By Jane Lewis
Pregabalin is no more effective than placebo in reducing leg pain and other symptoms associated with sciatica, reports an Australian trial published in The New England Journal of Medicine.
The trial was led by researchers at The George Institute for Global Health, Sydney. It follows earlier research showing pregabalin reduces some types of neuropathic pain and epidemiological studies suggesting that the use of pregabalin for neuropathic pain has increased, despite a lack of supporting evidence and concerns about potential side effects and misuse of the drug.
Commenting on the new trial, Professor Robert Helme, Honorary Professor in the Department of Medicine at Royal Melbourne Hospital, University of Melbourne, said that the term ‘sciatica’, as understood by the community and many healthcare professionals, does not always satisfy the criteria describing true neuropathic pain. Despite this, clinicians often treat sciatica pain as definite neuropathic pain, using adjuvant analgesics such as gabapentinoids and antidepressants.
‘Careful selection of, and explanation to, patients with “sciatica” is required before offering a trial of adjuvant analgesia,’ he advised. In the trial, 209 patients with moderate-to-severe sciatica of varying durations (mostly less than three months) were randomly assigned to receive either pregabalin (150 mg/day, adjusted to a maximum of 600 mg/day) or matching placebo for up to eight weeks. Compared with placebo, pregabalin offered no benefit, either in terms of reducing leg-pain intensity (scored at week 8 and week 52) or in the secondary outcomes that included back-pain intensity, extent of disability and quality of life measures (assessed at prespecified time points over the course of one year).
The incidence of adverse events was significantly higher in the pregabalin group than in the placebo group (227 vs 124 events), with dizziness the most commonly reported side effect. The trial was not powered to detect the risk of suicidality as an outcome.
Commenting on possible explanations for the study’s findings, Professor Helme suggested case selection may be a possible issue, with the presence of neuropathic pain assessed using a screening instrument of limited sensitivity (questionnaire) compared with an experienced clinician. Other explanations include that pregabalin is ineffective in the specific type of neuropathic pain associated with sciatica, or that its positive effect was masked by a natural history of improvement.
‘Better markers of neuropathic pain are sorely needed before advances in the treatment of neuropathic pain will occur,’ he told Pain Management Today.
The authors of an accompanying editorial pointed out that while the trial’s results indicate failure of pregabalin to improve sciatica symptoms, the design of the trial ‘does not exclude a possible benefit in chronic sciatica.’
N Engl J Med 2017; 376: 1111-1120.
N Engl J Med 2017; 376: 1169-1170.