Bob from Houston
This came from www.spinewire.com
For those of you that haven't visited this site, I suggest that you do and
bookmark/put it in your FAVORITES file and check with it often. Dr. Wise
Young has his own colume and has several articles. I believe that Sam Maddux
( Publisher of The Spinal Network, the most informative SCI book ever written
and the originator of New Mobility Magazine, which I believe he is no longer
affiliated with) is involved too! This looks to me like the best source for
current SCI information!!!
I only posted this one article because 4-AP is one of my interest and I try
to follow it like white on rice. There may be something on there for you and
it is updated frequently.
Karen Miner - Tallerance(AT)aol.com
May 1999
WiseWire
Research Q&A What About 4AP with Baclofen
Question:
I would like to know if taking the 4AP compound while taking baclofen for
spasticity could be harmful. Thank you.
Dr. Wise Young answers:
In most of the clinical trials of 4AP that have been carried out to date, the
subjects did not taper off baclofen and other medication when they took 4AP.
To my knowledge, there was no significant harmful effect of taking both
baclofen and 4AP at the same time in the clinical trials carried out to date.
To ensure no interaction, we should do a 4AP trial in patients that were
taking baclofen before the trial and randomized half to 4AP with no baclofen
and the other half to 4AP with baclofen. In theory, 4AP may antagonize
baclofen since the former is excitatory and the latter tends to be
depressive. At least one trial has reported that 4AP reduces spasticity,
although this needs to be confirmed. It is important to note that 4AP appears
to be reasonably safe in persons with spinal cord injury when limited to
certain dose ranges.
Early results from trials of 4AP to treat multiple sclerosis suggest that 4AP
may increased the likelihood of seizure activity. However, in over 300 people
with spinal cord injury that have received 4AP in clinical trials, none have
reported seizures associated with 4AP treatment. In summary, there is no
rigorous data concerning interaction of 4AP and baclofen, some data
indicating that there is no harmful interaction, and some theory but
insufficient data regarding whether baclofen antagonizes 4AP effects.
One of the difficulties of testing 4AP is the diverse effects it can have,
depending on whether and what spinal axons remain at the injury site, as well
as the state of their myelination. For some people, 4AP has dramatic effects,
including restoration of locomotion. For others, its effects may be limited
to the length of time that people can hold their urine and whether or not
they can initiate voluntary micturition.
For others, 4AP may reduce pain and spasticity. The effects are so diverse
that it has been very difficult to show statistically significant effects
based on clinical trial rules that the FDA imposes for proving therapeutic
effects. Until recently, the FDA required that all clinical trials must
select a specific primary outcome measure. However, in the last few years,
the FDA has begun to accept so-called "global outcome measures" where the
subject is asked to score the therapy on a scale from 0-10, without
specifying what the improvement must be. In several clinical trials now, 4AP
has improved the global outcome score but did not improve specific
neurologically defined outcome measures.
Some people are more sensitive to 4AP than others. For example, some people
find that 20 mg/day of 4AP significantly improves their function while others
may require 40-80 mg/day. This is also true of baclofen, where the effective
dose range can vary from 50-120 mg/day. The dose also depends on the severity
of injury and the symptoms.
Likewise, the side effects of 4AP are highly variable. Some people complain
of tingling in their lips at 30 mg/day while others find little or no
tingling even at 100 mg/day. Likewise, some people can tolerate 100 mg/day of
baclofen with little or no side-effects but others cannot. Thus, interactions
between 4AP and baclofen may be complex and variable from subject to subject.
Variable side effects are difficult to track down and require large-scale
clinical trials. Often these kinds of trials are carried out after the drug
has been shown to be efficacious and safe. After FDA approves the drug,
further clinical trials are often done to refine the dose and examine
interactions with other drugs. These so-called Phase 4 trials are very useful
for optimizing treatment protocols. For example, a trial can have all
patients receiving 4AP and then randomize half of them to baclofen therapy
and the other half to no baclofen therapy.
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--Wise Young, Ph.D., M.D., Professor II & Director W. M. Keck Center for Collaborative Neuroscience Rutgers, State University of New Jersey Nelson Biological Laboratories, 604 Allison Rd Piscataway, New Jersey 08854-8082 tel: 732/445-2061, fax: 732/445-2063