Is it safe to give a muscle relaxant, such as cyclobenzaprine (Flexeril), for neck pain with esketamine?

Muscle Relaxants with Esketamine: Safety Considerations

Caution is advised when combining muscle relaxants with esketamine due to potential additive central nervous system depression effects, and if necessary, cyclobenzaprine at a reduced dose (2.5-5mg) is preferred over benzodiazepines for neck pain. 1

Safety Concerns with Combination Therapy

Combining central nervous system (CNS) depressants presents significant risks:

• The combination of muscle relaxants and other CNS depressants can cause additive sedation, dizziness, and cognitive impairment 1
• Mortality rates are 3-10 times higher in patients co-prescribed opioids and benzodiazepines compared to opioids alone 2
• The FDA has added black box warnings to both opioids and benzodiazepines recommending against co-prescribing these agents 2

Specific Considerations for Esketamine

Esketamine has known CNS effects that may be potentiated by muscle relaxants:

• Common adverse effects of esketamine include dissociation (24.3%), dizziness (21.7%), and sedation 3
• These effects may be amplified when combined with muscle relaxants that also cause sedation

Recommended Approach for Neck Pain with Esketamine

If a muscle relaxant is deemed necessary for neck pain in a patient on esketamine:

1. First-line options:

   • Non-pharmacological approaches: physical therapy, heat therapy, and gentle stretching exercises 1
   • NSAIDs alone if not contraindicated 4

2. If muscle relaxant is necessary:

   • Cyclobenzaprine at reduced dosage (2.5-5mg TID) is preferred 5
     • 5mg TID is as effective as 10mg TID with fewer sedative effects 5
     • Consider starting at 2.5mg TID in patients on esketamine to minimize CNS effects

3. Avoid:

   • Benzodiazepines (e.g., diazepam) due to high risk of additive CNS depression 2
   • Carisoprodol due to concerns about dependence potential and higher toxicity 2, 6

Monitoring Recommendations

When combining esketamine with a muscle relaxant:

• Monitor closely for excessive sedation, dizziness, and cognitive impairment
• Consider administering the muscle relaxant at times distant from esketamine dosing
• Start with the lowest effective dose and titrate cautiously
• Educate the patient about potential additive effects and precautions (avoiding driving, etc.)

Duration of Therapy

• Limit muscle relaxant use to short-term therapy (7-14 days) 5
• Reassess frequently for continued need and adverse effects

Alternative Approaches

• Consider topical analgesics for localized neck pain
• Physical therapy and other non-pharmacological approaches should be emphasized
• If pain persists, consultation with pain management specialists may be warranted

The combination of muscle relaxants with esketamine requires careful consideration of risks versus benefits, with preference for non-pharmacological approaches or NSAIDs when possible, and using the lowest effective dose of cyclobenzaprine when a muscle relaxant is deemed necessary.