#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.
- Moderate pain relief (at least 30% improvement) or much/very much improved on a Patient Global Impression of Change scale:1,2
- 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.
- General activity, normal work activities, social relations, sleep, and life enjoyment: Unclear clinical benefit.3
- 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
- Morphine, oxycodone, and methadone versus placebo:
- Limitations: Concomitant pain treatment unclear, RCTs had small sample sizes and short duration of studies.
- Pain control:
- 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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