From the Guidelines
Muscle relaxants that do not exhibit serotonergic activity include metaxalone, typically administered at 800 mg every 6-8 hours 1, and other alternatives such as tizanidine, baclofen, and dantrolene.
Key Characteristics of These Agents
- Metaxalone does not act directly on skeletal muscle and has a unclear mechanism of action, but is known to have multiple central nervous system adverse effects, including drowsiness, dizziness, and irritability 1
- Tizanidine, baclofen, and dantrolene also lack significant serotonergic effects, making them suitable options for patients requiring muscle relaxation without the risk of serotonergic-related adverse effects ### Important Considerations
- Cyclobenzaprine is not a suitable option as it has serotonergic activity, specifically acting as a 5-HT2 receptor antagonist 2
- Patients with significant hepatic or renal dysfunction should avoid metaxalone due to its contraindication in these conditions 1
From the Research
Muscle Relaxants without Serotonergic Activity
- Cyclobenzaprine is a muscle relaxant that does not have serotonergic activity 3, 4, 5
- It is effective in improving muscle spasm, reducing local pain and tenderness, and increasing range of motion in acute, painful musculoskeletal conditions 3
- Other muscle relaxants such as metaxalone, orphenadrine, and tizanidine may also not have serotonergic activity, but their efficacy and safety in pain management are not well established 6
- Benzodiazepines, such as diazepam and triazolam, have serotonergic activity and are not recommended for long-term use due to their potential for abuse and dependence 6
Comparison of Muscle Relaxants
- Cyclobenzaprine extended-release (CER) 30 mg once daily has a similar pharmacokinetic profile to cyclobenzaprine immediate-release (CIR) 10 mg three times daily 4, 5
- CER 30 mg has a controlled release of cyclobenzaprine, resulting in sustained plasma concentrations, whereas CIR 10 mg has a fluctuating profile with multiple peaks and troughs 4
- The efficacy and safety of muscle relaxants, including cyclobenzaprine, metaxalone, and orphenadrine, vary depending on the clinical indication and patient population 7