“The present case highlights the marked improvement of FM symptoms in a patient who has been resistant to a wide variety of treatments for over seven years.“ Kararizou et. al. 2013
The Big Three (Lyrica, Cymbalta, Savella) Ghetto in Fibromyalgia
Finding a flexible, well-informed practitioner in critical in FM and ME/CFS
Don’t get stuck in a rut when your doctor only offers the three FDA-approved drugs to treat your FM (Lyrica, Cymbalta, and Savella). FDA-approval doesn’t mean ‘best in show’” Alan Spanos, M.D., Chapel Hill, NC From FMNETNews
The three drugs approved for fibromyalgia are a good thing, but doctors that focus entirely on them may be missing real opportunities. A case study of a fibromyalgia patient (with migraine) who responded spectacularly to a little-used drug demonstrates how important it is to stay informed, find a flexible doctor, and keep your options open.
A Case Study
A 41-year-old Greek woman with a history of severe headaches since she was 18 ends up in a neurologist’s office in Athens. She’s in trouble. She’s having about 10 (at 10 on a scale of 1 to 10 in severity) headaches a month. After giving birth seven years earlier she’d developed widespread pain, trouble sleeping, severe fatigue, and muscle stiffness. A psychiatrist was no help and several years later she was diagnosed with fibromyalgia.
All the treatments she’d tried (fluoxetine, venlafaxine, duloxetine, Lyrica, NSAIDs, physical therapy, exercise, and alternative medicine) bomb. By the time she reaches this neurologist’s office, she’s describing her symptoms as ‘devastating.’
The neurologist puts her on one medication, topiramate (25 mg once daily titrated up to 50 mg twice daily over the course of a month). Two months later her fibromyalgia pain has disappeared completely and her migraines are down to once every two months. Ten months later she remained symptom-free; her long ordeal with fibromyalgia and migraines appeared to be over.
Topamax (Topiramate)
Topiramate, an anticonvulsant, that reduces glutamate and increases GABA activity, may be underused in fibromyalgia
Topamax (topiramate), is an anticonvulsant that reduces brain activity. With brain scans showing enhanced activity in interoceptive and other brain regions that modulate pain in both fibromyalgia and chronic fatigue syndrome, the idea of reducing some brain activity makes sense. Anticonvulsants, of course, are nothing new to FM or ME/CFS, with Lyrica and gabapentin being used widely in both conditions, but Topamax is a bit different.
Topamax knocks down epileptic seizures by blocking sodium channels, by enhancing y-aminobutyric (GABA) receptor activity, and by antagonizing receptors for the main excitatory element in the central nervous system, glutamate. Check out Marco’s glutamate series in ME/CFS here and keep in mind a 2011 CDC study that implicated glutamate activity in ME/CFS. (Lyrica inhibits glutamate production in the brain but does not affect GABA functioning)
Topamax’s ability to enhance a inhibitory neurotransmitter (GABA) and reduce the main excitatory neurotransmitter (glutamate) indicates it works in multiple to reduce CNS activitation. It’s also able to reduce something called ‘cortical spreading depression’ some researchers think is present in both ME/CFS and FM.
A Migraine/Fibromyalgia/ME/CFS Connection Again
We recently reviewed a study that found high rates of migraine in chronic fatigue syndrome (ME/CFS). In fact, the authors reported so many similarities between migraine and ME/CFS, that they suggested ME/CFS might be a form of migraine (and vice versa). Some researchers believe fibromyalgia and migraine and other chronic pain disorders have similar roots.
FM, ME/CFS and migraine share many of the same symptoms, have a similar gender imbalance, often overlap, and display similar kinds of ‘hypersensitivity’ to pain, odors, light and/or other stimuli. Some migraine sufferers also experience unremitting ME/CFS-like fatigue that lasts much longer than their migraines.
Chronic fatigue syndrome is not often thought to be a ‘pain disorder,’ but pain issues such as allodynia and migraines, once thought to be associated with fibromyalgia, occur frequently in ME/CFS as well.
Now we have a case study, suggesting that an anti-migraine drug called Topamax (Topiramate) might be helpful, not just in migraine, but relieving the pain of fibromyalgia as well.
An Underused Drug?
Topamax is not commonly used in either fibromyalgia or chronic fatigue syndrome. PatientsLikeMe does not list it in the top 15 treatments for fibromyalgia. Compare the 1,000 plus evaluations of Lyrica and Cymbalta to the 37 at PatientsLikeMe. (I was unable to find the actual Topiramate rating page for fibromyalgia at PatientsLikeMe). No ratings for topiramate and fibromyalgia could be found at Curetogether.
It’s no surprise,therefore, to learn that no studies have examined the topiramate effectiveness in FM or ME/CFS. Seven of the 13 FM patients rating its effectiveness on Drugs.com, however, gave it a 9 or 10 out of 10. Several people reported the drug made them anxious and/or paranoid, but for others it was a godsend.
One woman on opioids for severe pain was able to get off them entirely by taking Topamax and Cymbalta. She reported that her pain was gone. Another saw her pain levels go from an unmanageable 7 or 8 to a very manageable 3 or 4. She also lost the weight she’d gained on Lyrica. (Weight loss is a common side effect.) Another called it a wonder drug. (Check out a discussion–Topamax as an alternative to Lyrica, here.)
Dr. Bateman calls Lyrica (and Neurontin) her two top choices for pain but brings Topamax into the discussion as well. (Dr. Klimas turns to low dose naltrexone first).
Dr. Bateman had this to say about Topamax ““Topamax (topiramate)…. must be dosed very carefully to avoid common debilitating side effects (e.g., fatigue, nausea, diarrhea, trouble concentrating). Start low (12.5 mg) and build very gradually (12.5 mg every one to two weeks), with the largest dose at night and little or none in the morning. Topamax may control the migraines, get your patient sleeping, and work as a mild pain modulator to minimize the FM during the day.”
Side Effects
Numbness or tingling, fatigue, weight loss (Dr. Bateman uses it as a weight-loss drug), and perhaps most troubling, more difficulty concentrating (eg… “Dopomax).
The Topamax Survey
Survey Results
As of 9/15 55 people had taken the survey.
- About 55% of people had never heard of it or knew little about it and 20 had tried it.
- Of those 20 almost three-quarters used it for migraine with 14% using it for pain. Thirty percent said it was very effective and 30 percent said it was moderately effective.35% said it was not effective.
- Thirty-eight percent said it had strong side effects, 10 percent said it had moderate side effects, 33% said it had mild side effect and 19% said it had no side effects. ‘
Here are some comments
- I used Topomax for Migraines in the past. It did help the severity and frequency of my migraines. The side effect of weight loss was great. The side effect I didn’t like was that it made my “word finding” ability worse.
- pain level down substantially, no migraines
- I got up 100mg before I almost lost my vision you have to get to 250mg according to my neurologist for Fibro help
- couldn’t tolerate the terrible fatigue and brain fog
- Side effects are dose dependent. I would be dead if it hadn’t worked for my migraines!
- My dosage had to keep being increased. I could not mentally function after awhile (forgot words, could not spell, talked very slowly).
- kidney stones
- I was on topomax for some time prescribed by my neurologist, and then when I moved to a different state, my doctor took me off of it and gave me tramadol…..didnt understand this, and have had more chronic to severe pain since being off of it and have also gained substantial weight
- Worked wonders for migraines, drowsy when starting, some tingling in fingers in toes, did nothing for fibro pain
- Perhaps my dosage wasn’t right, but it made me very dopey and did not seem to help the pain. However, if solid evidence is found by more studies that Topamax significantly helps,fibromyalgia, I would consider trying it again.
- i could not find my car keys even when they were in my hand. lol
- I would love to try it. Might as well, I’ve tried everything else.
- Doc kept increasing dosage because my migraines wouldn’t stop. By the time I was on the max dose I was experiencing rage like never before in my life. This drug made me go from calm to extremely angry very very quickly
- I am always sensitive to alot of drugs ..So I woudlnt be willing to try this either ..I guess I will just put up with the fibro…I have iss
In 2006 I began experiencing terrible 24/7 atypical migraines. My neurologist prescribed Topomax for me and my migraines were greatly reduced and I also experienced the great side-effect of losing a lot of weight. What I also started losing was my memory which is a hallmark symptom of Topomax which is also referred to as “Dopomax” since so many folks experience feeling “dumb.” Shortly after my symptoms escalated with body pain and I was diagnosed with Fibro. So my migraines are reduced and I fit back into my clothes but my long and short-term memory are going. Then fatigue hit me hard and I was unable to do anything other than sleep (even @ work) and wound up having to go on temp disability and finally resign. Then came the diagnosis of CFS! So could Topomax have started the downward spiral? There’s no “medical” evidence of this and although I also dealt with flu and trauma I personally believe Topomax did a lot of harm.
Thanks Sharon for sharing your experience. What a roller-coaster you’ve been on! Your experience – from migraine to FM mimicked the case study referred to in the blog but obviously your experiences did not.
I fully believe Topamax was your issue. I was fine other then my migraines two month into taking Topamax I had every symptom of fibromyalgia. My co worker went through the exact same thing and was diagnosed with fibromyalgia. Both of us stopped taking the horrible medication and all Fibromyalgia symptoms disappeared.
Can topamax help with back pain in the lower back got an assessment tommorrow on the phone with a specialist not sure what will get said
This is my story, exactly. However, since coming off of Topamax, a few months ago, I have gained over 60 pounds and am heavier than I’ve ever been in my life. Nerve pain has been unbearable and my memory and word-finding abilities have significantly declined. I cannot walk down stairs now, without significant pain and effort. I see my internal medicine specialist, this week, and am going to ask him about going back on Topamax. I was only taken off of it because of kidney stones forming. I cannot function as I currently am.
Sorry to hear that Wendy! Have you tried medical marijuana or low dose naltrexone?
The side effects (especially I’d you have glaucoma) are significant. Beware!
I am very glad to know that Topomax is being looked at for Fibromyalgia patients. I’ve been using it for Migraine prevention since about 2003ish and its been a godsend for me as far as migraine prevention and I think it probably has helped me with my fibro as well to a degree. I know that without it I would be bedridden. In my case following my hysterectomy I became a chronic migraineur almost immediately (4-6 days a week) once I no longer had ovaries and even with estrogen replacement that didn’t make any difference to my migraines and it was a real struggle to find medicines to help. I even stopped being responsive to imitrex and had to find something else to treat my migraines for an abortive. I did have weight loss with topomax which is a good thing as the preventives I tried prior to Topomax included depakote which caused me to gain about 70 lbs in 6 months and neurontin which did absolutely nothing for me. I have also tried gabapentin which after having tried neurontin I didn’t expect anything from gabapentin and I was right, nada, and savella which affected my blood pressure dramatically and after spending several years on prozac and working hard to get off of it I refuse to even try the snri, cymbalta fibro approval or not – Many dr’s give tricyclic antidepressants like elavil and nortriptyline to Fibro patients too and I cannot take them as they give me hallucinations so my dr and I decided long ago that I have to stay away from that class altogether! So I am glad that I’ve had good results from Topomax and that it has not only helped my migraines but probably also my fibro too.
I have been on topiramate for about two month and my health has improved dramatically. Prior, I had a migraine most of the time and muscle aches all over. My uncontrolled jerky movements have also resolved. I have not had any side effects but I am on only 25 mg at bedtime.
Pam Miller
If you want severe eye pain & double vision, it’s your drug. I tried it TWICE for migraines. The second time I got up to 100 mg. my Neuro said you had to get to 250mg for Fibro pain. This is a horrible drug. Not worth the side effects, which are many.
I’m STILL having eye problems 3 months later. Going to see a Neuro-Ophthamologist.
I’ve used 25mg twice daily now for 5+ years and it’s been a god send. Without it I don’t know what I’d do with my 24/7 6 years and counting headaches.I would spend many hours each day in a quiet dark room until I went to a headache specialist. I definitely have some memory loss, but pretty minor. I can only take a low dose, but the dose I’m on is the current recommended dose for migraines, other doses are old school or carry over from seizure treatment neurologists that aren’t current on it’s usage for migraines.
I would definitely be upset if I got glaucoma, but luckily no. It only affects my energy, appetite at higher doses.
I’m was curious about this. I’m already on 600 mgm of Lyrica and 30 mgm of Duloxetine. Last year I started developing seizures, which initially I was told was brought on by the combination of the above plus Tramadol lifting my serotonin levels too high. But then the neurologist who diagnosed me with “cryptogenic epilepsy” (i.e.. of unknown cause) said I was probably going to get it anyway! So now I’m also on Keppra to control my epilepsy, which it has, but my memory, especially long-term, is shocking (Although a neuropsychologist who tested me for amnesia told me I had a “pristine brain”, although I couldn’t navigate my way around once familiar places – geographic memory). Now recently, my ophthalmologist who monitors my right angle glaucoma (not so serious and not advancing) for which I only take Xalatan drops (!), says of my funny reactions to light in one eye, i.e.. losing vision at times for minutes, that its retinal migraine…..So my ears pricked up when I read the article. However, I think I better leave the ‘dopomax’ alone! As a clinical psychologist, I have patients with chronic nerve pain who have taken less than me of Lyrica and have had to stop because of its sedating effect! By the bye, I have been diagnosed with fibromyalgia “and probably CFS” by my rheumatologist in recent decades, although in my late teens and early twenties I experienced pain, which one doctor gave the then label of fibrositis and prescribed BTZ…I’ll be 70 next year….
It is interesting to observe, BTW, that a higher dose of Lyrica is required for us than for people with other types of pain.
I am sorry to hear of all these complications! My first instinct, although you might disagree because of course you know your story better than I do, is that you should get rid of these doctors and get a second opinion from one of the few doctors in the country who specialize in M.E./CFS. To me, taking drugs that CAUSE seizures and then adding new drugs to control the seizures, and then adding new drugs to deal with the side effects of those drugs, all under the supervision of rather apathetic doctors, is no way to live. Perhaps save the money being spent on all that and see if you can take a trip to see a specialist.
I saw numerous doctors before seeking out a specialist (who fortunately for me was near where I lived), and I encountered many who just shrugged their shoulders at the mounting Rx bills and new side effects. I had highly-rated doctors say “Well, I think you’ll always be in pain, I don’t think we can do anything about that” (this particularly from a cardiologist who seemed not too concerned that I may have developed myocarditis, a heart infection from the viruses I have contracted). I am so glad I left them and got second and fourth opinions – they were wrong, and the drugs they put me on were the wrong ones for my condition.
If it were me, I would not consider seizures a better tradeoff than ME/CFS symptoms, I would stick with the original illness and save my money on the Rxs. And anyway, M.E. and other similar chronic illnesses have a lot of natural things you can do to help alleviate symptoms with no side effects in the meantime, while we wait for better labs and a cure.
Hope you’ll consider this, and decide if maybe a specialist and a different treatment path are right for you.
What kind of specialist did you see? Just curious, I’m in the boat you used to be in. Have a million Drs and scripts and no one gives a crap.
I thought these articles were about the benefits of topirate,looks like a lot of complaints and I have been on cymbalta and desapramine and it intensified my burnning! I get stressed too easily ,my body goes stiff and I want to sleep and I have trouble sleeping any other time! i seen amytriptiline is at the top of list1 i thought I would try it again and see if it helps ,my friend has got to have it for that! i use lonesta but ,it don’t work as well no more .I use to get alprazalem before my lunesta ,it helped but thanks to the stars ,we can’t get it no more1 I want Mj federally legalised ! I had no trouble with sleep or constipation ! HA HA ! Blocked is more like it!
I have been diagnosed with ME/CFS for about a year now and currently take an antiviral and cymbalta. I have seen several Dr’s already including neurologists and infectious disease Dr. Unfortunately, I can’t find one that treats this disease. I even reached out the Mayo clinic and they wouldn’t even consider me. I would love to know which specialist you went to see. I would greatly appreciate any info you can give me. Thanks!
Could it help Peripheral Neuropathy i take Lyrica atm but im gaining so much weight
my son has been on 300mgs a day for his epilepsy and has been taking it for years with no problems………just my 2 cents worth……
I have lupus fibro and Graves now I also have Burning mouth syndrome It is HORRID anyone else have it hear of it ? Not alot of research I wish someone would look into it we need something other then giving us anti anxiety …I think its great that they found this drug works but I am not going to be trying it I do not do well with alot of meds I am much to sensitive and they make me sicker then the diseases I have …Its great if some of you can use it ..I wish they could come up with something without making you feel like a zombie ..! Please if anyone knows anything about burning mouth syndrome -BMS…. It would be great to hear ..I’m curious how many who have fibro have this ? Thank you ..
Donna, I also have burning mouth syndrome. I have had fibro about 10 years and about 5 years ago developed burning mouth syndrome. It’s just one more thing we could live without!!! Pam
Burning mouth! I do not know much about that! I do know ,I got my perineal nerve damage from antibiotics foe 2 yrs. straight for an undiagnosed MRSA infection and I get tossed around and dismissed and the doctors lie to get their way! They called it fibromyalgia! MY ASSS! It is permament nerve damage { peripheral neuropathy}
I caution those who want to try this to be aware of the side effects. I was on Topamax at one point due to a misdiagnosed mental illness (I had a rare blood disorder that mimicked bipolar, and was at the time also under severe stress). I have an exceptionally sharp memory – or did prior to the acute onset of M.E. anyway (at which point I lost much of my ability to make new memories). Topamax completely erased my ability to make memories at the time – I remember nearly every small detail of my life, up until those two years I was taking it, where I am told I did things and went places, but have absolutely no recollection of any of it. At the time, I was also forgetful, which affected my job and relationships. Even if it helps, you might never remember the life you gained back, or what you did with your newfound energy. For me personally, that cost would not be worth it. So if one considers taking it, be on the lookout for those symptoms and have a plan with loved ones, and if you get forgetful and confused, have them help guide you to work with your doctor to taper off immediately.
Having been through what I have with many of these haphazardly prescribed psychotropic drugs, I now believe most should never have been approved for the market – I find them dangerous and applied with a callousness that generally results in little improvement and much suffering. In my case, because there was no blood test for mental illness, I was diagnosed merely by the opinion of well-meaning doctors, and then subjected to a wide array of strong brain-altering chemicals with a policy of “let’s try each class and just see what happens – if you get worse and don’t kill yourself first, we’ll try a new one.” In my case (certainly not everybody’s), I found most to actually CAUSE depression, anxiety, psychosis, hallucinations. and other side effects like severe weight gain, memory loss, nausea, headaches, numbness, and grinding of the teeth in sleep such that I had to get reparative dental work and a mouth guard to sleep with. I think mental illness should be treated, but in many cases more gentle holistic means can do what’s needed without lining the pockets of a fairly unregulated mental health industry. For me, changing my diet to include the foods I needed for the blood disease (which meant eating more), learning better daily stress management, and losing an abusive husband, was all that I needed to stop showing the symptoms of a severe mental illness. Now I am very sick with M.E., but at least in great spirits! Our health care system should systematically start with the least invasive methods first that cause the fewest side effects, THEN work up as needed – not start with the harshest drugs pushed by drug reps in their office that week in exchange for free pens.
For Fibro, I found LDN and also consistent gentle floor/bed yoga to all but erase the pain patterns developed in my brain. It was very severe, and then nearly disappeared. The M.E. is still there, but Fibro is no longer a major issue. And for me, I did not have any major side effects with LDN aside from stomach pain when I first took it, that was alleviated by splitting the dose into 2 smaller doses 12 hours apart.
By the way, when I was first Dxed with Fibro (by a rheumatogist a few months before the M.E. diagnosis), I was put on Lyrica. I had severe hallucinations within 2 days and immediately discontinued. To me, LDN has a far better response rate with fewer reports of side effects, and should be tried before these strong drugs that severely alter your brain chemistry – if you’re going to try drugs at all and not gentle yoga/stretching and meditation first, which for many people does the trick. (Try “Healing Yoga” DVD by Sarah Bates, who cured her own Fibro with her routine, or try out the free videos being posted in the Yoga on the Path to Wellness series on the ME/CFS Community website.)
Thanks so much for this Sunshine. We have a tendency to go immediately for drugs – they’re alot easier in many ways – but I think stress management and relaxation tools should always be the first option…What a shift for you doing LDN and yoga has been!
Yeah, I was very behind industrialized/”Western” medicine when I first became sick. But after a good decade of being exposed to harsh medications that did not address the problem, but rather tried to cover up the symptoms (and in doing so caused new worse symptoms), I started to realize that some of this less-traditional stuff is actually a lot better at treating chronic illness than our healthcare system is. I would no longer call drugs the “easier” option! For a broken arm, I’d still go to an emergency room. But for a nagging set of symptoms that have no clear answer or cause, often the best thing you can do is help the body heal itself – it knows what is wrong with us even when we don’t! I’m glad they’ve discovered that LDN is very helpful for Fibro, and I hope testing continues to develop appropriate drugs and use them to pinpoint causes.
However, a free and natural solution like stretching and breathing to change pain pathways in the brain should definitely be checked out before going to the next level with more invasive and expensive stuff. At least, gentle floor/bed yoga tends to have plenty of POSITIVE side effects, so even if it doesn’t cure one’s Fibro it may help with a number of other problems besides the main one. How many drugs have positive side effects and no negative ones?
Here’s the current survey results….As always the variability in response to Topamax is high
Survey Results
Here are the comments thus far
pain level down substantially, no migraines
couldn’t tolerate the terrible fatigue and brain fog
“i could not find my car keys even when they were in my hand. lol”
LOL! I had trouble filling out the survey, the screen kept blipping so it did not take my answers. But, that line pretty much sums up my usage! Topamax is great if you want to feel better but never remember that you felt better! 🙂
Note, I don’t recall my dosage (or anything else from when I took it!), but I think it was pretty high. Maybe the key is with a very low dosage, like with LDN.
Still, I think LDN has more clinical proof of success for Fibro right now, with fewer side effects. I would think someone should try it first before trying the others. I was surprised that my insurance covered it the same as my other Rxs too!
I tried clonazepam six months ago after reading about it on Phoenix Rising. It is the worst drug I’ve ever tried! Dizziness, blurred vision, doped feeling, and the worst, serious suicidal thoughts – all well-known side effects of anticonvulsants. This was on a low dose, and after 1-2 weeks of use – extremely scary. I also had to deal with serious withdrawal symptoms several months after I went off the drug.
After reading about topiramat I get the feeling that topiramat and clonazepam are quite similar, both in effect and side effects. I will never try an anticonvulsant again, and I know I’m not the only ME/CFS-sufferer with adverse reactions to these drugs. Some groups of patients are helped by anticonvulsant and the like, but these drugs are definitely not targeting my disease and my symptoms. I recommend everyone to be ware of all aspects before considering trying drugs like this.
Most anticonvulsants would probably be as good or better for fibro as Lyrica. As mentioned in several comments, topiramate very often causes cognitive problems, sometimes very severe. I don’t think there’s any other drug as likely to do that (as long as we’re not talking about sedatives). In some countries piracetam is considered an anticonvulsant, but it improves cognitive function and rarely has any side effects (yes, really). Many people, me included, use it with great results.
PM: Topiramate is not at all related to clonazepam, though. In general the anticonvulsants have _very_ different modes of action. It’s not like antidepressants where you can just conclude that I’ve tried a few with terrible side effects, the rest will probably be the same. Some anticonvulsants increase GABA (gabapentin and pregabalin don’t, by the way, despite their names), some block ion channels, others NMDA receptors etc.
I agree that LDN should always be tried first. It treats the actual disease process, not just its symptoms, and has few side effects. In the CureTogether fibromyalgia study Lyrica, Cymbalta and Savella all ranked below zero, while LDN was rated by far the best treatment.
The big three ranked below zero at Curetogether! That’s amazing…Glad to hear about LDN – thanks for all the info.
Thank you for your response Maija I have had a brief discussion about topiramat with my GP, and due to my adverse reaction to clonazepam he is concerned about topiramat and will not recommend it to me.
I find it interesting though that we can have the same disease, practically the same symptoms, but still react so differently to a long range of drugs. I have both immunological and neurological symptoms and abnormalities, many doctors describing it as «classic» myalgic encephalomyelitis. I benefit a good deal from beta blockers while other patients don’t. I benefit somewhat from LDN while others might befit enormously or none at all. I’ve had adverse reactions to clonazepam and to prednisone, while others benefit from these drugs. I didn’t benefit at all from rituximab, even if I was fortunate enough to get several infusions over a year.
There must be a pattern in this, subgroups with more or less similar biochemistry, patients who respond somewhat similar to the same treatment and drugs etc. If we could get the insight and deeper knowledge of this we could maybe be spared of wasting our time, money and sparse health on treatment that doesn’t work. We’re all guinea pigs, our own doctors, it’s not at all reassuring.
Well, the same goes for many other illness too, maybe to a lesser extent since most illnesses are treated with a far lower number of drugs. Some people with depression benefit from drugs that increase dopamine. Others from drugs that decrease dopamine (antipsychotic drugs in lower doses may actually increase dopamine too, but I’m talking about larger doses).
In his superb book Tuning the Brain Jay Goldstein presents an “algorithm” for treating CFS/ME. If drug X works, you may also try Y, but if X gives a bad reaction, then Z is likely to work. Sadly while Goldstein’s med repertoire is large, it’s pretty much only neuromodulators, not immunomodulators, so things like LDN are not listed.
FWIW, I’ve never had a really bad reaction to any med (baclofen was pretty nasty for a few days, but then all the side effects went away and I’ve been taking it successfully for almost six years now). Prednisone helped me a lot (very unusual), but stopped working. LDN helps me a lot (as does nimodipine, even though I stopped taking it in 2008). Clonazepam didn’t help, but wasn’t terrible either. Beta blockers didn’t help, nor did they hurt. Lyrica seemingly helped me for one day, then stopped working, but caused pretty much no side effects.
A severely ill friend has benefited the most from LDN, IVIG, beta blockers and clonazepam (I believe prednisone was pretty much +-0 for her), though all effects have been relatively minor.
I have had daily migraines since December 2001. As far as migraines are concerned Topiramate does NOT work. Ever.
I think it would me more accurate to say it does not work for you. Several people have stated it works for them.
Suffering from migraines for more than 45 years, I was excited to try yet another drug that might help. I was a zombie. I was back in bed abd after 4 yrs, I was just crawling out after finding out and treating Hashi. Needless to say, after one wk, I returned to the dark hole, I stopped it. I was convinced to try it again, hopeful a lower dose and “sticking with it for a month” was key. I made it 5 days. 5 days gone from my life. All that said, neither rheumy nor neuro tried Dr Bateman’s protocol. Hmmmm. I have borderline glaucoma and I wasn’t alive enough to know if it helped my FM pain. As a ME/CFS patient w ith significant short term memory loss, my migrains are bad enough I might try it again.
2 of my daughters have tried Topamax. 1 for seizures 1 for migraines. The pediatrician referred to it as “Toxicmax” and said people seem extremely polarised in their response to it. It was horrible for my girls. Side effects were hallucinations, muscle tightness and pain, no sleep in 36 hours, severe mood dysregulation and cognitive dysfunction
I tried Topamax when Lyrica sent my weight spiraling out of control. Lyrica also gave me terrible thoughts. I’d never take it again even if it totally took away my pain. The doctor gave me the Phentermine/Topomax protocol and I lost the weight. I didn’t realize that it helped the pain until I stopped taking it.
It did help and I’m considering taking it again. It did change the taste of diet coke for me. Thats not a bad thing….I probably shouldn’t be drinking it anyway! I didn’t notice memory loss or the tingling of hands and legs.
Thanks for the article. I’ve looked for studies regarding Topamax and Fibromyalgia but there is very limited information for off label uses.
I tried Topamax when Lyrica sent my weight spiraling out of control. Lyrica also gave me terrible thoughts. I’d never take it again even if it totally took away my pain. The doctor gave me the Phentermine/Topomax protocol and I lost the weight. I didn’t realize that it helped the pain until I stopped taking it. It did help and I’m considering taking it again. It did change the taste of diet coke for me. Thats not a bad thing….I probably shouldn’t be drinking it anyway! I didn’t notice memory loss or the tingling of hands and legs. Thanks for the article. I’ve looked for studies regarding Topamax and Fibromyalgia but there is very limited information for off label uses. Rosemary Lee Seeking Equilibrium
Not surprisingly, given my recent blogging activity that suggests an imbalance between glutamate and GABA, I’ve a feeling that experiences with drugs like this are giving us a pretty strong insight into what’s happening in ME/CFS, fibro, migraine (or with those who have a mixture of all three sets of symptoms).
The mixed responses and intolerable ‘side effects’ are not at all unusual (google topiramate for migraine with autism and epilepsy and the reports are very similar). The problem I feel is that these drugs are very much a blunt weapon and we don’t know exactly where the problem lies (often the manufacturers themselves don’t know exactly why a drug works and it often turns out they’re effective for reasons other than the assumed mode of action). Dosages and treatment regimes are only approximations and we all vary in how we tolerate drugs.
I’ve a feeling that drugs like this may be effective but the dose and timing needs to be right and possibly tailored to the individual. 25Mg twice per day sounds a better bet to me than a single higher dose for reasons discussed below. Some of the side effects (dopamax) sound likely to be due to too high a dose. Other undesirable side effects like tingling, glaucoma, anxiety, rages etc sound to me like what would be expected with too much glutamate rather than too high a dose of Tpoamax – which might be due to neurological kindling. In other words a regime of continually blunting glutamate followed by a glutamate spike when the drug wears off can lead to self-perpetuating neurotoxicity over time as seen with benzodiazepine use and alcoholism.
We also don’t know what compensatory changes take place over time to, for example, endogenous GABA production or the sensitivity of glutamate receptors if we repeatedly block glutamate. Lets just say I wouldn’t want to go cold turkey after being on these drugs for a while.
The weight loss effect is interesting but on the face of it seems pretty irrelevant to ME/CFS and fibro (and migraine)… but :
Neuropeptide Y is known as the anti-stress hormone – raised in times of stress and responsible for the ‘raging munchies’ during periods of stress. NPY has been found to be elevated in ME/CFS and fibro :
http://www.behavioralandbrainfunctions.com/content/6/1/76
Lipkin has recently reported that another substance, leptin, is elevated in ME/CFS patients. Leptin also appears to be elevated in response to stress and acts (amongst many other functions) to counteract the appetite stimulating effects of NPY. In the wake of Lipkin’s recent findings some folks are puzzling over what raised leptin means.
I’d suggest that both raised NPY and leptin suggest a system under stress. Interestingly the US military are investigating NPY as a means of screening soldiers for selection for special forces (special forces troops have high levels of NPY). Don’t go volunteering yet though. Their NPY levels rapidly return to normal when not in a battle situation. Ours don’t appear to switch off.
Getting back to topiramate – adminstration lowers both leptin and NPY and also appears to improve glycemic regulation (another tenuous link between ME/CFS and diabetes?) :
http://www.ncbi.nlm.nih.gov/pubmed/23127262
Leptin also protects against glutamate neurotoxicity which suggests to me that elevated levels may be a protective response to excitatory glutamate.
http://www.ncbi.nlm.nih.gov/pubmed/23180096
The fall in NPY and leptin also suggests to me that topiramate may be able to short circuit this prolonged stress response. Other drugs might do this better.
More research into these areas would be nice.
I found the post Marco did about leptin and glutamate to be fascinating. I had written a LONG post and done lots of research and lost the whole thing. (I’ll do a condensed version of it.) I also found that leptin resistance can be connected to a high fat diet. I found an herbal that will correct leptin resistance called Irvingia and it for sure works to help with weight loss (makes the I’m full switch work). Leptin resistance can happen if one is overweight. But, they are also finding that leptin can help as a treatment for Alzheimer’s and depression. I know since I’ve been using this herbal, I hardly ever have “brain fog” anymore. Coincidence???
Here’s the links I had listed:
High fat diet and leptin resistance
http://ajpendo.physiology.org/content/302/4/E396
Leptin in Alzheimers
http://www.hindawi.com/journals/ijad/2012/594137/
Affect on CNS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2808539/
It is known that leptin plays an important role in normal brain function, however recent evidence indicates that alterations in the leptin system is also linked to a number of CNS-driven diseases and neurodegenerative disorders. Thus the ability of leptin to regulate glutamate receptor trafficking is likely to have important implications not only in health but also in diseases associated with leptin dysfunction.
Affect on CNS and depression
http://www.researchgate.net/publication/38085498_Regulation_of_glutamate_receptor_trafficking_by_leptin
Maybe, this connection between glutamate, leptin and diet – still on the FRONT burner.
Issie
Hi again Issie
We’re not the only ones thinking about these connections.
This thread discusses leptin, diet and autoimmunity in the context of ankylosing spondylitis :
“Leptin could represent the missing link among immune response, metabolic function, and nutritional status”
http://www.kickas.org/ubbthreads/ubbthreads.php?ubb=showflat&Number=394913
This is a much better paper on the neuroprotective effects of leptin than the one I previously linked to – and also discusses the potential benefits of a ketogenic diet :
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2634657/
Lots to mull over!
Yes, so many things to consider. Maybe the leptin/insulin resistance is the key here. Of course with those things also affecting glutamate response – maybe getting our bodies to recognize that will be helpful. Using the above herbal and my diet – I’m losing weight and many of the things I deal with are getting better (POTS, MCAS).
I’m trying to figure out if this plays a role in MPN (Myeloproliferative Neoplasams) of which mastocytosis can be a part of. As JAK2 is elevated with this and leptin also affects JAK2. Since MCAS can possibly be associated with this and many of us with HyperPOTS and EDS also have MCAS. (I was included in a study with 23&me for MPN, of which I have genetic markers for. But, do not show signs of illness – other than MCAS.)
I found the connection to AS interesting – as this is also one of my issues. My father also has it and he has had numerous strokes (which your above article suggested leptin as a treatment for).
INTERESTING – to say the least. Keep the info coming. I think we’re on the right track.
Issie
Will do Issie (when I can).
AS and strokes as well – ?
Yeah, when you have bad genetics – you get a bucket load of them. I’m just glad I’m figuring out some of the connections as it may help future generations in my family. (And so far, what I’m doing is helping me.) Dad also has cancer in his bones and there is nothing more to be done for it. He’s had 3 strokes, so far. So, lots of ugliness – and reasons for me to be searching for more answers.
Thanks, for helping me try to find the connections.
Issie
http://www.ncbi.nlm.nih.gov/pubmed/20194306
Connections to a high fat diet and leptin resistance and increase in sympathetic nervous system.
http://www.ncbi.nlm.nih.gov/pubmed/6874952
Ganglionic blockade produced a greater effect on NE turnover in fat-fed, as compared with chow-fed animals, consistent with increased sympathetic activity in the fat-fed group. When fat absorption was blocked with a bile acid binding resin (cholestyramine), the same high-fat diet did not increase cardiac NE turnover, indicating that fat absorption is required for the stimulatory effect on sympathetic activity.
http://www.ncbi.nlm.nih.gov/pubmed/8289676
Different kinds of oil and fat affect the sympathetic system in different ways.
http://www.ncbi.nlm.nih.gov/pubmed/13679250
The stimulation of the central nervous system (CNS) opioids and their receptors is associated with an increase in cardiovascular dynamics. In this study we hypothesized that obesity changed the CNS opioids and their receptors that could play a role in altered cardiovascular and autonomic nervous regulation in obesity.
So what I’m getting from this, is a high fat diet can increase leptin and insulin resistance. This could affect POTS people as this increases the sympathetic system activity and increases NE levels. Can also play a part in opioid receptors and can affect pain levels. This last article also showed connections to dopamine and also renal sympathetic nerve activity and blood pressure. (My low-fat, whole food, vegan diet is looking even more promising. Gives me more incentive to stick with it.)
Issie
Thanks for your comments Sunshine. However, all my treating doctors are specialists and are either professors or assistant professors at the University of Melbourne here in Australia! I guess it’s horses for courses Sunshine. I was a university lecturer for over twenty years and lectured on topics like psychopharmacology so I guess I’m already a convert to medicine. Not to say I don’t question and research everything. Done a bit of it in my time. Seems to me you have to question everything. One online store which most of us know sells all kinds of supplements with amazing claims. I’m still trying to work out how early celts could dive to the 1500 to 3000 feet to catch the the fish which is said to be used in one of the new supplements lives at! The historical references I read say that garum was made from the intestines of mackerels. So everyone has to find out for themselves what works and what doesn’t work, by reading the scientific evidence and trying it for themselves. BTW, Lyrica is no longer considered terribly effective as an anticonvulsant and is now hardly used for epilepsy. If I didn’t take it my fatigue would be terrible and even dropping it by 150mgm makes symptoms worse for me. I was commenting that I’m amazed at how I tolerate and even improve my functioning on drugs and doses which non cfs/me/fm people don’t seem able to manage!
Maybe pramipexole might be an alternative against pain when nothing else works. Pramipexole (Mirapex, Mirapexin, Sifrol) is a dopamine agonist of the non-ergoline class indicated for treating early-stage Parkinson’s disease (PD) and restless legs syndrome (RLS). It is also sometimes used off-label as a treatment for cluster headache.
I am only going to share my experience with topamax. When I was first prescribed it, I was excited. Who wouldn’t like what was promoted to me as a cure all pill for fibro once I reached the appropriate dose with the added benefit of losing weight. I sure did lose weight. I have IBS and could not make it through a meal without running to the bathroom. It totally ruined any romantic dinners out. I believe my dose was eventually 200 mg twice a day but it has been too long to remember exactly. The higher the dose I took, I started developing the pins and needles feeling in my hands and feet, similar to what one feels when their foot falls asleep and is starting to wake up. It wasn’t overly painful, just felt funny, but I mentioned it to my doctor. He said it was my nerves regrowing after having been on narcotics for a couple of years and was completely normal. As time went by the pins and needles became so painful that it hurt to walk. But, I kept taking it because the doctor assured me it was part of the healing process. His wife was his receptionist and I had called for refills. She forgot to call them in. After several days of calls and no refill called in, the weekend came and I was out of my topamax. The extreme pain I suffered from suddenly stopping it was indescribable other than saying that I actually prayed that God would let me die so that the pain would end. I never noticed any improvement in pain or for my migraines. The doctor is no longer allowed to practice for multiple reasons that I won’t bring up right now. Lyrica made some pain better, some pain worse, and made my brain mush. Even after weaning off, I still had some withdrawals with it. I just stopped taking plaquenil to see if it is the cause of my everyday all day migraines for 5 months now. Cymbalta seems to help or at least help me cope, not sure which. Interesting article though.
I have been on topamax 100mg a day for 6yrs and the doctor put on it for arthritis in my neck along with anti inflammatory and muscle relaxer , it has been wonderful has helped so much there was a time I could not even move my head with out pain .Now I am going to go on the generic topamax and i am worried it won’t b the same ,have read on line that it can b different . So if anyone out there has arthritis pain have or doc give it a try I had no side effects from the drug .
Thanks for passing that on Debbie and good luck with the drug 🙂
I take Topamax for Fibromyalgia & Intersticial Cystitis. It has given me my life back. I’m posting because I almost made the mistake of not starting this medicine 7 yrs ago, due to the horror stories I was reading online. Yes, it is difficult to start taking and yes, there are side effects and trade-offs to consider. But anyone who is to the point of considering Topamax knows by now that the rest of your life and mine are just this – trade-offs and hard considerations. For me, Topamax has restored a level of functionality I had thought was lost. No, it has not bestowed perfection but the spaciness, energy loss, dry mouth etc are the price I pay for being able to once again get out of the house, enjoy my family, drive carpool, travel, etc. I take 300 mg/day (100 mg/3x) and can tell the moment it begins to wear off. I’m grateful to my dr who’s been patient with my hesitations but got me to this point despite them.
Congratulations Kay and thanks for passing that on. Topamaax is one very interesting drug. I think on the internet we tend to hear more horror stories that good stories probably because the people with good stories out living their lives.
I have had fibromyalgia for over 30 years. Migraines for almost 40. I have been on Topamax for maybe close to 20 yrs. About 1 1/2 yrs ago the migraines ceased. Recently I started titrating off Topamax. Within about 3 weeks, the Fibro pain was so excruiating I couldn’t stand it. I researched topirimate and realized it was used to deaden nerve endings. Bingo! I started titrating back onto Topamax and the Fibro pain is now under control. I will not be getting off this medicine any time soon.
I tried all of the above mentioned medication and the side effects were too much for me. Cymbalta made me super depressed, but worked wonders on my migraines and fibro, neurontin gave me panic attacks, and Lyrica worked well for me, but I couldn’t add 2+3 on it. Even botox, opiods,pain blocks and holistics, none of it helped me get below an 8 pain scale without side effects that were just as debilitating as the diseases. My primary and I decided to give a combo of 100 mg of topirimate and 150 of wellbutrin a try. For me, it is like a miracle combo. Pain scale usually under 5 (I still have bad days) energy is way up and migraine days are down to about 4 a month as opposed to 4 or so without. The side effects are completely tolerable because it doesn’t give me that”dopamax” feeling” that everyone talks about. The main problems I have are neuropathy, which is no big deal since I already had it from nerve damage anyway and the change in appetite and taste.
Recently, I was planning to start using topiramate and found this article on the website I plan to start with a small dose and observe the common adverse reactions of topiramate This can try it while ensuring safety.