Medications: Overview of Evidence-Based Strategies Richard D. Guyer, M.D. Co-founder, Texas Back institute Past President NASS Associate Clinical Professor UT Southwestern Medical School Texas Back Institute

Introduction To date, various medications are commonly used in the treatment of acute and chronic LBP Often mentioned in treatment guidelines What evidence is there for this practice?

Evidence, What Evidence? Considering the large number patients receiving medication for LBP, there is little literature providing evidence for specific medications for specific indications

Challenges “Back pain” is a very generic dx at the level of care where many studies are conducted Often divided into only acute or chronic Should we expect all back pain dx to react to a medication the same way? Compliance with amount and timing of medication in studies?

Challenges What other treatments are being received during medication use: PT, modified activities, chiro, acupuncture, over the counter meds, home exercises seen on the Internet, etc.?

American Pain Society compiled extensive evidence-based review on LBP, including meds, 2009

NSAIDS Acute LBP: non-selective NSAIDs associated with moderate short-term pain relief and global improvement compared to placebo (6trials) (level of evidence: good) Chronic LBP: 1 higher-quality trial found non-selective NSAIDs more effective than placebo (level of evidence: fair) American Pain Society, 2009

NSAIDS Most trials evaluated mixed populations of pts +/- sciatica 3 trials (2 higher-quality) specifically evaluated pts with sciatica found no differences between non-selective NSAIDs and placebo (level of evidence: fair) American Pain Society, 2009

NSAIDS AHCPR guidelines: NSAIDs acceptable for treating acute LBP European COST : NSAIDs 2nd choice after paracetamol for acute LBP, and only for short-term exacerbations of chronic LBP American Pain Society, 2009

Acetaminophen Acute LBP: conflicting evidence from 4 lower-quality trials on efficacy of acetaminophen vs. NSAIDs, with 3 finding no difference in outcomes (level of evidence: fair) Chronic LBP: 1 higher quality trial found acetaminophen inferior to NSAID on an overall assessment of efficacy (level of evidence: fair) American Pain Society, 2009

Acetaminophen AHCPR guidelines: acetaminophen reasonably safe and acceptable for treating patients with acute LBP European COST guidelines: recommend acetaminophen as first choice when needed for pain relief in patients with acute LBP American Pain Society, 2009

High quality evidence that paracetamol is ineffective in reducing pain and disability or improving quality of life in patients with LBP 3 studies included in analysis

Muscle Relaxants (MR) Acute LBP: in multiple trials MR moderately more effective than placebo for short-term (<1 wk) relief and global response (level of evidence: good) Chronic LBP or sciatica: insufficient evidence American Pain Society, 2009

Muscle Relaxants (MR) AHCPR: recommend MR as option for LBP MR probably more effective than placebo, but not shown to be more effective than NSAIDs American Pain Society, 2009

Antiepileptic Drugs: Gabapentin and Pregabalin Radiculopathy: 2 small (n=50 and n=80) trials found gabapentin slightly superior for short-term relief compared to placebo No trials evaluated efficacy of gabapentin in patients with non-radicular low back pain American Pain Society, 2009

Gabapentin used to treat fibromyalgia and sometimes prescribed for pts w LBP+ radicular component 108 pts daily pain >6 mo, randomized, 12-week follow-up, gabapentin vs. placebo Pts stratified by those with and those w/o radicular leg pain

Gabapentin for LBP Pain in both groups improved significantly (~30%), no differences between groups, similar results on ODI No significant difference +/- radicular pain No significant correlation between gabapentin plasma concentration and pain intensity Conclusion: gabapentin appears ineffective in LBP +/- radicular pain Atkinson et al, Pain, 2016

Randomized study comparing pregabalin vs Randomized study comparing pregabalin vs. opioids in 65 pts aged >65 yrs with chronic LBP ADL improved more with opioids Pregabalin effective for LBP with neuropathic pain, opioids effective for non-neuropathic pain

Double-blind RCT, 269 pts Herniated disc, pain <3 mo Tapering 15-day course of oral prednisone or placebo (n = 88) Steroid group had modestly better improved function (ODI), no difference in pain or surgery rate, but had greater AE rate

Opioids Acute or chronic LBP: sparse evidence supporting opioids vs. placebo (1 trial showing moderate effects on pain American Pain Society, 2009

Opioids AHCPR: opioids option for time-limited course for acute LBP European COST : recommend weak opioids for nonspecific chronic LBP for pts who do not respond to other treatment modalities American Pain Society, 2009

Narcotics most powerful painkillers available Opioids Then What is lacking is not the way to treat pain effectively but the will to do it Pain specialists warn that pain is undertreated in US originally meant for cancer patients Narcotics most powerful painkillers available Drs afraid to prescribe them due to fear of addiction Pts also concerned about addiction

Because of this philosophy Pain management and other physicians have used opioids for chronic low back pain and sciatica often inappropriately Their use is often in the absence of behavioral medicine support which is extremely important especially for the chronic pain patient And as a result……

Cost of Opioid Abuse: Top 10 States Matrix Global Advisors, LLC April 2015

Estimated Cost of Opioid Abuse Health care costs: $25 billion Criminal justice system: $5 billion Lost workplace productivity: $25.5 billion Birnbaum et al, 2011 Total societal costs of opioid abuse in US: $55 billion a yr Matrix Global Advisors, LLC, April 2015

Opioids Now "For the vast majority of patients, the risks will outweigh the benefits for chronic pain," Thomas Frieden, CDC Director The drugs killed more than 47,000 people in 2014 - more than the 32,000 who died in road accidents

CDC rx opioid checklist

Opioids: State of TX Shift from Schedule III to Schedule II Change in regulations prohibits: Physicians from delegating NP/PAs authority to prescribe opioids outside of a hospital or hospice setting Physicians from calling in prescriptions for opioids to pharmacies Refills of opioid prescriptions without a pt visit or consultation

Reminder Many medications do carry risks of side effects including GI, liver/kidney damage, cardiovascular, neurological, bleeding, etc. Particularly with long-term use and/or combined use with other meds Physicians prescribing meds are responsible for monitoring pts

Future Steps Can we increase targeting of specific prescriptions for specific symptoms?

Goal: Target Medication to Match Individual Patient’s Problem Pain Mechanism Medication Pain Mechanism Target Poor Fit, No Response Likely Arthroplasty Pain Mechanism Medication Medication Pain Mechanism Pathology Partial Fit, Some Response Likely Perfect Fit Good Response Likely

Randomized, double blinded, placebo controlled cross-over study Assigned to imipramine, oxycodone, or clobazam versus placebo Assessing predictive value of central hypersensitivity and endogenous pain modulation may allow use of mechanism-based treatment strategy in individual patients

Summary Little evidence available to support use of a specific medication for a specific spine condition Such studies are very difficult and expensive to conduct

Summary In recent years more high-quality RCTs for specific dx are being conducted Generally finding investigated med not very effective Great challenges in such studies: Identifying appropriate population Patient compliance

Summary Must keep in mind all meds do have some risk involved All definitely have a cost involved When prescribing, must carefully and continually monitor which meds pts are using, what for, beneficial, side effects, etc. Opioid use is much too common and often used inappropriately

Thank You