REM Suppression Medications
REM suppression medications include clonazepam, melatonin, tricyclic antidepressants, SSRIs, and acetylcholinesterase inhibitors, with clonazepam and melatonin being the most recommended first-line treatments for REM sleep behavior disorder (RBD). 1
Primary REM Suppression Medications
Benzodiazepines
- Clonazepam (0.25-2.0 mg at bedtime): Most commonly prescribed medication for RBD, effective in approximately 90% of cases by promoting GABAergic inhibition through increased frequency of chloride channel opening 1
- Other benzodiazepines with limited evidence include temazepam, triazolam, and alprazolam 1
- Caution: Appears on the American Geriatrics Society Beers Criteria list of potentially inappropriate medications in older adults 1
Melatonin
- Immediate-release melatonin (3-15 mg at bedtime): Binds to M1 and M2 receptors, suppressing REM sleep motor tone and normalizing circadian features of REM sleep 1
- Benefits include fewer side effects than benzodiazepines and continued efficacy for several days after discontinuation 1
- Available over-the-counter in the US and Canada but requires prescription in the European Union and UK 1
Secondary REM Suppression Medications
Antidepressants
- Tricyclic antidepressants (e.g., amitriptyline, desipramine): Strongly suppress REM sleep 2
- SSRIs (e.g., paroxetine): May help treat cataplexy and REM sleep intrusion symptoms 1
- Venlafaxine: Used to treat cataplexy, hypnagogic hallucinations, and sleep paralysis 1
- Caution: Some antidepressants may paradoxically induce or worsen RBD symptoms 1, 3
Dopaminergic Agents
- Pramipexole (0.125-2.0 mg at bedtime): May reduce RBD symptoms, though efficacy studies show contradictory results 1
- Mechanism in RBD unclear as RBD is not caused by dopaminergic dysfunction 1
- Side effects include nausea, orthostasis, headache, daytime sleepiness, and impulse control disorders 1
Acetylcholinesterase Inhibitors
- Rivastigmine (4.6-13.3 mg daily via transdermal patch): Shown to decrease dream enactment in adults with mild cognitive impairment and treatment-resistant RBD 1
- Donepezil (10-15 mg): Limited evidence suggests efficacy in some cases of RBD 1
- Mechanism: Enhancing cholinergic effects by blocking enzymatic degradation of acetylcholine 1
Other Medications with Limited Evidence
- Zopiclone (3.75-7.5 mg): Limited evidence suggests efficacy in some RBD cases 1
- Carbamazepine (100-1500 mg daily): Sparse evidence of effectiveness 1
- Sodium oxybate: Limited case reports of efficacy 1
- Yi-Gan San (herbal medication, 2.5 g three times daily): Small case series showed efficacy in patients intolerant to clonazepam 1
Clinical Implications and Monitoring
Medication Selection Considerations
- For isolated RBD: Clonazepam or melatonin are first-line treatments 1
- For RBD with cognitive impairment: Consider acetylcholinesterase inhibitors 1
- For RBD with periodic limb movements: Pramipexole may be beneficial 1
Monitoring and Adjustments
- Patients may require dose adjustments over time due to age-related changes in drug metabolism or progression of neurologic disease 1
- Monitor for cognitive, motor, and autonomic deficits as patients with isolated RBD are at high risk for developing neurodegenerative disorders 1
- REM-suppressing medications should be discontinued prior to multiple sleep latency testing to avoid false negative results 4
Pitfalls and Caveats
- Some medications can both cause and treat RBD depending on dosage and individual factors 1
- REM suppression may impair hippocampus-dependent learning while enhancing striatum-dependent procedural learning 5
- Older adults may be more susceptible to side effects of benzodiazepines and require lower doses 1
- Combination therapy (e.g., clonazepam plus melatonin) is common in clinical practice for inadequate monotherapy response, though evidence for combinations is limited 1