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.
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.
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.