Harden Cynthia L, Goldstein Martin A
Comprehensive Epilepsy Center, Weill Medical College of Cornell University, New York, New York 10021, USA.
CNS Drugs. 2002;16(5):291-302. doi: 10.2165/00023210-200216050-00002.
Patients with epilepsy are at high risk for depression because of an incompletely understood combination of factors that may be both psychosocial and neurological. Interictal depression in patients with epilepsy is an undertreated condition, in part because of concern regarding drug interactions and the risk of exacerbating seizures with antidepressant treatment. Bipolar disorder is not described as occurring with a higher than expected frequency in the population with epilepsy, but high rates of depression and suicide are well recognised, highlighting the need for more emphasis on antidepressive treatment in this group of at-risk patients. Neurological factors, including site and lateralisation of seizure focus, may be important for the development of depression, with left-sided seizure foci having a higher association with depressive symptoms. Forced normalisation may be a factor in the paradoxical onset of depression in patients with epilepsy whose seizures suddenly become well controlled by anti-seizure treatment. Lowering of folic acid levels by some antiepileptic drugs (AEDs) may also influence the expression of depression in patients with epilepsy. New AEDs continue to emerge as beneficial treatments themselves for mood disorders, with lamotrigine, gabapentin and, to a lesser extent, topiramate having clinical trials data to support their use in patients with bipolar disease. Similar positive data are available for vagal nerve stimulation. Mood effects of AEDs can be complicated, however, as many of these drugs (e.g. tiagabine) have also been reported to cause depression as an adverse effect. Electroconvulsive therapy in depressed patients with epilepsy requires special consideration. The selective serotonin reuptake inhibitors (SSRIs) and antidepressants that act at multiple receptors (e.g. nefazodone, venlafaxine) are the most appropriate treatments for depressed patients with epilepsy. Among these agents, citalopram has a low risk of interactions with AEDs. Bupropion, clomipramine and maprotiline are associated with a greater risk of seizures compared with other antidepressants and consequently should be used with caution in the treatment of depression in patients with epilepsy.
癫痫患者因多种因素（可能包括心理社会因素和神经因素）的综合作用而面临较高的抑郁风险，这些因素尚未完全明确。癫痫患者的发作间期抑郁是一种治疗不足的病症，部分原因是担心药物相互作用以及抗抑郁治疗会增加癫痫发作的风险。双相情感障碍在癫痫患者群体中的发生率并未高于预期，但抑郁和自杀的高发生率已得到充分认识，这凸显了在这一高危患者群体中更加强调抗抑郁治疗的必要性。神经因素，包括癫痫病灶的部位和定位，可能对抑郁的发生发展很重要，左侧癫痫病灶与抑郁症状的关联性更高。强制正常化可能是癫痫患者的癫痫发作突然通过抗癫痫治疗得到良好控制后出现抑郁矛盾发作的一个因素。一些抗癫痫药物（AEDs）导致叶酸水平降低也可能影响癫痫患者抑郁的表现。新型抗癫痫药物本身也不断成为治疗情绪障碍的有益药物，拉莫三嗪、加巴喷丁以及程度稍轻的托吡酯有临床试验数据支持其用于双相情感障碍患者。迷走神经刺激也有类似的阳性数据。然而，抗癫痫药物的情绪影响可能很复杂，因为据报道，许多这类药物（如噻加宾）也会导致抑郁作为不良反应。癫痫抑郁患者的电休克治疗需要特别考虑。选择性5-羟色胺再摄取抑制剂（SSRIs）和作用于多种受体的抗抑郁药（如奈法唑酮、文拉法辛）是癫痫抑郁患者最适合的治疗药物。在这些药物中，西酞普兰与抗癫痫药物相互作用的风险较低。与其他抗抑郁药相比，安非他酮、氯米帕明和马普替林与癫痫发作的风险更高，因此在治疗癫痫患者的抑郁时应谨慎使用。
