Should I add a selective serotonin reuptake inhibitor (SSRI) to clonazepam (Klonopin) in a patient with REM sleep behavior disorder (RBD)?

Management of REM Sleep Behavior Disorder (RBD) with Clonazepam: Should SSRIs be Added?

Melatonin should be considered as the first-line addition or alternative to clonazepam for RBD treatment rather than adding an SSRI, which may actually worsen RBD symptoms. 1, 2

Current Treatment Status and Considerations

Clonazepam as Primary Treatment

• Clonazepam (0.25-2.0 mg at bedtime) is a well-established treatment for RBD with significant efficacy in reducing dream enactment behaviors
• In one case series, clonazepam reduced sleep-related injury rates from 80.8% pre-treatment to 5.6% post-treatment 1
• Mechanism of action likely involves suppression of phasic locomotor activity at the brainstem level without restoring REM atonia 1

Concerns with Clonazepam

• Side effects include:
  • Morning sedation and motor incoordination
  • Cognitive impairment (particularly concerning in elderly patients)
  • Potential worsening of sleep apnea
  • Risk of falls, especially in those with subtle postural instability 1
• Up to 58% of patients may experience moderate to severe side effects, leading to discontinuation in some cases 1

Why SSRIs Should NOT Be Added

SSRIs May Worsen RBD

• SSRIs and other antidepressants are actually known to potentially induce or exacerbate RBD symptoms 2
• The American Academy of Sleep Medicine (AASM) recommends considering medications with lower risk of RBD exacerbation when antidepressant therapy is required 2

Better Alternative: Melatonin

• The AASM suggests immediate-release melatonin as either first-line treatment or as an add-on to clonazepam 1, 2
• Melatonin offers several advantages over SSRIs:
  • Demonstrated efficacy in reducing dream enactment behaviors
  • Safer profile with fewer adverse effects than clonazepam
  • Less impact on cognition, making it preferable for patients with cognitive impairment
  • Minimal drug-drug interactions 2
  • Effective in patients with RBD refractory to clonazepam 3

Treatment Algorithm for RBD Management

1. Optimize current clonazepam therapy:

   • Ensure proper dosing (0.25-2.0 mg at bedtime)
   • Evaluate for side effects and tolerability

2. Add or switch to melatonin:

   • Starting dose: 3 mg at bedtime
   • Titrate in 3 mg increments up to 15 mg as needed 1, 2
   • Consider as add-on therapy or replacement if clonazepam causes side effects

3. Consider underlying conditions:

   • If patient has comorbid depression, note that depression is associated with poorer treatment response to both clonazepam and melatonin (odds ratio=3.76) 4
   • For patients with cognitive impairment or Parkinson's disease, consider transdermal rivastigmine as an alternative 2

4. Implement safety measures (essential regardless of medication choice):

   • Remove potentially dangerous objects from bedroom
   • Pad sharp furniture corners
   • Place soft carpet/rug next to bed
   • Consider separate sleeping arrangements for severe cases 2

Monitoring and Follow-up

• Regular assessment of efficacy and side effects
• Monitor for emergence of neurodegenerative symptoms, as RBD often precedes synucleinopathies
• Evaluate for comorbid sleep disorders, particularly sleep apnea, which can be worsened by clonazepam 1

Important Caveats

• Recent critical reviews note that while observational studies show benefit with clonazepam (66.7% of 1,026 patients) and melatonin (32.9% of 137 patients), small randomized controlled trials have not consistently demonstrated superiority over placebo 5
• Long-term treatment (≥6 months) with melatonin appears necessary for sustained benefit 2
• If drug-induced RBD is suspected, consider discontinuation of the offending medication if possible 1

In conclusion, adding an SSRI to clonazepam for RBD treatment is not recommended and may worsen symptoms. Instead, adding or switching to melatonin offers a safer and potentially effective alternative with fewer side effects, particularly in elderly patients or those with cognitive impairment.