By Chris Faubel, MD —
Mayo Clin Proc. 2010 Mar;85(3 Suppl):S3-14.
Recommendations for the pharmacological management of neuropathic pain: an overview and literature update.
Dworkin RH, O’Connor AB, Audette J, Baron R, Gourlay GK, Haanpää ML, Kent JL, Krane EJ, Lebel AA, Levy RM, Mackey SC, Mayer J, Miaskowski C, Raja SN, Rice AS, Schmader KE, Stacey B, Stanos S, Treede RD, Turk DC, Walco GA, Wells CD
http://www.mayoclinicproceedings.com/content/85/3_suppl/S3.abstract
ABSTRACT
The Neuropathic Pain Special Interest Group of the International Association for the Study of Pain recently sponsored the development of evidence-based guidelines for the pharmacological treatment of neuropathic pain. Tricyclic antidepressants, dual reuptake inhibitors of serotonin and norepinephrine, calcium channel alpha(2)-delta ligands (ie, gabapentin and pregabalin), and topical lidocaine were recommended as first-line treatment options on the basis of the results of randomized clinical trials. Opioid analgesics and tramadol were recommended as second-line treatments that can be considered for first-line use in certain clinical circumstances. Results of several recent clinical trials have become available since the development of these guidelines. These studies have examined botulinum toxin, high-concentration capsaicin patch, lacosamide, selective serotonin reuptake inhibitors, and combination therapies in various neuropathic pain conditions. The increasing number of negative clinical trials of pharmacological treatments for neuropathic pain and ambiguities in the interpretation of these negative trials must also be considered in developing treatment guidelines. The objectives of the current article are to review the Neuropathic Pain Special Interest Group guidelines for the pharmacological management of neuropathic pain and to provide a brief overview of these recent studies.
HIGHLIGHTS
“Neuropathic pain (NP) has recently been redefined as pain arising as a direct consequence of a lesion or disease affecting the somatosensory system.”
“In randomized clinical trials (RCTs) that have examined pharmacotherapy, no more than half of patients experience clinically meaningful pain relief, which is almost always partial but not complete relief. This is consistent with several studies of NP in the community, which have also shown that patients continue to have, on average, pain of moderate severity despite taking prescribed medications for their pain.”
Keep in mind that, despite there being numerous types of peripheral and central NP in clinical practice, most RCTs evaluated the effectiveness of medications against postherpetic neuralgia (PHN) and painful diabetic peripheral neuropathy (DPN). Also, very few head-to-head comparisons have been performed.
“The lack of direct comparisons of different medications makes it difficult to contrast and rank medications on the basis of efficacy, safety, and tolerability. Therefore, the choice of medication in an individual patient with NP depends on a number of factors, including the potential for adverse effects, treatment of comorbidities (eg, depression, sleep disorders), drug interactions, risks of misuse and abuse, and cost.”
“These consensus guidelines were NOT intended to apply to pédiatrie patients, patients with trigeminal neuralgia (for which separate treatment recommendations are available), or conditions that are not clearly NP (eg, fibromyalgia and irritable bowel syndrome).”
Most importantly: NO ONE MEDICATION IS UNIVERSALLY EFFECTIVE. NEARLY EVERY PATIENT WILL NEED MULTIPLE MEDICATIONS FROM VARIOUS CLASSES
First-line medications:
- Antidepressants With Both Norepinephrine and Serotonin Reuptake Inhihition
- Tricyclic antidepressants: amitriptyline (Elavil), nortriptyline (Pamelor)
- Selective serotonin/norepinephrine reuptake inhibitors: duloxetine (Cymbalta), venlafaxine (Effexor)
- Calcium channel α2-δ ligands: gabapentin (Neurontin), pregabalin (Lyrica)
- Topical lidocaine: Lidoderm (5% lidocaine patch), Lidocaine gel/ointment (5%)
Second-line (that are appropriate for first-line use in certain circumstances):
“As a result of concerns regarding their long-term safety relative to the first-line medications, the guidelines recommend that tramadol and opioids should typically be reserved for patients who have not responded to first-line medications”
- Opioids: **the guidelines didn’t actually list the separate opioids/opiates below. I’m just listing them for reference
- Codeine
- Propoxyphene – Darvon, Darvocet
- Tramadol – Ultram, Ultram-ER
- Hydrocodone – Lorcet, Lortab, Norco, Vicodin, Zydone
- Oxycodone – Percocet, Percodan, Roxicodone, OxyContin
- Hydromorphone – Dilaudid
- Oxymorphone – Opana, Opana ER
- Morphine sulfate – MS Contin, Kadian, Avinza
- Methadone
- Fentanyl – Duragesic (transdermal), Actiq (lollipop), Fentora (buccal)
- Butorphanol – Stadol
- Buprenorphine – Buprenex, Subutex, Suboxone
Third-line:
- Antidepressants: bupropion (Wellbutrin, Wellbutrin SR, Wellbutrin XL, Zyban), citalopram (Celexa), paroxetine (Paxil, Paxil CR), escitalopram (Lexapro)
- Antiepileptics: carbamazepine (Tegretol, Tegretol XR), lamotrigine (Lamictal, Lamictal XR), oxcarbazepine (Trileptal), topiramate (Topamax), valproic acid, lacosamide (Vimpat)
- Topical low-concentration capsaicin
- High-concentration capsaicin patch (Qutenza)
- Dextromethorphan
- Memantine (Namenda)
- Mexiletine
Conditions that seem to be refractory to many first-line therapies in RCTs
- HIV neuropathy
- Chemotherapy-induced peripheral neuropathy
- Lumbosacral radiculopathy – although failed back surgery syndrome responds well to spinal cord stimulation
Final Commentary:
- Don’t forget about incorporating psychosocial interventions, physical therapy, and encouraging an active lifestyle
- Prevention is the best therapy — but then again, most of our patients already have these conditions
- Prevent PHN by encouraging patients over 60 to get the herpes zoster vaccine
- Prevent painful diabetic peripheral neuropathy by encouraging better blood sugar control
