Cochrane for Clinicians

Putting Evidence into Practice

Carbamazepine for Acute and Chronic Pain

Jennifer J. Buescher, M.D., M.S.P.H., Clarkson Family Medicine Residency, Omaha, Nebraska

The Cochrane Abstract on the next page 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 evidence-based answer and a full critique of the review.

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/reviews/en/ab005451.html.

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

Practice Pointers

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).

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

The Author

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: jbuescher@nebraskamed.com). Reprints are not available from the author.

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 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.

Cochrane Briefs

CLARISSA KRIPKE, M.D.

Screening for Depression

Clinical Question

Are screening tools for depression effective in primary care practice?

Evidence-Based Answer

Sensitive and specific screening tools and effective treatments are available for depression. However, screening for depression has not been shown to increase the number of patients who receive treatment or to improve patient outcomes. This may be because the positive predictive values of screening tests for depression are lower in primary care, or because physicians already are adept at identifying those patients most likely to benefit from treatment (i.e., those who have the most severe symptoms and the greatest functional limitations).

Practice Pointers

There is evidence to suggest that depression is underrecognized in primary care and that patients who are depressed use health care resources more frequently. Therefore, improving care for patients with depression has the potential to improve outcomes and lower costs. A number of validated screening tools have been developed to identify patients with depression in primary care, but research has found mixed results on clinical outcomes.1 In 2002, the U.S. Preventive Services Task Force (USPSTF) found at least fair evidence to recommend that adults should be screened for depression in clinical practices that have systems in place to ensure accurate diagnosis, effective treatment, and follow-up.2 Clinical outcomes are better when the screening is followed up with treatment. The USPSTF did not find data to help physicians design effective diagnosis, treatment, and follow-up procedures.

Gilbody and colleagues revisited this topic in 2005. They searched the literature for randomized controlled trials of screening instruments for depression in primary care settings and found 12 studies with a total of 5,693 patients. Overall, they found that using a screening instrument only slightly increased the detection of depression (relative risk, 1.38; 95% confidence interval, 1.04 to 1.83). However, the results were heterogeneous. There was an insignificant trend toward increased intervention when screening instruments were used. Furthermore, three out of four studies showed patients who were screened had no difference in clinical outcome. No studies on cost-effectiveness were found. It is possible that an enhanced model of care for follow-up on screening results may improve outcomes. However, no studies included follow-up with enhanced models of care such as case management or collaborative care.

Until models of care are developed that improve health care outcomes for patients with depression, family physicians should spend their limited time on other interventions. Unstructured observation by physicians may be sufficient to identify those patients with significant functional limitations who will benefit the most from treatment.

Source: Gilbody S, et al. Screening and case finding instruments for depression. Cochrane Database Syst Rev 2005;(4):CD002792.

REFERENCES

1. Pignone MP, Gaynes BN, Rushton JL, Burchell CM, Orleans CT, Mulrow CD, et al. Screening for depression in adults: a summary of the evidence for the U.S. Preventive Services Task Force. Ann Intern Med 2002;136:765-76.

2. U.S. Preventive Services Task Force. Screening for depression. 2002. Accessed online February 13, 2006, at: http://www.ahrq.gov/clinic/uspstf/uspsdepr.htm.

Dietary Advice to Lower Cardiovascular Risk

Clinical Question

Does dietary advice to patients achieve sustained dietary change or improvements in cardiovascular risk profile?

Evidence-Based Answer

Dietary advice to lower fat and salt intake and increase intake of fruits, vegetables, and fiber produces modest improvements in cardiovascular risk factors. More intensive counseling yields greater effects.

Practice Pointers

Weight loss of 4 to 8 percent of body weight is associated with a decrease in blood pressure of 3 mm Hg (systolic and diastolic) and may decrease the need for medication in patients with hypertension.1 Salt reduction lowers blood pressure,2 and a low-fat diet can reduce cardiovascular risk.3 Obesity is associated with a variety of poor health outcomes. However, it is not clear whether dietary advice alone is enough to help patients make healthy eating choices that could prevent or delay the onset of disease.

Brunner and colleagues searched for randomized trials comparing dietary advice with no advice for the improvement of cardiovascular risk factors or for achieving sustained dietary changes in healthy adults. They found 23 trials with a total of 24,443 patients. The intervention arms consisted predominantly of individual counseling, group sessions, or written advice to lower fat and salt intake while increasing fruit, vegetable, and fiber intake. The least intensive interventions were single encounters. The most intensive included 50 hours of counseling over four years. Patients were followed for three months to four years with a median duration of nine months.

In the four trials that reported on blood pressure, dietary advice resulted in nonsignificant reductions of 2.1 mm Hg in systolic blood pressure and 1.6 mm Hg in diastolic blood pressure. Seven trials of dietary advice reported total blood cholesterol; these showed a statistically significant mean reduction in low-density lipoprotein cholesterol of 5 mg per dL (0.13 mmol per L) with no effect on high-density lipoprotein cholesterol or triglycerides. The 10 studies that measured dietary fat showed a mean reduction of 6 percent in the total dietary fat intake as a percentage of total calories. In eight studies, dietary advice increased patient intake of fruits and vegetables by 1.2 servings per day. Four studies showed that advising patients to increase dietary fiber led to a mean increase in fiber intake of 7.2 g per day. More intensive interventions tended to have greater effects. Based on their findings, the authors estimate that dietary advice may reduce the incidence of coronary heart disease by 12 percent.

The National Heart, Lung, and Blood Institute has a variety of resources for dietary advice available online. Patients who want to learn about healthy lifestyles can visit http://www.nhlbi.nih.gov/health/index.htm#tools. Among the resources available at the Web site are a body mass index calculator, a Portion Distortion quiz, an interactive menu planner, recipes, and general and disease-specific dietary advice.

Source: Brunner EJ, et al. Dietary advice for reducing cardiovascular risk. Cochrane Database Syst Rev 2005;(4):CD002128.

REFERENCES

1. Mulrow CD, Chiquette E, Angel L, Cornell J, Summerbell C, Anagnostelis B, et al. Dieting to reduce body weight for controlling hypertension in adults. Cochrane Database Syst Rev 1998;(4):CD000484.

2. He FJ, MacGregor GA. Effect of longer-term modest salt reduction on blood pressure. Cochrane Database Syst Rev 2004;(1):CD004937.

3. Hooper L, Summerbell CD, Higgins JP, Thompson RL, Clements G, Capps N, et al. Reduced or modified dietary fat for preventing cardiovascular disease. Cochrane Database Syst Rev 2000;(2):CD002137.

The series coordinator for AFP is Clarissa Kripke, M.D., Department of Family and Community Medicine, University of California, San Francisco.

A collection of Cochrane for Clinicians published in AFP is available online at http://www.aafp.org/afp/cochrane.

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