In moderate-to-severe sciatica, pregabalin did not reduce leg pain intensity or improve quality of life

Question In patients with moderate-to-severe sciatica, does pregabalin reduce intensity of leg pain compared with placebo? Methods Design Randomized placebo-controlled trial (Pregabalin in Addition to Usual Care for Sciatica [PRECISE] trial). Australian and New Zealand Clinical Trials Registry ACTRN12613000530729. Allocation Concealed. * Blinding Blinded* (patients, clinicians, research staff, and statisticians). Follow-up period 8 and 52 weeks. Setting 47 centers in New South Wales, Australia. Patients 209 patients 18 years of age (mean age 54 y, 56% women) who had moderate-to-severe sciatica (pain radiating below the knee in 1 leg with nerve-root or spinal-nerve involvement), current episode lasting 1 week and 1 year, and leg pain with at least moderate intensity or at least moderate interference with daily activities in the past week. Exclusion criteria included serious pathologic spinal conditions; potential for spinal surgery or other interventional procedure for sciatica in the next 8 weeks; need for continued use of sedatives or medication for neuropathic pain, epilepsy, or depression; or severe depression or suicidal thoughts. Intervention Pregabalin, started at 75 mg twice/d and titrated to 300 mg twice/d (n =108), or placebo (n =101) for 8 weeks. Outcomes Primary outcome was leg pain intensity at 8 weeks. Other outcomes included leg pain intensity at 52 weeks, disability (Roland Disability Questionnaire for Sciatica [RDQS]), back pain intensity, and quality of life. Adverse event data were collected. 204 patients were needed to detect clinically important differences between groups in leg pain intensity (1.5-point difference in the 10-point pain score) and disability (3-point difference in the 23-point RDQS) at 8 weeks (90% power, 2-sided =0.05). Patient follow-up 92% at 8 weeks and 85% at 52 weeks (intention-to-treat analysis). Main results Pregabalin and placebo did not differ for pain, disability, or quality of life at 8 weeks (Table) or 52 weeks (all P >0.10). Pregabalin increased adverse events (64% vs 43%, P =0.002) but not serious adverse events (1.9% vs 5.9%, P =0.16) compared with placebo. Conclusion In moderate-to-severe sciatica, pregabalin did not reduce leg pain intensity or improve quality of life but increased adverse events compared with placebo. Pregabalin vs placebo in patients with moderate-to-severe sciatica Outcomes Unadjusted mean scores Adjusted mean difference (95% CI) at 8 weeks Pregabalin Placebo Leg pain intensity 3.7 3.1 0.5 (0.2 to 1.2) Disability 9.1 8.5 0.1 (1.8 to 2.0) Back-pain intensity 3.5 3.1 0.2 (0.6 to 1.0) Quality of life, physical component 40.4 41.5 0.7 (3.5 to 2.1) Quality of life, mental component 49.1 48.8 0.7 (2.4 to 3.9) CI defined in Glossary. Adjusted for baseline leg pain and symptom duration. Numeric rating scale for mean pain intensity in the past 24 h; score range 0 (no pain) to 10 (worst possible pain). Roland Disability Questionnaire for Sciatica; score range 0 to 23, higher scores = greater disability. Short-Form Health Survey 12, version 2; score range 0 to 100, higher scores = better quality of life. Commentary The PRECISE trial is well-designed and shows that 8 weeks of pregabalin does not improve acute sciatica. The cited clinically important difference in the pain scale of 1.5 out of 10 points is small (1). In addition, a novel subgroup analysis showed lack of benefit regardless of presence of neuropathic symptoms. However, PRECISE does not indicate whether benefit may have occurred in patients with long-standing symptoms who are less likely to have spontaneous improvement. The results of other trials collected in our ongoing living review of gabapentinoids, which is updated as new evidence is published (http://openmetaanalysis.github.io/sciatica-gabapentinoids/), are consistent with the PRECISE trial. Regarding effect on long-standing pain, an unpublished trial sponsored by Pfizer (ClinicalTrials.gov NCT01838044) showed that pregabalin did not relieve pain in patients with more chronic symptoms. In addition, a pooled analysis of 2 other trials showed that gabapentin did not improve pain relief. How should physicians treat sciatica? The American College of Physicians provides a guideline for noninvasive therapy (2), and we also refer readers to a recent, expert narrative review (3).