Treatment of Neuropathic Pain: An Overview of Recent Guidelines
Section snippets
General Considerations Regarding Guidelines for the Treatment of Neuropathic Pain
Although consensus guidelines for the treatment of neuropathic pain are based on synthesizing results from RCTs, a large number of gaps in the literature exist. For example, most of the pharmacotherapy trials have investigated patients with postherpetic neuralgia or painful diabetic peripheral neuropathy, yet there are many patients with neuropathic pain who have a different lesion or disease as the cause of their pain. This raises an important concern: to what extent is it reasonable to
International Association for the Study of Pain Neuropathic Pain Special Interest Group Guidelines for the Treatment of Neuropathic Pain
The NeuPSIG guidelines recommend medications as first-line treatment if multiple RCTs have demonstrated consistent efficacy in Neuropathic Pain (Oxford Centre for Evidence-based Medicine grade A recommendation16) and the authors believed them to be good first choices for patients with neuropathic pain; as second-line if multiple RCTs demonstrated consistent efficacy in neuropathic pain (grade A recommendation) but the authors had reservations about their use relative to the first-line
Antidepressants with Both Norepinephrine and Serotonin Reuptake Inhibition (TCAs and SSNRIs)
Numerous placebo-controlled RCTs have established the efficacy of TCAs for treating a variety of types of neuropathic pain (Table 2). However, RCTs in some neuropathic pain conditions, such as painful HIV and chemotherapy peripheral neuropathies, have been negative.13, 18
The biggest advantages of TCAs are their low cost, once-daily dosing, and beneficial effects on depression, which is a common comorbidity with neuropathic pain. Importantly, TCAs appear to have equivalent analgesic benefits in
Second-Line Medications Appropriate for First-Line Use in Certain Circumstances
Opioid analgesics and tramadol have been found to be efficious in several high-quality RCTs in patients with various types of neuropathic pain (grade A recommendation). However, owing to concerns over their long-term safety (relative to first-line medications), they are recommended principally for patients who have not responded to the first-line medications, except in certain clinical circumstances (i.e., for the treatment of acute neuropathic pain, episodic exacerbations of severe neuropathic
Third-Line Medications
A number of other medications have shown efficacy in neuropathic pain in a single RCT or inconsistent results in different RCTs (grade B recommendation). In general, these medications should be reserved for patients who do not tolerate or respond to the first- and second-line medications, or for whom the first- and second-line medications are contraindicated.
Several additional antidepressant medications have been studied for treatment of neuropathic pain.18 Single RCTs have shown efficacy for
Central Neuropathic Pain
The NeuPSIG guidelines note that few medications have been found to be efficacious in neuropathic pain originating from a lesion in the central nervous system. RCTs have demonstrated efficacy for TCAs in central poststroke pain, and for calcium channel α2-δ ligands in spinal cord injury and poststroke central neuropathic pain (Table 2).13, 35
Cannabinoids have demonstrated efficacy in pain associated with multiple sclerosis, but their use is limited by availability and concerns over long-term
Canadian Pain Society Guidelines
The Canadian Pain Society created 4 levels of recommendation, with first- and second-line medications differentiated by “the quality of evidence and the evidence of efficacy” based on NNTs.15 Medications were classified as third-line treatments if they have good evidence of efficacy, but require specialized monitoring and follow-up not required of drugs at the other levels. Fourth-line medications were described as having “at least 1 positive RCT, but required further study”.15
The authors
European Federation of Neurological Societies Pharmacological Treatment Guidelines
As with the NeuPSIG and Canadian Pain Society guidelines, the EFNS guidelines grade the level of evidence for different available treatments. However, unlike the other 2 sets of guidelines, separate recommendations were made for the treatment of patients with painful polyneuropathies (including painful diabetic peripheral neuropathy), postherpetic neuralgia, trigeminal neuralgia, and central neuropathic pain.14
Consistent with the NeuPSIG and Canadian Pain Society guidelines, the EFNS guidelines
European Federation of Neurological Societies Guidelines for Neurostimulation Therapy in Patients with Neuropathic Pain
An EFNS task force recently reviewed the literature on neurostimulation therapy and developed guidelines for its use in neuropathic pain. In general, the quality of evidence was inadequate to make specific recommendations for many types of neuropathic pain. One noteworthy problem in many studies assessing neurostimulation interventions, which are typically only applied to patients who are refractory to pharmacologic treatment, is the absence of a good control or comparator (e.g., a placebo or
Summary
Three evidence-based consensus guidelines for the pharmacologic treatment of neuropathic have been published recently. These guidelines all recommend TCAs, gabapentin, and pregabalin as first-line treatment options for patients with neuropathic pain (excluding trigeminal neuralgia). They also recommend reserving opioid analgesics and tramadol as second- or third-line options in most cases, despite evidence of efficacy in neuropathic pain. In 2 of the guidelines, topical lidocaine is recommended
Author Disclosures
The authors who contributed to this article have disclosed the following industry relationships:
Alec B. O'Connor, MD, MPH, has no disclosures to report.
Robert H. Dworkin, PhD, In the past 12 months, has worked as a consultant to Allergan, Inc., Astellas Pharma US, Inc., Avigen, Inc., Balboa Biosciences Inc., Bristol-Myers Squibb Company, Cara Therapeutics, Inc., Cervelo Pharmaceuticals Inc., Eli Lilly and Company, Endo Pharmaceuticals, EpiCept Corporation, Fralex Therapeutics Inc.,
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Dr. O'Connor has received support from the Mayday Fund, and the US National Institutes of Health (NIH). Dr. Dworkin has received support from the NIH and the US Veterans Administration (VA). He is a Special Government Employee of the US Food and Drug Administration Center for Drug Evaluation and Research (FDA CDER).
Statement of author disclosure: Please see the Author Disclosures section at the end of this article.