Sunday, 21 October 2012

Intrathecal Baclofen inhibits Spasticity

Health Quality Ontario. Intrathecal baclofen pump for spasticity: an evidence-based analysis. Ont Health Technol Assess Ser. 2005;5(7):1-93. Epub 2005 May 1.

OBJECTIVE: To conduct an evidence-based analysis of the effectiveness and cost-effectiveness of intrathecal baclofen for spasticity.

THE TECHNOLOGY: Spasticity is a motor disorder characterized by tight or stiff muscles that may interfere with voluntary muscle movements and is a problem for many patients with multiple sclerosis (MS), spinal cord injury (SCI), cerebral palsy (CP), and acquired brain injury (ABI).(1). Increased tone and spasm reduces mobility and independence, and interferes with activities of daily living, continence and sleep patterns. Spasticity may also be associated with significant pain or discomfort (e.g., due to poor fit in braces, footwear, or wheelchairs), skin breakdown, contractures, sleep disorders and difficulty in transfer. Goals of treatment are to decrease spasticity in order to improve range of motion, facilitate movement, reduce energy expenditure and reduce risk of contractures. Existing treatments include physical therapy, oral medications, injections of phenol or botulinum toxin, or surgical intervention. Baclofen is the oral drug most frequently prescribed for spasticity in cases of SCI and MS.(1) Baclofen is a muscle relaxant and antispasticity drug. In the brain, baclofen delivered orally has some supraspinal activity that may contribute to clinical side effects. The main adverse effects of oral baclofen include sedation, excessive weakness, dizziness, mental confusion, and somnolence.(2) The incidence of adverse effects is reported to range from 10% to 75%.(2) Ochs et al. estimated that approximately 25-30% of SCI and MS patients fail to respond to oral baclofen.(3;4) Adverse effects appear to be dose-related and may be minimized by initiating treatment at a low dose and gradually titrating upwards.(2) Adverse effects usually appear at doses >60 mg/day.(2) The rate of treatment discontinuation due to intolerable adverse effects has generally been reported to range from 4% to 27%.(2) When baclofen is administered orally, only a small portion of the original dose crosses the blood brain barrier and enters the central nervous system (CNS) fluid, which is the site of drug action. In order to bypass the oral route, baclofen may be administered intrathecally by infusion directly to the CNS. Candidates for intrathecal baclofen infusion are patients with spasticity who have intractable spasticity uncontrolled by drug therapy, or who experience intolerable side effects from oral baclofen. Advantages of intrathecal baclofen infusion are: Direct drug administration to the cerebrospinal fluid (CSF)The central side effects of oral baclofen, such as drowsiness or confusion, appear to be minimized with intrathecal administration.The intrathecal delivery of baclofen concentrates the drug in the CSF at higher levels than those attainable via the oral route.Intrathecal administration can use concentrations of baclofen of less than one hundredth of those used orally.(5) Adjustable/programmable continuous infusion makes it possible to finely titrate patients' doses and to vary the doses over the hours of the day. For example, the dose can be relatively low to give the patients the extensor tone needed for ambulation during the day and increased at night, thereby improving quality of sleep.Reversible (in contrast to surgery).A patient who is a candidate for intrathecal baclofen infusion must have no contraindications to the insertion of an intrathecal catheter (e.g., anticoagulant therapy, coagulopathy, local or systemic infection, anatomical abnormality of the spine).

REVIEW STRATEGY: The Medical Advisory Secretariat reviewed the literature to assess the effectiveness, safety, and cost-effectiveness of intrathecal baclofen to treat patients who have intractable spasticity uncontrolled by drug therapy, or who experience intolerable side effects to oral baclofen. The Medical Advisory Secretariat used its standard search strategy to retrieve international health technology assessments and English-language journal articles from selected databases.

SUMMARY OF FINDINGS: Level 2 evidence supports the effectiveness of intrathecal baclofen infusion for the short-term reduction of severe spasticity in patients who are unresponsive or cannot tolerate oral baclofen. Level 3 evidence supports the effectiveness of intrathecal baclofen for the long-term reduction of severe spasticity in patients who are unresponsive or cannot tolerate oral baclofen. Level 4 qualitative evidence demonstrates functional improvement for patients who are unresponsive or cannot tolerate oral baclofen. Intrathecal baclofen is cost-effective with costs which may or may not be avoided in the Ontario health system. True functional use remains to be determined.

Intrathecal pumps can make major improvements to spasticity. You can read the post.

CoI: MD founded and has shares in a University Spin-Out Company that is actively developing an alternative to baclofen. 


  1. This year marked the 50th anniversary of balofen. This drug, which was initially tested as an epilepsy treatment, remains the primary medicine for spasticity in MSers. It’s a horrible medicine that turns MSers into zombies. As it works on the brain’s GABA receptors, it evokes hardened sedentary side-effects that court cognitive impairment and lethargy. Even this paper is 7 years old, which makes me wonder why you featured it?

    It’s disappointing to realize that science has failed to offer any alternatives to such a blunt treatment. When it comes to inventing drugs that offer immediate measurable benefits then it seems neurology has failed, massively. When it comes to inventing expensive medicines whose benefits will only become apparent in 20 years, then it seems neurology is ace. I’ll argue that even those drugs are largely hopeless, the passage of time allowing for maximum profit to be generated by which time some other monetized product can be ushered in and the cycle starts over.

    1. You are correct, I did not notice the date. There much have been a glitch in the search Engine as it only surfaced a few days ago. Your comment reminded me to add a conflict of interest statement on this one. This has not been done.

      The problem with baclofen is the short duration of action and the intolerable side effects. This is because it blocks nerve action and causes the rag doll effect because it turns nerve function off. Spasticity is caused by too much stimulation of the muscles. The side effects are a problem especially when used as a pill, the intrathecal pump aims to treat spasticity in the spinal cord, whilst limiting entry into the brain, where zombieism occurs. If it works and the your spasticity specialists have got it fine tunes you can get activity and this may all other meds, which add to the zombieism to be withdrawn.

      It is wrong to say nothing has changed anti-symptom wise for example sativex has been licensed for treatment of spasticity in UK, PCT have yet to fund it because it is too expensive. In my opinion it also has side-effect potential because this is inherent in the biology of activity. Likewise Fampyra/Ampyra has come to improve walking and this will serve to wake pharma up that they can make money in this aim and could be just as lucrative as with the DMT and the trials only take a few weeks to do rather than a few years.

      Now look on clinical and you can see there is a study planned with
      a new anti-spastic drug called BGG492 (Selurampanel) NCT01649050, this blocks excitation of nerves, rather than stimulating inhibition of nerves as baclofen does. It would be interesting to know what Accorda the inventors of Ampryra have found when they tested the drug as an anti-spastic agent in spinal cord injury in phase III trials (NCT00041717)

      Now for CoI. I agree that there are problems with current anti-spastic agents and we have invented some that are as active as baclofen but without the side effects. Now for the shameful plug. Any investors want to invest or Pharma want to buy the University spin out with human studies planned for next year. Check out (

      However the blog is about research and this is a direct product of our research.

      Furthermore Team G have found a number of other avenues that will give an alternative to baclofen.

  2. Re - "... spin out with human studies planned for next year"

    How can I get on your planned trials next year for this anti-spastic drug?

    1. The trials will be phase I, which are safety trials and these are not typically undertaken in MSers. MSers will be required for phase II assuming everything is OK with the phase I. Recruitments depends on where the trials take placce, Prof G usually puts up details of what trials and the requirements for the studies done at Barts on the BLOG. This will be expanded no doubt to studies within University College London Partners. Symptom control studies are more likely to be with our friends at Queen Square, London. Also keep an eye of clinical trials. gov and the NMSS websites for trials in your country/area.

  3. Is there any research into treatments for spasticity that work locally like botox, but that might not be so limited in the amount you can use before they stop working (due to toxicity or antibodies? Some advantages would seem to be the lack of systemic effects and a steady dose over a long period of time. Or is there a reason that that approach isn't viable or is less desirable?

    1. Yes, Botox is licensed to treat focal spasticity and we use it a lot in MSers. Antibodies are a problem. You can't use it systemically as it is toxic.


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