Pharmacotherapy for Neuropathic Pain in Adults

Frank J. Domino, MD

Review

Lancet Neurology 2015; 14(2): 162-73

Study Methods:

Between April 2013 and January 2014 a systematic review and meta analysis of literature was conducted of randomized, double blind, controlled trials of both oral and topical pharmacotherapy for neuropathic pain.

Outcomes:

Two hundred and twenty-nine studies were included in this meta analysis. There was a possible risk of publication bias identified, including a 10% over-statement of treatment effects (publication bias exists when unpublished trials do not show a benefit while published data does show a drug’s benefit implying researchers, often funded by the drug’s manufacturer, do not seek to publish unsuccessful research). Studies published in peer-reviewed journals reported greater effects on neuropathic pain than some unpublished studies. According to the research presented, benefits of treatment were at best modest.

Oral medication that was considered most efficacious was serotonin-noradrenaline reuptake inhibitors (mainly duloxetine) that resulted in a number needed to be treated (NNT) of 6.4 (95% CI = 5.2-8.4). For pregabalin the NNT = 7.7 (95% CI = 6.5-9.4). For gabapentin the NNT = 7.2 (5.9-9.2). Some of the studies included gabapentin in an extended release form as part of the research.

For topical capsaicin high concentration patches the NNT = 10.6 (7.4-19.0). The NNTs were lower for tricyclic antidepressants, tramadol, botulinum toxin A. Use of strong opioids showed considerably lower benefit. There was also little statistical benefit from topical lidocaine patches. Quality of evidence was considered moderate or high for all treatments with the exception of lidocaine patches. Topical agents were considered to be better tolerated and to have lower risk. The authors also reported that cost was least for tricyclic antidepressants and tramadol.

Conclusion

This data supports a strong recommendation for first line use of serotonin-noradrenaline reuptake inhibitors, over pregabalin, and gabapentin. A weak recommendation for use was made for second line capsaicin high concentration patches, and tramadol. Finally a very weak recommendation was proposed for third line including strong opioids and botulinum toxin A.

Discussion

This systematic review and meta-analysis sheds a great light on the management of neuropathic pain. The strengths of this study are its completeness and ability to provide a refined and comprehensive review of the published literature. Its weakness is the fact that how commonly used pain treatments, like acetaminophen (paracetamol) or non-steroidal anti-inflammatory agents were not reviewed.

The single greatest finding here reinforces other systematic reviews that have found opioids of no benefit for chronic pain (Cochrane Database Syst Rev. 2013 Aug 27;8:CD004959). The American Academy of Neurology went a step further, writing a position paper stating clearly that the risk of death from accidental opioid overdose is far greater than any possible benefit (Neurology September 30, 2014 vol. 83 no. 14 1277-1284). The CDC also recently released their best data suggesting about 120 people die per day from accidental prescription overdose, with the opioid class representing over 80% of these accidental deaths (http://www.cdc.gov/homeandrecreationalsafety/overdose/facts.html).

Encourage patients who have their lives limited by chronic pain to use safe agents like acetaminophen 1,000 mg QID (for those over 65 years, TID) as first line, with PRN NSAID’s. If this proves inadequate, add on to the acetaminophen a medication like duloxetine, and if no improvement at maximal dosages, add on gabapentin or the more expensive pregablin. These are safe agents with little risk for drug-drug interaction and no great risk for accidental death or overdose.