SAN DIEGO – Medications for chronic neuropathic pain share similar efficacy, so choose therapy based on safety, tolerability, and ease of use, according to Scott M. Fishman, M.D.
“Each drug that we use has been studied in one or two different neuropathic pain disorders and found to be relatively efficacious, but there's no drug that's been tested in all the disorders,” and few head-to-head comparisons exist, he added at a psychopharmacology congress sponsored by the Neuroscience Education Institute.
One exception in efficacy may apply to patients with shooting, lightening-bolt types of neuropathic pain as is seen with trigeminal neuralgia. For these patients, carbamazepine, baclofen (Lioresal), or tizanidine (Zanaflex) may be more effective than other medications, said Dr. Fishman, chief of the pain medicine division and professor of anesthesiology and pain medicine at the University of California, Davis. For other chronic neuropathic pain, traditional oral analgesic therapies contain either anticonvulsant or antiarrhythmic properties. An explosion in the number of anticonvulsants in the past decade has brought safer options to market.
Nationally, gabapentin (Neurontin) is the top first-line drug used in pain clinics to treat chronic neuropathic pain, not because it's most effective but because it's safer, he said. Dr. Fishman has been a speaker and researcher for Pfizer Inc., the company that makes Neurontin.
Neurontin is not metabolized by the liver, nor does it bind to protein–two traits that greatly reduce the risk of drug-drug interactions, compared with other conventional anticonvulsants including carbamazepine, valproic acid, lamotrigine (Lamictal), and topiramate (Topamax).
“If patients have neuropathic pain, they tend to have systemic diseases, they're often on a lot of other drugs, and drug interactions are a big concern,” he said.
Both the newer and older anticonvulsants for neuropathic pain can still cause major side effects, especially a “cognitive clouding” distinct from fatigue or sleepiness, he added. Other common side effects include fatigue, anorexia, kidney stones, rash, dizziness, drowsiness, visual side effects, and enzyme induction that can decrease the effectiveness of oral contraceptives. Less common side effects include hepatotoxicity, myeloma, and behavioral disinhibition syndromes.
Recent approval of pregabalin (Lyrica), which Dr. Fishman called “son of Neurontin” because it has the same mechanism of action, offers the advantages of easier dosing, linear pharmacokinetics, quicker onset of action, and efficacy from relatively modest doses in treating neuropathic pain, he said. Pfizer Inc. makes Lyrica; Dr. Fishman has been a speaker and researcher for the company.
Another medication, duloxetine (Cymbalta), won approval recently after a speedy review as both an antidepressant and an analgesic for diabetic polyneuropathy, “which really can translate to all the neuropathic pain states,” he said. The dual serotonin-noradrenaline reuptake inhibitor “is the first drug I've seen in my career get approved by the Food and Drug Administration for pain without a single published trial” on pain relief.
Tricyclic antidepressants also could provide dual relief for depression and neuropathic pain if you could get patients to tolerate high enough doses, but a long list of serious side effects makes that impossible. Many primary care physicians and primary care specialists may not be aware of the potential for seizures and cardiac problems with tricyclic antidepressants, he added.
“We see patients being put on tricyclics for diabetic neuropathy all the time without getting an ECG, and these are patients who almost certainly have small-vessel cardiac disease and a high probability of proarrhythmic potential,” he warned.
Among other antidepressants, venlafaxine (Effexor) may be a potent neuropathic analgesic, preliminary studies suggest. The mechanism of its analgesic properties is not understood.