A Blockbuster Drug
Lyrica truly merits the description ‘blockbuster drug’. FDA approved for seizures, neuropathic pain, fibromyalgia (2007), and generalized anxiety disorder (Europe), Lyrica (pregabalin) sales hit their peak in the last quarter in the US, bringing in over $550 million for Pfizer.
Lyrica’s enormous success despite its side effect and efficacy issues, highlights the needs for better pain relieving drugs.
Lyrica’s success – despite issues with side effects and efficacy in a significant number of fibromyalgia patients – highlights the tremendous need for drugs that relieve neuropathic pain. Fifteen years in development, Lyrica was originally developed to reduce seizures by increasing GABA levels, but was later found to reduce glutamate, substance P and norepinephrine levels instead.
Researchers know the pharmacological effects Lyrica has, but they don’t know what parts of the brain it’s affecting. It’s great to have a drug that works (for some people) but finding out why and where a drug works can help us understand what went wrong in the first place. This type of reverse engineering is happening in ME/CFS with Drs. Fluge and Mella (rituximab), and Dr. Montoya and Dr. Kogelnik (antivirals).
In this study as FM and healthy controls got their thumbnails pressed to induce pain, fMRIs were used to determine which parts of their brains became activated before and after they took Lyrica. Reduced brain activation in concert with reduced pain should reveal which parts of a fibromyalgia patient’s brain were producing pain.
Results
With their exquisite sense of pain, it perhaps wasn’t surprising to see almost 50% more brain regions light up in the presence of pain in the FM patients than in the healthy controls pre-Lyrica. Post-Lyrica things changed, at least for some.
The study showed that when Lyrica works, it really works. It was only effective in less than half those who tried it (9/21) but it cut the responders’ pain in half, dropped their ‘pain sensitivity’ down to normal levels, and their sleep and fatigue scores improved significantly.
Post-Lyrica the responders’ brains were very different as well. Now, the same number of brain regions as in healthy controls became activated during pain. It was as if a sort of “pain infection” that had infected neighboring brain regions had been stopped and reversed. Reductions in insula, somatosensory cortex, and thalamus activity suggested these regions, in particular, play an important role in pain in FM.
Focus on Mind/Body Integration in the Insula
A small slice of brain sitting not far from the brainstem, the insula affects both physiology and mood
One of the most interesting organs in the brain, the insula plays an important role in both physiology and emotion. One of the chief homeostatic organs in the brain, the insula is in charge of adjusting the body’s physiology (heart rate, temperature, blood sugar, etc., to maintain an even, healthy state. It helps determine how much pain you experience. It lights up in the presence of fear. It’s associated with awareness and cognitive issues. It’s involved in determining ‘anticipation’; i.e., if just the thought of doing something makes you feel ill, that could be your over-active insula talking.
Lyrica’s ability to reduce activity in two areas of the insula and the cingulate cortex suggested that the ‘motivational affective component of pain’, i.e., the part of pain that is so unpleasant that it makes you want to crawl out of your skin, is increased in FM.
Arousal and Sensory Integration in the Deep Brain: Focus on the Thalamus
The reduced level of thalamus and somatosensory cortex activity post-Lyrica suggested that the aberrant pain signaling process in FM may begin deep in the brain. The thalamus, which sits right on top of the brainstem, relays sensory and motor signals from the spinal cord to the rest of the brain and regulates sleep and alertness. Long thought as a ‘switchboard’, it’s now clear that the thalamus processes and determines the flow of information to the rest of the brain.
Lyrica reduced activation of the thalamus – the main regulator on sensory input into the brain in fibromyalgia
An overactive thalamus could conceivably reflect breakdowns earlier in the sensory routing system (the Lights’ and Van Elzekker’s suggestion of over-active sensory neurons) that caused massive amounts of sensory information to smack the thalamus.
The thalamus’s regulation of arousal and alertness also suggests it could contribute to the wired and tired issues in ME/CFS/FM. Lyrica’s ability to reduce pain and fatigue and improve sleep and reduce fatigue suggests pain and arousal may be two sides of the same coin in FM, something that certainly makes subjective sense.
This study and others suggest insula, thalamus, and somatosensory cortex over-activation is wreaking havoc with the pain levels, arousal, and possibly emotions in fibromyalgia, and perhaps in ME/CFS.
(A successful Lyrica chronic fatigue syndrome study currently under way could tell us more about Lyrica’s mode of action and the genetics of pain production in ME/CFS. By charting gene expression levels in ME/CFS patients pre- and post-Lyrica, the Lights are hoping they can identify specific genes that are responsible for pain, arousal, sleep problems and other issues in ME/CFS.)
Sidebar – Why Cognitive Behavioral Therapy (CBT) May Not Work Well in Fibromyalgia/ME/CFS
A fascinating study used insula activity to determine whether people with depression do better with an antidepressant (Lexapro) or ‘talk therapy’ (Cognitive Behavioral Therapy). It turned out that while people with low insula activity responded well to CBT, those with high insula activity responded better to Lexapro. Given the increased insula activity generally found in FM/ME/CFS, this suggests that antidepressants or other agents might work better than CBT.
Turning Down Insula and Thalamic/Somatosensory Activity in FM and ME/CFS
If insula, thalamus, and somatosensory cortex activity is increasing your pain, upping your stress levels with negative anticipation, dysregulating your autonomic nervous system and physiology, and overall just giving you a bad time, what can you do about it?
Some treatments that can reduce insula, thalamus and somatosensory cortex are below:
- Meditation – has been found to reduce somatosensory cortex activity and pain.
- Lyrica – reduces insula and somatosensory cortex activity in some people with FM.
- Tropisetron – Tropisetron, a serotonin 5-HT 3 receptor antagonist, reduced pain and blood flow in the somatosensory cortex, the insula, and the anterior cingulate cortex in fibromyalgia.
- Deep brain stimulation and trans-cranial magnetic stimulation appears to be able to reduce activity in these areas.
- Antidepressants – While the study noted earlier used Lexapro, a similar effect might be found with similar antidepressants.
- ???
Cort,
I continue to be amazed by and grateful for the number of high-quality articles you’ve been cranking out lately. You are my go-to source for breaking news and in-depth reports in the field. Keep up the good work!
Laurel
Thanks. I’m writing away – that’s for sure 🙂
Go Cort!
I do need to express an opinion on Lexapro as I was on a low dosage of that drug for a time. I have ME/ CFS and fibromyalgia. I also have been in treatment (before ever being diagnosed with the above) for major depression and anxiety.
My experience was this .. I took that drug for awhile.. I was in treatment (my usual)
for ME/ CFS/ fibro with a primary doctor, Dr Derek Enlander. his treatments have greatly improved my illness, although I am not well.
I began noticing after a time some weird things going on with me in terms of becoming irritable for really no reason; mood swings, and some other things I cannot recall now as this was quite awhile ago.
My pharmacist inadvertently helped me out; when I filled prescriptions one month, he had put the side effects info they print out in with my prescription.. When I got home in reading this, I was shocked to see that all these things I had felt were side
course from Lexapro. Well, thanks Lexapro, but no thanks!!
I do still take Cymbalta (yes; I was on both). It would be a cold day in hell before I took Lexapro again!!
I will say I’ve been extremely sensitive to some drugs in the past which my doctors all know.
I doubt I shall take Lyrica. Currently it’s the same as ever; I take Lectrolyte which for me helps both pain and brain fog.
Thanks for sharing your experience with Lexapro, Jane. Glad you figured that out :)….Is Lectrolyte an blood volume enhancer?
Years after your article was submitted but hoping I will get a reply. Cort, do you think that Jane meant electrolytes when she mentioned taking lectrolytes? Does electrolytes help with brain fog and pain?
I’m sure she did. I suppose it’s possible that if electrolytes help with blood volume they could increase blood flows to the brain (???)
Between my back and my arms and legs,the pain is almost overwhelming yet,the oxycodone,15 mgs,does not help my arms and legs. Plus the depression is getting really bad,caused from the pain and sleep problems..I don’t take much of the oxycodone,would like to stop it altogether,and take tramadol if I can find relief,with this lyrica/I was on it one time a few years ago,and had some unnatural side effects aka (Hallucinations)…Scared me..Plus the dr had put me on morphine..I later found that the morphine,was causing me to be short of breath,which at the time,I had been put on 3 different new drugs,so I stopped them all,out of fear.I have since discovered it was the morphine ,causing the shortness of breath..Do you think I should try the lyrica again,and some tramadol for my bad back.I don’t want to die with (DRUG ADDICT) stamped to my head….Thank you.C A
That would be a lousy thing to have on your tombstone….jeez. I don’t know. Dr. Bateman finds that Lyrica is her best pain reliever but it only works in a third to a half of FM patients. I wonder if the morphine/Lyrica combination contributed to the hallucinations. Have you tried Low Dose Naltrexone? I think that or medical marijuana, if you can get it, would be my first choice. LDN is Dr. Klimas first choice for pain in FM/ME/CFS and she tries, I’ve been told, to get her patients off of opiates.
Lexapro was my demise. I’ve been on Cymbalta since 2007 and it does help. I was also recently diagnosed with Shingles at the age of 30. The pain is the absolute worst I’ve ever experienced. Muscle relaxers have helped me more than any opiate ever has.
Hi again Cort,
you mentioned Dr Bateman’s best pain reliever is Lyrica but that Dr. Klimas tries to get people off opiates. Lyrica is an opiate isn’t it?
Lyrica is actually a calcium-channel blocker – https://en.wikipedia.org/wiki/Pregabalin
Carol,
The lyrica has saved my life. I rarely get any of the miserable die affects listed. I do take it alongside nortriptyline, hydrocodone and tramadol. Between the four and regular chiropractic care my fibro has had it’s ass kicked pretty well.
I still battle with manic moments since I have so much to do and seemingly no time to do it all as I fight the fatigue. It’s a vicious cycle.
On my really really bad pain days (like today, sadly) I’ve discovered a bath full of Epsom Salt and Sombra, a pain relieving gel like biofreeze or bengay, massively help my pain levels.
I just pray that they find a way to fix us for good. That or more awareness. I’m tired of people thinking I’m faking my pain! Why would someone fake being in miserable amounts of pain?!
Ha Epsom salts. Dr. Teitelbaum recommends them. It’s great when simple things work.
Glad to hear you found a good cocktail….Pain may be the quintessential invisible illness; a close friend has incredible pain issues and looks great!
Carol I feel you!! I work 5 jobs no one seems to understand the level of body pain until I have a flare up and can barely move let alone work and be tollerable! I just started lyraca less than a week ago and it is amazing how well it is working already!! Have you tried energy healing like IET or polarity therapy? Those also help me so I am not on too many opioids… Need to think to work 5 jobs… Best of luck with your pain. L&L J
Lyrica has also helped my fibromyalgia incredibly. It has from the beginning. Gabapentin didn’t work for me as it had too many side effects.
I also take oxycodone. But I have to tell you that fibromyalgia isn’t my only problem. I also have MS and some of the symptoms can be similar, mainly the pain.
Allow me to express my frustration with looking normal most of the time vs. feeling so horrible with pain that I cry. It is rare if someone understands this.
Thank you for sharing this and providing a safe place for me to share my experience. Although I still don’t understand if my brain is the cause of the pain or if the medication is going to help or hurt in the long run, which is my original reason for looking up this article.
Cort, I have read your articles before and appreciate that you put the information out here! You are very good at communicating this stuff.
Thank you.
Thanks Payne. Have you tried low dose naltrexone and medical marijuana? They can be very helpful with pain as well.
I use Tramadol and take gabapentin instead of the Lyrica. My doctor told me it is only slightly different in molecular structure, and studies in Europe showed it worked just as well. Since it is a generic drug, it is less expensive as well.
Morphine is a ending drug given to Hospice patients ! Don’t take it ! Be very careful mixing pain meds even if both a doctor or pharmacist says it’s ok. Do the research !
I have transferred to Pristiq 150mg for depression but mostly severe chronic anxiety and Pristiq has combatted both to the point that l have had no anxiety attacks since.
l can’t recommend pristiq highly enough. I have been on Lyrica 75mg for the past four months and must say l am not happy with it at all, my side affects are brain fog, memory loss, twitching of my hands causing me to drop things on a regular basis and l wondered if Lyrica was responsible for my mood swings and since reading more about Lyrica l am now convinced Lyrica is responsible for this as well. I note also that my mother in law was hospitalised after a major fall while in a nursing home and the Wodonga Hospital Doctor took her off Lyrica immeadiately as it was causing her hellucinations, these side affects are not forgiving as in l can’t remember things that l once could recall down to the last detail and l am having headaches on a regular basis which l normally don’t have. This morning l have decided to stop taking it and l will see if my memory improves at all and l will report back here the results. I know, l hear you all saying don’t just go off it, but l cannot handle these side affects, l would rather put up with withdrawals than these side affects.
I hope you managed to stop taking Lyrica. I noticed memory problems and speech problems when I started taking Lyrica, I continued on it for about 3 months and then developed a rash. Needless to say I had to stop taking it. The sad part is my memory has never recovered and this is something I will have to deal with for the rest of my life. I have read articles that have been published explaining how Lyrica destroys the brains ability to hold onto memories and also stops the brain from creating new “synapses” (that sounds right, hope I have used the correct word). I cannot blame all of this on Lyrica but it was very much the precursor.
Does it take away the pain? Hell yes!
Are the negative effects worth it? NEVER in a million years.
I couldn’t answer the sleep question, as I take Xyrem for sleep, and it knocks me out!
What a great article! I have had fibro for 22 years and tried many medications. Nothing has consistently helped because I end up getting side effects or they just stop working. I weaned off Cymbalta for money reasons. Unfortunately, it seemed to really help while I took it the last few years. I take oxy 15 mg and it only takes the pain edge away–still have lots of widespread pain. May try gabapentin again since is the cousin to lyrica but less expensive. I also take prozac for depression which has been a cheaper reliable alternative for me. Thanks so much for printing this article. Guess there is always a reason to continue to hope for a cure!!!
Me too??? I’ve had fibro 21 years and nothing has helped like Lyrica w neuropathic pain and now I’m hearing it’s a death sentence and brain destroyer:( veryupset
Death Sentence? Brain destroyer? I hope not. Who is saying that? If Lyrica is working I would stick with it. It should be rebalancing your central nervous system – I would think that would be a good thing.
My doctor wants me to take 50 mg of lyrica before bedtime. I’m so scared of the adverse reactions plus hearing it can be a brain damaging. I am scared because my dad died of dementia and also my sister died due to dementia & Alzheimer’. I have neuropathy.. tingling in my hands 24/7 and at nite numbness in my arms and hands.
Interesting article. I’ve had FM for 25 years and it effects everyone so differently. For me, 1000mg of Tylenol works well with Ultram. I’ve been taking Ambien for 15 years and this lets me sleep, which helps cope with the pain. But the best is just moving! Walk daily, easy gardening and hot showers. And symptoms change so the key is to be nice to yourself and keep track of meds and how you feel. Also cut out dairy and feel much better. Do your own trials and document how you feel….. because you won’t remember 🙂 Laugh every day, even if it’s thru your tears.
Thanks for tips Paula and relating your experience. I agree that finding something to laugh at can only help.
Lyrica as a prescription has destroyed my brain
I join the others in thanking you for the quality of what you’re putting out Cort. Thank you!
I think I’ve mentioned before about how people are amazed at how I function on 600mgm of Lyrica and 30 of Cymbalta, as well as the Keppra I also take for the seizures caused by too much serotonin (No more tramadol!) plus a Norspan patch and panadeine forte. Its interesting, because I have the constant pain of osteoarthritis to control, as well as the pain and fatigue of FM/ME. So whilst opiates aren’t apparently effective for one, they are for the other. Hence the combination, which somehow keeps me upright and coping with driving etc., although I still find I can cope with only so much mental or physical activity. For example, we have moved into a new home and my wife is asking me how I feel about hanging a print here or an ornament there and I find I just can’t cope with that amount of decision-making/stimulus at once. I have to ask her to let me spend time looking and thinking. She’s had to cope with a lot, one way or another, with all I’ve been through in the last few years.
After all that, I would be interested to hear if others with a dual diagnosis, i.e. osteo and FM/ME have fun juggling there pain management too!
Thanks Mike,
Hey I know about decision-making – that ability really took a hit with ME/CFS for some reason….It’s bizarre.
I’ll bet there are alot of people with osteoarthritis who end up having fibromyalgia/ME/CFS as well. You’ve got your constant pain input – at that point maybe all you need is for your central nervous system to bug out as well.
Studies have shown a pretty high rate of ‘fibromyaglia-ness’ in osteoarthritis patients.
🙂
I couldn’t take Lyrica or Cymbalta –both were horrible for me.
We need to take something to help with inflammation. We can mask the pain with meds —but, that’s not getting to the core issue. There are many herbals that will help with inflammation (Devils Claw, Turmeric, Ginger, Boswellia, Astaxanthin). But, then there’s the old stand-by Advil (if you don’t have issues with your kidneys —I do, so can’t take that). Then if you still need more help with pain after that – then put the Band-Aid on and mask it. I have found that Tramadol and Bentyl have been helpful for this. I not only have FMS but then got an EDS DX added to that. (Not to mention arthritis and spondylitis pain too.)
Lot’s of new studies coming out. Got a new one last night. Good info coming out.
Issie
Would love to see some studies done on acupuncture and brain fMRI changes…
Hey, I currently take Lyrica, have been on it for 4 years now, after being unsuccessful with Gabapentin (too many side affects), I was then combining Lyrica with Amitryptiline, but felt like a zombie most days, so weaned myself off the Amitryptiline… but then discovered Acupuncture…. wow, it radically changed my life!! i cannot recommend it highly enough, especially with a traditional chinese practitioner… I went form 9 weeks of hardly being able to walk to 4 weeks after starting treatment , being able to dance all night at a party. I still take Lyrica, but the dose has been cut to 200mg per day… and i have acupuncture every 4 weeks now.
I urge you to try it if you can 🙂
Congratulations Sam 🙂
Hello, This article it’s interesting, however you did not mention the authors of this study. Is it the group of Dr Montoya?, it would be very useful if you make references to the original article or magazine where this was published.
Thanks
Elena
I did have a link to it but it’s pretty hidden – http://www.ncbi.nlm.nih.gov/pubmed/24040178. In the future I’ll post the title of the study in the blog – thanks for the reminder.
Thanks a lot. You know without references it doesn’t look serious.
Just watched a TV program from the BBC in England, which showed at least 1 patient getting great relief from trans-cranial magnetic stimulation. Looks very interesting!
Your articles are very informative and I read them regularly. Thanks for your hard work.
Yes, Transcranial magnetic stimulation provides real promise. I’m going to look into it more. Thanks!
This was sent to another page on the blog…
I was diagnosed with Fibromyalgia 7 years ago after suffering for more than a year. I also suffer from chronic fatigue and RLS. I take a steady stream of Lyrica daily that causes an extreme case of memory fog. I have a hard time remembering things that just happened or that I was on my way to do. I have also been taking Lexapro for the last 6.5 years.
Prior to Lexapro, I tried Cymbalta and had a very bad experience with it. I had more severe anxiety and panic attacks, my sleep issues were far worse than my usual problems. I was awake with zero sleep for 7 days!!! On the 8th day, I quit taking Cymbalta and went med free for a few months, by far the worse few months of my life this far.
A Lexapro/Lyrica combo has worked very well for me up until the last few months. Lately, I have increased bad days and far fewer good days. If I over exert on my good days, I pay for it big time on my bad days. My pain is an 8 all day every day and I am wondering why even bother with the meds if they aren’t working. Then I imagine the pain I could be in off the meds and I remember why I take them.
My doc has given me Flexiril and Tramadol to help with the bad days but they are becoming and every day crutch just to be able to function even partially normal in order to be able to take care of my family. I am convinced that there has got to be a better way, we just need to find it.
Cort,
Thanks for another great article. I wonder how this correlates with those with ME/FM/CFS who have a partial Empty Sella? Also I have been on Cymbalta for eight years, although a life-saver I really question this length of time and it’s benefits. As a long time person who’s Subset for this illness puts me in the high pain category, this research makes a lot of sense to me.
Thanks Cort!
Thanks so much for another very hopeful article Cort. It really is sometimes the only med that works to keep me holding on when having such a bad time of it. Peace, love & continued strength to you as you continue to provide this great info 🙂
Thanks Lisa, glad to hear you are on the Lyrica responders. I hope they are working on ‘Lyrica II’ which is even better. Lyrica with its 2-3 billion a year sales in the US certainly showed the market is there.
Thank you so much for this article. I was diagnosed with Fibromyalgia last week. But I have been dealing with it for over a year and a half. I thought it could have been a gluten problem, some sort of allergies and my blood sugar kept dropping when I had sugar. So I cut all of it out of my diet and stayed away from gluten. I was getting frustrated and didnt understand why I felt so bad everyday. I am a photographer, and it takes me 2 days to recover from a wedding. I went in to a pain management dr for my back and hip problems. After a few exams and a whole lot of questions he tells me that I have fibro. His guess was that it was caused by the arthritis and the fact I have been in so much pain for 13 years. He tried to give me lyrica and after the first day waking up feeling like i was drunk and unable to function, i told him no. Currently he has me on gabapentin and norco. I have taken gabapentin before for sciatica and it worked great. It seems to be helping a little bit, but I have only been on it for a week. Now that I know what the problem is, I can take the steps to help it and improve my quality of life. My young daughters dont need to suffer because I am. The reality of it hit hard and I cried for two days. But I wont let it take me down. Reading articles like this gives me a greater understanding of the condition and gives me hope. Thank you so much for this.
Thank you so much for your work on this blog!
I know exactly how much effort it takes to scan all the medical news, make sense of it, pick out the significant items, and then write about and present them in an understandable way. I know because I’m doing the same thing for Ehlers-Danlos Syndrome and Chronic Pain at http://edsinfo.wordpress.com.
I’ll be following you on Twitter to “piggy-back” off your research because it’s closely related to what I’m doing.
Thanks! I look forward to reading your blog….and learning more about EDS and Chronic pain :)_
Lyrica is the most effective single drug I’ve taken to reduce FMS pain. It also mitigates the ME sleep problems. I don’t know what I’d do without it.
Thanks for the enlightening review of the study, Mr. Incredibly Productive!
I have taken it, and the side effects makes me worse off.:(
Yes it kill pain, but it also kill your liver,kidneys and Brain…….:(
Another drug that is Toxic:(
Beware LYRICA – IMOHO&E – It almost killed me! It grossly swelled my Optic Nerves, which can kill me IF they burst, and also take my sight! Also, medicating pain should not be done till ALL PATHOGENS are RULED OUT! (Both Biotic & Viral – especially in CFS/FM go to SPECIALIST, like Teitlebaum’s Clinics, with effective LAB to test for atypical pathogens).
Byron J. Richards from ‘Wellness Resources’ wrote in Oct. 2009 that Neurontin and Lyrica are a death sentences for Brain Synapses … do you have any comments on that Cort?
I have no idea about that…Sorry..
Cort ,
I find it a bit alarming that you have no idea about the studies that have shown that Lyrica is harmful to your brain in long term studies . Having severe Fibromyalgia myself and hearing the others with it ask you about these studies deeming it harmful , and you have no clue about them . It is in the spotlight right now how it is harmful to your brain , and it is in multiple places showing these studies – so I wonder how you can possibly miss this ?? You don’t have to do much digging to find these studies . I am very concerned taking Lyrica for about 2 years now , that the long term effects are so harmful to our brains , and you have no idea about these studies – how is this possible ?? I would think that having heard it from multiple people you would do a little research on the topic . The studies are everywhere and very easy to find – simply google it and you will come up with many places to view these studies and the harmful effects of Lyrica . I hope you do look into it , and would love to hear your opinion on it . It is very alarming and the sooner the better you look into it because of the awful effects it has on people , you may change your mind about the drug and it’s helpfulness for Fibro patients . Thank you for listening !
Chris
Hi Chris – You got me digging. I’ve gone through pages and pages of Pubmed studies on Lyrica. I’m afraid I haven’t found anything suggesting it’s harmful to your brain. Indeed, more and more uses of Lyrica are popping up. Check out some abstracts of Lyrica studies including a few long term ones. Please send me the links to the studies you mention.
I’m definitely not an expert on any drug but I’m willing to learn.
Arthritis Care Res (Hoboken). 2013 Aug 27. doi: 10.1002/acr.22111. [Epub ahead of print]
Twice Daily vs Nightly Dosing of Pregabalin for Fibromyalgia: A Double blind, Randomized Clinical Trial of Efficacy and Safety.
Nasser K, Kivitz AJ, Maricic MJ, Silver DS, Silverman SL.
Source
Osteoporosis Medical Center, Beverly Hills, CA.
Abstract
Objective: To compare efficacy, discontinuation rates and safety of once nightly (HS) dosing vs twice daily (BID) dosing of pregabalin in a community based trial. Methods: This multicenter, double-blind, 8-week randomized clinical trial compared the effects of 300mg daily dose of pregabalin given either twice daily or once nightly for the treatment of fibromyalgia in 177 patients. The primary outcome was the comparison of end point mean pain scores derived from a daily diary. Results: Both BID (88 patients randomized) and HS (89 patients) dosing of pregabalin significantly reduced the average severity of pain experienced by patients (BID, HS, p<0.001). Treatment-emergent adverse events were reported by significantly more BID patients than HS patients (p=0.023). There were no significant differences between the arms for the frequencies of individual adverse events (all p values >0.05). There was no significant difference in adverse events or efficacy in patients taking both pregabalin and an SNRI (serotonin norepinephrine uptake inhibitor) or SSRI (selective serotonin uptake inhibitor).
Mod Rheumatol. 2012 Dec 1. [Epub ahead of print]
An open-label long-term phase III extension trial to evaluate the safety and efficacy of pregabalin in Japanese patients with fibromyalgia.
Ohta H, Oka H, Usui C, Ohkura M, Suzuki M, Nishioka K.
Source
Pfizer Japan Inc., 3-22-7, Yoyogi, Shibuya-ku, Tokyo, 151-8589, Japan.
Abstract
OBJECTIVES:
To assess the long-term safety and efficacy of pregabalin for the treatment of Japanese patients with fibromyalgia (FM).
METHODS:
This 53-week, open-label extension study was conducted at 20 study sites in Japan in patients with FM who had completed a preceding 16-week, placebo-controlled, double-blind trial. Patients received pregabalin, starting at 150 mg/day and increasing to a maintenance dose of 300 or 450 mg/day. The primary endpoint was safety, and secondary endpoints included measures of pain, sleep, and physical functioning.
RESULTS:
106 patients entered the trial and received at least one dose of the study drug. The most common treatment-related adverse events were somnolence, dizziness, increased weight, and constipation. There were no treatment-related serious or severe adverse events. There were five (4.7 %) discontinuations due to adverse events, of which three (2.8 %) were considered related to the study drug. Most adverse events resolved over time and could be managed without dose reduction or treatment discontinuation. Improvements in secondary efficacy endpoints of pain, sleep, and physical functioning emerged early in the study and were maintained for the duration of treatment.
CONCLUSIONS:
These data indicate that the long-term treatment of Japanese FM patients with pregabalin may be both safe and effective.
Pasted from <http://www.ncbi.nlm.nih.gov/pubmed/23203241>
Arthritis Res Ther. 2012 Oct 12;14(5):R217. [Epub ahead of print]
A randomized, double-blind, multicenter, placebo-controlled phase III trial to evaluate the efficacy and safety of pregabalin in Japanese patients with fibromyalgia.
Ohta H, Oka H, Usui C, Ohkura M, Suzuki M, Nishioka K.
Source
Institute of Innovative Medical Science and Education, Tokyo Medical University, 6-1-1 Shinjyuku, Shinjyuku-ku, Tokyo 160-8402, Japan. imse-kn@tokyo-med.ac.jp.
Abstract
ABSTRACT:
INTRODUCTION: Fibromyalgia is a chronic disorder characterized by widespread pain and tenderness. Prior trials have demonstrated the efficacy of pregabalin for the relief of fibromyalgia symptoms, and it is approved for the treatment of fibromyalgia in the United States. However, prior to this study, there has not been a large-scale efficacy trial in patients with fibromyalgia in Japan.
METHODS:
This randomized, double-blind, multicenter, placebo-controlled trial was conducted at 44 centers in Japan to assess the efficacy and safety of pregabalin for the symptomatic relief of pain in fibromyalgia patients. Patients aged ≥18 years who had met the criteria for fibromyalgia were randomized to receive either pregabalin, starting at 150 mg/day and increasing to a maintenance dose of 300 or 450 mg/day, or placebo, for 15 weeks. The primary efficacy endpoint was mean pain score at final assessment. Secondary endpoints included Patient Global Impression of Change (PGIC) together with measures of sleep, physical functioning and quality of life.
RESULTS:
A total of 498 patients (89% female) were randomized to receive either pregabalin (n = 250) or placebo (n = 248). Pregabalinsignificantly reduced mean pain score at final assessment (difference in mean change from baseline, compared with placebo -0.44; P = 0.0046) and at every week during the study (P <0.025). Key secondary endpoints were also significantly improved with pregabalin treatment compared with placebo, including PGIC (percentage reporting symptoms "very much improved" or "much improved", 38.6% vs 26.7% with placebo; P = 0.0078); pain visual analog scale (difference in mean change from baseline, compared with placebo -6.19; P = 0.0013); Fibromyalgia Impact Questionnaire total score (-3.33; P = 0.0144); and quality of sleep score (-0.73; P <0.0001). Treatment was generally well tolerated, with somnolence and dizziness the most frequently reported adverse events.
CONCLUSIONS:
This trial demonstrated that pregabalin, at doses of up to 450 mg/day, was effective for the symptomatic relief of pain in Japanese patients with fibromyalgia. Pregabalin also improved measures of sleep and functioning and was well tolerated. These data indicate that pregabalinis an effective treatment option for the relief of pain and sleep problems in Japanese patients with fibromyalgia.
Pasted from <http://www.ncbi.nlm.nih.gov/pubmed/23062189>
Clin Ther. 2012 May;34(5):1092-102. doi: 10.1016/j.clinthera.2012.03.003. Epub 2012 Apr 14.
Safety profile and tolerability of up to 1 year of pregabalin treatment in 3 open-label extension studies in patients with fibromyalgia.
Arnold LM, Emir B, Murphy TK, Zeiher BG, Pauer L, Scott G, Petersel D.
Source
Women’s Health Research Program, Department of Psychiatry and Behavioral Neuroscience, University of Cincinnati College of Medicine, Ohio, USA. Lesley.Arnold@uc.edu
Abstract
BACKGROUND:
Pain relief and an acceptable safety profile have been reported in randomized controlled trials (RCTs) of pregabalin in the treatment of fibromyalgia (FM) for up to 14 weeks.
OBJECTIVE:
To evaluate the safety profile and tolerability of pregabalin (75-300 mg BID) treatment for up to 1 year in patients with FM.
METHODS:
Twelve-week data were pooled from 3 open-label extension studies of pivotal RCTs. Study 1 was a 1-year extension of a 13-week RCT, and studies 2 and 3 were 12-week extensions of 14-week RCTs. The 1-year data were separately evaluated. The open-label data are summarized using descriptive statistics.
RESULTS:
Overall, 1206 patients (92.4% female) with a mean (SD) age of 48.8 (10.7) years received open-label extended pregabalin treatment. A total of 119 of 1206 patients (9.9%) permanently discontinued study participation due to treatment-emergent adverse events (all causality) at 12 weeks (pooled data) and 53 of 429 (12.4%) within 1 year. Consistent with previous RCTs, the most commonly reported treatment-emergent adverse events with open-label pregabalin treatment were dizziness, somnolence, headache, peripheral edema, and increased weight. The highest incidence rates in the pooled 12-week data were for dizziness (214 of 1206; 17.7%) and somnolence (96 of 1206; 8.0%). In ratings of severity (mild, moderate, severe), most were reported as mild to moderate. The mean (SD) change in patient-reported visual analog scale pain scores (0-100) from the open-label baseline to the end of treatment was -21 (30.5) in study 1 (1 year), -26.7 (28.8) in study 2 (12 weeks), and -20.1 (26.8) in study 3 (12 weeks).
CONCLUSIONS:
The data from these extension studies suggest that the adverse event safety profile and tolerability of patients with FM treated with open-label pregabalin (75-300 mg BID) for up to 1 year were stable and were consistent with those of previous studies. ClinicalTrials.gov identifiers: NCT00151528 (A0081057 [study 1]), NCT00282997 (A0081078 [study 2]), and NCT00346034 (A0081101 [study 3]).
Pasted from <http://www.ncbi.nlm.nih.gov/pubmed/22503162>
Eur J Clin Pharmacol. 2012 Jun;68(6):903-12. doi: 10.1007/s00228-012-1213-x. Epub 2012 Jan 21.
The adverse event profile of pregabalin across different disorders: a meta-analysis.
Zaccara G, Perucca P, Gangemi PF.
Source
U.O. Neurologia, Azienda Sanitaria di Firenze, Florence, Italy. gaetano.zaccara@asf.toscana.it
Abstract
PURPOSE:
In a recent meta-analysis of 38 double-blind randomized controlled trials (RCTs) comparing pregabalin (PGB) to placebo, we found 20 adverse events (AEs) to be significantly associated with PGB treatment. In the present study, we evaluated whether the incidence of these 20 AEs differs across distinct disorders in which PGB was investigated.
METHODS:
Among the 38 previously identified RCTs of PGB, we selected only those including a PGB 600 mg/day arm and subsequently classified them into four distinct groups according to the disorder in which PGB was investigated: (1) drug-resistant partial epilepsy, (2) psychiatric disorders, (3) fibromyalgia, and (4) neuropathic pain. We used risk differences (RDs) to quantify the placebo-corrected proportion of subjects discontinuing PGB due to intolerable AEs and to determine the placebo-corrected incidence of each of the 20 PGB AEs across the four disorders.
RESULTS:
Twenty-two RCTs were included in this study. Neither the proportion of subjects discontinuing PGB due to intolerable AEs nor the incidence of PGB AEs (with the exception of ataxia) differed significantly across the four disorders. Ataxia was more common in drug-resistant partial epilepsy compared to fibromyalgia. When limiting analyses to subjects on placebo, most vestibulo-cerebellar AEs (ataxia, diplopia, and blurred vision) were found to be more common in drug-resistant partial epilepsy compared to all other disorders. Diplopia and blurred vision were more common in epilepsy than in neuropathic pain; and ataxia had a higher incidence in epilepsy than in anxiety disorder and fibromyalgia. Among other CNS AEs, somnolence was more common in epilepsy compared to neuropathic pain and in anxiety disorders alone compared to neuropathic pain and fibromyalgia. Asthenia was also more common in epilepsy than in neuropathic pain and fibromyalgia.
CONCLUSIONS:
Although drug-resistant partial epilepsy is associated with a higher probability of developing vestibulo-cerebellar AEs, the risk for PGB toxicity does not differ across distinct disorders.
Pasted from <http://www.ncbi.nlm.nih.gov/pubmed/22271298>
J Rheumatol. 2011 Dec;38(12):2643-52. doi: 10.3899/jrheum.110569. Epub 2011 Oct 1.
An international, randomized, double-blind, placebo-controlled, phase III trial of pregabalin monotherapy in treatment of patients with fibromyalgia.
Pauer L, Winkelmann A, Arsenault P, Jespersen A, Whelan L, Atkinson G, Leon T, Zeiher B; A0081100 Investigators.
Collaborators (74)
Source
Pfizer Global Research and Development, Groton, CT 06340, USA. lynne.pauer@pfizer.com
Abstract
OBJECTIVE:
To evaluate the efficacy and safety of pregabalin monotherapy versus placebo for symptomatic pain relief and improvement of patient global assessment in patients with fibromyalgia (FM) enrolled from countries outside the United States.
METHODS:
This international, multicenter, double-blind, placebo-controlled trial randomly assigned 747 patients with FM to placebo or 300, 450, or 600 mg/day pregabalin twice daily for 14 weeks. Primary efficacy measures were endpoint mean pain scores and Patient Global Impression of Change (PGIC). Secondary outcomes included assessments of sleep and function.
RESULTS:
Patients in the 450 mg/day pregabalin group showed significant improvements versus placebo in endpoint mean pain score (-0.56; p = 0.0132), PGIC (73% improved vs 56% placebo; p = 0.0017), and function [Fibromyalgia Impact Questionnaire (FIQ) total score -5.85; p = 0.0012]. PGIC was also significant for 600 mg/day pregabalin (69% improved; p = 0.0227). Results for these endpoints were nonsignificant for pregabalin at 300 mg/day and for pain and FIQ score at 600 mg/day. Early onset of pain relief was seen, with separation from placebo detected by Week 1 in allpregabalin groups. All pregabalin doses demonstrated superiority to placebo on the Medical Outcomes Study-Sleep Scale Sleep Disturbance subscale and the Sleep Quality diary. Dizziness and somnolence were the most frequently reported adverse events.
CONCLUSION:
Pregabalin demonstrated modest efficacy in pain, global assessment, and function in FM at 450 mg/day, and improved sleep across all dose levels, but it did not provide consistent evidence of benefit at 300 and 600 mg/day in this study. Pregabalin was generally well tolerated for the treatment of FM. (Clinical trial registry NCT00333866).
Pasted from <http://www.ncbi.nlm.nih.gov/pubmed/21965636>
Neurol Res. 2013 Jul 1. [Epub ahead of print]
Evaluation of analgesic, antioxidant, cytotoxic and metabolic effects of pregabalin for the use in neuropathic pain.
Sałat K, Librowski T, Nawiesniak B, Gluch-Lutwin M.
Abstract
OBJECTIVE:
The aim of this research was to evaluate analgesic, antioxidant, metabolic, and cytotoxic effects of pregabalin (PGB), which is widely applied for the treatment of neuropathic pain syndromes in diabetic patients.
METHODS:
We used the streptozotocin (STZ) model of painful diabetic neuropathy (PDN) in mice and we measured the effect of intraperitoneally administered PGB on tactile and thermal nociceptive thresholds in the von Frey and hot plate assays, respectively. The influence of PGB on the motor coordination of diabetic animals was investigated in the rotarod test. In vitro in HepG2 and 3T3-L1 cell lines cytotoxicity of PGB, its influence on glucose utilization, and lipid accumulation were assessed. The antioxidant capacity of PGB was evaluated spectrophotometrically using 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical method.
RESULTS:
Pregabalin was a very efficacious antiallodynic and analgesic drug capable of increasing the pain thresholds for tactile allodynia and thermal hyperalgesia in diabetic mice. In the von Frey test at a dose of 30 mg/kg it elevated the pain threshold for 168% versus diabetic control and in the hot plate test this dose prolonged the latency time to pain reaction for 130% versus control value of diabetic mice. No motor deficits were observed in PGB-treated diabetic animals. In vitro PGB did not influence glucose utilization or lipid accumulation. No antioxidant or cytotoxic effects of PGB were observed at concentrations 1-100 μM.
DISCUSSION AND CONCLUSION:
Our experiments demonstrated significant antiallodynic and analgesic properties of PGB in mice. In vitro studies showed that this drug is metabolically neutral. It did not cause motor coordination impairments in diabetic animals either. These effects might be of great importance for diabetic patients.
Pasted from <http://www.ncbi.nlm.nih.gov/pubmed/23816319>
Curr Med Res Opin. 2013 Oct;29(10):1223-30. doi: 10.1185/03007995.2013.820694. Epub 2013 Aug 19.
Long-term treatment of anxiety disorders with pregabalin: a 1 year open-label study of safety and tolerability.
Montgomery S, Emir B, Haswell H, Prieto R.
Source
Imperial College School of Medicine, University of London , London , UK.
Abstract
Abstract Objective: Short-term clinical trials have demonstrated the efficacy and safety of pregabalin in the treatment of generalized anxiety disorder (GAD). This study examined long-term safety and tolerability of pregabalin in patients with GAD, social anxiety disorder (SAD), or panic disorder (PD). Research design and methods: Patients (n = 528) completing one of four randomized, double-blind, placebo-controlled trials of pregabalin for GAD, SAD, or PD were treated, open label, with flexible-dose pregabalin (150-600 mg/day) for 1 year. Clinical trial registration: NCT00150449. Main outcome measures: The primary outcomes were safety and tolerability. Illness severity was assessed at baseline and Weeks 27/52 using the Clinical Global Impression of Severity (CGI-S) scale. Patients were characterized as ‘responders’ or ‘non-responders’ based on CGI-S scores ≤2 and >2, respectively. Analyses were performed on the total anxiety (GAD, SAD and PD) and GAD groups. Results: During 1 year of treatment with pregabalin, dizziness (12.5%) was the only treatment-related adverse event (AE) occurring ≥10%. Somnolence, weight gain, headache and insomnia occurred at 7.6%, 5.5%, 5.3% and 4.7%, respectively. Few treatment-related AEs were rated as severe in the total anxiety (5.1%) or GAD (3.6%) groups. Discontinuation rates due to AEs were similar (9.7% and 10.6%, respectively). No clinically significant laboratory, electrocardiogram, or other treatment-related safety findings were noted, except for treatment-related weight gain, which occurred in both the total (24.4%) and GAD (19.4%) groups. Mean CGI-S scores were similar at baseline in the total (n = 528; score, 3.4) and GAD groups (n = 330; score, 3.6), and CGI-S responder rates were similar at last-observation-carried-forward endpoint (51.3% and 48.1%, respectively).
Conclusions: Pregabalin was generally well tolerated in the long-term treatment of anxiety disorders. Improvement in illness severity was maintained over time. The key limitations of this study were that it was not randomized and neither placebo- nor active-comparator-controlled.
Pasted from <http://www.ncbi.nlm.nih.gov/pubmed/23808960>
Curr Pharm Des. 2013;19(35):6367-74.
The potential of pregabalin in neurology, psychiatry and addiction: a qualitative overview.
Martinotti G, Lupi M, Sarchione F, Santacroce R, Salone A, De Berardis D, Serroni N, Cavuto M, Signorelli M, Aguglia E, Valchera A, Iasevoli F, Di Giannantonio M.
Source
National Health Service, Department of Mental Health, Psychiatric Service of Diagnosis and Treatment, “G. Mazzini” Hospital, p.zza Italia 1, 64100 Teramo (Italy). dodebera@aliceposta.it.
Abstract
Pregabalin is an anticonvulsant drug that binds to the α2δ (alpha2delta) subunit of the voltage-dependent calcium channel in central nervous system (CNS). Pregabalin decreases the release of neurotransmitters, including glutamate, norepinephrine, substance P and calcitonin gene-related peptide. Purpose of this paper is to offer a qualitative overview of the studies currently available in literature about this drug, examining the effectiveness ofpregabalin in its various fields of application. Our analysis, conducted on a final selection of 349 scientific papers, shows that pregabalin may help to reduce pain in diabetic neuropathy, in post-herpetic neuralgia and in some patients affected by fibromyalgia. It is also effective for the treatment of diverse types of seizures and has similar efficacy to benzodiazepines and venlafaxine in anxiety disorder. Moreover, pregabalin may be a therapeutic agent for the treatment of alcohol abuse, in both withdrawal phase and relapse prevention. Possible implications in the treatment of benzodiazepines dependence are emerging, but a potential abuse or misuse of the drug has also been reported. Range of dosage may fluctuate considerably, from 75 mg to 600 mg per day. Further studies are needed to completely understand pregabalin mechanism of action in the different diseases.
Pasted from <http://www.ncbi.nlm.nih.gov/pubmed/23782139>
Thank you for the article. I have been on lyrica for 2 years(300 mg /day) and it is a lifesaver.
I have fibro with arthritis of the spine and the pain is horrible.
The lyrica is helpful,but does not kill the pain.
In any event,with respect to the thalmus being the controller-I suffered a cerebral concussion 8 yrs ago , and a serious head injury. Chronic headaches and post concussion syndrome.
The syndrome initiated fibromyalgia.
The pain for headaches comes from deep inside the head, excruciating, I cannot even stand
having an MRI-the noise gives me severe sick headaches. Earplugs dont help.
I think you are on to something with the pain centre deep in the brain,keep up the good work, omg we need you guys out there helping.
They did try every drug in the book(over 40 types) and only lyrica helped. It doesn’t kill the pain,it takes the edge off.But that helps. i was even up to 2400 mg gabapentin per day and nothing!
Well, keep going , we need to find the answers.Thanks
Hi Cort,
Firstly, I think you’re doing a great job in disseminating a lot of diffuse information. You write very clearly, which helps those of us who have cognitive issues due to our health conditions.
Having said that, it’s true that there are many negative reports on Lyrica coming to the surface. These normally aren’t given any priority coverage, or any coverage at all, in the medical journal articles that have often been written by researchers funded by the drug companies themselves. A recent case has just seen a doctor charged with 21 counts of ‘fudging’ research data; in fact in some of his so-called studies he actually made the data up. These results were published in the major journals like Pub-med. Let me see if I can find you the link:
http://www.yourlawyer.com/articles/title/-doctor-accused-of-falsifying-drug-studies-pleads-guilty
Sorry…you’ll have to copy and paste that by the looks of it. I have no idea how to turn it into a link for you. 🙂
And here’s another article linking lyrica with suicidal ideation:
http://www.yourlawyer.com/topics/overview/lyrica
The following article is rather long and tedious but it’s worth looking further down the page at the Nervous System Adverse Reactions. The link to that page is here:
http://www.rxlist.com/lyrica-drug/side-effects-interactions.htm
I have personally suffered from a number of these extremely disturbing CNS issues while taking Lyrica. I would frequently not be able to discern whether something had happened or if I had dreamt it. I had to ask my husband to clarify for me. I also started to have mini-seizures – micro-second blackouts that happened perhaps dozens of times a day sometimes. My memory, already compromised because of my ME/fibromyalgia, then became worse. I began to ‘lose’ 2 or 3 hours at a stretch and was often told by my husband that I had been ‘raging’ and occasionally violent. I have always been an exceptionally calm and rational person. When I first went on the Lyrica, I had no problems, and noticed a tiny decrease in pain levels. As the months went by, the negative effects of the lyrica began and gradually worsened. Because it took several months to a year for them to appear, I didn’t make the connection. This appears to be a common experience for people. Many of us begin taking it without a problem, but as time goes by the damage seems to come to light.
For me, the damage has been catastrophic in terms of the loss of my marriage and property…as well as my capacity to work and earn an income. My hearing is very poor also – and this is not an uncommon happening for people who take Lyrica. The hearing loss is permanent – never returns to normal, even after stopping the drug. Other people have experienced extreme vision loss – which also never returns to normal. I feel as though I have dumbed down and slowed down considerably (and who needs that on top of a condition that already dumbs and slows us down???)
I would be very careful with Lyrica. I know that it truly does work extremely well for some people. But do we know if that will be longterm? Or will they begin to deteriorate over time? I’ve had a brain SPECT scan that shows decreased blood flow in three key areas of my cortex – frontal, temporal and parietal lobes. The pattern of reduced flow is indicative of alzheimer’s dementia. I’m 53 years old with no history of alzheimers in my family. I have read on a couple of different websites that lyrica is being linked with dementia also. I’m a little too tired to go in search of that information for you at the moment, but if you’d like me to, just let me know. I’d be more than happy to help keep people informed of both sides of the lyrica debate.
For me though, it has been life-changing in the most damaging of ways. Thanks for listening to my rant. I’m currently following up on a class action suit. I’ll need half a dozen more Australians who have also been damaged by Lyrica to join me. If there are any of you out there, perhaps we can somehow co-ordinate an exchange of emails or something…whatever is the politically correct way of doing things. If you’re able to help, Cort, that would be wonderful.
Thanks again for this great blog.
Thanks for all the info Melinda. I note that a recent overview of the drugs available for FM was not very positive; lots of work to me done!
so, does Lyrica cause dementia??
I hate Lyrica! It steals my brain. My spontaneous recall and ability to retrieve data from my memory has been severely impaired by Lyrica. It does help reduce my pain, but I am very concerned that I am on the fast track to early dementia. We won’t know about Lyrica’s connection with dementia until my generation (that’s all of us present today) have sustained 10 or 20 years of continuous use of the drug. I don’t tout the merits of oxycodone (it is also a bad drug) but I never experienced such difficulties with thought and information recall as I do now thanks to Lyrica. What really bothers me most is a feeling that pain management MDs are prescribing Lyrica to chronic pain patients more in the interest of eliminating their potential liabilities in wrongful death lawsuits than in the interest of helping people, like me, suffering from chronic pain resulting from injuries, advanced age and widespread arthritis. I want to divorce from Lyrica – I despise the stuff – but I am, otherwise, racked with more pain than I can handle. I don’t know what to do.
Can I take astaxanthin, red marine algae, lysine Immuno-shield while taking Lyrica?
I’m not very good at things like this but, here goes. I was diagnosed with FM 22 years ago at Mayo Clinic. I also had extreme restless leg syndrome. At first my doctor put me on Demerol then he put me on a Fentanyl patch ( watch out!!!). I simply suffered with the pain that no one understood. I was labeled a drug addict even though a doctor gave me these meds. I never asked for them. Years later doc finally off the opioids he put me on Lyrica. At first I thought it was an answer to prayer. A Miracle!!! But I soon learned it was a drug from hell!! I went from 50mg a day to 400mg a day when I finally decided on my own to stop. I had been taking it for some 15 years or more. My weight had exploded, my personality had changed, I stayed in the bed most of the time. I had no life and wanted to die. It’s ruined my relationship with my husband. Now I’m divorced after a 48+ year marriage. I tried to commit suicide. Finally after doing my own research I stopped the Lyrica. I learned how to control my restless legs and the pain of fibro. I have been off of it and all the other meds I took for over three years now. I feel human again!! No more depression, no more wanting to sleep all the time (well not sleep just stay in the bed). I still have problems with my memory and my weight. I am now totally holistic, no prescription meds at all. Being judged by strangers is bad but by friends and family that say they love you is way worse. I’ve learned to accept that and move on with my life. One little hint, stop ALL caffeine!!!!! No matter how little. You’ll be surprised how much that helps. I wish I could sue Pfizer but that will never happen. This country runs on drugs (all kinds from all kinds of people) and drug companies. Most tv commercials are big pharm co. hawking their meds or lawyers wanting you to hire them to sue the big pharms. I have a right to my opinion. It was my life it (almost) ruin.