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#214 Nerve-ous About Opioids? Treatment of neuropathic pain with opioids


CLINICAL QUESTION
QUESTION CLINIQUE
What are the risks and benefits of opioids for neuropathic pain?


BOTTOM LINE
RÉSULTAT FINAL
Compared to placebo, high-dose opioids moderately (at least 30%) reduce pain for an additional 1 in every 5-8 people over 4-12 weeksOpioid-related adverse events lead to discontinuation for 1 in every 11-12 people over placebo. Other medications (like tricyclic antidepressants, gabapentin/pregabalin, and duloxetine) are similarly effective with less adverse events. Opioids should only be considered in patients with refractory pain after multiple therapeutic trials.   



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EVIDENCE
DONNÉES PROBANTES
  • Four systematic reviews of 5-31 Randomized Control Trials (RCTs) with 236-1,769 patients followed for 4-12 weeks. Mean age ~60all versus placebo, in diabetic neuropathy, phantom limb pain, or post-herpetic neuralgia. Morphine equivalent dosing ranged from 7.5 mg/day to 180-240 mg/day.1-5  
    • Pain control: 
      • Moderate pain relief (at least 30% improvement) or much/very much improved on a Patient Global Impression of Change scale:1,2  
        • Morphine: 63% versus 36%, Number Needed to Treat (NNT)=4. 
        • Oxycodone as monotherapy and/or add-on44% versus 27%, NNT=6. 
          • Monotherapy NNT=5 or add-on NNT=8. 
      • At least 33% improvement (morphine and oxycodone):3,4 
        • 57% versus 34%, NNT=5. 
        • Meta-analysis by Tools for Practice authors (five RCTs, 429 patients): Reduce pain 1.2 points more than placebo on 10-point scale.  
    • Function: 
      • General activity, normal work activities, social relations, sleep, and life enjoyment: Unclear clinical benefit.3 
        • Example: Outcomes improved between ~0.7 to ~1.7 points out of 10 with morphine or oxycodone versus placebo 
      • Mood and walking measures: No benefit. 
    • Adverse Events: 
      • Morphine, oxycodone, and methadone versus placebo: 
        • Withdrawal due to adverse events: 3,4 Number Needed to Harm (NNH)=11-12.  
        • Constipation (NNH=4-5),2,3 dizziness (NNH=8),2,3 drowsiness/somnolence (NNH=6-7),2,3 nausea (NNH=6),2,3 vomiting (NNH=12).3 
    • Limitations: Concomitant pain treatment unclear, RCTs had small sample sizes and short duration of studies. 
Context: 
  • Guidelines suggest serotonin-norepinephrine reuptake inhibitors, tricyclic antidepressants, or gabapentin/pregabalin as first-line agents for neuropathic pain.6,7 
    • Generally, work as well (similar NNT) as high-dose opioids.8  
    • Opioids inconsistently recommended: From not starting in primary care without specialist advice6 to second-line therapy.7  
  • Between 2006-2008, 58% of drug-related deaths in Ontario were opioid-related.9 


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Author(s)
Auteur(s)
  • Joey Ton PharmD
  • Danielle Perry RN
  • G. Michael Allan MD CCFP

1. Cooper TE, Chen J, Wiffen PJ, et al. Cochrane Database Syst Rev. 2017; 5:CD011669.

2. Gaskell H, Derry S, Stannard C, et al. Cochrane Database Syst Rev. 2016; 7:CD010692.

3. McNicol ED, Midari A, Eisenberg E. Cochrane Database Syst Rev. 2013; 8:CD006146.

4. Sommer C, Welsch P, Klose P, et al. Schmerz. 2015; 1:35-46.

5. Busse JW, Craigie S, Juurlink DN, et al. CMAJ. 2017; 189(18):E659-E666.

6. National Institute for Health and Care Excellence. NICE Guideline (CG96). Available from: https://www.nice.org.uk/guidance/cg173/evidence/neuropathic-pain-pharmacological-management-full-guideline-191621341. Last Accessed: March 6, 2018.

7. Moulin D, Boulanger A, Clark AJ, et al. Pain Res Manag. 2014; 6:328-35.

8. C-TOP Tool. Available at: www.pain-calculator.com. Last Accessed: March 28, 2018.

9. Madadi P, Hildebrandt D, Lauwers A, et al. PLoS One. 2013; 8(4):e60600. 

Authors do not have any conflicts of interest to declare.

Les auteurs n’ont aucun conflit d’intérêts à déclarer.