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Published online by Cambridge University Press: 06 October 2020
THERAPEUTICS
Brands
• Xyrem
Generic?
• No (Available only through Xyrem Success Program)
Class
• Psychostimulant
Commonly Prescribed for
(FDA approved in bold)
• Cataplexy in narcolepsy
• Excessive daytime sleepiness (EDS) in narcolepsy
• Alcohol withdrawal
• Fibromyalgia
• Cluster headache
How the Drug Works
• Sodium oxybate, sodium 4-hydroxybutyrate, is the sodium salt of an endogenous cerebral neurotransmitter gamma-hydroxybutyric acid (GHB). It binds to GHB receptor (excitatory) and weakly to GABAB receptor (inhibitory). At high concentrations it inhibits noradrenergic, dopaminergic, serotonergic, and cholinergic neurons. At low concentrations it stimulates dopamine release. Its mechanism of action is mediated primarily through GABAB receptors. It increases slow wave activity during non-REM sleep. It simultaneously alleviates cataplexy, EDS and nocturnal sleep disruption, and consolidates wakefulness
How Long Until It Works
• 5–15 minutes
If It Works
• Continue to use at lowest effective dose. Monitor for risk of altered mental alertness, depression, confusion, and parasomnia
If It Doesn't Work
• Re-evaluate treatment of underlying cause of narcolepsy and cataplexy. Consider adding armodafinil or venlafaxine
Best Augmenting Combos for Partial Response or Treatment-Resistance
• May add armodafinil for excessive sleepiness. May add venlafaxine for cataplexy
Tests
• None required
ADVERSE EFFECTS (AEs)
How the Drug Causes AEs
• Unknown but most AEs are likely related to drug actions on CNS neurotransmitters
Notable AEs
• Nausea, dizziness, vomiting, somnolence, enuresis, confusion, tremor, parasomnia, weight loss, memory impairment
Life-Threatening or Dangerous AEs
• Concomitant use of CNS depressants may increase the risk of respiratory depression
• Suicidality
• Abuse potential (seizure, death)
• Central apnea
• Psychosis and hallucinations have been reported
Weight Gain
• Unusual
Sedation
• Common
What to Do About AEs
• Lower the dose
Best Augmenting Agents to Reduce AEs
• Most AEs do not respond to adding other medications
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