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