Pregabalin ineffective for reducing sciatica pain in PRECISE study
Pregabalin did not significantly reduce symptoms of sciatica, including radiating posterolateral leg pain and back pain, compared with placebo, according to data from the PRECISE* trial.
Sciatica is a type of neuropathic pain caused by compression of the sciatic nerve, resulting in lower back pain radiating down the leg, sensory loss, weakness, and reflex abnormalities. [BMJ 2007;334:1313-1317; N Engl J Med 2015;372:1240-1248]
At week 8, there was no significant difference in leg pain intensity between the pregabalin and placebo groups (pain intensity scores, 3.7 vs 3.1, adjusted mean difference [adjMD], 0.5, 95 percent confidence interval [CI], -0.2 to 1.2; p=0.19). The difference remained nonsignificant at week 52 (3.4 vs 3.0, adjMD, 0.3, 95 percent CI, -0.5 to 1.0; p=0.46). [N Engl J Med 2017;376:1111-1120]
Among the secondary outcomes, there was no significant effect in both the pregabalin and placebo arms at week 8 and week 52 in terms of back pain intensity (adjMD, 0.2; p=0.56 and adjMD, 0.6; p=0.14, respectively) and extent of disability (adjMD, 0.1; p=0.96 and adjMD, 0.2; p=0.85, respectively).
Adverse event rates were higher in the pregabalin arm compared with the placebo arm (227 vs 124 events; p=0.002), with dizziness being the most prevalent in the pregabalin arm. Serious adverse events were similar in both the pregabalin and placebo arms (2 vs 6 events; p=0.16), two of which were suicide-related events (one hospitalization for suicide attempt in the placebo arm and one report of suicidal thoughts in the pregabalin arm).
Given the incidence of suicide-related adverse events in both treatment arms, as well as the increased suicidality associated with pregabalin use [N Engl J Med 2010;363:542-51], the researchers underscored that precautionary measures in prescribing pregabalin is essential in patients vulnerable to self-injuries.
In this double-blind, placebo-controlled trial, 209 patients with sciatica were randomized to pregabalin (n=108) or placebo (n=101). Initial pregabalin dose was 150 mg/day (75 mg twice daily), which was adjusted to a maximum dose of 600 mg/day (300 mg twice daily) and administered for up to 8 weeks. Leg pain intensity scores were evaluated at weeks 8 and 52. Leg pain in both treatment arms was most commonly associated with the first sacral root (S1) with predominant dermatomal pain.
Overall, the findings suggest that pregabalin was ineffective as it did not reduce the pain intensity in patients with moderate to severe sciatica, noted the researchers.
“The lack of treatment effect of pregabalin in these patients with sciatica may reflect differences in pathophysiological features between other types of neuropathic pain and sciatica and suggests that the recommendations from guidelines regarding neuropathic pain may not extend to sciatica,” said the researchers.
However, Dr Benjamin Tow, orthopaedic surgeon at the Orthopedic and Spine Clinic at Mount Elizabeth Medical Centre, Singapore, who was not affiliated with the study, disagrees, saying pregabalin is effective for sciatica, and that it is actually more effective than gabapentin in relieving nerve pain.
Tow believed that the perceived ineffectiveness of pregabalin may be due to low medication compliance. “Some patients are noncompliant with medication and do not obtain the expected effect … [My] advice [is] to start at a lower dose and [continue] daily … [as] the therapeutic effect takes time to build up,” he said.