抗癫痫药物相关性的精神行为异常在成人癫痫中的研究_Journal of Epilepsy

Authors：

杨欣睿 , 许韬 ,  陈阳美

重庆医科大学附属第二医院神经内科（重庆 400010）;

Corresponding author：

陈阳美, Email: chenym1997@cqmu.edu.cn

Keywords：

抗癫痫药物; 癫痫; 精神行为异常; 治疗; 评估

DOI：

10.7507/2096-0247.20200084

Video：

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抗癫痫药物（AEDs）是控制癫痫发作的主要治疗手段，但使用 AEDs 所致的精神和行为异常（Psychiatric and behavioral side effects，PBSEs）在癫痫患者（Patients with epilepsy，PWE）中较为常见，这可能会导致 PWE 对 AEDs 不耐受，以至减药、停药，严重影响患者的生活质量。但并非每种 AEDs 均会引起 PBSEs。本文根据既往的研究，现将常用的 AEDs 与成人 PWE 出现 PBSEs 之间的相关性、危险因素、评估方法、治疗措施等方面作一综述。

Citation： 杨欣睿, 许韬, 陈阳美. 抗癫痫药物相关性的精神行为异常在成人癫痫中的研究. Journal of Epilepsy, 2020, 6(6): 510-515. doi: 10.7507/2096-0247.20200084 Copy

1.	Du Y, Lin J, Shen J, et al. Adverse drug reactions associated with six commonly used antiepileptic drugs in southern China from 2003 to 2015. BMC Pharmacol Toxicol, 2019, 20(1): 7.
2.	Chen B, Choi H, Hirsch LJ, et al. Psychiatric and behavioral side effects of antiepileptic drugs in adults with epilepsy. Epilepsy Behav, 2017, 76: 24-31.
3.	Du YR, Lin JH, Mei PN, et al. Analysis of risk factors for antiepileptic drug-induced adverse psychotropic effects in Chinese outpatients with epilepsy. J Clin Neurosci, 2019, 63: 37-42.
4.	Weintraub D, Buchsbaum R, Resor SR Jr, et al. Psychiatric and behavioral side effects of the newer antiepileptic drugs in adults with epilepsy. Epilepsy Behav, 2007, 10(1): 105-110.
5.	Wood H. Epilepsy: psychiatric adverse effects of levetiracetam linked to genetic variation in dopamine signalling. Nat Rev Neurol, 2012, 8(10): 532.
6.	Jalihal V, Shankar R, Henley W, et al. Eslicarbazepine acetate as a replacement for levetiracetam in people with epilepsy developing behavioral adverse events. Epilepsy Behav, 2018, 80: 365-369.
7.	Rocamora R, Ley M, Molins A, et al. Effect of lacosamide on depression and anxiety symptoms in patients with focal refractory epilepsy: a prospective multicenter study. Epilepsy Behav, 2018, 79: 87-92.
8.	Galanti M, Newport DJ, Pennell PB, et al. Postpartum depression in women with epilepsy: influence of antiepileptic drugs in a prospective study. Epilepsy Behav, 2009, 16(3): 426-430.
9.	Dussaule C, Bouilleret V. Psychiatric effects of antiepileptic drugs in adults. Geriatr Psychol Neuropsychiatr Vieil, 2018, 16(2): 181-188.
10.	Robertson MM, Trimble MR. Depressive illness in patients with epilepsy: a review. Epilepsia, 1983, 24(Suppl 2): S109-116.
11.	Kanner AM. Management of psychiatric and neurological comorbidities in epilepsy. Nat Rev Neurol, 2016, 12(2): 106-116.
12.	Mula M, Sander JW. Negative effects of antiepileptic drugs on mood in patients with epilepsy. Drug Saf, 2007, 30(7): 555-567.
13.	Brodie MJ, Besag F, Ettinger AB, et al. Epilepsy, antiepileptic drugs, and aggression: an evidence-based review. Pharmacol Rev, 2016, 68(3): 563-602.
14.	Kwon OY, Park SP. Depression and anxiety in people with epilepsy. J Clin Neurol, 2014, 10(3): 175-188.
15.	Perucca P, Mula M. Antiepileptic drug effects on mood and behavior: molecular targets. Epilepsy Behav, 2013, 26(3): 440-449.
16.	Stephen LJ, Wishart A, Brodie MJ. Psychiatric side effects and antiepileptic drugs: Observations from prospective audits. Epilepsy Behav, 2017, 71(Pt A): 73-78.
17.	Mula M. Epilepsy and psychiatric comorbidities: drug selection. Curr Treat Options Neurol, 2017, 19(12): 44.
18.	Chen B, Choi H, Hirsch LJ, et al. Cross-sensitivity of psychiatric and behavioral side effects with antiepileptic drug use. Seizure, 2018, 62: 38-42.
19.	Alfaro A, Asensio M, García-Escrivá A, et al. LAM study: effects of lacosamide on behaviour and quality of life in patients with epilepsy. Neurologia, 2019, 34(1): 1-6.
20.	Schmitz B, Dimova S, Zhang Y, et al. Tolerability and efficacy of lacosamide and controlled-release carbamazepine monotherapy in patients with newly diagnosed epilepsy and concomitant psychiatric conditions: post hoc analysis of a prospective, randomized, double-blind trial. Epilepsy Res, 2020, 159: 106220.
21.	Zhu LN, Chen D, Xu D, et al. Newer antiepileptic drugs compared to levetiracetam as adjunctive treatments for uncontrolled focal epilepsy: An indirect comparison. Seizure, 2017, 51: 121-132.
22.	White JR, Walczak TS, Marino SE, et al. Zonisamide discontinuation due to psychiatric and cognitive adverse events: a case-control study. Neurology, 2010, 75(6): 513-518.
23.	Werhahn KJ, Trinka E, Dobesberger J, et al. A randomized, double-blind comparison of antiepileptic drug treatment in the elderly with new-onset focal epilepsy. Epilepsia, 2015, 56(3): 450-459.
24.	Rugg-Gunn F. Adverse effects and safety profile of perampanel: a review of pooled data. Epilepsia, 2014, 55(Suppl 1): 13-15.
25.	Silberstein SD. Preventive migraine treatment. Neurol Clin, 2009, 27(2): 429-443.
26.	Hesdorffer DC, Ishihara L, Mynepalli L, et al. Epilepsy, suicidality, and psychiatric disorders: a bidirectional association. Ann Neurol, 2012, 72(2): 184-191.
27.	Kim HJ, Jeon JY, Kim HW, et al. Comparison between the Neurological Disorders Depression Inventory for Epilepsy and the Patient Health Questionnaire-9 in patients with epilepsy according to antiepileptic drug load. Seizure, 2020, 74: 14-19.
28.	Tong X, An D, Lan L, et al. Validation of the Chinese version of the Neurological Disorders Depression Inventory for Epilepsy (C-NDDI-E) in West China. Epilepsy Behav, 2015, 47: 6-10.
29.	Fiest KM, Patten SB, Jetté N. Screening for depression and anxiety in epilepsy. Neurol Clin, 2016, 34(2): 351-361.
30.	Diem SJ, Blackwell TL, Stone KL, et al. Use of antidepressants and rates of hip bone loss in older women: the study of osteoporotic fractures. Arch Intern Med, 2007, 167(12): 1240-1245.
31.	Mula M, Trimble MR, Lhatoo SD, et al. Topiramate and psychiatric adverse events in patients with epilepsy. Epilepsia, 2003, 44(5): 659-663.
32.	Mula M, Hesdorffer DC, Trimble M, et al. The role of titration schedule of topiramate for the development of depression in patients with epilepsy. Epilepsia, 2009, 50(5): 1072-1076.
33.	Henning OJ, Nakken KO. Psychiatric comorbidity and use of psychotropic drugs in epilepsy patients. Acta Neurol Scand Suppl, 2010, (190): 18-22.
34.	Hamid H, Kanner AM. Should antidepressant drugs of the selective serotonin reuptake inhibitor family be tested as antiepileptic drugs? Epilepsy Behav, 2013, 26(3): 261-265.
35.	Thomé-Souza MS, Kuczynski E, Valente KD. Sertraline and fluoxetine: safe treatments for children and adolescents with epilepsy and depression. Epilepsy Behav, 2007, 10(3): 417-425.
36.	Specchio LM, Iudice A, Specchio N, et al. Citalopram as treatment of depression in patients with epilepsy. Clin Neuropharmacol, 2004, 27(3): 133-136.
37.	伍文清, 肖玉莲, 陈葵. 盐酸帕罗西汀治疗癫痫并发抑郁的临床研究. 中国康复理论与实践, 2012, 18(2): 169-171.
38.	王颖, 孙美珍. 5-羟色胺1A 受体激动剂枸橼酸坦度螺酮对癫痫后抑郁与焦虑的疗效研究. 中华脑科疾病与康复杂志(电子版), 2014, 4(2): 12-15.
39.	Michaelis R, Tang V, Wagner JL, et al. Psychological treatments for people with epilepsy. Cochrane Database Syst Rev, 2017, 10: CD012081.
40.	Mula M. The pharmacological management of psychiatric comorbidities in patients with epilepsy. Pharmacol Res, 2016, 107: 147-153.
41.	Judge BS, Rentmeester LL. Antidepressant overdose-induced seizures. Psychiatr Clin North Am, 2013, 36(2): 245-260.
42.	Alper K, Schwartz KA, Kolts RL, et al. Seizure incidence in psychopharmacological clinical trials: an analysis of Food and Drug Administration (FDA) summary basis of approval reports. Biol Psychiatry, 2007, 62(4): 345-354.
43.	Devinsky O, Pacia SV. Seizures during clozapine therapy. J Clin Psychiatry, 1994, 55(Suppl B): 153-156.
44.	Cock HR. Drug-induced status epilepticus. Epilepsy Behav, 2015, 49: 76-82.

1. Du Y, Lin J, Shen J, et al. Adverse drug reactions associated with six commonly used antiepileptic drugs in southern China from 2003 to 2015. BMC Pharmacol Toxicol, 2019, 20(1): 7.
2. Chen B, Choi H, Hirsch LJ, et al. Psychiatric and behavioral side effects of antiepileptic drugs in adults with epilepsy. Epilepsy Behav, 2017, 76: 24-31.
3. Du YR, Lin JH, Mei PN, et al. Analysis of risk factors for antiepileptic drug-induced adverse psychotropic effects in Chinese outpatients with epilepsy. J Clin Neurosci, 2019, 63: 37-42.
4. Weintraub D, Buchsbaum R, Resor SR Jr, et al. Psychiatric and behavioral side effects of the newer antiepileptic drugs in adults with epilepsy. Epilepsy Behav, 2007, 10(1): 105-110.
5. Wood H. Epilepsy: psychiatric adverse effects of levetiracetam linked to genetic variation in dopamine signalling. Nat Rev Neurol, 2012, 8(10): 532.
6. Jalihal V, Shankar R, Henley W, et al. Eslicarbazepine acetate as a replacement for levetiracetam in people with epilepsy developing behavioral adverse events. Epilepsy Behav, 2018, 80: 365-369.
7. Rocamora R, Ley M, Molins A, et al. Effect of lacosamide on depression and anxiety symptoms in patients with focal refractory epilepsy: a prospective multicenter study. Epilepsy Behav, 2018, 79: 87-92.
8. Galanti M, Newport DJ, Pennell PB, et al. Postpartum depression in women with epilepsy: influence of antiepileptic drugs in a prospective study. Epilepsy Behav, 2009, 16(3): 426-430.
9. Dussaule C, Bouilleret V. Psychiatric effects of antiepileptic drugs in adults. Geriatr Psychol Neuropsychiatr Vieil, 2018, 16(2): 181-188.
10. Robertson MM, Trimble MR. Depressive illness in patients with epilepsy: a review. Epilepsia, 1983, 24(Suppl 2): S109-116.
11. Kanner AM. Management of psychiatric and neurological comorbidities in epilepsy. Nat Rev Neurol, 2016, 12(2): 106-116.
12. Mula M, Sander JW. Negative effects of antiepileptic drugs on mood in patients with epilepsy. Drug Saf, 2007, 30(7): 555-567.
13. Brodie MJ, Besag F, Ettinger AB, et al. Epilepsy, antiepileptic drugs, and aggression: an evidence-based review. Pharmacol Rev, 2016, 68(3): 563-602.
14. Kwon OY, Park SP. Depression and anxiety in people with epilepsy. J Clin Neurol, 2014, 10(3): 175-188.
15. Perucca P, Mula M. Antiepileptic drug effects on mood and behavior: molecular targets. Epilepsy Behav, 2013, 26(3): 440-449.
16. Stephen LJ, Wishart A, Brodie MJ. Psychiatric side effects and antiepileptic drugs: Observations from prospective audits. Epilepsy Behav, 2017, 71(Pt A): 73-78.
17. Mula M. Epilepsy and psychiatric comorbidities: drug selection. Curr Treat Options Neurol, 2017, 19(12): 44.
18. Chen B, Choi H, Hirsch LJ, et al. Cross-sensitivity of psychiatric and behavioral side effects with antiepileptic drug use. Seizure, 2018, 62: 38-42.
19. Alfaro A, Asensio M, García-Escrivá A, et al. LAM study: effects of lacosamide on behaviour and quality of life in patients with epilepsy. Neurologia, 2019, 34(1): 1-6.
20. Schmitz B, Dimova S, Zhang Y, et al. Tolerability and efficacy of lacosamide and controlled-release carbamazepine monotherapy in patients with newly diagnosed epilepsy and concomitant psychiatric conditions: post hoc analysis of a prospective, randomized, double-blind trial. Epilepsy Res, 2020, 159: 106220.
21. Zhu LN, Chen D, Xu D, et al. Newer antiepileptic drugs compared to levetiracetam as adjunctive treatments for uncontrolled focal epilepsy: An indirect comparison. Seizure, 2017, 51: 121-132.
22. White JR, Walczak TS, Marino SE, et al. Zonisamide discontinuation due to psychiatric and cognitive adverse events: a case-control study. Neurology, 2010, 75(6): 513-518.
23. Werhahn KJ, Trinka E, Dobesberger J, et al. A randomized, double-blind comparison of antiepileptic drug treatment in the elderly with new-onset focal epilepsy. Epilepsia, 2015, 56(3): 450-459.
24. Rugg-Gunn F. Adverse effects and safety profile of perampanel: a review of pooled data. Epilepsia, 2014, 55(Suppl 1): 13-15.
25. Silberstein SD. Preventive migraine treatment. Neurol Clin, 2009, 27(2): 429-443.
26. Hesdorffer DC, Ishihara L, Mynepalli L, et al. Epilepsy, suicidality, and psychiatric disorders: a bidirectional association. Ann Neurol, 2012, 72(2): 184-191.
27. Kim HJ, Jeon JY, Kim HW, et al. Comparison between the Neurological Disorders Depression Inventory for Epilepsy and the Patient Health Questionnaire-9 in patients with epilepsy according to antiepileptic drug load. Seizure, 2020, 74: 14-19.
28. Tong X, An D, Lan L, et al. Validation of the Chinese version of the Neurological Disorders Depression Inventory for Epilepsy (C-NDDI-E) in West China. Epilepsy Behav, 2015, 47: 6-10.
29. Fiest KM, Patten SB, Jetté N. Screening for depression and anxiety in epilepsy. Neurol Clin, 2016, 34(2): 351-361.
30. Diem SJ, Blackwell TL, Stone KL, et al. Use of antidepressants and rates of hip bone loss in older women: the study of osteoporotic fractures. Arch Intern Med, 2007, 167(12): 1240-1245.
31. Mula M, Trimble MR, Lhatoo SD, et al. Topiramate and psychiatric adverse events in patients with epilepsy. Epilepsia, 2003, 44(5): 659-663.
32. Mula M, Hesdorffer DC, Trimble M, et al. The role of titration schedule of topiramate for the development of depression in patients with epilepsy. Epilepsia, 2009, 50(5): 1072-1076.
33. Henning OJ, Nakken KO. Psychiatric comorbidity and use of psychotropic drugs in epilepsy patients. Acta Neurol Scand Suppl, 2010, (190): 18-22.
34. Hamid H, Kanner AM. Should antidepressant drugs of the selective serotonin reuptake inhibitor family be tested as antiepileptic drugs? Epilepsy Behav, 2013, 26(3): 261-265.
35. Thomé-Souza MS, Kuczynski E, Valente KD. Sertraline and fluoxetine: safe treatments for children and adolescents with epilepsy and depression. Epilepsy Behav, 2007, 10(3): 417-425.
36. Specchio LM, Iudice A, Specchio N, et al. Citalopram as treatment of depression in patients with epilepsy. Clin Neuropharmacol, 2004, 27(3): 133-136.
37. 伍文清, 肖玉莲, 陈葵. 盐酸帕罗西汀治疗癫痫并发抑郁的临床研究. 中国康复理论与实践, 2012, 18(2): 169-171.
38. 王颖, 孙美珍. 5-羟色胺1A 受体激动剂枸橼酸坦度螺酮对癫痫后抑郁与焦虑的疗效研究. 中华脑科疾病与康复杂志(电子版), 2014, 4(2): 12-15.
39. Michaelis R, Tang V, Wagner JL, et al. Psychological treatments for people with epilepsy. Cochrane Database Syst Rev, 2017, 10: CD012081.
40. Mula M. The pharmacological management of psychiatric comorbidities in patients with epilepsy. Pharmacol Res, 2016, 107: 147-153.
41. Judge BS, Rentmeester LL. Antidepressant overdose-induced seizures. Psychiatr Clin North Am, 2013, 36(2): 245-260.
42. Alper K, Schwartz KA, Kolts RL, et al. Seizure incidence in psychopharmacological clinical trials: an analysis of Food and Drug Administration (FDA) summary basis of approval reports. Biol Psychiatry, 2007, 62(4): 345-354.
43. Devinsky O, Pacia SV. Seizures during clozapine therapy. J Clin Psychiatry, 1994, 55(Suppl B): 153-156.
44. Cock HR. Drug-induced status epilepticus. Epilepsy Behav, 2015, 49: 76-82.

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