Oral Baclofen Effective Only for Multiple Sclerosis

Baclofen is a muscle relaxant approved for the treatment of reversible muscle spasms in patients with multiple sclerosis and for the treatment of patients with spinal cord injuries or other spinal cord diseases.[1] It was first approved by the Food and Drug Administration in 1977.[2] Only generic forms of oral baclofen are marketed in the U.S. How baclofen relaxes muscles is not known.[3]

Public Citizen’s Health Research Group has designated baclofen as a Limited Use drug. Although it is safe and effective for the treatment of multiple sclerosis, its effectiveness for the treatment of patients with spasticity due to spinal cord injury or other spinal cord diseases has not been demonstrated adequately.

Multiple sclerosis and spinal cord dysfunction

Multiple sclerosis is a potentially debilitating disease of the central nervous system (brain and spinal cord) that is characterized by damage, which is often progressive, to the protective sheathes that surround nerve fibers.[4] This damage leads to disrupted communication between nerves in the brain and spinal cord.

Multiple sclerosis can cause an array of symptoms, including weakness, numbness, vision problems, difficulty walking or loss of control of various bodily functions, such as bladder and bowel control. Another common symptom that can develop over time in multiple sclerosis patients is involuntary muscle spasms (also known as spasticity).[5]

In addition, spinal cord injuries and certain other conditions that damage the spinal cord often are eventually associated with muscle spasticity.[6]

Evidence of effectiveness of baclofen

A 2003 study analyzed all randomized controlled trials (of at least seven days in duration) of baclofen in subjects with a diagnosis of multiple sclerosis.[7] The review found that, compared with placebo, baclofen significantly improved subjects’ spasticity on a range of measures: increased ability to flex their muscles, improved muscle tone, reduction in painful spasms and general improvement in perceived functioning. When combined with exercise, baclofen also significantly improved muscle tone, as measured by a standardized scale.

A more recent randomized trial that compared baclofen use to treatment with low-voltage electrical stimulation via electrodes placed on the skin (a treatment know as transcutaneous electrical nerve stimulation or TENS) found that both baclofen and TENS significantly improved muscle tone in multiple sclerosis patients after four weeks of treatment, with the greatest improvement occurring in the TENS group.[8]

By contrast, there is no good evidence that baclofen is effective for treating spinal cord injuries. A study initially conducted in 2000 and later updated in 2009 analyzed all randomized controlled trials of baclofen (and other drugs) in subjects with spinal cord injury who reported severe spasticity.[9] The review found that, for oral baclofen and a number of other drugs, “the results did not provide evidence for clinically significant effectiveness.” Even baclofen administered directly into the fluid surrounding the spinal cord had minimal evidence to demonstrate its effectiveness in such patients — just two studies comprising 14 total subjects have been conducted with this formulation of baclofen for spinal cord injury.

Risks of baclofen

There is a risk of hallucinations and seizures when patients stop taking baclofen suddenly rather than gradually tapering down the dose.[10] Because the concentration of baclofen in the blood may increase to dangerous levels in patients with impaired kidney function, the drug may need to be given at reduced doses in such patients. Baclofen also is poorly tolerated in, and does not seem to benefit, patients who have had a stroke.

Baclofen is a sedating drug. In one controlled study of 175 subjects, temporary drowsiness was found to have occurred in 63 percent of subjects receiving baclofen compared with 36 percent of subjects given a placebo. Therefore, the label warns patients not to drive a car, operate dangerous machinery or engage in other activities that would be hazardous with decreased alertness while taking this drug. The risk of sedation is increased if baclofen is taken with alcohol or drugs known to reduce alertness, such as benzodiazepines (for example, diazepam [VALIUM]).

Patients with multiple sclerosis who rely on muscle spasms to maintain upright posture and balance while moving also should use baclofen with caution because the drug may increase the risk of falling in such cases. There have been occasional reports of an increased risk of seizures in patients with epilepsy while they were taking baclofen.

Other adverse reactions that commonly occur in patients taking baclofen include dizziness, weakness, fatigue, confusion, headache, insomnia, nausea, constipation and frequent urination.

Because of animal studies showing fetal damage with high doses of baclofen (no human studies of baclofen in pregnant women have been conducted), the drug’s label warns that baclofen should be used during pregnancy only if the benefits clearly outweigh any potential risk to the fetus. In addition, because it is not known whether baclofen is excreted in breast milk, mothers should refrain from breastfeeding while taking baclofen.

What You Can Do

For muscle spasticity of any cause, it is important to have a comprehensive treatment program that addresses the spasticity and quality of life. A 2013 study analyzed all randomized controlled trials of non-drug treatments for spasticity in multiple sclerosis patients. The studies overall were very small and of short duration but suggested that two weeks of physical therapy and exercise therapy led to significant improvements in spasticity.[11] For patients with spinal cord injury-related spasticity, there is no evidence that such interventions are beneficial.[12]

If your muscle stiffness is due to multiple sclerosis and your health care provider believes that you need drug therapy, then baclofen is a relatively safe and effective option. The label notes, however, that if benefits are not apparent after a reasonable trial period, baclofen should be slowly withdrawn.

If you have spinal cord injury and suffer from long-term muscle stiffness, you should not use baclofen. Instead, you should consult with your doctor to discuss a comprehensive treatment plan that might include physical therapy, exercise or other drug treatments.

References

[1] Upsher-Smith Laboratories. Label: baclofen. January 2018. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=29af8fe6-66ca-4575-b0ef-cd3a63d80924. Accessed March 12, 2018.

[2] Food and Drug Administration. Drugs@FDA. Baclofen (LIORESAL). https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&ApplNo=017851. Accessed March 12, 2018.

[3] Upsher-Smith Laboratories. Label: baclofen. January 2018. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=29af8fe6-66ca-4575-b0ef-cd3a63d80924. Accessed March 12, 2018.

[4] Mayo Clinic. Multiple Sclerosis: Symptoms and causes. https://www.mayoclinic.org/diseases-conditions/multiple-sclerosis/symptoms-causes/syc-20350269. Accessed March 12, 2018. National Multiple Sclerosis Society. Spasticity. https://www.nationalmssociety.org/Symptoms-Diagnosis/MS-Symptoms/Spasticity. Accessed March 12, 2018.

[5] National Multiple Sclerosis Society. Spasticity. https://www.nationalmssociety.org/Symptoms-Diagnosis/MS-Symptoms/Spasticity. Accessed March 12, 2018.

[6] Elbasiouny SM, Moroz D, Bakr MM, Mushahwar VK. Management of spasticity after spinal cord injury: Current techniques and future directions. Neurorehabil Neural Repair. 2010;24(1):23-33.

[7] Shakespeare DT, Boggild M, Young C. Anti-spasticity agents for multiple sclerosis. Cochrane Database Syst Rev. 2003;Issue 4: Art. No. CD001332.

[8] Shaygannejad V, Janghorbani M, Vaezi A, et al. Comparison of the effect of baclofen and transcutaneous electrical nerve stimulation for the treatment of spasticity in multiple sclerosis. Neurol Res. 2013;35(6):636-641.

[9] Taricco M, Adone R, Pagliacci C, Telaro E. Pharmacological interventions for spasticity following spinal cord injury. Cochrane Database Syst Rev. 2000;Issue 2:Art. No. CD001131.

[10] Upsher-Smith Laboratories. Label: baclofen. January 2018. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=29af8fe6-66ca-4575-b0ef-cd3a63d80924. Accessed March 12, 2018.

[11] Amatya B, Khan F, La Mantia L, et al. Non pharmacological interventions for spasticity in multiple sclerosis. Cochrane Database Syst Rev. 2013;Issue 2:Art. No. CD009974.

[12] Khan F, Amatya B, Bensmail D, Yelnik A. Non-pharmacological interventions for spasticity in adults: An overview of systematic reviews. Ann Phys Rehabil Med. 2017. pii: S1877-0657(17)30415-3. doi: 10.1016/j.rehab.2017.10.001. [Epub ahead of print]. PDF p. 5-7