American Family Physician - Carbamazepine for acute and chronic pain
Clinical Scenario
A 52-year-old man with diabetic neuropathic pain has read on the Internet that some seizure medicines are helpful, and he asks for your recommendation.
Clinical Question
How effective is carbamazepine (Tegretol) in controlling pain?
Evidence-Based Answer
Two small trials have shown carbamazepine to be beneficial in the treatment of diabetic neuropathic pain. Carbamazepine shows similar clinical effect to gabapentin (Neurontin) and phenytoin (Dilantin), but there have been no head-to-head trials directly comparing these drugs. Carbamazepine is effective in the treatment of trigeminal neuralgia and may be effective for other types of neuropathic pain, but the data are limited. Carbamazepine is not beneficial for the treatment of acute pain. (1)
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Many drugs are used for the treatment of neuropathic pain syndromes, including opioid analgesics, tricyclic antidepressants, seizure medicines, capsaicin (Zostrix), clonidine (Catapres), tramadol (Ultram), mexiletine (Mexitil), and lidocaine (Xylocaine). Seizure medicines used for neuropathic pain include carbamazepine, gabapentin, duloxetine (Cymbalta), lamotrigine (Lamictal), clonazepam (Klonopin), oxcarbazepine (Trileptal), phenytoin, valproate (Depacon), and pregabalin (Lyrica). (2-5)
After reviewing trials for various neuropathic pain syndromes, Wiffen and colleagues I found that carbamazepine was effective for pain control. However, the largest study in this review included only 77 patients. There was no evidence that carbamazepine causes more serious adverse effects than placebo. Although the number of patients was small, studies in those given the drug for seizures confirm its overall safety.
In the treatment of trigeminal neuralgia, many consider a positive response to carbamazepine to be diagnostic for the condition. However, only seven controlled studies met inclusion criteria for the Cochrane review, and only two studies included data that could be used to calculate the number needed to treat (NNT), which was 1.8. From the data in these small studies, slightly more than 50 percent of patients with trigeminal neuralgia can be expected to have pain relief from carbamazepine.
In the treatment of postherpetic neuralgia, one study reported improvement in pain compared with transcutaneous electronic nerve stimulation. One study of carbamazepine in poststroke pain found that the drug was more effective than placebo and was as effective as amitriptyline. There is little evidence for the use of carbamazepine in other chronic, nonneuropathic pain syndromes, and carbamazepine is not effective in the treatment of acute pain.
Although diabetic neuropathy is a common problem in primary care practice, there are few data evaluating the effectiveness of carbamazepine for diabetic neuropathic pain. Two studies met criteria for inclusion in this review, and although they showed evidence of decreased pain with the use of carbamazepine, they were too small to calculate an NNT. A meta-analysis3 conducted in 2005 also reviewed the use of antiepileptic drugs in chronic diabetic neuropathic pain. This review (3) included a double-blind, placebo-controlled, one-week crossover trial comparing carbamazepine with placebo that was not included in the Cochrane analysis. The NNT reported for the use of carbamazepine in diabetic neuropathy was 3.3 (95% confidence interval, 2 to 9.4).
Two drugs were approved by the U.S. Food and Drug Administration in 2004 for treating diabetic neuropathic pain. Duloxetine, an antidepressant, was approved for the treatment of peripheral diabetic neuropathic pain; initial short-term studies show an NNT of approximately 4. (4) Pregabalin, an antiepileptic drug, was approved for the treatment of pain associated with diabetic neuropathy. (5) Pregabalin is classified by the U.S. Drug enforcement Administration as a Schedule V controlled substance because of concerns about potential physical dependence. (5,6)
REFERENCES
(1.) Wiffen PJ, McQuay HJ, Moore RA. Carbamazepine for acute and chronic pain. Cochrane Database Syst Rev 2005;(3):CD005451.
(2.) Tremont-Lukats IW, Challapalli V, McNicol ED, Lau J, Carr DB. Systemic administration of local anesthetics to relieve neuropathic pain: a systematic review and metaanalysis. Anesth Analg 2005;101:1738-49.
(3.) Vinik A. Clinical review: use of antiepileptic drugs in the treatment of chronic painful diabetic neuropathy. J Clin Endocrinol Metab 2005;90:4936-45.
(4.) Duloxetine (Cymbalta) for diabetic neuropathic pain. Med Lett Drugs Ther 2005;47:67-8.
(5.) New drug: Lyrica (pregabalin). Pharmacist’s Lett/ Prescriber’s Lett 2005;21:210809.
(6.) Lyrica (pregabalin). Product information. New York, N.Y.: Pfizer, 2005.
JENNIFER J. BUESCHER, M.D., M.S.P.H., is a faculty physician at Clarkson Family Medicine Residency, a community-based residency program associated with the Nebraska Medical Center in Omaha, Neb. Dr. Buescher completed her residency and a faculty development fellowship at the University of Missouri-Columbia.
