Pregabalin Not Effective for Sciatica Treatment

The annual prevalence of sciatica is as high as 45%, although rates vary widely because of inconsistent definitions and terms used to describe the condition.
The annual prevalence of sciatica is as high as 45%, although rates vary widely because of inconsistent definitions and terms used to describe the condition.

A randomized trial reported in the New England Journal of Medicine found that pregabalin is not more effective than placebo in treating sciatica, and resulted in more adverse effects.1

According to some estimates, the annual prevalence of sciatica is as high as 45%, although rates vary widely because of inconsistent definitions and terms used to describe the condition.2 There is also a lack of consensus and a dearth of evidence regarding effective treatments for sciatica.

“We know that people can benefit from advice to stay active and be reassured that they will recover from sciatica, but beyond that we don't know what treatments are effective other than epidural injections and surgery,” Christine Lin, PhD, an associate professor at the University of Sydney, and senior research fellow at the musculoskeletal division of the George Institute for Global Health in Australia, told Clinical Pain Advisor. Those strategies are not effective for all patients, and the effects of epidural injections are only short-term.

Pregabalin was found to lead to improvement in several types of neuropathic pain, including diabetic peripheral neuropathy, postherpetic neuralgia, and central neuropathic pain.3,4 “Its analgesic and antiepileptic properties have been attributed to binding to α 2–δsubunits of voltage-gated calcium channels, which results in decreased neurotransmitter release,” wrote the authors of the current study.

An earlier randomized controlled trial that evaluated the effectiveness of the drug for sciatica, and specifically chronic lumbosacral radiculopathy, found no significant difference in outcomes between pregabalin and placebo.5 However, that study had flaws that prevent conclusions about efficacy.

To further investigate the effectiveness of pregabalin for sciatica treatment, Dr Lin and colleagues conducted a double-blind, placebo-controlled trial in which patients were randomly assigned to 1 of 2 conditions for 8 weeks: placebo (n = 101) or 150 mg daily pregabalin (n = 106), which was adjusted to a maximum of 600 mg per day.

At the end of 8 weeks, the mean unadjusted leg pain intensity score was 3.7 in the pregabalin group vs 3.1 in the placebo group (adjusted mean difference, 0.5; 95% confidence interval [CI], -0.2 to 1.2; P =.19). At 52 weeks, the mean unadjusted score was 3.4 in the pregabalin group vs 3.0 in the placebo group (adjusted mean difference, 0.3; 95% CI, -0.5 to 1.0; P =.46).

There were no significant differences at either time in secondary outcomes of disability, back-pain intensity, or quality of life. Adverse events were more commonly reported in the pregabalin group compared with the placebo group (227 vs 124), and dizziness occurred more frequently in the pregabalin group. 

“It could be that the drug is not targeting the right pain pathway for this condition, or it could be that sciatica has a reasonable natural recovery, and the drug is unable to give more pain relief in addition to the natural recovery,” said Dr Lin. She and colleagues plan to investigate additional treatment options for sciatica. “For example, we want to establish whether other pain relief medicines can help, or whether physical therapies such as spinal manipulation, acupuncture, exercise are effective.”

Summary and Clinical Applicability

Pregabalin is not effective for sciatica treatment and is associated with a significant number of adverse effects. 

Disclosures

Dr Maher reports lecture fees from Pfizer; Dr McLachlan reports grant support from GlaxoSmithKline Australia; Dr Day reports consulting and other fees from GlaxoSmithKline Australia and Reckitt Benckiser. No other potential conflicts were reported.

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References

  1. 1Mathieson S, Maher CG, McLachlan AJ, et al. Trial of pregabalin for acute and chronic sciatica. N Engl J Med. 2017; 376(12):1111-1120. doi:10.1056/NEJMoa1614292
  2. Andersson GB. Epidemiological features of chronic low-back pain. Lancet. 1999; 354(9178):581-5. doi:10.1016/S0140-6736(99)01312-4
  3. Moore RA, Straube S, Wiffen PJ, Derry S, McQuay HJ. Pregabalin for acute and chronic pain in adults. Cochrane Database Syst Rev. 2009; (3):CD007076. doi:10.1002/14651858.CD007076.pub2
  4. Finnerup NB, Attal N, Haroutounian S, et al. Pharmacotherapy for neuropathic pain in adults: a systematic review and meta-analysis. Lancet Neurol. 2015; 14(2):16273. doi:10.1016/S1474-4422(14)70251-0
  5. Baron R, Freynhagen R, Tölle TR, et al . The efficacy and safety of pregabalin in the treatment of neuropathic pain associated with chronic lumbosacral radiculopathy. Pain. 2010; 150(3):420-7. doi:10.1016/j.pain.2010.04.013
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