THERAPEUTICS

Brands

• Rozerem

Generic?

• No

Class

• Melatonin receptor agonist

Commonly Prescribed for

(FDA approved in bold)

• Insomnia characterized by difficulties with sleep onset

• Adjunctive for bipolar disorder

• REM-associated sleep behavior disorder in patients with Parkinson's disease (PD)

• Prevention of delirium

How the Drug Works

• Selectively binds to melatonin receptors (MT1, MT2; similar affinity) in the suprachiasmatic nuclei (SCN). It increases the activity of MT1 receptors (inhibits arousal from SCN) for sleep onset and stimulates MT2 receptors (synchronizes the circadian clock to day–night cycle) for circadian phase shifting

• No affinity for GABA, dopamine, norepinephrine, acetylcholine, opiate receptors

How Long Until It Works

• Onset in less than an hour. Optimum improvement may take days

If It Works

• Continue to use at lowest required dose with appropriate monitoring

If It Doesn't Work

• Increase dose or combine with other antiinsomnia agents. Re-evaluate underlying conditions

Best Augmenting Combos for Partial Response or Treatment-Resistance

• Often depends on the comorbidity. For insomnia, may use low dose of antihistamine, TCAs, benzodiazepines, or antipsychotics

Tests

• Not available

ADVERSE EFFECTS (AEs)

How the Drug Causes AEs

• CNS depressant

Notable AEs

• Most common: dizziness, daytime somnolence, headache

• Uncommon: hallucination, abnormal thinking, behavioral change

Life-Threatening or Dangerous AEs

• Complex sleep behavior (e.g., sleep-driving)

• Worsening of depression/suicidal ideation

• Respiratory suppression (not fully studied)

Weight Gain

• Unusual

Sedation

• Problematic

What to Do About AEs

• Reduce dose or discontinue

Best Augmenting Agents to Reduce AEs

• Most AEs cannot be reduced by use of augmenting agent

DOSING AND USE

Usual Dosage Range

• 8mg

Dosage Forms

How to Dose

• Start with 8mg within 30 minutes of going to bed

Dosing Tips

• Do not take with high-fat meal, which delays its absorption

Overdose

• Dose-dependent increases in the frequency and duration of somnolence. No antidote available

Long-Term Use

• Safe for long-term use with appropriate monitoring