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Gabapentinoids – Not Only Ineffective But Harmful

July 17, 2019

Written by Clay Smith

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Gabapentinoids were associated with increased risk of suicidal behavior, overdose, injuries, and car crashes.

Why does this matter?
Gabapentinoids, like gabapentin or pregabalin, are often used as adjuncts for pain, especially neuropathic pain. The efficacy of these agents has been called into question for most painful conditions. But are these agents harmful?

Gabapentinoids – not only ineffective but harmful
This was a large population database study of 191,973 people in Sweden who were prescribed gabapentinoids. They found an increased risk for: “suicidal behaviour and deaths from suicide (age adjusted hazard ratio 1.26, 95% confidence interval 1.20 to 1.32), unintentional overdoses (1.24, 1.19 to 1.28), head/body injuries (1.22, 1.19 to 1.25), and road traffic incidents and offences (1.13, 1.06 to 1.20).” There was no association with violent crime. When stratified by drug, gabapentin was not associated with any of the above and was, in some cases protective; pregabalin was associated with all of the above. Younger patients had a stronger association with adverse outcomes. In particular, patients aged 15-24 years were at increased risk for all of the above outcomes. The strength of this study is that each patient acted as his or her own control, as periods in which they were on the drugs were compared to those in which they were not. This helps reduce confounding. They also found a dose-response with the outcomes of interest, which strengthens the case. The major weakness is it is a large registry, and misclassification may have occurred. It also does not prove causality. However, given that these drugs are largely ineffective and now associated with harm, it’s hard to give a rousing recommendation for their use. If you choose to use them, it seems gabapentin may be a safer choice than pregabalin, and using them in patients over 24 years might be best.

Associations between gabapentinoids and suicidal behaviour, unintentional overdoses, injuries, road traffic incidents, and violent crime: population based cohort study in Sweden. BMJ. 2019 Jun 12;365:l2147. doi: 10.1136/bmj.l2147.

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Reviewed by Thomas Davis

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