Gabapentinoids in Chronic Low Back Pain

Ashley Daniel MD, PGY1University of Kansas School of Medicine- Wichita

Family Medicine Residency at Ascension Via Christi

June 8th, 2019

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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.

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.

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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

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Current evidence: What we know…

Post-herpetic neuralgia

Refractory partial seizures

RCTs showing benefit off-label:

Diabetic neuropathy

Prophylaxis of frequent migraine headaches

Fibromyalgia

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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 and a lack of randomized controlled clinical trials for all but a small number of indications;

Bipolar disorder, peripheral neuropathy, complex regional pain syndrome, attention deficit disorder, restless legs syndrome, trigeminal neuralgia, periodic limb movement disorder of sleep, and alcohol withdrawal syndrome.

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Current evidence: What we know…

Use has tripled over 2002-2015 [Journal Watch]

Likely secondary to opioid epidemic

Especially in regards to non-specific low back pain

Older adults on narcotics

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POEM | Patient Oriented Evidence That Matters

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

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POEM | Patient Oriented Evidence That Matters

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 analgesics9

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, including selection bias and inadequate concealment of randomization

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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

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Benefits: Limited Evidence

Gabapentinoids have tripled in use 2002-2015 [Journal Watch]

No functional outcomes reported

Consider how we assess efficacy of opioids [PEG scale]

1) What number best describes your pain on average?

2)How pain has interfered with your enjoyment of life?

3) How pain has interfered with your general activity?

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Adverse Effects

Inconsistent reporting of treatment harms

Adverse Effects:

Dizziness - NNTH=7; 95% CI 4-30

Fatigue - NNTH=8; 95% CI 4-44

Altered mentation - NNTH=6; 95% CI 4-15

Vision disturbance - NNTH=6; 95% CI 4-13

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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???

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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

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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

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Bottom Line:

High rate of adverse effects

Few studies have assessed function, Those that do found no improvement

Considered Level 2A-

Fails to provide a conclusive answer due to single result with wide confidence interval vs systematic review with some heterogeneity

USPSTF NOT RECOMMENDED

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Social Determinants of Health

AAFP the conditions under which people are born, grow, live, work, and age

Indicators of socioeconomic status often used interchangeably

Longitudinal study: education, job position, income, multidimensional index

Back Pain & Disability; surveyed pre & post therapy

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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

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References Benefits & Safety of Gabapentinoids in chronic low back pain: A

systematic review and meta-analysis of randomized controlled trials. Shanthanna H et al, PLoS Med, 2017 Aug 15; 14 (8).

POEMs https://www.aafp.org/afp/viewRelatedDepartmentsByDepartment.htm?departmentld=111&page=0). Am Fam Physician. 2017 Dec 15; 96 (12):online.

The choice that matters: the relative influence of socioeconomic status indicators on chronic back pain-a longitudinal study. Michael Fliesser, Jessie De Witt Huberts, Pia-maria Wippert. BMC Health Serv Res. 2017; 17: 800.

Thomas L. Schwenk, MD reviewing Johansen ME. JAMA Intern Med 2018 Jan 2.

Journal Watch: https://www.jwatch.org/na48857/2019/04/02/markedly-increased-label-use-gabapentinoid-drugs-pain

https://www.jwatch.org/na45067/2017/09/19/gabapentinoids-are-largely-ineffective-chronic-low-back

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Questions?

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Thank you.

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