Inclusion of Lyrica in Workers' Compensation Medicare Set-Aside Arrangements

Lyrica (pregabalin) is an analog of the neurotransmitter gamma-aminobutryic acid, or GABA. Within the brain and nervous system, GABA plays an important role in behavior, cognition and the body’s response to stressful situations. A deficiency in naturally-occurring levels of GABA has been linked to conditions such as schizophrenia, depression, anxiety and various sleep disorders.  While Lyrica is structurally similar to GABA, it does not exert its pharmacological action through GABA’s neural system. The exact mechanism of action for Lyrica is not known, although it is believed to decrease the release of certain central nervous system (CNS) neurotransmitters by binding to calcium channels within the CNS.

Lyrica was approved in the United States in 2004 and upon approval, it was listed as a schedule V controlled substance. Schedule V controlled substances have a low potential for abuse. For example, codeine-containing cough syrup is often classified as schedule V. Despite its schedule V designation, there are increasing reports of Lyrica being used in combination with heroin and other opioids to enhance the euphoric effects of these drugs. A recent population study in the Annals of Internal Medicine found an increased risk of opioid-related death in patients who are prescribed both Lyrica and opioids.  The risk of opioid-related death was found to increase with higher doses of Lyrica.[1]

Many of the side effects observed with Lyrica are attributable to its effect on the CNS. The most commonly reported adverse events associated with Lyrica are dizziness and sleepiness. Other common side effects include dry mouth, swelling of the hands and feet, blurred vision, weight gain and difficulty concentrating. Those with decreased kidney function have an increased risk of adverse events. Therefore, reduced dosages are recommended in this population.

Lyrica is FDA approved to treat neuropathic pain associated with diabetic peripheral neuropathy, spinal cord injury and post-herpetic neuralgia; fibromyalgia; and as adjunctive therapy for partial onset seizures. However, it is widely utilized for various off-label indications such as chronic pain and anxiety disorder. In fact, Lyrica is approved in Europe to treat generalized anxiety disorder. Use of Lyrica to treat back pain, radiculopathy and neuropathic pain not described above, represents an off-label use that should not be covered by Medicare.

In the past, the Workers’ Compensation Review Contractor (WCRC) excluded Lyrica from Workers’ Compensation Medicare Set-Aside Arrangements (WCMSAs), when the medication was prescribed for pain or radiculopathy; however, recently the WCRC has started to include Lyrica in certain situations, citing the WCMSA Reference Guide, Section 9.4.6.2, which states, “FDA approved drugs used for indications other than what is indicated on the official label may be covered under Medicare if the carrier determines the use to be medically accepted, taking into consideration the major drug compendia, authoritative medical literature and/or accepted standards of medical practice.” A brief review of the medical literature, including a March 2017 study published in the New England Journal of Medicine, reveals questionable efficacy for Lyrica when used in the treatment of acute and chronic sciatica. This randomized clinical trial involved a total of 209 patients, who were randomized to one of two groups. One group received pregabalin at a starting dose of 150mg/day (titrated up to a maximum of 600mg/day) and the other group received placebo. The primary study endpoint was leg-pain intensity score (0-10) measured at 8 weeks and 52 weeks. Secondary study endpoints included extent of disability, back pain intensity and quality of life measures taken periodically over the course of one year. The researchers concluded that Lyrica did not statistically reduce the intensity of leg pain associated with sciatica, and did not produce statistically significant improvement in other endpoints.[2]

Researchers in Canada published the results of a meta-analysis last year, finding little evidence that Lyrica is effective in treating chronic low back pain. The researchers also concluded that the use of Lyrica poses a significant risk of adverse events. A systematic review of the literature found very few randomized controlled trials that have assessed the benefit of using Lyrica for the treatment of chronic low back pain. In the trials that were conducted, the researchers found that Lyrica was minimally effective compared to placebo and inferior compared to other analgesics. Additionally, the research showed an increase in adverse events such as dizziness, fatigue, visual disturbances and diminished mental activity.[3]

Given that the FDA indications and non-FDA approved uses have not changed in the major drug compendia and the literature appears to indicate a general lack of efficacy, it is surmised the WCRC is relying on the accepted standards of medical practice exclusion to include Lyrica in WCMSAs. In consideration of the current landscape, prior to approving payment for Lyrica, a primary payer may want to consider the potential implications of covering this medication under a claim.

[1] Gomes T, Greaves S, van der Brink W, Antoniou T, Mamdani MM. Pregabalin and the risk for opioid-related death: a nested case-control study. [published online August 21, 2018]. Ann Intern Med. doi:10.7326/M18-1136).

[2] Mathieson, S. et al. NEJM 2017; 376:1111-1120.

[3] Shanthanna H, Gilron I, Rajarathinam M, AlAmri R, Kamath S, Thabane L, et al. (2017) Benefits and safety of gabapentinoids in chronic low back pain: A systematic review and meta-analysis of randomized controlled trials. PLoS Med 14(8): e1002369. https://doi.org/10.1371/journal.pmed.1002369.

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