Gabapentinoids in Chronic Low Back Pain

1. Gabapentinoids in Chronic Low Back Pain Ashley Daniel MD, PGY1 University of Kansas School of Medicine- Wichita Family Medicine Residency at Ascension Via Christi June 8th, 2019

2. Ashley Daniel, MD Ashley Daniel is a family medicine resident at Via Christi. She completed her medical school and undergraduate education at the University of Missouri-Columbia. She plans to practice full-scope family medicine internationally after graduation. Her special interests include obstetrics and the integration of medical and behavioral health.

3. Learning Objectives Describe current evidence regarding the use of gabapentinoids for chronic low pain. Discuss the benefits and adverse effects related to the use of gabapentinoids for chronic low back pain. Discuss future areas of research regarding the use of gabapentinoids for chronic low back pain.

4. Current evidence: What we know… Chronic Low Back Pain: 51-80% lifetime prevalence We know the MOA of analgesia and anti-epileptic activity is UNKNOWN Gabapentinoids have demonstrated benefit in neuropathic conditions , but their use is on the rise for non-specific CLBP

5. Current evidence: What we know… • FDA approval for: • Post-herpetic neuralgia • Refractory partial seizures • RCTs showing benefit off-label:  • Diabetic neuropathy • Prophylaxis of frequent migraine headaches • Fibromyalgia

6. Current evidence: What we know… • Multitude of off-label/open label uses •  A common theme in the medical literature for gabapentin is the prevalence of open-label studies • A lack of randomized controlled clinical trials for all but a small number of indications

7. Current evidence: What we know… • Multitude of off-label/open label uses • Bipolar disorder, • Peripheral neuropathy, • Complex regional pain syndrome, • Attention deficit disorder, • Restless legs syndrome, • Trigeminal neuralgia, • Periodic limb movement disorder of sleep, • Alcohol withdrawal syndrome

8. Current evidence: What we know… • Use has tripled over 2002-2015 (JAMA Internal Med) • Likely secondary to opioid epidemic • Especially in regards to non-specific low back pain • Older adults on narcotics

9. POEM | Patient Oriented Evidence That Matters • Gabapentinoids for Chronic Low Back Pain: Limited Evidence, More Harm Than Benefit. Am Fam Physician. 2017 Dec 15;96(12):online. • Primary source: Shanthanna H, Gilron I, Rajarathinam M, et al. Benefits and safety of gabapentinoids in chronic low back pain: A systematic review and meta-analysis of randomized controlled trials. PLoS Med. 2017;14(8):e1002369.

10. Meta-Analysis • Clinical Question: Are gabapentinoids safe and effective in treating patients with chronic low back pain? • Metanalysis, RCTs from Cochran Review, MEDLINE & EMBASE Databases • Databases searched from inception to 2016

11. Meta-Analysis • Searched RCTs reporting use of gabapentinoids for LBP > 3 months in adult patients • Pain relief and safety profile were the primary outcomes • 8 total studies found; 3 comparison groups • Gabapentin vs placebo • Pregabalin vs “Other analgesics” • Pregabalin as an adjunct to other analgesics

12. Heterogenous Results • 2 Studies using pregabalin as an adjuvant (n=423) • Largest of them showed no benefit of adding pregabalin to tapentadol • ~Tramadol (mu-opioid agonist/NERI) • Data not pooled due to heterogeneity of results • Methodological quality issues • selection bias • Inadequate concealment of randomization

13. Benefits: Limited Evidence • 3 studies, 332 patients: • pregabalin vs “other analgesics” • Greater improvement in the other analgesic group •  tramadol, amitriptyline, celecoxib • 3 studies, 185 patients: • Gabapentin vs placebo • Minimal improvement in pain

14. Benefits: Limited Evidence • Gabapentinoids have tripled in use 2002-2015 (JAMA Internal Med) • No functional outcomes reported • Consider how we assess efficacy of opioids [PEG scale] • What number best describes your pain on average? • How pain has interfered with your enjoyment of life? • How pain has interfered with your generalactivity?

15. Adverse Effects • Inconsistent reporting of treatment harms • Adverse Effects: • Dizziness - NNH=7; 95% CI 4-30 • Fatigue - NNH=8; 95% CI 4-44 • Altered mentation - NNH=6; 95% CI 4-15 • Vision disturbance - NNH=6; 95% CI 4-13

16. Adverse Effects  GRADE [Grading of Recommendations Assessment, Development, and Evaluation] : evidence quality low or moderate Functional outcomes and emotional improvements not reported or showed no significant improvements Cost???

17. Future Areas of Research: • Large high quality trials to more definitively inform this issue- POEM • Interaction with prescription narcotics? • Many already on prescription pain medications • Does it increase the risk of addiction, respiratory depression and death? • Older adults on gabapentinoids • Interactions with anti-depressants or mood stabilizers

18. Bottom Line: There is evidence for its use in post-herpetic neuralgia, refractory partial seizures, off-label: diabetic neuropathy and prophylaxis of frequent migraine headaches Limited number of studies; Limited quality Inconsistent reporting of treatment harms Pain reduction low-moderate

19. Bottom Line: • High rate of adverse effects • Few studies have assessed function, those that do found no improvement • Considered Level 2A- • Centre for Evidence-Based Medicine at Oxford • Systematic review with homogeneity of cohort studies • Fails to provide a conclusive answer due to systematic review with some heterogeneity • Equivalent to Grade D Evidence [USPSTF]  NOT RECOMMENDED

20. Social Determinants of Health AAFP  the conditions under which people are born, grow, live, work, and age Economic inequality is increasing in most countries and is associated with a variety of negative outcomes Indicators of socioeconomic status often used interchangeably

21. Social Determinants of Health Fliesser M, De Witt Huberts J, Wippert P. The choice that matters: The relative influence of socioeconomic status indicators on chronic back pain- A longitudinal study. BMC Health Serv Res. 2017; 17: 800. Longitudinal study: education, job position, income, multidimensional index Back Pain & Disability; surveyed pre & post therapy

22. Social Determinants of Health • Linear regression for predictive strength of each determinant of SES • Intensity best predicted by multidimensional index > job position > education. • Income had no effect • Disability most strongly predicted by education > job position. • Multidimensional index and income had no effect • Interventions should therefore focus on this group of people

23. References Gabapentinoids for Chronic Low Back Pain: Limited Evidence, More Harm Than Benefit. Am Fam Physician. 2017 Dec 15;96(12):online. Shanthanna H, Gilron I, Rajarathinam M, et al. Benefits and safety of gabapentinoids in chronic low back pain: A systematic review and meta-analysis of randomized controlled trials. PLoS Med. 2017;14(8):e1002369. Goodman CW and Brett AS. A clinical overview of off-label use of gabapentinoid drugs. JAMA Intern Med 2019 Mar 25; [e-pub]. https://doi.org/10.1001/jamainternmed.2019.0086. Fliesser M, De Witt Huberts J, Wippert P. The choice that matters: The relative influence of socioeconomic status indicators on chronic back pain- A longitudinal study. BMC Health Serv Res. 2017; 17: 800.

24. Questions?

25. Thank you.