Evidence Lacking for Current Rx Treatment of Neuropathic Pain

Evidence Lacking for Current Pharmacologic Treatment of Neuropathic Pain – Pain Medicine News – May 19, 2017

Successful management of neuropathic pain remains elusive despite the variety of pharmacologic classes prescribed to treat it, new research suggests.

Furthermore, the actual evidence supporting drugs used on an everyday basis is remarkably deficient, according to Richard W. Rosenquist, MD, the study’s author and chairman of the Department of Pain Management at the Cleveland Clinic, in Ohio

The Cleveland Clinic has become notorious for denying opioid pain medication to patients who desperately need them. 

Evidence Lacking for Current Pharmacologic Treatment of Neuropathic Pain

“We’d like better evidence, but we don’t really have it,” Dr. Rosenquist said. “There is marginal evidence for the use of a broad range of oral agents to treat neuropathic pain.”

He surveyed the literature on current pharmacologic management of neuropathic pain and shared the “frustrating, surprising and maybe even appalling” results at the 2016 annual meeting of the American Society of Regional Anesthesia and Pain Medicine (ASRA).

Anticonvulsant Drugs

A review of gabapentin use for chronic neuropathic pain patients demonstrated no first-tier evidence for analgesic efficacy in chronic neuropathic pain and fibromyalgia (Cochrane Database Syst Rev 2014;4:CD007938).

The research, which is an update of a review published in 2011 (Cochrane Database Syst Rev 2011;3:CD007938), included data from 37 studies and 5,633 participants looking at oral gabapentin at daily doses of 1,200 mg or higher to treat 12 chronic pain conditions.

Second-tier evidence for an outcome of at least 50% pain intensity reduction showed that gabapentin was not significantly better than placebo for treating postherpetic neuralgia.

A separate analysis composed of data pooled from 18 randomized controlled trials comparing the therapeutic response to pregabalin in patients with neuropathic pain showed no significant differences between patients who had recceived gabapentin and those who did not, in extent of pain relief and relief of pain-related sleep interference for any dose (Pain Pract 2016 Sept 9. [Epub ahead of print]).

Dr. Rosenquist said these findings highlight the importance of tailoring treatment of neuropathic pain based on individual patient response to different treatments, including the trial of multiple agents within the same mechanistic class

Until the field of medicine became so intensely financially motivated and managed, medicine was all about the individual patient, not some “standard” rules of treatment.

We don’t need guidelines, we need old fashioned individualized treatment that works with us and our particular symptoms and responses to various medications.


Although a variety of antidepressants commonly are used to treat chronic neuropathic pain, amitriptyline is often recommended as first-line therapy, according to researchers.

However, an updated version of a 2012 review follows the “same disturbing trend” as anticonvulsants, Dr. Rosenquist said. Researchers found no first- or second-tier evidence for amitriptyline in treating any neuropathic pain condition; only third-tier evidence was available (Cochrane Database Syst Rev 2015;7:CD008242).

Even though these findings were disappointing, the authors pointed out that “a lack of supportive, unbiased evidence for a beneficial effect should be balanced against decades of successful treatment in many people with neuropathic pain.”

The gap between “scientific evidence” and “real life” seems to be widening. Many medications that work very well for some of us may not work at all for others.

Out of 100 people, if it works very well for 20 people and not at all for the rest, the average becomes meaningless. There is no “in between” and only trial and error can determine the usefulness of a medication in a particular patient.

They recommended that amitriptyline should continue to be used as part of the treatment of neuropathic pain, “but only a minority of people will achieve satisfactory pain relief.”

Benzodiazepines and Opioids

Benzodiazepines commonly are not used to treat neuropathic pain, and with the FDA’s recent black box warning about mixing benzodiazepines and opioids, many clinicians are revisiting their use of these agents.

Opioids are in the headlines every day and mostly in a negative way, Dr. Rosenquist noted. A Cochrane review on fentanyl use for neuropathic pain in adults—at any dose and by any route of administration—showed insufficient evidence to support or refute the suggestion that fentanyl works in any neuropathic pain condition (Cochrane Database Syst Rev 2016;10:CD011605).

I believe this is because the drug doesn’t work “somewhat”, but either completely or not at all. This skews the statistics used in the study to show only a low average effectiveness.

Using averages in these cases may not be the right approach. Like with gender, this variable is usually “either or” and never an average of male and female.

The average person would have one testicle and one breast, which is just as nonsensical as many of these studies – which are targeted at this same ridiculous statistically “average patient”.

At least one glimmer of hope, however, can be found in the first study to compare the effects of methadone with fentanyl in cancer patients with a neuropathic pain component (Eur J Cancer 2016;65:121-129).

“Based on the results,” Dr. Rosenquist said, “methadone should be considered in the treatment of oncologic pain with a neuropathic component. … There may be a role for using methadone in this subset of patients.”

Oxycodone, in contrast, demonstrated very low-quality evidence for the treatment of painful diabetic neuropathy or postherpetic neuralgia, with no evidence for other neuropathic pain conditions (Cochrane Database Syst Rev 2016;7:CD010692).

Why is there so little evidence for efficacy when anecdotal reports show success?

Because these studies are all calibrated for “average patients”, they completely ignore the variability of individual people, which may be the most important variable for any medication response.


Another glimmer of hope may come from a small short-term, placebo-controlled trial of inhaled cannabis that demonstrated a dose-dependent reduction in diabetic peripheral neuropathy pain in patients with treatment-refractory pain (J Pain 2015;16:616-627). This finding adds preliminary evidence to support further research on the efficacy of the cannabinoids in neuropathic pain, the study authors noted

New Drugs Needed

“When we examine the published recommendations on neuropathic pain, we end up with a consensus statement without a strong evidentiary basis,” Dr. Rosenquist summarized.

“Further guidance regarding appropriate patient selection and drug and dose strategies is needed to improve management with current drugs. If we’re really going to make a difference for our patients going forward, new drug development to treat these conditions with greater reliability and a smaller side-effect profile is urgently needed.”

Side effects are sometimes worse than desired effects

Author: Kevin Vorenkamp, MD, director of the pain medicine fellowship at Virginia Mason Medical Center, in Seattle, said this survey of the literature underscores the challenges of a very difficult patient population.

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