I have been on it for two weeks (10 mg twice a day) and I have had to take a laxative for the first time in a year. I also seem to have more spasticity and pressure pain. I wonder if I should increase the dose to see if it really works.
10 mg twice a day is not the highest dose. You can go up to 10 mg four times a day. 2 weeks is long enough for most of the side-effects to go away. What you may be experiencing are the actual effects of 4-AP and they may not always be beneficial.
I tried 4AP last year for four months. I ramped it to the maximum does. Mine was time released and ordered from Bellevue Pharmaceuticals. While taking it, I was able to contract my quads and hamstrings, something I could not do before taking 4AP. It also made me have to move my bowels more frequently. However, the movement in my legs was not enough to enable me any further independence. After much daily PT, including riding my Ergys Bike 2x weekly (I also hired a personal trainer three weeks before and during the four month application of 4AP), in the hopes that I could increase my abilities, I discontinued its use. The movement in my legs quickly disappeared after use. While taking 4AP, I noticed my body to be less spastic and feel at a "heightened sense" and it make me feel anxious. Since I cannot get myself onto the toilet, the additional bowel movements was constantly a concern to me and my spasms were minimal before taking 4AP-no medication needed for these before or after taking 4AP. So, in the end, I felt the cons outweighed the pros.
Dear Dr. Young,
There is this 7yo boy, C4 injured, no movement, but reflexes work and he feels pain in stomatch sometimes.
1. Does it indicate that axons are intact but remyelinated?
2. Do you suggest 4AP treatment for this boy? If not why not, if yes how he could do it, he does not get 4AP here from doctors.
1. Does it indicate that axons are intact but remyelinated?
I meant "demyelinated" sorry
Out of the third that can maybe benefit, is it usually complete/incomplete, higher level/lower level? --thanks
Bubo, there is very little experience with the use of 4-AP in children and I don't know enough to be able to recommend the treatment for children. It is difficult to predict how much function will return.
12many, the conventional wisdom regarding 4-AP is that people with incomplete injuries will benefit the most. However, I think that this is misleading to some extent. Most people with so-called "complete" spinal cord injury have axons that remain and are demyelinated at the injury site. What one should expect is that areas of poor sensation and weak motor control will improve and areas that have no sensation and no motor control would show little benefit. On the other hand, increased bowel movements and even bladder control may occur.
Just wanted to tell you about my experience with 4ap.
I am a C7 asia A complete with a posteriorly tethered spinal cord.
I have chronic pain in my right shoulder, arm and hand from things that come from the C8 region, the area of tethering.
I had been on 4ap for almost 2 years and I had noticed positive changes from the beginning when I was ramping up on the 4ap.
I didn't gain any skin sensation, but I did feel like I gained more internal sensation throughout my body as well as just having a sense that my entire body was just "there". The only real motor function that I gained was that I had felt that I gained more trunk control. It never decreased my spasticity, it only increased it. While I was ramping up on the drug when I reached my maximum dose, I seemed to peak for a short time and actually had some positional movement of my legs one day that for the most part, but not completely went away just as quickly as it came, apparently from my body adjusting to being on the drug. Recently I had been considering getting off of the drug for a couple of reasons. When I started taking 4ap it was in or soon to be in clinical trials and I thought that it would be approved for use. This would mean that there would be information available to doctors and patients on it's safety and dosing recommendations. Every time I went to the doctor or the hospital, they would ask me about the medications that I was taking. I would tell them that I was taking SR 4ap, that it was not approved and I had to get it from a compounding pharmacy. It was the same every time. Nobody cared and went about their business as usual. It was obvious that if they killed me due to a complication with 4ap, it was my problem and not theirs. The other problem that I had was that my pain in my right shoulder, arm and hand was getting worse and I thought that if I quit taking the 4ap it might get better.
The straw that broke the camels back was one night I accidently took an extra dose of 4ap.
I had taken 25mg at breakfast and then took another 25mg at supper, and then at bedtime I accidently grabbed the pills that were for breakfast time the following morning. So for the day I had a total of 75mg.
When I realized that I had overdosed on the drug, I also realized that if it was a problem there was nobody to help. My wife looked on the internet at some dosing information and we had decided that the amount I had taken probably wouldn't kill me , so I just stayed awake and monitored my own condition for several hours. The only negative symptom I noticed was that my spasticity was quite a bit more than normal. After that, I decided that I would go ahead and try getting off the 4ap.
The day following my last dose of 4ap, I peed like a doped race horse. I don't know where all that fluid came from. I also noticed that my trunk control was all but gone. I'm slumping like a sack of potatoes right now. The pain in my right shoulder, arm and hand did subside, but didn't go away. My nerve pain in my torso, pelvic region and legs has increased. My total body sensation has decreased. I'm just not very aware of my body even being there, other than just a burning abyss. 4ap never gave me bladder control, but I was doing pretty good at managing it. I have a tingling sensation in my back that I've always had whether I'm on 4ap or not that let's me know, go pee now or pee all over the place. While on the 4ap I knew when my body was going to dump fluid and when the sensation came on generally I wasn't surprised and many times would cath in advance just to avoid it happening in a inconvenient situation. It may work itself out, but right now there is no pattern to my bladder management. My back tingles and I run (roll).
Overall, I'm considering going back on the 4ap, but I sure wish that it would be FDA approved so there would be more information on this.
PC, thank you for your detailed and very insightful description of your experience with 4-AP. Let me comment briefly:
1. internal sensation. A number of people that I have talked to have described a similar improvement in "internal sensations".
2. SR compounding pharmacy formulation. I have heard of SR formulations from compounding pharmacies but, to my knowledge, none have been tested for pharmacokinetics (i.e. the time course of drug blood levels). The bioavailability of drug depends on the SR formulation and how it was made. I suspect that the formulation at 25 mg bid (twice a day) is probably not providing the optimal level of drug. For example, the Acorda Therapeutics SR formulation that was in clinical trial in spinal cord injury was 40 mg bid. The amount that you took 25 mg tid (3 times a day) was probably not an overdose and the side-effects that you experienced were correspondingly mild.
3. Getting off 4-AP. Your description of feeling like a "doped race horse" is a very apt one. In addition, when the drug has a significant effect on spasticity, most people find that going off 4-AP results in an increase in spasticity. It is one of the reasons why it is important to ramp down on the drug. I hope that you did.
4. Pain. In an early clinical trial of 4-AP, a number of patients reported that they had reduction of neuropathic pain when they were on 4-AP. This is probably the reason why your "nerve pain" in your torso, pelvic region, and legs increased when you went off the drug. Burning type pain is typical of neuropathic pain. However, the drug does increase sensitivity to noxious pain, actual pain sensations. I suspect that you probably had a mixture of both, i.e. your right shoulder, arm, and hand pain is a result of the tethering of your spinal cord, i.e. the pain is coming from actual pain sensations being generated from compression of your spinal roots.
Your example illustrates why it has been so difficult to design a clinical trial to show efficacy of 4-AP in spinal cord injury. Most of the effects that you describe are very difficult to measure. For example, we currently don't have any validated outcome measure for postural control or feeling like a "doped race horse". In the clinical trials, Acorda had a subject global outcome measure, i.e. a 10-point scale where people were asked to rate the drug or placebo treatment as being "terrible" to "delighted". A majority of the people, even when they don't show any specific improvement in spasticity (the primary outcome measure of the trial), motor strength, or sensory improvement gave the drug positive global outcome scores. People were also asked to indicate whether they would take the drug again. Significantly more people said that they would do so when they were on the drug than when they were on placebo.
After two weeks of 10 mg twice a day, I upped the dose to 30 mg and my symptoms got worse, so I stopped and I am already feeling more energetic this morning. 4 AP made me feel tired and a bit nauseated. It also made me constipated. I seemed to have more neuropathic pain and some spasticity which I didn't have before. However, I may not be the norm so I do not want to discourage others who may be tempted to try it. I have the same reaction to every pain killer I was prescribed during ,and after my surgery, and my avm is 1 % of 30 % of avms.
4AP did not increase sensations. I had hoped it would as I am experiencing returns in my foot and my therapist has noted a great improvement in my range of motion (ankle and quads) , since I have been riding my recumbent bicycle, but before I started taking 4 AP,. I had been encouraged to ride a bike after reading articles by other members on the site. My husband screwed a tennis shoe on the left pedal because my left foot was much weaker than the right one and kept slipping. Someone with less strength might want to do both feet. It has given me a sense of freedom. I am up to an hour a day! I find that it increases circulation in my legs and feet and I have increased sensations when I am done. I can feel the contact of the socks. I just don't know if this will be a permanent improvement.