Pregabalin versus placebo to prevent chronic pain after whiplash injury in at-risk individuals: results of a feasibility study for a large randomised controlled trial

ABSTRACT: There are few effective treatments for acute whiplash-associated disorders (WAD). Early features of central sensitisation predict poor recovery. The effect of pregabalin on central sensitisation might prevent chronic pain after acute whiplash injury. This double blind, placebo-controlled randomised controlled trial (RCT) examined feasibility and potential effectiveness of pregabalin compared to placebo for people with acute WAD. Twenty-four participants with acute WAD (<48 hours) and at risk of poor recovery (pain ≥ 5/10) were recruited from hospital Emergency Departments in Queensland, Australia and randomly assigned by concealed allocation to either pregabalin (n=10) or placebo (n=14). Pregabalin was commenced at 75 mg bd, titrated to 300 mg bd for 4 weeks, and then weaned over 1 week. Participants were assessed at 5 weeks, 3, 6 and 12 months. Feasibility issues included recruitment difficulties and greater attrition in the placebo group. For the primary clinical outcome of neck pain intensity, attrition at 5 weeks was: pregabalin: 10%, placebo: 36%, and at 12 months was: pregabalin: 10%, placebo: 43%. Pregabalin may be more effective than placebo for the primary clinical outcome of neck pain intensity at 3 months [Mean Difference: -4.0 (95% CI -6.2 to -1.7)] on an eleven point numerical rating scale. Effects were maintained at 6 but not 12 months. There were no serious adverse events. Minor adverse events were more common in the pregabalin group. A definitive large RCT of pregabalin for acute whiplash injury is warranted. Feasibility issues would need to be addressed with modifications to the protocol.