Can trazodone be used to treat REM (Rapid Eye Movement) behavior disorder?

Trazodone for REM Behavior Disorder: Limited Evidence with Significant Safety Concerns

Trazodone is not recommended for treating REM behavior disorder based on current clinical practice guidelines, which instead recommend clonazepam or melatonin as first-line treatments. 1, 2

Guideline-Recommended Treatments for RBD

The American Academy of Sleep Medicine's 2023 clinical practice guideline does not include trazodone among recommended pharmacologic treatments for RBD. 1 The established first-line options are:

• Clonazepam (0.25-1.0 mg at bedtime) is conditionally recommended, effective in approximately 90% of cases by promoting GABAergic inhibition. 1, 2
• Immediate-release melatonin (3-15 mg at bedtime) is conditionally recommended, suppressing REM sleep motor tone and normalizing circadian features of REM sleep. 1, 2
• Pramipexole and rivastigmine may also be considered as conditional recommendations for isolated RBD. 1

The 2010 AASM Best Practice Guide similarly lists multiple medications with varying levels of evidence (clonazepam Level B, melatonin Level B, and various Level C options including zopiclone, desipramine, clozapine, carbamazepine, and sodium oxybate) but does not mention trazodone. 1

Safety Concerns with Trazodone in Older Adults

The AASM explicitly warns against trazodone use in older adults with sleep disturbances, noting significant risks including priapism, orthostatic hypotension, and cardiac arrhythmias, with virtually no evidence-based data supporting its efficacy in this population. 1 This is particularly concerning because:

• RBD predominantly affects older adults, with approximately 1 in 20 older individuals having the condition. 1
• Older adults are the primary demographic at risk for RBD and its associated neurodegenerative progression. 1
• The risks of falls from orthostatic hypotension and cardiac complications are especially dangerous in this vulnerable population. 1

Emerging Case Report Evidence

Despite guideline recommendations, a 2024 case series reported successful treatment of isolated RBD with trazodone in 3 patients who did not respond adequately to traditional treatments. 3 Key findings:

• Doses of 50-100 mg at bedtime over 4-6 months resulted in significant clinical improvement. 3
• The authors suggest trazodone could serve as an alternative when traditional treatments fail at submaximal dosages. 3

However, this represents only Level C evidence (case series with 3 patients), far below the evidence quality for guideline-recommended treatments. 3

Clinical Decision Algorithm

When managing RBD, follow this approach:

1. First-line therapy: Initiate clonazepam 0.25-1.0 mg at bedtime OR melatonin 3-15 mg at bedtime, based on patient comorbidities. 1, 2

   • Avoid clonazepam in patients with dementia, gait disorders, or obstructive sleep apnea. 1
   • Melatonin has fewer side effects and is safer in older adults. 1, 2

2. If inadequate response: Consider pramipexole or rivastigmine as alternative monotherapy, or combination therapy (clonazepam plus melatonin). 1, 2

3. Refractory cases: Only after exhausting guideline-recommended options at optimal doses should experimental treatments be considered, with careful risk-benefit assessment. 3

Critical Safety Priority

Environmental modifications are Level A recommendations and must be implemented regardless of pharmacotherapy choice. 1 This includes:

• Lowering the bed mattress to the floor. 1
• Padding furniture corners. 1
• Installing window protection. 1
• Removing loaded firearms, especially handguns, from the bedroom. 1
• Creating a barrier between patient and bed partner or separate sleeping arrangements. 1

These interventions directly reduce morbidity and mortality from dream enactment injuries, which is the primary outcome concern in RBD management. 1