Baclofen was originally developed in the 1960s to treat epilepsy. It has a good effect on spastic seizures. Since 2009, it has also been used to combat alcohol addiction.
What is baclofen?
Baclofen was originally developed in the 1960s to treat epilepsy. Since 2009, it has also been used to combat alcohol addiction. Baclofen – chemically C10H12ClNO2 – belongs to the class of muscle relaxants. They relieve pathologically increased muscle tension. The active substance binds to the GABA-B receptors and acts there as an antagonist. In doing so, it takes advantage of the fact that it has a similar molecular structure to these proteins. Synthesized baclofen is an odorless, crystalline, white powder with very poor water solubility. The muscle relaxant can be manufactured in two ways and is available in the drugs Lioresal, Lebic, and several generics. For milder disease processes, it is administered orally in tablet form (10 mg or 25 mg). However, if severe multiple sclerosis is present, for example, the physician administers the drug into the spinal fluid (intrathecally). In children and adolescents under 18 years of age, it is administered orally only. Corresponding studies on intrathecal application in this patient group do not exist to date. This route of administration is also not used if the patient has impaired reflexes and slowed circulation of cerebrospinal fluid.
Pharmacologic action
Sustained transmission of nerve signals to other nerve cells and from there to muscle cells results in permanent muscle tension, which eventually leads to muscle spasm. One possible cause of this overuse of skeletal muscle is lack of signal control by the brain and/or spinal cord. Baclofen uses its chemical structure, which is similar to gamma-aminobutyric acid (GABA), by blocking the transmission of the nerve signal between the spinal cord nerve cells. This prevents them from reaching the muscle in the first place. Because of its muscle-decongestant effect, it also dampens brain activity. In patients taking baclofen, voluntary muscle activity is also impaired. Baclofen alters liver enzyme levels in the blood, so test results may be distorted. For this reason, the patient should be sure to inform the attending physician that he or she is being prescribed baclofen. If those affected by liver disease have to use the drug, their liver values must be checked regularly. Diabetics should have their blood sugar levels checked more frequently. Patients who must take preparations containing baclofen should refrain from driving and operating tools and machinery, because the active substance impairs reaction time.
Medical application and use
Baclofen has been shown to be markedly effective in treating individuals with multiple sclerosis, spinal cord injury, central nervous system disorders, polio (cerebral palsy), cerebrovascular disorders, and muscle spasms caused by faulty signal transmission from the spinal cord and/or brain. In multiple sclerosis patients suffering from severe painful spasms, the physician administers it intrathecally to avoid the severe side effects of oral administration: If taken orally, baclofen would have to be ingested in very high doses, otherwise the drug would arrive in too low a concentration where it is supposed to do its job. Multiple sclerosis patients are given a spinal catheter that has a computer-controlled pump, which is used to permanently deliver baclofen to the body at a much lower dosage than would be given orally. The pump depot can be refilled through the skin as needed. The drug targets spinal cord reflex arches by mimicking the anticonvulsant action of GABA receptors on Renshaw cells. If baclofen is administered orally, it becomes ineffective after 4 hours at the latest. The body excretes it largely unchanged in the urine. As a clinical study from the 1990s shows, in alcohol-dependent individuals who also suffer from depression and/or anxiety disorders, as an antagonist of the GABA receptors it apparently combats the craving so feared by substance-dependent individuals.It has the same high efficacy as diazepam, for example – but without having such damaging side effects. Further clinical studies and innovative imaging techniques support the efficacy of baclofen in alcohol-dependent patients. Unlike in France, where the drug has been approved for this use for several years, in Germany it can only be used for this purpose off-label. In animal studies, baclofen was also effective in treating depression and anxiety.
Risks and side effects
When taking baclofen, fatigue, drowsiness, lightheadedness, and nausea are very common. Depression, nightmares, and in elderly patients confusion, headache, tremor, unsteady gait, dizziness, sleep disturbances, blurred vision and other visual disturbances, decreased heart function, low blood pressure, vomiting, diarrhea, constipation, strong urination, skin rashes, muscle weakness, and sweating have been frequently observed. It should not be used in case of hypersensitivity to the active substance, severe kidney damage, Parkinson’s disease, brain disease caused by injury, and rheumatism. Baclofen should be administered to pregnant women only after a thorough risk-benefit assessment and only orally, as the active ingredient can pass into the placenta. It may also be present in breast milk of nursing mothers. Although no harm has yet occurred in infants from baclofen, the drug is best used in low doses, if at all. Baclofen medications are taken gradually before discontinuation to avoid adverse effects such as confusion, delusions, seizures, and impaired concentration. Baclofen potentiates the effects of antihypertensive agents, other muscle relaxants, psychotropic drugs, analgesics, and certain antidepressants. Delusions may occur with concomitant administration of dopamine-containing agents. To eliminate unpredictable risks, it should not be taken with alcohol under any circumstances.
