Pregabalin for neuropathic pain: balancing benefits and harms

In this blog, Sarah Chapman looks at the latest Cochrane evidence on the benefits and harms of pregabalin for neuropathic pain and reflects on her husband’s experience of finding a balance between them.

I suspect that people who live with chronic health conditions know a lot about balance. About the trade-offs that need to be considered when it comes to activities, perhaps; about adjustments made to diet, rest or medication to keep things level, or at least within the realms of what feels acceptable. Adding a new treatment threatens that balance. There is the hope it will bring benefits, but it might cause unwelcome side-effects. Here’s a new thing to juggle.

I’ve seen this up close over the past year, as my husband Tim has been living with neuropathic pain. Neuropathic pain comes from nerve damage, from a variety of causes and sometimes an unknown cause. It may not respond well to what we think of as ‘painkillers’ and other types of drugs may be tried. When Tim found no relief with various painkillers, his GP suggested pregabalin, an anti-epileptic drug that can be effective for relief of neuropathic pain. Can be. It’s also associated with side-effects, especially dizziness and sleepiness, and Tim has had rather too much experience of dizziness as a result of another condition. Yet he was willing to chance it. “At this point, I was awake for much of the night in intense pain, too tired to stand up and in too much pain to lie down. I was in a very difficult place. I was prepared to take anything that was offered, and I’d heard good things about pregabalin from health professional colleagues. I was warned by my GP about side-effects but I’d have taken bigger risks to get rid of the pain.”

So began a period of juggling, trying to find the right balance. Months down the line, we were very interested to see the publication of a Cochrane Review on the benefits and harms of pregabalin for adults with neuropathic pain. What information would this offer for others making decisions about taking it?

New Cochrane evidence on pregabalin

The review includes 45 studies (lasting two to 16 weeks) with almost 12000 adults. Most people had postherpetic neuralgia (pain after shingles), diabetic neuropathy or mixed neuropathic pain and the review looks at the evidence for people grouped by condition and also altogether. Oral pregabalin at daily doses of 150mg, 300mg and 600mg were compared with placebo.

Pain reduction for some

The bottom line of the review is that oral pregabalin is helpful for some people with chronic neuropathic pain, but it isn’t possible to know who will benefit and who won’t. At doses of 300mg and 600mg, it probably has an important effect in some people with moderate or severe neuropathic pain after shingles or due to diabetes, and it may be effective for some after trauma due to stroke or spinal cord injury. It is probably not effective for pain in people with HIV. There isn’t reliable evidence on the effects of pregabalin on other types of neuropathic pain.

How much pain reduction is worthwhile?

A very personal consideration perhaps, but pain intensity reduction of at least 50% has been identified as a useful treatment outcome by people with chronic neuropathic pain and is associated with important benefits for sleep, fatigue, depression, work and quality of life. The evidence in the review suggests that more than half of those taking pregabalin won’t get this much pain relief: around three or four people out of ten, compared with one or two taking placebo.

Possible harms

The review has high-certainty evidence about harms, so the review authors feel confident that future research is not likely to paint a very different picture, although they note that the effects of pregabalin on sexual function may not be well represented in the trials and nor was the issue of substance abuse with pregabalin addressed.

Serious side effects were rare and were not different between those taking pregabalin and those taking placebo tablets. However, less serious adverse events were common, particularly dizziness and sleepiness. Out of ten people taking pregabalin, six or seven will experience one or more adverse event, though so will five or six out of ten people taking placebo.

Taking all the neuropathic pain conditions together, the results show a minimal increase in the rate of adverse events at a daily dose of 600mg compared with 300mg, while in general the 150mg dose did not produce an excess of adverse events, except sleepiness in people with neuropathic pain following shingles.

The challenges for future research include providing information about who is likely to benefit and how the drug can be titrated to minimize adverse events.

Benefits and harms: a personal balancing act

 Tim increased his pregabalin dose slowly, as advised, but it took some experimentation to get the dose ‘right’ for him. “At 200mg it got rid of the pain and allowed me to sleep at night, but I was falling asleep all the time during the day. Going down to 100mg I had pain in the night again. Settling at 150mg a day it’s debatable whether I’ve got the best or the worst of both worlds – I’m still sleepy during the day but I’m not too sleepy to work, and I still have some pain but it’s manageable.”

But that’s not all. Tim explains: “I’m enjoying the trippy dreams and I’m feeling more relaxed than I’ve felt in my life – which is really great! These side effects are benefits for me! What’s less good is that I sometimes lose bits of time; I can find it hard to remember what I did earlier in the day or the day before. Yet I am also thinking more clearly; when I’m working, being more relaxed seems to mean that my recall of systems and activities is sharper. How much is down to the pregabalin I don’t know – but don’t take it away!”

A complex reality

Of course, it’s complicated. Neuropathic pain is only one facet of Tim’s health profile and pregabalin one treatment among several. As he acknowledged, it’s not certain that everything he describes is down to the pregabalin. There’s guesswork, trial and error, in the mix, even with this new evidence providing more information than was previously available.

What matters to each of us differs and that could be crucial in decisions about treatments. A side effect that is intolerable to me might not bother you. It’s complicated. Once recommendations and decisions about a treatment have been made, hopefully informed by the best available evidence, collecting a drug from the pharmacy may be just the beginning of a long and complex relationship, as we discover what it does for and to us, and how it fits (or doesn’t) in the day-to-day business of managing our health.

Join in the conversation on Twitter with @SarahChapman30 @CochraneUK @CochranePaPaS or leave a comment on the blog.

Reference: Derry  S, Bell  RF, Straube  S, Wiffen  PJ, Aldington  D, Moore  RA. Pregabalin for neuropathic pain in adults. Cochrane Database of Systematic Reviews 2019, Issue 1. Art. No.: CD007076. DOI: 10.1002/14651858.CD007076.pub3.

Sarah Chapman has nothing to disclose.



Sarah Chapman

About Sarah Chapman

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Sarah's work as a Knowledge Broker at Cochrane UK focuses on disseminating Cochrane evidence through social media, including Evidently Cochrane blogs, blogshots and the ‘Evidence for Everyday’ series for nurses, midwives, allied health professionals and patients. A former registered general nurse, Sarah has a particular interest making evidence accessible and useful to practitioners and to others making decisions about health. Before joining Cochrane, Sarah also worked on systematic reviews for the University of Oxford and the Royal College of Nursing Institute, and obtained degrees in History from the University of Oxford and in the history of women’s health and illness in early modern England (MPhil., University of Reading).

11 Comments on this post

  1. Avatar

    I have been on Pregabalin for about 10 years on and off. I tolerate very well and have no side affects whatsoever. I was prescribed it for generalised anxiety. I was very sceptical about taking at first as I never thought it would work. But the next day the anxiety was gone. This is how effective I find pregabalin. I know its not down to any form of placebo affect as like I stated, I never thought it would work. I now have sciatica and am in a lot of pain. My GP has increased the dose considerably, but I have never found it works reducing pain unfortunately. I have never found it addictive and am able to come off without any issues. I know of people who were prescribed it for neuropathic pain and have got addicted to it because they are using it as a “chill pill”. I have not experienced this and thankfully all it does is relieves the anxiety.

    Stuart Brown / Reply
  2. Avatar

    I’ve been on pregabalin for 4 years now and it Is highly addictive.
    It helps me with anxiety but makes my nerves worse and I shake alot.
    I’m also aware in prisons in the UK it’s prescribed like smarties and there’s 1000s of people on it.
    I really wish I could come off it but now I’m stuck on it and can’t as I become depressed, anxious and can’t leave the house unless I take it.
    Stay well away from it if your offered it and look for an alternative as once your on it, it’s extremely hard to come off.
    I’ve heard herion addicts say it’s worse coming off pregabalin than herion and the worse detox of their life’s.
    Ill say it again stay well away from it as I’m tired all day, can’t function properly and now classed as disabled as a result and got severe mental health problems

    Buster brown / Reply
  3. Avatar

    I have just started taking pregabalin for diabetic neuropathy and am taking 75 mg twice a day. Right now I am finding that the medication seems to increase the pain in my feet and not reduce it in any way. Hopefully this is only temporary and i manage to receive some benefit from further medicating myself.

    Bob Harvey / Reply
    • Avatar

      Hi bob, I was taking 75mg and found it didn’t work and made there pain worse. GP upped my does to 100mg yesterday and I Found the pain had become worse, Iv had the worst night sleep yet. The pain in my foot is unbearable!
      Keeping fingers crossed that it soon kicks in and works.

      Nikita Williams / (in reply to Bob Harvey) Reply
    • Avatar

      im having same trouble now with lyrica. Im torn between if its working at all or making worse I really don’t know. right now im off it 4 days trying to survive through it. did you find anything that works?

      mike / (in reply to Bob Harvey) Reply
  4. Avatar

    This was an interesting article. What kills me is that doctors really do not know a thing about his medication, but prescribe it anyway. It is very well known that in reality no one knows how it works on the nervous system, or why. However, once again, as with so many things in the health field, there just isnt anything else. So we guinea pig ourselves, because lets be honest, being in pain 24/7 is not for anyone and life goes on. The thing I agree most on here is the balance between pain and feeling like nutcase. This is a very delicate balance, and it will be very different for EVERYONE. There is no perfect potion. Of course Phizer being the money grubbing self serving people that they are, made sure that the pills cant be cut, using the other pill form, but I found a way around that, just open it and put it in water if you have to cut it down. Generics have been authorized finally as well, so the 4.2 billion made is now going to have to be shared. I have found that nerves go nuts at night, for me taking this crap during the day just makes me nuts. I take one pill 75mgs in them morning and that is it. I deal with the bit of pain I have. At night however, I take 300mgs starting at 5pm, then 7pm, then around 8pm, and 10pm these are all 75mg pills, and for some odd reason, I cant handle the 100 mgs at a time. Weird I know. This cuts the pain off at night, ( most of it), and allows me to sleep. I will also say that I have experienced dry mouth, dehydration like feelings with water retention. ( honestly I have never taken longer pee’s then on this medication ever! in the morning). I have tried to keep this medication as low as possible, but what I have also found is that there is a backlash to taking it. Your nerves react to the medication by acting out against it and becoming more aggressive, therefore leaving you with having to take more medication to get them to calm down. This is just my experience. The medication wears off after 4 to 6 hours, ( one pill), and some doctors would say to take them all day long, but of course they themselves have not been on it. Unfortunately, this has been labeled a times medication, making it hard to try different dosses, and leaving pharmacists looking at you weird when you come in to get your meds, and you have changed a dose etc. Believe me if I didnt have to take this crap I wouldnt. I am not sure why they labeled it timed because the side effects are less then positive. I dont know many people who are like hey! give me some more of that drug that makes me feel nuts, dizzy, gain weight, dry mouth, and like im on acid all day, and MAYBE take away a bit of pain, but thats just me. I have found a way to make this medication work for me, but I say that loosely. It works a bit, not perfect. But hey that is all there is!!!

    Christa / Reply
  5. Avatar

    I was put on Pregabalin for anxiety 2 years ago by a psychiatrist, it helped initially for 3 months but then your body gets used to it and you need higher and higher doses which I couldn’t tolerate, the side effects were awful, memory loss, blurred vision, tinnititus, rapid heart beat, insomnia and depression and it made anxiety worse….I have now been tapering off it for 18 months very slowly and it’s been a nightmare – all of the above as well as bad nausea and joint pain, I’m nearly off it but there is not doubt in my mind that your body becomes dependent on it and coming off it is very difficult. My GP is now in agreement with me and will not prescibe it. In America there is even a support group of over 8000 people called Lyrica Survivors which has more evidence of people struggling to come off it, mostly people whom were given it for pain relief. I have done a lot of research into it and I know that it has a very addictive quality and it has now become a ‘street drug’. Please warn people of the side effects and withdrawal problems.

    Clare Baillieu / Reply
  6. Avatar

    I was on Pregabalin for a very short time and tapered off it which was hell. 7 months down the line I am suffering still from tinnitus, visual disturbance, horrendous sweating and strange feeling of being high which toward the end of the day turns to a sickening feeling. The doctor will not except the Pregabalin caused all this upset to my life but I know it was. As she refuses to believe me I am left with no help in a state of despair not knowing how much longer I can deal with this or where it is going to end it is a truly horrendous place to be and any advice on how I could move forward would be gratefully received. How can I make the doctor see the drug she gave me is infact making my life hell 7 months after I stopped taking it? I have chatted to others and we have concluded some people have a real bad time when ceasing to take this drug even if they have only taken it for a short time. I would say it is worrying but it is far more than that I would say its life threatening due to the daily despair.

    Tracy Davies / Reply
    • Sarah Chapman

      Sorry to hear you are having these problems. I hope things improve for you soon.
      Best wishes,
      Sarah Chapman [Editor]

      Sarah Chapman / (in reply to Tracy Davies) Reply
  7. Avatar

    I’m on this for pain in my feet it works for me.

    Sheila Godfrey / Reply
  8. Avatar

    I was a GP and my main problem with pregabalin was that it was widely abused in the community and had a marked street value. In addition, once patients were taking it they had problems stopping it, mainly with anxiety. I got the impression pregabalin is addictive and I tried to use as little possible

    Christopher Johnstone / Reply

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