Top

Published in:

01-06-2011

Are Antiepileptic Drugs Used in the Treatment of Migraine Associated with an Increased Risk of Suicidality?

Author: Andres M. Kanner

Published in: Current Pain and Headache Reports | Issue 3/2011

Abstract

Three antiepileptic drugs (AEDs), valproic acid, gabapentin, and topiramate (TPM), are used frequently in the prophylactic treatment of migraines. In December 2008, the US Food and Drug Administration issued a warning suggesting that the use of all AEDs is associated with an increased risk of suicidal ideation and behavior. This warning has been received by the medical community with great skepticism, and the validity of the findings of the meta-analysis that led to its publication has been questioned because of various methodological problems. Yet, migraine by itself is associated with an increased risk of suicidal ideation and behavior as well as with an increased risk of psychiatric disorders that facilitate the development of suicidal behavior. Furthermore, TPM has been associated with psychiatric adverse events that potentially could result in suicidal ideation and behavior. In this article, we review data to determine whether the AEDs used in the prevention of migraine are associated with an increased risk of suicidality.

• Jette N, Patten S, Williams J, et al. Comorbidity of migraine and psychiatric disorders--a national population-based study. Headache. 2008;48:501–516. This is an important reference that illustrates the high prevalence of psychiatric comorbidities in the general population of patients who suffer from migraine. PubMedCrossRef

Breslau N, Lipton RB, Stewart WF, et al. Comorbidity of migraine and depression: investigating potential etiology and prognosis. Neurology. 2003;60:1308–12.PubMed

• Rogawski MA. Common pathophysiologic mechanisms in migraine and epilepsy. Arch Neurol. 2008;65:709–14. This review paper provides a comprehensive review of the pathogenic mechanisms operant in migraine and epilepsy and explain the rationale for the use of antiepileptic drugs in the prophylactic treatment of migraines.PubMedCrossRef

Brandes JL, Saper JR, Diamond M, et al. MIGR-002 Study Group. Topiramate for migraine prevention: a randomized controlled trial. JAMA. 2004;25(291):965–73.CrossRef

Mathew NT, Rapoport A, Saper J, et al. Efficacy of gabapentin in migraine prophylaxis. Headache. 2001;41:19–128.

Freitag FG, Collins SD, Carlson HA, et al. A randomized trial of divalproex sodium extended-release tablets in migraine prophylaxis. Neurology. 2002;58:1652–9.PubMed

U.S. Department of Health and Human Services, Food and Drug Administration, Center for Drug Evaluation and Research, Office of Translational Sciences, Office of Biostatistics (2008). Statistical review and evaluation: Antiepileptic drugs and suicidality. May 21, 2008.

Kessler RD, Borges G, Walters EE. Prevalence of and risk factors for lifetime suicide attempts in the National Comorbidity Survey. Arch Gen Psychiatry. 1999;56:617–26.PubMedCrossRef

Saaman Z, Farmer A, Craddock N, et al. Migraine in recurrent depression: case-control study. Br J Psychiatry. 2009;194:350–4.CrossRef

10.

Fasmer OB. The prevalence of migraine in patients with bipolar and unipolar affective disorders. Cephalalgia. 2001;21:894–5.PubMedCrossRef

11.

Breslau N, Schultz LR, Stewart WF, et al. Headache types and panic disorder: directionality and specificity. Neurology. 2001;56:350–4.PubMed

12.

Breslau N, Lipton RB, Stewart WF, et al. Comorbidity of migraine and depression: investigating potential etiology and prognosis. Neurology. 2003;60:1308–12.PubMed

13.

Breslau N, Davis GC, Andreski P. Migraine, psychiatric disorders, and suicide attempts: an epidemiologic study of young adults. Psychiatry Res. 1991;37:11–23.PubMedCrossRef

14.

Wang SJ, Juang KD, Fuh JL, et al. Psychiatric comorbidity and suicide risk in adolescents with chronic daily headache. Neurology. 2007;68:1468–73.PubMedCrossRef

15.

•• Demarquay G, Lothe A, Royet JP, Costes N, Mick G, Mauguière F, Ryvlin P. Brainstem changes in 5-HT1A receptor availability during migraine attack. Cephalalgia. 2011;31:84–94. This is a state-of-the-art study that demonstrates the pathogenic role of serotonin in migraine. PubMedCrossRef

16.

Ferrari MD. Sumatriptan in the treatment of migraine. Neurology. 1993;43(6 Suppl 3):S43–7.PubMed

17.

Sargent PA, Kjaer KH, Bench CJ, et al. Brain serotonin 1A receptor binding measured by positron emission tomography with [11 C]WAY-100635: effects of depression and antidepressant treatment. Arch Gen Psychiatry. 2000;57:174–80.PubMedCrossRef

18.

Drevets WC, Frank E, Price JC, et al. PET imaging of serotonin 1A receptor binding in depression. Biol Psychiatry. 1999;46:1375–87.PubMedCrossRef

19.

Neumeister A, Bain E, Nugent AC, et al. Reduced serotonin type 1A receptor binding in panic disorder. J Neurosci. 2004;24:589–91.PubMedCrossRef

20.

Asberg M, Bertilsson L, Martensson B. Indolamine metabolites, depression and suicide. Adv Biochem Psychopharmacol. 1984;39:87–97.PubMed

21.

Lester D. The concentrations of neurotransmitter metabolites in the cerebrospinal fluid of suicidal individuals: a meta-analysis. Pharmacopsychiatry. 1995;28:45–50.PubMedCrossRef

22.

Oquendo MA, Placidi GP, Malone KM, et al. Positron emission tomography of regional brain metabolic responses to a serotonergic challenge and lethality of suicide attempts in major depression. Arch Gen Psychiatry. 2003;60:14–22.PubMedCrossRef

23.

Arango V, Underwood MD, Gubbi AV, Mann JJ. Localized alterations in pre- and postsynaptic serotonin binding sites in the ventrolateral prefrontal cortex of suicide victims. Brain Res. 1995;688:121–33.PubMedCrossRef

24.

Arango V, Huang YY, Underwood MD, Mann JJ. Genetics of the serotonergic system in suicidal behavior. J Psychiatr Res. 2003;37(5):375–86.PubMedCrossRef

25.

Sareen J, Cox BJ, Afifi TO, et al. Anxiety disorders and risk for suicidal ideation and suicide attempts: a population-based longitudinal study of adults. Arch Gen Psychiatry. 2005;62:1249–57.PubMedCrossRef

26.

Brent DA, Crumrine PK, Varma RR, Allan M, Allman C. Phenobarbital treatment and major depressive disorder in children with epilepsy. Pediatrics. 1987;80:909–17.PubMed

27.

Trimble RM, Rϋsch N, Betts T, Crawford PM. Psychiatric symptoms after therapy with new antiepileptic drugs: Psychopathological and seizure related variables. Seizure. 2000;9:249–54.PubMedCrossRef

28.

Mula M, Trimble MR, Lhatoo SD, Sander JW. Topiramate and psychiatric adverse events in patients with epilepsy. Epilepsia. 2003;44:659–63.PubMedCrossRef

29.

Mula M, Trimble MR, Yuen A, Liu RS, Sander JW. Psychiatric adverse events during levetiracetam therapy. Epilepsia. 2007;61:704–6.

30.

Mula M, Sander JW. Suicidal ideation in epilepsy and levetiracetam therapy. Epilepsy Behav. 2007;11:130–2.PubMedCrossRef

31.

Redden L, Pritchett Y, Robieson W, Kovacs X, Garofalo M, Tracy K, et al. Suicidality and divalproex sodium: analysis of controlled studies in multiple indications. Ann Gen Psychiatry. 2011;18;10:1.CrossRef

32.

Gibbons RD, Hur K, Brown CH, Mann JJ. Gabapentin and suicide attempts. Pharmacoepidemiol Drug Saf. 2010;19:1241–7.PubMedCrossRef

33.

• Hesdorffer DC and Kanner AM. The FDA alert on suicidality and antiepileptic drugs: Fire or false alarm? Epilepsia. 2009;50:978–86. This article provides a critical assessment of the FDA meta-analysis and points out methodological problems that question the conclusion that all AEDs can increase the risk of suicidality. PubMedCrossRef

34.

GlaxoSmithKline (2006) Briefing Document: Paroxetine Adult Suicidality Analysis: Major Depressive Disorder and non-Major Depressive Disorder. Available at: (http://www.gsk.com/media/par_current_analysis.htm) [Accessed April 5, 2006].

35.

Dr. Katz memo and briefing document to PCNS and PD Advisory Committees (2008) Briefing document for the July 10, 2008 Advisory Committees to discuss antiepileptic drugs (AEDs) and suicidality. Available at: http://www.fda.gov/ohrms/dockets/ac/08/briefing/2008-4372b1-01-FDA-Katz.pdf.

36.

Greenland S, Robins JM. Estimation of a common effect parameter from sparse follow-up data. Biometrics. 1985;41:55–68.PubMedCrossRef

37.

French JA, Kanner AM, Bautista J, et al. Efficacy and tolerability of the new antiepileptic drugs I: treatment of new onset epilepsy: Report of the Therapeutics and Technology Assessment Subcommittee and Quality Standards Subcommittee of the American Academy of Neurology and the American Epilepsy Society. Neurology. 2005;64:172–4.

38.

Gibbons RD, Jur K, Brown CH, Mann JJ. Relationship between antiepileptic drugs and suicide attempts in patients with bipolar disorder. Arch Gen Psychiatry. 2009;66:1354–60.PubMedCrossRef

39.

Olesen JB, Hansen PR, Erdal J, et al. Antiepileptic drugs and risk of suicide: a nationwide study. Pharmacoepidemiol Drug Saf. 2010;19:518–24.PubMed

40.

Patorno E, Bohn RL, Wahl PM, Avorn J, Patrick AR, Liu J, et al. Anticonvulsant medications and the risk of suicide, attempted suicide, or violent death. JAMA. 2010;303:1401–9.PubMedCrossRef

41.

VanCott AC, Cramer JA, Copeland LA, Zeber JE, Steinman MA, Dersh JJ, et al. Suicide-related behaviors in older patients with new anti-epileptic drug use: data from the VS hospital system. BMC Med. 2010;8:4.PubMedCrossRef

42.

Arana A, Wentworth CE, Ayuso-Mateos JL, Arellano FM. Suicide-related events in patients treated with antiepileptic drugs. N Engl J Med. 2010;363:542–51.PubMedCrossRef

43.

Hesdorffer DC, Berg AT, Kanner AM. An update on antiepileptic drugs and suicide: are there definitive answers yet? Epilepsy Curr. 2010;10:137–45.PubMedCrossRef

44.

Zigmond AS, Snaith RP. The hospital anxiety and depression scale. Acta Psychiatr Scand. 1983;67:361–70.PubMedCrossRef

45.

Beck AT, Steer RA, Garbin MG. Psychometric properties of the Beck Depression Inventory: twenty-five years of evaluation. Clin Psychol Rev. 1988;8:77–100.CrossRef

46.

Beck AT, Brown G, Epstein N, Steer RA. An inventory for measuring clinical anxiety: psychometric properties. J Consult Clin Psychol. 1988;56:893–7.PubMedCrossRef

47.

Sheehan BV, Lecrubier Y, Sheehan KH, Amorim P, Janavs J, Weiller E, et al. The Mini International Neuropsychiatric Interview (MINI): the development and validation of structured diagnostic psychiatric interview for DSM-IV and ICD-10. J Clin Psychiatry. 1998;59 Suppl 20:22–33.PubMed

Title: Are Antiepileptic Drugs Used in the Treatment of Migraine Associated with an Increased Risk of Suicidality?
Author: Andres M. Kanner
Publication date: 01-06-2011
Publisher: Current Science Inc.
Published in: Current Pain and Headache Reports / Issue 3/2011
Print ISSN: 1531-3433
Electronic ISSN: 1534-3081
DOI: https://doi.org/10.1007/s11916-011-0199-x

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Are Antiepileptic Drugs Used in the Treatment of Migraine Associated with an Increased Risk of Suicidality?

Abstract

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 3/2011

Advances in Translational Neuropathic Research: Example of Enantioselective Pharmacokinetic–Pharmacodynamic Modeling of Ketamine-induced Pain Relief in Complex Regional Pain Syndrome

ICHD-3: What Changes Do We Need Regarding Migraine?

Sarcoidosis and Small-fiber Neuropathy

Alcohol and Migraine: What Should We Tell Patients?

How Close Are We in Utilizing Functional Neuroimaging in Routine Clinical Diagnosis of Neuropathic Pain?

Neuronal Hyperexcitability: A Substrate for Central Neuropathic Pain After Spinal Cord Injury