Cochrane for Clinicians
Putting Evidence into Practice
Carbamazepine for Acute and Chronic Pain
Am Fam Physician. 2006 May 1;73(9):1549-1550.
This clinical content conforms to AAFP criteria for evidence-based continuing medical education (EB CME). EB CME is clinical content presented with practice recommendations supported by evidence that has been reviewed systematically by an AAFP-approved source. The practice recommendations in this activity are available online at http://www.cochrane.org/cochrane/revabstr/AB005451.htm.
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.
How effective is carbamazepine (Tegretol) in controlling pain?
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
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 colleagues1 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 review3 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).
Background. Anticonvulsant drugs have been used in the management of pain since the 1960s. The clinical impression is that they are useful for chronic neuropathic pain, especially when the pain is lancinating or burning.
Objectives To evaluate the analgesic effectiveness and adverse effects of the anticonvulsant medicine carbamazepine for pain management in clinical practice and to identify a clinical research agenda. Migraine and headache studies are not included in this review.1
Search Strategy. Randomized trials of anticonvulsants in acute, chronic, or cancer pain were identified by MEDLINE (1966–2004), EMBASE (1994–2004), SIGLE (1980–2004), and the Cochrane Controlled Trials Register (CENTRAL\CCTR; Cochrane Library Issue 3, 2003). In addition, 41 medical journals were hand searched for a previous version of this review. Additional reports were identified from the reference list of the retrieved papers and by contacting investigators. Date of most recent search: November 2004.
Selection Criteria. Randomized trials reporting the analgesic effects of carbamazepine in patients, with subjective pain assessment as the primary or a secondary outcome.
Data Collection and Analysis. Data were extracted by two independent reviewers, and trials were quality scored. Numbers needed to treat (NNTs) were calculated from dichotomous data for effectiveness, adverse effects, and drug-related study withdrawal, for individual studies and for pooled data.
Primary Results. Twelve studies were included (404 participants). Four studies included trigeminal neuralgia patients. Two studies that provided assessable data yielded an NNT for effectiveness of 1.8 (95% confidence interval [CI], 1.4 to 2.8). For diabetic neuropathy there were insufficient data for an NNT to be calculated.
Numbers needed to harm (NNHs) were calculated where possible by combining studies for each drug entity irrespective of the condition treated. The result for minor harm was carbamazepine 3.7 (95% CI, 2.4 to 7.8); NNHs for major harm were not statistically significant for carbamazepine compared with placebo. There is no evidence that carbamazepine is effective for acute pain.
Reviewers' Conclusions. There is evidence to show that carbamazepine is effective, but trials are small.
These summaries have been derived from Cochrane reviews published in the Cochrane Database of Systematic Reviews in the Cochrane Library. Their content has, as far as possible, been checked with the authors of the original reviews, but the summaries should not be regarded as an official product of the Cochrane Collaboration; minor editing changes have been made to the text (http://www.cochrane.org)
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
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.
Address correspondence to Jennifer J. Buescher, M.D., M.S.P.H., Clarkson Family Medicine Residency, 4200 Douglas, Omaha, NE 68131 (e-mail: firstname.lastname@example.org). Reprints are not available from the author.
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 meta-analysis. 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.
The Cochrane Abstract is a summary of a review from the Cochrane Library. It is accompanied by an interpretation that will help clinicians put evidence into practice. Jennifer J. Buescher, M.D., M.S.P.H., presents a clinical scenario and question based on the Cochrane Abstract, followed by an evidencebased answer and a full critique of the review.
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