抗癫痫药物与自杀的关系——国际抗癫痫联盟治疗方法委员会手术治疗协作组报告_Journal of Epilepsy

Authors：

 郭佳南 ,  慕洁

四川大学华西医院神经内科, 成都, 610041;

Corresponding author：

慕洁, Email: mujie2010@foxmail.com

Keywords：

癫痫; 自杀; 抗癫痫药物; 抑郁

DOI：

10.7507/2096-0247.20160013

Video：

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在2008年, 美国食品及药品管理局(Food and drug administration, FDA)警告医务工作者关于接受抗癫痫药物(AEDs)治疗的患者自杀观念及自杀行为的风险均有增高。自此以后, 一系列回顾性队列研究及病例对照研究均致力阐明这一议题, 但不同研究的结果却相互矛盾。这是一份来自国际抗癫痫联盟(ILAE)神经心理生物学工作组的专家共识。尽管部分(并非全部)AEDs与治疗中出现的自杀观念与自杀行为相关(目前预计风险很低), 但仍需要进一步评估。此外, 停止AEDs治疗或拒绝开始AEDs治疗会明显加重病情, 带来严重后果甚至引起患者死亡。癫痫患者的自杀问题是多因素的, 不同的变量在其中发挥作用。临床医生应当注意观察并选用合适的筛查工具评估患者是否存在自杀的风险。必要时应当推荐患者去看精神科医师, 即使患者出现自杀倾向也不应当停用AEDs。当启用一种新的AED治疗或替换AED时, 应注意询问患者近期是否有情绪的改变或出现自杀观念。关于治疗时出现的精神异常事件等资料应被记录, 不仅仅记录治疗相关的安全信息, 还应记录对照研究的信息, 在患者开始新的AED治疗时告知患者及家属新药上市的时间

Citation： 郭佳南, 慕洁. 抗癫痫药物与自杀的关系——国际抗癫痫联盟治疗方法委员会手术治疗协作组报告. Journal of Epilepsy, 2016, 2(1): 67-71. doi: 10.7507/2096-0247.20160013 Copy

1.	Andersohn F, Schade R, WillichSN, et al. Use of antiepileptic drugs in epilepsy and the risk of self-harm or suicidal behavior. Neurology, 2010, 75(13): 335-340.
2.	Arana A, Wentworth CE, Ayuso-Mateos JL, et al. Suiciderelated events in patients treated with antiepileptic drugs. N Engl J Med, 2010, 36(3): 542-551.
3.	Barraclough BM. The suicide rate of epilepsy. Acta Psychiatr Scand, 1987, 76(2): 339-345.
4.	Bell GS, Gaitatzis A, Bell CL, et al. Suicide inpeople with epilepsy: how great is the risk?. Epilepsia, 2009, 50(21):1933-1942.
5.	Busco M. FDA advisory members agree antiepileptics pose suicidalityrisk, need for black-box warning. Medscape medical news, 2008, 13(3): 1-4.
6.	Christensen J, Vestergaard M, Mortensen PB, et al. (2007)Epilepsy and risk of suicide: a population-based case-control study.Lancet Neurol, 2007, 6(2):693-698.
7.	Dodrill CB, Troupin AS. Psychotropic effects of carbamazepine inepilepsy: a double-blind comparison with phenytoin. Neurology, 1977, 27(10):1023-1028.
8.	Ettinger AB. Psychotropic effects of antiepileptic drugs. Neurology, 2006, 67(13):1916-1925.
9.	FDA. (2008a) Antiepileptic drugs and suicidality. Available at: http://www.fda.gov/ohrms/dockets/ac/08/briefing/2008-4372b1-01-FDA.pdf.
10.	FDA. (2008b) Information for healthcare professionals: suicidal behavior andideation and antiepileptic drugs. Available at: http://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/ucm100192.html.
11.	Gelder MG. New oxford textbook of psychiatry. Oxford University Press, Oxford, 2009: 1-1088.
12.	Gibbons R, Hur K, Brown CH, et al. Relationship between antiepilepticdrugs and suicide attempts in patients with bipolar disorder.Arch Gen Psychiatry, 2009, 66(17):1354-1360.
13.	Gibbons RD, Hur K, Brown CH, et al. Gabapentin and suicideattempts. Pharmacoepidemiol Drug Saf, 2010, 19(8):1241-1247.
14.	Hara E, Akanuma N, Adachi N, et al. Suicideattempts in adult patients with idiopathic generalized epilepsy. Psychiatry Clin Neurosci, 2009, 63(12):225-229.
15.	Harris EC, Barraclough B. Suicide as an outcome for mental disorders: a meta-analysis. Br J Psychiatry, 1997, 170(32):205-228.
16.	Hecimovic H, Salpekar J, Kanner AM, et al. Suicidality and epilepsy: a neuropsychobiological perspective. Epilepsy Behav, 2011, 22(18):77-84.
17.	Hesdorffer DC, KannerAM. The FDA alert on suicidality and antiepilepticdrugs: fire or false alarm?Epilepsia, 2006, 50(11):978-986.
18.	Hesdorffer DC, Hauser WA, Olafsson E, et al.Depression and suicide attempt as risk factors for incidentunprovoked seizures. Ann Neurol, 2006, 59(21):35-41.
19.	Hesdorffer DC, Berg AT, Kanner AM. An update on antiepilepticdrugs and suicide: are there definitive answers yet?.Epilepsy Curr, 2010, 10(7):137-145.
20.	Hesdorffer DC, Tomson T, Benn E, et al. Combined analysis of risk factors for SUDEP. Epilepsia, 2011, 52(11): 1150-1159.
21.	Kanner AM, Wuu J, Faught E, et al.A past psychiatric history may be a risk factor for topiramate related psychiatric and cognitive adverse events. Epilepsy Behav, 2003, 4(1):548-552.
22.	Kanner AM, Soto A, Gross-Kanner H. Prevalence and clinical characteristics of postictal psychiatric symptoms in partial epilepsy. Neurology, 2004, 62(10):708-713.
23.	Kanner AM, Schachter SC, Barry JJ, et al.Depression and epilepsy, pain and psychogenic non-epilepticseizures: clinical and therapeutic perspectives. Epilepsy Behav, 2012, 24(5):169-181.
24.	Kapur N, Cooper J, King-Hele S, et al. The repetition of suicidal behavior: a multicenter cohortstudy. J Clin Psychiatry, 2006, 67(9):1599-1609.
25.	Levinson DF, Devinsky O. Psychiatric adverse events during vigabatrintherapy. Neurology, 1999, 53(12):1503-1511.
26.	Mula M, Hesdorffer DC. Suicidal behavior and antiepileptic drugsin epilepsy: analysis of the emerging evidence. Drug Healthc Patient Saf, 2011, 3(1):15-20.
27.	Mula M, Sander JW. Negative effects of antiepileptic drugs onmood in patients with epilepsy. Drug Saf, 2007, 30(5):555-567.
28.	Mula M, Sander JW. Antiepileptic drugs and suicide risk: couldstopping medications pose a greater hazard?.Expert Rev Neurother, 2010, 10(8): 1775-1776.
29.	Mula M, Trimble MR, Lhatoo SD, et al. Topiramateandpsychiatric adverse events in patients with epilepsy. Epilepsia, 2003, 44(10): 659-663.
30.	Mula M, Trimble MR, Yuen A, et al. Psychiatricadverse events during levetiracetam therapy. Neurology, 2003, 61(10): 704-706.
31.	Mula M, Trimble MR, Sander JW. Are psychiatric adverse events ofantiepileptic drugs a unique entity? A study on topiramate and levetiracetam.Epilepsia, 2007, 48(21): 2322-2326.
32.	Mula M, Hesdorffer DC, Trimble M, et al. The role of titrationschedule of topiramate for the development of depression inpatients with epilepsy. Epilepsia, 2009, 50(24):1072-1076.
33.	Mula M, Bell GS, Sander JW. Suicidality in epilepsy and possibleeffects of antiepileptic drugs. Curr Neurol Neurosci Rep, 2010, 10(8):327-332.
34.	Olesen JB, Hansen PR, Erdal J, et al. Antiepileptic drugs and risk of suicide: a nationwide study. Pharmacoepidemiol Drug Saf, 2010, 19(5): 518-524.
35.	Owens D, Horrocks J, House A. Fatal and non-fatal repetition ofself-harm. Systematic review. Br J Psychiatry, 2002, 18(1):193-199.
36.	Patorno E, Bohn RL, Wahl PM, et al.Anticonvulsant medications and the risk of suicide, attemptedsuicide, or violent death. JAMA, 2010, 30(3): 1401-1409.
37.	Posner K, Brown GK, Stanley B, et al. TheColumbia-Suicide Severity Rating Scale: initial validity and internalconsistency findings from three multisite studies with adolescents and adults. Am J Psychiatry, 2011, 168(35): 1266-1277.
38.	Redden L, Pritchett Y, RobiesonW, et al. Suicidality and divalproex sodium: analysis of controlledstudies in multiple indications. Ann Gen Psychiatry, 2011, 10(6): 1.
39.	Ring HA, Crellin R, Kirker S, et al. Vigabatrin and depression.J Neurol Neurosurg Psychiatry, 1993, 56(5): 925-928.
40.	Robertson MM, Trimble MR. Depressive illness in patientswithepilepsy: a review. Epilepsia, 1983, 24(Suppl 2):109-116.
41.	Rodin EA, Rim CS, Kitano H, et al. A comparisonof the effectiveness of primidone versus carbamazepine in epileptic outpatients.J Nerv Ment Dis, 1976, 16(3): 41-46.
42.	Ryvlin P, Cucherat M, Rheims S. Risk of sudden unexpected deathin epilepsy in patients given adjunctive antiepileptic treatment forrefractory seizures: a meta-analysis of placebo-controlled randomizedtrials. Lancet Neurol, 2011, 10(7): 961-968.
43.	Sadock BJ, Sadock VA, Ruiz P. Kaplan and Sadock's comprehensivetextbook of psychiatry. Wolters Kluwer Health/Lippincott Williams & Wilkins, Philadelphia, PA, London, 2009: 1-4884.
44.	Trimble MR, Rusch N, Betts T, et al. Psychiatric symptomsafter therapy with new antiepileptic drugs: psychopathologicaland seizure related variables. Seizure, 2000, 9(5): 249-254.
45.	van Cott AC, Cramer JA, Copeland LA, et al. Suiciderelatedbehaviors in older patients with new anti-epileptic drug use: datafrom the VA hospital system. BMC Med, 2010, 8(3): 4.

1. Andersohn F, Schade R, WillichSN, et al. Use of antiepileptic drugs in epilepsy and the risk of self-harm or suicidal behavior. Neurology, 2010, 75(13): 335-340.
2. Arana A, Wentworth CE, Ayuso-Mateos JL, et al. Suiciderelated events in patients treated with antiepileptic drugs. N Engl J Med, 2010, 36(3): 542-551.
3. Barraclough BM. The suicide rate of epilepsy. Acta Psychiatr Scand, 1987, 76(2): 339-345.
4. Bell GS, Gaitatzis A, Bell CL, et al. Suicide inpeople with epilepsy: how great is the risk?. Epilepsia, 2009, 50(21):1933-1942.
5. Busco M. FDA advisory members agree antiepileptics pose suicidalityrisk, need for black-box warning. Medscape medical news, 2008, 13(3): 1-4.
6. Christensen J, Vestergaard M, Mortensen PB, et al. (2007)Epilepsy and risk of suicide: a population-based case-control study.Lancet Neurol, 2007, 6(2):693-698.
7. Dodrill CB, Troupin AS. Psychotropic effects of carbamazepine inepilepsy: a double-blind comparison with phenytoin. Neurology, 1977, 27(10):1023-1028.
8. Ettinger AB. Psychotropic effects of antiepileptic drugs. Neurology, 2006, 67(13):1916-1925.
9. FDA. (2008a) Antiepileptic drugs and suicidality. Available at: http://www.fda.gov/ohrms/dockets/ac/08/briefing/2008-4372b1-01-FDA.pdf.
10. FDA. (2008b) Information for healthcare professionals: suicidal behavior andideation and antiepileptic drugs. Available at: http://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/ucm100192.html.
11. Gelder MG. New oxford textbook of psychiatry. Oxford University Press, Oxford, 2009: 1-1088.
12. Gibbons R, Hur K, Brown CH, et al. Relationship between antiepilepticdrugs and suicide attempts in patients with bipolar disorder.Arch Gen Psychiatry, 2009, 66(17):1354-1360.
13. Gibbons RD, Hur K, Brown CH, et al. Gabapentin and suicideattempts. Pharmacoepidemiol Drug Saf, 2010, 19(8):1241-1247.
14. Hara E, Akanuma N, Adachi N, et al. Suicideattempts in adult patients with idiopathic generalized epilepsy. Psychiatry Clin Neurosci, 2009, 63(12):225-229.
15. Harris EC, Barraclough B. Suicide as an outcome for mental disorders: a meta-analysis. Br J Psychiatry, 1997, 170(32):205-228.
16. Hecimovic H, Salpekar J, Kanner AM, et al. Suicidality and epilepsy: a neuropsychobiological perspective. Epilepsy Behav, 2011, 22(18):77-84.
17. Hesdorffer DC, KannerAM. The FDA alert on suicidality and antiepilepticdrugs: fire or false alarm?Epilepsia, 2006, 50(11):978-986.
18. Hesdorffer DC, Hauser WA, Olafsson E, et al.Depression and suicide attempt as risk factors for incidentunprovoked seizures. Ann Neurol, 2006, 59(21):35-41.
19. Hesdorffer DC, Berg AT, Kanner AM. An update on antiepilepticdrugs and suicide: are there definitive answers yet?.Epilepsy Curr, 2010, 10(7):137-145.
20. Hesdorffer DC, Tomson T, Benn E, et al. Combined analysis of risk factors for SUDEP. Epilepsia, 2011, 52(11): 1150-1159.
21. Kanner AM, Wuu J, Faught E, et al.A past psychiatric history may be a risk factor for topiramate related psychiatric and cognitive adverse events. Epilepsy Behav, 2003, 4(1):548-552.
22. Kanner AM, Soto A, Gross-Kanner H. Prevalence and clinical characteristics of postictal psychiatric symptoms in partial epilepsy. Neurology, 2004, 62(10):708-713.
23. Kanner AM, Schachter SC, Barry JJ, et al.Depression and epilepsy, pain and psychogenic non-epilepticseizures: clinical and therapeutic perspectives. Epilepsy Behav, 2012, 24(5):169-181.
24. Kapur N, Cooper J, King-Hele S, et al. The repetition of suicidal behavior: a multicenter cohortstudy. J Clin Psychiatry, 2006, 67(9):1599-1609.
25. Levinson DF, Devinsky O. Psychiatric adverse events during vigabatrintherapy. Neurology, 1999, 53(12):1503-1511.
26. Mula M, Hesdorffer DC. Suicidal behavior and antiepileptic drugsin epilepsy: analysis of the emerging evidence. Drug Healthc Patient Saf, 2011, 3(1):15-20.
27. Mula M, Sander JW. Negative effects of antiepileptic drugs onmood in patients with epilepsy. Drug Saf, 2007, 30(5):555-567.
28. Mula M, Sander JW. Antiepileptic drugs and suicide risk: couldstopping medications pose a greater hazard?.Expert Rev Neurother, 2010, 10(8): 1775-1776.
29. Mula M, Trimble MR, Lhatoo SD, et al. Topiramateandpsychiatric adverse events in patients with epilepsy. Epilepsia, 2003, 44(10): 659-663.
30. Mula M, Trimble MR, Yuen A, et al. Psychiatricadverse events during levetiracetam therapy. Neurology, 2003, 61(10): 704-706.
31. Mula M, Trimble MR, Sander JW. Are psychiatric adverse events ofantiepileptic drugs a unique entity? A study on topiramate and levetiracetam.Epilepsia, 2007, 48(21): 2322-2326.
32. Mula M, Hesdorffer DC, Trimble M, et al. The role of titrationschedule of topiramate for the development of depression inpatients with epilepsy. Epilepsia, 2009, 50(24):1072-1076.
33. Mula M, Bell GS, Sander JW. Suicidality in epilepsy and possibleeffects of antiepileptic drugs. Curr Neurol Neurosci Rep, 2010, 10(8):327-332.
34. Olesen JB, Hansen PR, Erdal J, et al. Antiepileptic drugs and risk of suicide: a nationwide study. Pharmacoepidemiol Drug Saf, 2010, 19(5): 518-524.
35. Owens D, Horrocks J, House A. Fatal and non-fatal repetition ofself-harm. Systematic review. Br J Psychiatry, 2002, 18(1):193-199.
36. Patorno E, Bohn RL, Wahl PM, et al.Anticonvulsant medications and the risk of suicide, attemptedsuicide, or violent death. JAMA, 2010, 30(3): 1401-1409.
37. Posner K, Brown GK, Stanley B, et al. TheColumbia-Suicide Severity Rating Scale: initial validity and internalconsistency findings from three multisite studies with adolescents and adults. Am J Psychiatry, 2011, 168(35): 1266-1277.
38. Redden L, Pritchett Y, RobiesonW, et al. Suicidality and divalproex sodium: analysis of controlledstudies in multiple indications. Ann Gen Psychiatry, 2011, 10(6): 1.
39. Ring HA, Crellin R, Kirker S, et al. Vigabatrin and depression.J Neurol Neurosurg Psychiatry, 1993, 56(5): 925-928.
40. Robertson MM, Trimble MR. Depressive illness in patientswithepilepsy: a review. Epilepsia, 1983, 24(Suppl 2):109-116.
41. Rodin EA, Rim CS, Kitano H, et al. A comparisonof the effectiveness of primidone versus carbamazepine in epileptic outpatients.J Nerv Ment Dis, 1976, 16(3): 41-46.
42. Ryvlin P, Cucherat M, Rheims S. Risk of sudden unexpected deathin epilepsy in patients given adjunctive antiepileptic treatment forrefractory seizures: a meta-analysis of placebo-controlled randomizedtrials. Lancet Neurol, 2011, 10(7): 961-968.
43. Sadock BJ, Sadock VA, Ruiz P. Kaplan and Sadock's comprehensivetextbook of psychiatry. Wolters Kluwer Health/Lippincott Williams & Wilkins, Philadelphia, PA, London, 2009: 1-4884.
44. Trimble MR, Rusch N, Betts T, et al. Psychiatric symptomsafter therapy with new antiepileptic drugs: psychopathologicaland seizure related variables. Seizure, 2000, 9(5): 249-254.
45. van Cott AC, Cramer JA, Copeland LA, et al. Suiciderelatedbehaviors in older patients with new anti-epileptic drug use: datafrom the VA hospital system. BMC Med, 2010, 8(3): 4.

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抗癫痫药物与自杀的关系——国际抗癫痫联盟治疗方法委员会手术治疗协作组报告

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