Is baclofen safe for long-term use compared to cyclobenzaprine or tizanidine (Zanaflex)?

From the Guidelines

Baclofen is generally considered safer for long-term use compared to cyclobenzaprine or tizanidine (Zanaflex) due to its established protocols for maintenance therapy and lower risk of tolerance development. When considering the safety of these medications for long-term use, it's essential to weigh the potential benefits against the risks of adverse events. According to a systematic review published in the Annals of Internal Medicine 1, skeletal muscle relaxants, including baclofen, have been found to be moderately superior to placebo for short-term pain relief in acute low back pain. However, the review notes that there is insufficient evidence to conclude that any specific muscle relaxant is superior to others for benefits or harms.

Some key points to consider when evaluating the safety of these medications for long-term use include:

• Baclofen has been used long-term for conditions like multiple sclerosis and spinal cord injuries, with established protocols for maintenance therapy and dosing ranges from 5-25 mg three times daily 1.
• Cyclobenzaprine is generally recommended for short-term use (2-3 weeks) due to anticholinergic side effects and sedation that can worsen with prolonged use 1.
• Tizanidine (Zanaflex) requires more liver monitoring requirements than baclofen and falls somewhere in between in terms of safety for long-term use 1.
• All three medications require careful discontinuation through gradual tapering to avoid withdrawal symptoms, particularly with baclofen where abrupt discontinuation can cause serious effects including seizures.

In terms of specific conditions being treated, individual response, and side effect profiles, the choice between these medications should be based on ongoing medical supervision and careful consideration of the potential risks and benefits. Overall, baclofen is a safer option for long-term use due to its established safety profile and lower risk of tolerance development.

From the FDA Drug Label

Cyclobenzaprine hydrochloride tablets should be used only for short periods (up to two or three weeks) because adequate evidence of effectiveness for more prolonged use is not available Clinical experience with long-term use of tizanidine at doses of 8 to 16 mg single doses or total daily doses of 24 to 36 mg (see DOSAGE AND ADMINISTRATION) is limited There is no information about baclofen in the provided drug labels. The FDA drug label does not answer the question.

From the Research

Safety of Baclofen for Long-Term Use

• Baclofen has been found to be a safe and effective agent in the management of spasticity, with beneficial effects persisting throughout the follow-up period 2.
• A study comparing intrathecal and oral baclofen found that long-term treatment with intrathecal baclofen is associated with reduced spasm frequency and severity, as well as greater dose stability, compared to oral baclofen 3.
• However, baclofen therapy is also associated with potential complications, including life-threatening toxicity and withdrawal syndrome, which can develop following administration of either oral or intrathecal baclofen 4.

Comparison with Cyclobenzaprine and Zanaflex

• A systematic review found that baclofen, tizanidine, and dantrolene are effective compared to placebo in patients with spasticity, and that baclofen and tizanidine are roughly equivalent for efficacy in patients with spasticity 5.
• The same review found that cyclobenzaprine, carisoprodol, orphenadrine, and tizanidine are effective compared to placebo in patients with musculoskeletal conditions, but that there is limited or inconsistent data regarding the effectiveness of metaxalone, methocarbamol, chlorzoxazone, baclofen, or dantrolene compared to placebo in patients with musculoskeletal conditions 5.
• A real-world cohort study found that baclofen is associated with a higher risk of fall compared to tizanidine, but a comparable risk of fall and fracture compared to cyclobenzaprine in older adults 6.

Key Findings

• Baclofen is a safe and effective agent for the management of spasticity, but may be associated with a higher risk of fall compared to some other muscle relaxants.
• The risk of fracture associated with baclofen is comparable to that of cyclobenzaprine and tizanidine.
• Baclofen therapy requires careful monitoring and management to minimize the risk of complications, including toxicity and withdrawal syndrome 4.