Pregabalin (LYRICA): Neither Effective nor Safe for Treating Sciatica Leg Pain

Sciatica is a common type of neuropathic pain (pain resulting from nerve damage) that afflicts approximately 5 to 10 percent of patients with low-back pain.[1] Sciatica typically occurs on one side of the body and radiates from the buttock down the back or side of the leg.[2] The condition is caused most commonly by nerve compression from a herniated disk, bone spur or narrowing of the spinal canal (spinal stenosis) in the lower (lumbar) spine (see the text box below to learn more about sciatica).[3]

Doctors often prescribe pregabalin (LYRICA) for neuropathic pain conditions, including sciatica.[4] Although the drug is approved by the Food and Drug Administration (FDA) for some neuropathic pain disorders, it is not approved for treating sciatica. The first well-designed clinical trial testing pregabalin in sciatica patients was published in the New England Journal of Medicine (NEJM) in March 2017. The trial revealed that the medication is no better than a placebo in relieving symptoms of sciatica but does cause significantly more adverse effects.

Pregabalin overview

The FDA has approved pregabalin for treatment of neuropathic pain that occurs in patients with diabetes and in those who have had a shingles skin infection (which is caused by the chickenpox virus) or a spinal cord injury.[6] The drug also is approved for fibromyalgia, a poorly understood condition that is characterized by widespread muscle and joint pains; fatigue; and problems with memory, sleep and mood. For many years, Public Citizen’s Health Research Group has designated pregabalin as Do Not Use for all of these pain conditions because the benefits have not been shown to outweigh the drug’s potentially serious adverse effects (see the text box below).[7]

The FDA also approved pregabalin for treatment of partial onset seizures, the condition for which the drug was originally developed.[8] Partial onset seizures — also called focal seizures — are caused by abnormal electrical activity in a limited area of the brain. We have concluded that the benefits of pregabalin for treating partial onset seizures outweigh the risks for some patients and have designated it as a Limited Use drug for this use.[9] Many patients who experience partial onset seizures respond inadequately to other available seizure drugs. Up to 12 percent of adults with this condition may become seizure-free by adding pregabalin to other seizure drugs.[10], [11], [12], [13], [14]

The NEJM trial[16]

The NEJM trial was conducted by researchers in Australia and the Netherlands and was funded by the National Health and Medical Research Council of Australia, a government research agency similar to the U.S. National Institutes of Health.

From September 2013 to March 2015, the researchers enrolled 209 adults who had experienced moderate- to-severe sciatica symptoms for at least one week and as long as one year. The researchers randomly assigned the subjects to receive either pregabalin or placebo capsules for eight weeks. To minimize the potential for bias, neither the researchers nor the subjects knew which subjects were taking pregabalin and which were taking placebo capsules.

All subjects received standard medical advice for managing sciatica, such as avoiding bed rest and remaining physically active. They also could be prescribed physical therapy or analgesic pain relievers as needed during the trial.

Subjects rated the severity of their leg pain and completed standard surveys measuring physical disability and quality of life just prior to taking the pregabalin or placebo capsules and periodically thereafter for up to one year.

The researchers found no significant differences between the two trial groups in the severity of leg pain, disability scores and quality of life scores at eight weeks and one year after enrollment in the trial. On average, subjects in both groups had similar improvements in all of these outcomes, with most of the improvement occurring within the first eight weeks of the trial. These results clearly demonstrate that pregabalin is not effective for treating sciatica.

In addition to lacking any benefit, pregabalin also caused harm. Significantly more subjects receiving pregabalin suffered an adverse event than those receiving a placebo did (64 percent versus 43 percent, respectively). The most common adverse event was dizziness, which occurred in 40 percent of pregabalin-treated subjects but only 13 percent of those receiving a placebo.

What You Can Do

We recommend that you not use pregabalin for sciatica or any other neuropathic pain condition. If you are currently using the drug for such conditions, take this article to your doctor and discuss other treatment options. Be aware that pregabalin must not be stopped suddenly because seizures may occur. When discontinuing the drug, the dose should be gradually tapered over a week.

References

[1] Koes BW, van Tulder MW, Peul WC. Diagnosis and treatment of sciatica. BMJ. 2007;334(7606):1313-1317.

[2] Ropper AH, Zafonte RD. Sciatica. N Engl J Med. 2015;372(13):1240-1248.

[3] Mayo Clinic. Diseases and conditions: Sciatica. August 14, 2015. http://www.mayoclinic.org/diseases-conditions/sciatica/basics/preparing-for-your-appointment/con-20026478?p=1. Accessed September 5, 2017.

[4] Robertson K, Marshman LA, Plummer D. Pregabalin and gabapentin for the treatment of sciatica. J Clin Neurosci. 2016 April;26:1-7.

[5] Mayo Clinic. Diseases and conditions: Sciatica. August 14, 2015. http://www.mayoclinic.org/diseases-conditions/sciatica/basics/preparing-for-your-appointment/con-20026478?p=1. Accessed September 5, 2017.

[6] Pfizer. Label: pregabalin (LYRICA). June 2017. https://dailymed.nlm.nih.gov/dailymed/getFile.cfm?setid=c1ca3940-3135-4c55-9abf-b185a59cc7b0&type=pdf&name=c1ca3940-3135-4c55-9abf-b185a59cc7b0. Accessed September 5, 2017.

[7] Pregabalin (LYRICA): OK for certain seizures, but not pain. Worst Pills, Best Pills News. December 2014. /newsletters/view/932. Accessed September 5, 2017.

[8] Pfizer. Label: pregabalin (LYRICA). June 2017. https://dailymed.nlm.nih.gov/dailymed/getFile.cfm?setid=c1ca3940-3135-4c55-9abf-b185a59cc7b0&type=pdf&name=c1ca3940-3135-4c55-9abf-b185a59cc7b0. Accessed September 5, 2017.

[9] Pregabalin (LYRICA): OK for certain seizures, but not pain. Worst Pills, Best Pills News. December 2014. /newsletters/view/932. Accessed September 5, 2017.

[10] Arroyo S, Anhut H, Kugler AR, et al. Pregabalin add-on treatment: a randomized, double-blind, placebo-controlled, dose-response study in adults with partial seizures. Epilepsia. 2004;45(1):20-27.

[11] Beydoun A, Uthman BM, Kugler AR, et al. Safety and efficacy of two pregabalin regimens for add-on treatment of partial epilepsy. Neurology. 2005;64(3):475-480.

[12] Elger CE, Brodie MJ, Anhut H, et al. Pregabalin add-on treatment in patients with partial seizures: a novel evaluation of flexible-dose and fixed-dose treatment in a double-blind, placebo-controlled study. Epilepsia. 2005 Dec;46(12):1926-1936.

[13] French JA, Kugler AR, Robbins SL, et al. Dose-response trial of pregabalin adjunctive therapy in patients with partial seizures. Neurology. 2003;60(10):1631-1637.

[14] Miller R, Frame B, Corrigan B, et al. Exposure-response analysis of pregabalin add-on treatment of patients with refractory partial seizures. Clin Pharmacol Ther. 2003;73(6):491-505.

[15] Pfizer. Label: pregabalin (LYRICA). June 2017. https://dailymed.nlm.nih.gov/dailymed/getFile.cfm?setid=c1ca3940-3135-4c55-9abf-b185a59cc7b0&type=pdf&name=c1ca3940-3135-4c55-9abf-b185a59cc7b0. Accessed September 5, 2017.

[16] Mathieson S, Maher CG, McLachlan AJ, et al. Trial of pregabalin for acute and chronic sciatica. N Engl J Med. 2017;376(12):1111-1120.