Pregabalin reduces neuropathic pain but increases risk for adverse events

  • Onakpoya IJ & al.
  • BMJ Open
  • 21 Jan 2019

  • curated by Antara Ghosh
  • UK Clinical Digest
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Takeaway

  • Very low-to-moderate quality evidence suggests some reduction in neuropathic pain with pregabalin.
  • However, pregabalin was associated with significantly higher risk for adverse events including weight gain, somnolence, dizziness, dry mouth, peripheral oedema, fatigue, visual disturbances, ataxia, non-peripheral oedema, vertigo and euphoria.

Why this matters

  • Several guidelines recommend pregabalin as the first-line pharmacological agent for management of neuropathic pain.
  • However, recent evidences of increased mortality associated with pregabalin in the United Kingdom have cautioned clinicians about the risk for harms when prescribing, particularly for patients using heroin and those who misuse gabapentinoids.

Study design

  • Meta-analysis of 28 phase 3 randomised, placebo-controlled trials involving 6087 adults (aged ≥18 years) with neuropathic pain who were randomly allocated to receive either pregabalin or placebo.
  • Funding: None disclosed.

Key results

  • Pain (mean pain score) reduced significantly with pregabalin vs placebo (standard mean deviation [SMD], −0.49; P<.00001 i>2, 88%; 21 studies).
  • Effect was significant for peripheral neuropathic pain (P<.00001 but not for central neuropathic pain>
  • Pregabalin was associated with significantly reduced sleep interference scores vs placebo (SMD, P<.00001 i>2, 32%; 21 studies).
  • Pregabalin vs placebo was significantly associated with higher odds of adverse events (risk ratio [RR], 1.33; P<.00001 i>2, 52%).
  • Patients using pregabalin vs placebo were more likely than placebo to discontinue drug because of adverse events (RR, 1.91; P<.00001 i>2, 0%).
  • No difference was observed for anxiety and depression scores.

Limitations

  • Low-to-moderate quality evidence.
  • Possibility of sampling bias.
  • Extent to which different pregabalin doses influenced outcomes not assessed.

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