate, enteral clonidine, and phenobarbital are three agents with increasing evidence supporting their use. Potential benefits associated with their utilization are cost minimization and safe administration after transition out of the ICU. This literature review describes the historical context, pharmacologic characteristics, supportive data, and practical considerations associated with the administration of these agents for comfort in critically ill adult patients.

Keywords: agitation; clonidine; critical care; delirium; divalproex; phenobarbital; sedation; valproate; valproic acid.

Publication types

  • Review

MeSH terms

  • Administration, Oral
  • Administration, Sublingual
  • Adult
  • Clonidine / administration & dosage
  • Clonidine / therapeutic use*
  • Critical Illness
  • Drug Repositioning*
  • Humans
  • Hypnotics and Sedatives / administration & dosage
  • Hypnotics and Sedatives / therapeutic use*
  • Intensive Care Units*
  • Patient Comfort
  • Phenobarbital / administration & dosage
  • Phenobarbital / therapeutic use*
  • Valproic Acid / administration & dosage
  • Valproic Acid / therapeutic use*


  • Hypnotics and Sedatives
  • Valproic Acid
  • Clonidine
  • Phenobarbital