Cochrane for Clinicians

Putting Evidence into Practice

Anticonvulsant Medications for Migraine Prevention

JOSHUA STEINBERG, M.D.

State University of New York Upstate Medical University, Syracuse, New York

The Cochrane Abstract below is a summary of a review from the Cochrane Library. It is accompanied by an interpretation that will help clinicians put evidence into practice. Joshua Steinberg, M.D., presents a clinical scenario and question based on the Cochrane Abstract, along with the evidence-based answer and a full critique of the abstract.

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 systematically reviewed by an AAFP-approved source. The practice recommendations in this activity are available online at http://www.cochrane.org/cochrane/revabstr/AB003266.htm.

Clinical Scenario

A 31-year-old woman asks for help with frequent migraines. She gets good response from abortive medication but had no success with the two preventive medications she has tried. You consider trying an anticonvulsant.

Clinical Question

Do anticonvulsant medications reduce headache frequency in patients with migraine headache?

Evidence-Based Answer

Good evidence supports the use of anticonvulsants as a class with overall reduction in number of headaches per month and overall increase in patients achieving 50 percent reduction of headache frequency. Of the medications within this heterogeneous group, valproic acid and divalproex have the strongest evidence to support their use for this indication.

Practice Pointers

Migraine headaches affect approximately 6 percent of men and 15 to 17 percent of women.2 It is difficult to determine which, if any, preventive medication may reduce the patient's burden. Therefore, it is helpful to have a variety of drug classes to try.

The American Academy of Neurology and American Academy of Family Physicians3 reviewed the treatment of migraine, including the use of prophylactic drugs. Effective agents for migraine prevention include beta blockers, tricyclic antidepressants, selective serotonin reuptake inhibitors, calcium channel blockers, vitamins and supplements (e.g., riboflavin, feverfew, magnesium), nonsteroidal anti-inflammatory drugs, centrally acting antiadrenergic agents, and anticonvulsants.3,4

This Cochrane review should ease physicians' concerns about using anticonvulsants for migraine prophylaxis. Statistically and clinically significant benefit was found for sodium divalproex, valproic acid, carbamazepine, gabapentin, and topiramate. Each drug was studied in one to five clinical trials, and the dosages used for migraine prevention were uniformly lower than antiepileptic dosages. Although side effects and withdrawal from treatment did occur, the rates were moderate.

The mnemonic STEPS can guide physicians in choosing from the many agents available for migraine prophylaxis: Safety, Tolerability, Efficacy, Price, and Simplicity. In a typical young, healthy patient with migraine, beta blockers, divalproex sodium, and tricyclic antidepressants (especially amitriptyline) are safe, inexpensive, and well tolerated, and have the best track record for efficacy. Vitamins and supplements have smaller bodies of evidence to support them and sometimes are hard to find in the recommended dosing forms, but they are effective. Generic fluoxetine also is inexpensive, well tolerated, and convenient.

Tolerability of anticonvulsants ranges from good to fair. Efficacy is similar to that of other drugs.3 Valproic acid and carbamazepine are less expensive than gabapentin and topiramate. All anticonvulsants have once- or twice-daily dosing, but safety is a distinguishing issue. Most patients with migraine are women of childbearing age. Like many of the options for migraine prophylaxis, valproic acid and carbamazepine are pregnancy category D agents; other agents used for migraine prophylaxis are category C. Hepatotoxicity also is a concern with valproic acid and carbamazepine. Although anticonvulsant medications are not the first choice for migraine prevention, they are a welcome option that broadens the options for treating patients with migraine.

---

The Author

Joshua Steinberg, M.D., is assistant professor of family medicine at the State University of New York Upstate Medical University, Syracuse.

Address correspondence to Joshua Steinberg, M.D., Department of Family Medicine, State University of New York Upstate Medical University, 475 Irving Ave., Suite 200, Syracuse, NY 13210 (e-mail: steinbej@upstate.edu). Reprints are not available from the author.

REFERENCES

1. Chronicle E, Mulleners W. Anticonvulsant drugs for migraine prophylaxis. Cochrane Database Syst Rev 2004;(4):CD003226.

2. Stewart WF, Shechter A, Rasmussen BK. Migraine prevalence. A review of population-based studies. Neurology 1994;44(6 suppl 4):S17-23.

3. Ramadan NM, Silberstein SD, Freitag FG, Gilbert TT, Frishberg BM. Evidence-based guidelines for migraine headache in the primary care setting: pharmacological management for prevention of migraine. Accessed online February 15, 2005, at: http://www.aan.com/professionals/practice/pdfs/gl0090.pdf.

4. Linde K, Rossnagel K. Propranolol for migraine prophylaxis. Cochrane Database Syst Rev 2004;(4):CD003225.

Cochrane Briefs

Is Pharmacotherapy Useful in Social Phobia?

Clinical Question

What are the effects of medications for social phobia?

Evidence-Based Answer

In adults, medications may improve the symptoms of social phobia in the short term, but their usefulness may be overstated because of publication bias. Selective serotonin reuptake inhibitors (SSRIs) have the strongest evidence of efficacy and the most favorable side-effect profile.

Practice Pointers

Social phobia affects about 5.3 million Americans. Persons with social phobia fear and avoid social situations or doing things in front of others. It may be limited to certain situations such as public speaking, or it can be generalized. Some persons have such severe fear that they are unable to work or leave their homes. Stein and colleagues searched for published and unpublished trials of pharmacotherapy for treatment of social phobia.

A total of 36 randomized controlled trials (RCTs) with 4,268 patients were found. Most of the RCTs followed patients for less than 14 weeks, and 17 of the studies reviewed SSRIs. A variety of other medications were studied, including monoamine oxidase inhibitors (MAOIs), reversible inhibitors of monoamine oxidase A, benzodiazepines, buspirone, beta blockers, and gabapentin. Because of the wide variation in study design, it is difficult to make specific therapeutic recommendations.

In general, treated patients were more likely to respond than patients who received placebo. The relative risk of nonresponse for treated patients was 0.63 (95 percent confidence interval, 0.55 to 0.72). Average symptom scores were better in patients who took SSRIs and MAOIs. However, funnel-plot analysis of treatment response suggests possible publication bias (i.e., small studies finding little or no benefit may not have been published).

This review supports the view that medications, especially SSRIs, are beneficial for selected patients with social phobia, at least in the short term.1,2

CLARISSA KRIPKE, M.D.

Stein DJ, et al. Pharmacotherapy for social phobia. Cochrane Database Syst Rev 2004;(4):CD001206.

REFERENCES

1. Van Ameringen M, Allgulander C, Bandelow B, Greist JH, Hollander E, Montgomery SA, et al. WCA recommendations for the long-term treatment of social phobia. CNS Spectr 2003;8(8 suppl 1):40-52.

2. Ballenger JC, Davidson JR, Lecrubier Y, Nutt DJ, Bobes J, Beidel DC, et al. Consensus statement on social anxiety disorder from the International Consensus Group on Depression and Anxiety. J Clin Psychiatry 1998;59(suppl 17):54-60.

Copyright © 2005 by the American Academy of Family Physicians. This content is owned by the AAFP. A person viewing it online may make one printout of the material and may use that printout only for his or her personal, non-commercial reference. This material may not otherwise be downloaded, copied, printed, stored, transmitted or reproduced in any medium, whether now known or later invented, except as authorized in writing by the AAFP. Contact afpserv@aafp.org for copyright questions and/or permission requests.

---

---