Treatment of Neuropathic Pain

Kristen Jefferies, Pharm.D.

Disclosures

Semin Neurol. 2010;30(4):425-432. 

In This Article

Medications with Less Efficacy Data

Serotonin Reuptake Inhibitors (SSRIs)

A Cochrane review published in 2007[7] assessed the efficacy of antidepressants for the treatment of neuropathic pain. This review included three small studies that compared paroxetine (Paxil®), citalopram (Celexa®; Forest Laboratories), and fluoxetine (Prozac®, Eli Lilly & Company) to placebo for the treatment of painful diabetic neuropathy. The SSRIs were superior to placebo in all studies. A comparative study of 26 patients with painful diabetic neuropathy concluded that paroxetine was superior to placebo but less effective than imipramine. Escitalopram (Lexapro®; Forest Laboratories) was superior to placebo in a recent randomized, blinded, crossover study in 41 patients with painful diabetic neuropathy.[18] Seven patients reported good pain relief with escitalopram compared with no patients reporting good pain relief with placebo. Bupropion (Wellbutrin®; GlaxoSmithKline, Brentford, Middlesex, UK) was superior to placebo in a small, single center, randomized, placebo controlled trial in 21 patients with various types of neuropathic pain.[19]

Other Antiepileptic Drugs

Lamotrigine (Lamictal®; GlaxoSmithKline) is FDA-approved for the treatment of bipolar disorder and as adjunctive treatment or monotherapy for various types of seizures.[20] It is thought to exert its pain-relieving effect by blocking voltage-dependent sodium channels. This inhibits presynaptic release of excitatory amino acids.[3] A Cochrane review[21] assessed the efficacy of lamotrigine for acute and chronic pain. This review included one study of 59 patients with painful diabetic neuropathy. Twelve of 27 patients on lamotrigine reported a 50% reduction in pain compared with 5 of 26 patients on placebo. This was not statistically significant. A more recent study also concluded lamotrigine was "inconsistently effective" compared with placebo for the treatment of painful diabetic neuropathy.[22] Lamotrigine was similar to amitriptyline for the treatment of painful diabetic neuropathy in a crossover trial of 46 patients.[23] However, only six patients were evaluated at the end of the first six week treatment phase and only three patients were evaluated at the end of the second phase. Lamotrigine was similar to placebo in a combination trial of 220 patients with various types of neuropathic pain.[24] This study included patients whose pain was not controlled by gabapentin, TCAs, or nonopioid analgesics. The addition of lamotrigine was not associated with more benefit than placebo.

Lacosamide (Vimpat®; UCB Pharma, Smyrna, GA) was recently FDA-approved for adjunct treatment of partial onset seizures.[25] It has been studied for the treatment of painful diabetic neuropathy, but the FDA did not approve it for this indication. It is thought to control neuronal excitation by inactivating voltage-gated sodium channels. It may also have some beneficial effects on pain by modulating NMDA receptors.[26] Clinical trials of lacosamide for painful diabetic neuropathy have mixed results, with some showing slight improvement in pain and some showing no difference from placebo.

Carbamazepine (Tegretol®; Novartis Pharmaceuticals, East Hanover, NJ) is approved in the United States for the treatment of pain associated with trigeminal neuralgia and various types of seizures. Limited data exists to evaluate its role in other types of neuropathic pain.[27]

Other antiepileptic drugs, including oxcarbazepine (Trileptal®; Novartis Pharmaceuticals), topiramate (Topamax®; Ortho-McNeil, Inc., Raritan, NJ), levetiracetam (Keppra®; UCB Pharma), and valproic acid (Depakote®; Abbott Laboratories, Abbott Park, IL), have limited evidence and/or inconsistent results in the treatment of neuropathic pain.[3,5,6,28,29]

Miscellaneous Medications

Intradermal botulinum toxin was superior to placebo in a single study of 29 patients with DPN.[30] Studies in PHN have inconsistent results.[29] Further research is needed to determine its role in neuropathic pain treatment.

Mexiletine (Mexitil®; Teva Pharmaceuticals, North Wales, PA) and lidocaine are sodium channel blockers. In a metanalysis,[31] intravenous lidocaine and its oral analog, mexiletine, were superior to placebo for the treatment of various types of neuropathic pain. No other randomized controlled trials of lidocaine or mexiletine in the treatment of neuropathic pain have been published.

NMDA receptor antagonists have been used for painful neuropathies. Memantine (Namenda®; Forest Pharmaceuticals) is FDA-approved for the treatment of Alzheimer's dementia. Trials of memantine for the treatment of neuropathic pain have inconsistent results, including one study of painful diabetic neuropathy that showed it was not better than placebo.[32] Dextromethorphan is another NMDA glutamate receptor antagonist with inconsistent results for the treatment of neuropathic pain.[4] A combination of dextromethorphan and quinidine has been studied for pseudobulbar affect associated with multiple sclerosis and amyotrophic lateral sclerosis with promising results. Low dose quinidine inhibits the metabolism of dextromethorphan, leading to a longer half-life and higher concentrations of dextromethorphan. A single open-label study[33] assessed the safety of this combination in the treatment of DPN. Dropout rates and side effects were similar to those in previous studies for pseudobulbar affect. More research is needed to assess the efficacy of dextromethorphan combined with quinidine for neuropathic pain conditions.

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