What is the strongest muscle relaxant?

From the Guidelines

The strongest muscle relaxant is tizanidine, which has been found to be efficacious for acute low back pain in 8 trials, although there is insufficient evidence to conclude that it is superior to others for benefits or harms 1. When considering muscle relaxants, it's essential to weigh the benefits and risks, as they are associated with a higher total number of adverse events and central nervous system adverse events compared to placebo 1. Some key points to consider when prescribing muscle relaxants include:

• Tizanidine is approved by the Food and Drug Administration for spasticity and has been found to be effective for acute low back pain 1.
• Cyclobenzaprine is another option, but the evidence for its use in chronic low back pain is limited and of lower quality 1.
• Baclofen and dantrolene are also available, but there is only sparse evidence for their use in low back pain, with only 2 trials evaluating their efficacy 1.
• The duration of therapy for muscle relaxants is typically 2 weeks or less, with the exception of a single 3-week trial 1.
• Common side effects of muscle relaxants include drowsiness, dizziness, and dry mouth, and they can be sedating and potentially addictive, so they should only be used under medical supervision and for short-term use (2-3 weeks) 1.

From the FDA Drug Label

Clinical Pharmacology Cyclobenzaprine HCl relieves skeletal muscle spasm of local origin without interfering with muscle function. Cyclobenzaprine reduced or abolished skeletal muscle hyperactivity in several animal models Evidence suggests that the net effect of cyclobenzaprine is a reduction of tonic somatic motor activity, influencing both gamma (γ) and alpha (α) motor systems

The FDA drug label does not answer the question.

From the Research

Muscle Relaxants

• The strongest muscle relaxant is a matter of debate, with various studies suggesting different options.
• According to a study published in 2003 2, cyclobenzaprine 5 mg TID was as effective as 10 mg TID, and was associated with a lower incidence of sedation.
• A review of three commonly prescribed skeletal muscle relaxants published in 2000 3 found that metaxalone, cyclobenzaprine, and carisoprodol have equal efficacy, but their side effects vary considerably.
• Another study published in 2022 4 found that cyclobenzaprine exhibits low nanomolar affinity for the cloned human H1R, and blocks histamine-mediated H1R functional activity in a noncompetitive manner.

Comparative Efficacy and Safety

• A systematic review published in 2004 5 found that cyclobenzaprine, carisoprodol, orphenadrine, and tizanidine are effective compared to placebo in patients with musculoskeletal conditions.
• The review also found that cyclobenzaprine has been evaluated in the most clinical trials and has consistently been found to be effective.
• A study published in 1978 6 found that cyclobenzaprine hydrochloride was effective in patients with long-term intractable pain of cervical and lumbar origin aggravated by skeletal muscle spasm and tenderness.

Side Effects and Safety

• The most common adverse events associated with cyclobenzaprine are somnolence and dry mouth, which are mild and dose-related 2.
• A review published in 2000 3 found that metaxalone has the fewest reports of side effects, and no reports of major safety issues.
• A study published in 2022 4 found that cyclobenzaprine's sedative effects are likely modulated by its off-target central antagonism of H1R.