Gabapentinoids - the next drug in the analgesic hall of shame?

In amongst a global pandemic, primary care carries on unabated, as does the seemingly never-ending list of prescriptions in our workflow! One group of drugs I’m sure you will all have signed off this week, probably on a number of occasions, are the gabapentinoids. And of those, how many were for chronic pain conditions, back pain, or sciatica? Probably the majority, if you are a typical GP like me. But we are not alone…By 2017 pregabalin was one of the highest-selling drugs globally, and in 2018 over 14 million prescriptions of the gabapentinoids were signed off in the UK. Given how busy we are currently I thought I’d highlight an important change in NICE guidance regarding the use of these drugs in sciatica (NG 59), which could easily have flown under the radar.

I’m sure many of us have been getting increasingly uncomfortable about prescribing these drugs for a while. Are they really effective in sciatica? Hmm, not really sure. A lot of my patients don’t seem to tolerate them that well, or is it just me? Bob says he wakes in the morning feeling really groggy likes he’s had ‘one too many’ the night before. Mrs Jones says she feels terribly wobbly and is worried she will fall over. And poor Jim (who it turns out had a bit of a boozing problem in the background) comes back to see you admitting he’s been sourcing black market versions due to worsening tolerance and is now clearly addicted.

So how on earth did we get here? For drugs that were originally licensed for seizure disorders, they have come a long way to the point where the majority of our prescriptions are for pain conditions, including sciatica. It appears to be a classic case of murky evidence, muddy guidelines, a real lack of options, and a (well-meaning) desire to move away from opiate prescribing. As discussed in the BMJ last year (BMJ 2020;369:m1315), despite the increasingly widespread use of gabapentinoids for sciatica there has never really been any evidence to support their use in this condition. There is evidence to support their use in post-herpetic neuralgia and diabetic neuropathy. The idea of their benefit in neuropathic pain conditions led to them being incorporated in the NICE neuropathic pain guideline as an option. This guideline was cross-referenced by the previous iteration of the NICE back pain/sciatica guideline, implying we should consider gabapentinoids for sciatica (despite limited evidence). Thus the snowball grew and we found ourselves prescribing these drugs for an ever-increasing range of conditions including many chronic pain conditions, with a very limited evidence base. 

But the tide has changed dramatically in the last 12-24 months. In 2019 the gabapentinoids were changed to class C controlled drugs, due to concerns over misuse and addiction. By 2020, as discussed in the BMJ review above, we had good evidence that the gabapentinoids were not effective in many of the conditions for which they were being prescribed - back pain, sciatica, spinal stenosis, and migraine. Later in 2020, the draft NICE guidance on chronic pain came out specifying that gabapentinoids should not be used for chronic primary pain conditions. Then the NICE back pain and sciatica guideline was updated towards the end of 2020 also specifying that gabapentinoids should not be used for sciatica and that we should consider withdrawing people off these drugs. This NICE guideline had already recommended gabapentinoids should not be used for low back pain as far back as 2016, but the previous guidance to consider them for sciatica made this a grey area, and one ripe for confusion. Whilst the discussions around withdrawing people off these drugs will not be easy, it may be a discussion our patients will thank us for. As eluded to above the side effect profile of these drugs is substantial. The BMJ review concludes that as many as 50-70% of people suffer adverse events on these drugs (albeit with quite a high nocebo effect), with dizziness, somnolence, and gait disturbance being the most common, not to mention the risks of misuse and addiction.

No one is suggesting this is an easy area to navigate - it absolutely is not, and we will cover the incredibly difficult area of managing chronic pain more generally in our upcoming Hot Topics courses. But by reducing our prescribing of these drugs we may well improve the quality of life for many people with sciatica and back pain, given the unfavourable benefit/harm ratio.