From Pages to Practice
Ms. Hasberry, a 64-year-old woman, presents to the primary care clinic reporting 6 months of worsening shooting pain radiating from her left buttock to the back of her thigh and down her leg, limiting her ability to play with her granddaughter. On examination, her pain is reproduced on straight leg raising test. Diagnosed with sciatica, physical therapy is recommended to help with the pain and restriction of mobility. However, her symptoms persist during the next 6 months. What treatment options does she have?
Pregabalin, an analgesic and antiepileptic drug, has been shown to reduce neuropathic pain in postherpetic neuralgia, diabetic peripheral neuropathy, allodynia, and hyperalgesia from several conditions. Therefore, it stands to reason that pregabalin should also be helpful in controlling sciatica. However, only one randomized controlled trial has evaluated its use in sciatica and that trial failed to come to a firm conclusion because of methodological issues. Nevertheless, pregabalin is increasingly prescribed for management of sciatica in patients like Ms. Hasberry.
In this week’s issue of NEJM, Mathieson et al. explore the utility of pregabalin the PRECISE study — a randomized, double-blind, placebo-controlled trial conducted in 207 patients with a current episode of sciatica lasting 1 week to 1 year and causing moderate-to-severe pain and interference with daily activities. The study’s primary outcome was leg-pain intensity on a 10-point scale at week 8 (with 0 representing no pain and 10 representing the worst possible pain). Secondary outcomes included disability, back-pain intensity, and quality-of-life measures at 8 weeks and 1 year.
Of the 106 patients who received pregabalin (titrated to a maximum dose of 300 mg, given twice a day for up to 8 weeks) and 101 who received placebo, 74% in each group took at least 80% of their assigned treatment. At week 8, there were no statistically significant differences between the two groups in leg-pain intensity or any of the secondary outcomes. The results were similar at 1-year follow up. Although patients in both groups experienced some improvement in symptoms of sciatica over time, patients in the pregabalin group experienced significantly more adverse effects than those in the placebo group (227 vs. 124; P=0.002). Dizziness was more frequent with pregabalin and 1 patient in the pregabalin group (versus 0 in the placebo group) experienced suicidal ideation. Therefore, caution is still advised.
NEJM Deputy Editor Dr. Allan Ropper comments, “This was a straightforward pragmatic study that informs us about the use of pregabalin in one of the most common disorders in general practice, sciatica. We do not know how many of the participants had lumbar disc disease that would be amenable to surgery but current practice is to wait a few weeks to see if sciatica resolves, almost no matter the underlying cause. The wide range of duration of symptoms can be viewed as a strength or weakness of the trial; many patients had sciatica for less than 3 months, which is typical of office consultations for the condition. The editorialists on this paper point out biological reasons why pregabalin may have failed.”
PRECISE is an adequately powered and well-designed study that failed to establish the role of pregabalin in the management of sciatica. This could potentially be explained by the difference in pathophysiology of sciatica with respect to other diseases associated with or causing neuropathic pain. Given the higher rate of side effects associated with pregabalin, the authors do not recommend including this drug in guidelines for management of recent onset moderate-to-severe sciatica. PRECISE provides an objective refutation of clinical observation; further evidence-based interventions need to be explored for this difficult condition.