acute low back or neck pain: placebo was a bit better than opiates

acute low back or neck pain: placebo was a bit better than opiates

MG

Modest, Geoffrey (HMFP - Medicine)

To:

• Modest, Geoffrey (HMFP - Medicine)

Thu 8/17/2023 2:38 PM

Acute low back pain and neck pain seem to do better with placebo than opiates!!  (see low back pain acute no better with opioids lancet2023 in dropbox, or https://doi.org/10.1016/S0140-6736(23)00404-X ) 

 

Details:

-- 347 participants in Australia were recruited from 2016-2022 in the OPAL trial, a triple-blinded randomized controlled trial (i.e. neither the patient nor the researchers nor the statistical analyzers were aware of what the participants were taking)

-- patients were recruited through their general practitioners or hospital emergency departments with a complaint of low back pain (pain between the 12^th rib and buttock crease) or neck pain (pain below the occiput to the most distal cervical spine) or both, having pain for 12 weeks or less and preceded by at least one month of being pain-free; also the pain was of moderate severity as determined by the SF-36 questionnaire (Short Form Health Survey with 36 items). Women who were planning conception, pregnant, or breast-feeding were excluded

-- 49% female, mean age 45, mean BMI 29, low back pain in 80%/neck pain in 10%/both in 9%, low back pain extending into the legs in 62%, neck pain extending into the arms 60%, pain duration mean of 18 days, number of episodes mean of 6

-- currently employed 70%, professions pretty evenly divided between office and manual workers, health insurance status none in 50%

-- pain severity 5.7 (0-10, the higher the worse), pain interference 5.8 (0-10, higher is worse), Roland Morris Disability Questionnaire 15.7 (24 item scale questionnaire, score 0-24, higher suggesting more pain-related disability), Neck Disability Index 40 (>34=complete disability), quality of life scores physical component 36/mental component 46 (0-100, higher score is better, 50=normative value)

-- prior use of opioids: 35%

-- patients received an opiate (a modified release tablet of 5 mg oxycodone and 2.5 mg of naloxone), twice a day with gradual increases to 10 mg twice a day on the basis of individual participant progress, tolerability, and sedation score. Naloxone was added to prevent treatment induced constipation, which could undo the blindness of the study. The placebo group received identical looking tablets. All patients received guideline-recommended care.

-- primary outcome: pain intensity (measured on a 0 to 10 scale by the Brief Pain inventory Pain Severity Subscale) at six weeks after randomization

 

Results:

-- 97% of patients were recruited from primary care practices

-- medication adherence rates (taking at least 80% of the prescribed dose): 55% in the opioid group and 56% in the placebo group

-- blinding was successful (patients not knowing which group they were randomized to): 52% in the opioid group and 54% in the placebo group, with 24% in the opioid group and 31% in the placebo group guessing correctly which group they were in

    -- ie, RCT design worked quite well. patients were really not aware of what group they were in

 

-- pain scores at six weeks, comparing opioid group versus placebo:

    -- pain severity: opioid group 2.78 versus placebo 2.25, mean difference of 0.53 (0-1.07), p=0.051 (rather close to being significantly in favor of placebo)

    -- physical functioning: 2.64 versus 2.12, mean difference 0.52 (-0.08 to 1.12), p=0.88

    -- physical functioning, back: 8.89 versus 6.56, mean difference 2.33 (0.55-4.11), p=0.011, statistically significant

    -- physical functioning, neck: 22.7% versus 20.9%, mean difference 1.73% (-9.16% to 12.61%), p=0.75

    -- quality of life, physical score: 43.78 versus 44.62, mean difference -0.84 (-3.17 to 1.50), p=0.48

    -- quality of life, mental score: 48.01 versus 51.26, mean difference -3.25 (-5.63 to -0.7), p=0.0075, a small but significant difference favoring placebo

    -- global perceived effect scale: 2.27 versus 2.46, mean difference -0.19 (-0.85 to 0.47), p=0.58

 

-- Graph of mean pain severity score over time (note that curves are largely diverging for 26 weeks, favoring placebo):

 

 

 

-- no difference in outcomes and pain scores for males vs females or between participants with low back pain or neck pain

-- overall the difference between groups at week 12 as well as by week 52: a small difference favoring placebo

    -- ie, all of these that were statistically significant favored the placebo group.....

-- no difference in time to recovery, work absenteeism, or healthcare utilization during the treatment period

-- more people in the opiate group had ongoing pain at weeks 26 and 52 than in the placebo group

-- at 12 months follow-up: no difference in overall healthcare use, those undergoing imaging, having physiotherapy, seeing specialist doctors, or seeking other healthcare

 -- on review of these numbers, there was a nearly statistically significant benefit of placebo in terms of total hours off paid work (24 on opioids versus 12 on placebo)

--  and, there was a significant difference in the risk of misuse of opioids (24 on opioids and 13 on placebo)

 

-- no difference between groups and proportion of patients reporting serious adverse events; and there were 27 nonserious adverse events in the opioid group and 91 in the placebo group

    -- there were more reports of nausea, constipation and dizziness in those on opiates

 

Commentary:

-- this article found a few major points:

    -- opiates did not help patients with acute low back or neck pain who received guideline-based care

    -- no significant difference at 6 weeks in pain severity if on placebo (though pretty close to significant improvement with placebo over opiates)

    -- a divergence of the pain benefit curves over the study (see graph above), such that at 52 weeks, there was a small but significant benefit for placebo over opiates

        -- by day 14, there was evidence of the superiority of placebo

    -- for all of the other outcomes assessed, there was either no benefit for opiates or small benefits for placebo

    -- and the benefits seemed to be similar in those with radicular and non-radicular pains

    -- adverse effects were somewhat more prevalent in those on opiates, especially nausea, constipation and dizziness in those on opiates

    -- a greater risk of opiate misuse at week 52 in those on opiates, per the Current Opioid Misuse Measure assessing “signs and symptoms of intoxication, emotional volatility, addiction and problematic medication behavior”, even in those on a short course of opiates

        -- another Australian study found that 2.6% of adults prescribed opiates for noncancer pain were still using opiates 12 months later, especially those on transdermal formulations, receiving oral morphine equivalent of >750 mg, having underlying depression or psychosis,  or those previously on acetaminophen, pregabalin or benzos (see Predictors of persistent prescription opioid analgesic use among people without cancer in Australia - PubMed (nih.gov). Also see the references below to similar findings elsewhere. [i will review this Australian study next]

-- For the 2022 CDC practice guideline on opiate prescribing: http://gmodestmedblogs.blogspot.com/2022/11/new-cdc-document-on-opiate-prescribing.html

 

Limitations:

-- These were patients who presented to their general practitioners for low back or neck pain, and these patients may be different (less severe pain) than those presenting to an emergency room, limiting generalizability to all people with acute back or neck pain

-- medication adherence was spotty: about 55% of patients took at least 80% of prescribed meds. This is similar to findings in other studies but may suggest that the pain was either not so severe or resolved pretty quickly

-- 25% of the data were missing at the 6-week mark (the primary outcome), reducing the validity of the results, though mathematical correction validated the results, as also found in several sensitivity analyses

-- unclear about adherence to guideline-based care, or if other meds/nonpharmacologic therapies were used (presumably this should have evened out in the 2 groups through randomization, but perhaps there were different additive effects of these interventions in those on opiates vs placebo: eg, did those on opiates have more “brain fog” and were less likely to participate in other potentially helpful interventions???, we do have suggestive results from this study that the quality of life was worse in those on opiates)

-- no information about the specific effect of sociodemographic conditions on the results, though they did sample people who were rural and urban, in different socioeconomic conditions, and with lots of cultural and linguistic diversity. Still unclear about the generalizabilty to other areas in the world, since this study was based in only one geographical area

 

So, yet another study finding that opiates are really no more effective than placebo (and, in this study seem to be inferior…). That being said, my guess is that over time many of us have prescribed opiates to those with severe pain, or those with pain not responsive to acetaminophen/nsaids, and patients do seem to respond to the opiates. A few comments:

-- there may well be a significant placebo effect here: patients may well believe that opiates are really stronger pain relievers and expect/have better responses

-- in the past, we may have been less attuned to the potential benefits of nonpharmacologic interventions, or even to adjunctive medical treatments:

   -- duloxetine, venlafaxine, tricyclics seem to help, though gabapentinoids are of questionable value: http://gmodestmedblogs.blogspot.com/2023/02/pain-management-review-of.html (which includes a few references to the lack of gabapentinoid benefit in musculoskeletal pain even if neuropathic or radicular)

    -- topical NSAIDs (eg diclofenac gel) seems to be more effective than NSAIDs (http://gmodestmedblogs.blogspot.com/2020/08/acute-musculoskeletal-pain-topical.html ). And, per my experience (have not seen studies on this), adding other topicals to the mix (lidocaine, capsaicin) may improve pain control

 

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-- there are many studies suggesting that the benefit of opiates is questionable and the addictive potential quite high for the patient and those around them (see http://gmodestmedblogs.blogspot.com/search?q=opiates for a general search on the slew of prior blogs on opiate-related articles). Also http://gmodestmedblogs.blogspot.com/2021/12/fracture-surgery-weak-opiates-after.html , which refers to several of the many blogs on opiates

 

    -- some articles on opiate use for surgery:

        -- a study found that adding acetaminophen plus ibuprofen decreased the need for morphine in the 1st 24 hours after total hip arthroplasty (see http://gmodestmedblogs.blogspot.com/2019/03/decreasing-opiates-after-total-hip.html ) 

         -- a study finding that  clinicians are majorly overprescribing opiates post-op, much more than the patients need, with left-over opiates (on average 80% of what was prescribed); and each additional opiate refills was associated with a 44% increase in opiate misuse (defined as having a subsequent diagnostic code for opioid dependence, abuse, or overdose): see http://gmodestmedblogs.blogspot.com/2018/01/post-op-surgery-opiates-and-subsequent.html 

         --a surgery study found that a cancer center using an ultra-restrictive opioid prescription protocol for patients getting major gyn surgery led to dramatically fewer opiates given without a difference in post-op pain compared to before this intervention:  http://gmodestmedblogs.blogspot.com/2019/01/restrictive-postop-opioids-fewer-given.html

        -- dental societies have pushed to decrease opiate prescribing for their procedures, noting that ibuprofen 400 mg plus acetaminophen 1000 mg was superior to opioid-containing meds: http://gmodestmedblogs.blogspot.com/2018/04/new-opioid-guidelines-or-directives.html

 

    --some articles on opiate use in EDs:

        -- ED study finding that patients with acute extremity pain did not seem to have much difference if given an opiate vs ibuprofen 400 plus acetaminophen 1000: http://gmodestmedblogs.blogspot.com/2017/11/opioids-not-better-than-nsaids-for.html

        -- ED study finding that opiates were no better than naproxen for patients with acute low back pain: http://gmodestmedblogs.blogspot.com/2015/10/opiates-for-acute-low-back-pain.html 

        -- systematic review of 20 trials with 1613 patients finding that there was greater pain reduction with NSAIDs than opiates and less need for rescue analgesia for acute pain from kidney stones (typically considered one of the worst pains): https://www.ncbi.nlm.nih.gov/pubmed/15178585 , or see for example: Teichman J. N Engl J Med 2004; 350:684)

    -- and simply letting ED clinicians know about the frequency of their opiate prescriptions (which they often underestimated, by 65% in this study) led to significantly fewer subsequent prescriptions 12 months later: http://gmodestmedblogs.blogspot.com/2018/03/ed-intervention-to-decrease-opioids.html

 

-- article on opiate use for chronic pain:

    --opiates are not better for chronic back/hip/knee pain: http://gmodestmedblogs.blogspot.com/2018/03/opioids-not-better-for-chronic.html . and many non-drug modalities work (eg yoga, tai chi, mindfulness training, home-based CBT)

-- some other articles on the striking addiction potential of opiates after short courses of prescribed opiates, and subsequent opiate misuse:

    -- the future misuse of opiates after surgery was more related to the length of opiate prescriptions than the dose prescribed: http://gmodestmedblogs.blogspot.com/2018/01/post-op-surgery-opiates-and-subsequent.html

    -- an interesting/pretty powerful retrospective study in older patients who were naive to opiates (mean age 69) finding that those seeing high-intensity opiate prescribing ED physicians vs low-intensity ones for similar clinical conditions had a 30% increased likelihood of long-term use of opiates (see http://gmodestmedblogs.blogspot.com/2017/02/opiate-prescribing-in-elderly-and.html /)

    --12th graders at low-risk of future subsequent substance use disorder but were prescribed opiates for a clinical indication were at a 3-fold increased risk of SUD by age 23 (see http://gmodestmedblogs.blogspot.com/2015/10/prescribed-opioids-and-future.html)

 

--and, bottom line: an article noting that there is a much higher opiate prescription rate post-op in the US than in the rest of the world: http://gmodestmedblogs.blogspot.com/2021/01/opioids-very-high-rate-of-prescriptions.html

 

 

geoff

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