Tools for Practice


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


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

BOTTOM LINE
Compared to placebo, high-dose opioids moderately (at least 30%) reduce pain for an additional 1 in every 5-8 people over 4-12 weeks. Opioid-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
  • Four systematic reviews of 5-31 Randomized Control Trials (RCTs) with 236-1,769 patients followed for 4-12 weeks. Mean age ~60, all 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-on: 44% 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 
June 18, 2018

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Author(s):

  • Danielle Perry RN
  • G. Michael Allan MD CCFP
  • Joey Ton PharmD

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.