Sharma Rakesh Kumar, Singh Tanveer, Mishra Awanish, Goel Rajesh Kumar
Department of Pharmaceutical Sciences and Drug Research, Punjabi University, Patiala, Punjab, India.
J Epilepsy Res. 2017 Jun 30;7(1):25-32. doi: 10.14581/jer.17005. eCollection 2017 Jun.
Depression is one of the major psychiatric comorbidities associated with epilepsy. The inconclusive results of antidepressants (ADs) regarding their safety in regard to convulsions have strongly contributed towards under treatment of depression in people with epilepsy (PWE). Thus, the present study was envisaged to assess the relative safety of four different classes of ADs regarding their convulsive potential in kindled/epileptic animals.
Kindling (an animal model to induce chronic epilepsy) was induced in male Swiss albino mice by administration of pentylenetetrazole subconvulsive doses (35 mg/kg, i.p.) at an interval of 48 ± 2 h for 42 days. The epileptic animals were treated with saline; imipramine (20 mg/kg/day i.p.); fluoxetine (20 mg/kg/day i.p.); venlafaxine (10 mg/kg/day i.p.) and mirtazapine (10 mg/kg/day i.p.) for 15 days. Except naive, animals were challenged with pentylenetetrazole subconvulsive dose (35 mg/kg, i.p.) on every 5 day to determine convulsion severity score, latency to first myoclonic jerk, latency to first tonic-clonic convulsions and numbers of tonic-clonic convulsions. Depression was also evaluated every 5 day employing tail suspension test 2 h after pentylenetetrazole subconvulsive dose.
All ADs have been reported significant antidepressant potential however regarding their safety in regard to convulsions in epileptic animals, variable results are obtained. Chronic administration of venlafaxine and mirtazapine were found to have significant anticonvulsant effect in epileptic animals. The behavioral data was further corroborated by neurochemical findings.
The treatment with venlafaxine and mirtazapine can be considered safe for treatment of depression in epilepsy and may enhance anticonvulsant potential of antiepileptic drugs as an adjuvant therapy. However, pharmacokinetic studies are warranted before translating these findings in PWE.
抑郁症是与癫痫相关的主要精神共病之一。抗抑郁药（ADs）在惊厥安全性方面的结果尚无定论，这在很大程度上导致癫痫患者（PWE）的抑郁症治疗不足。因此，本研究旨在评估四类不同抗抑郁药在点燃/癫痫动物中的惊厥潜力的相对安全性。
通过以48±2小时的间隔腹腔注射亚惊厥剂量的戊四氮（35毫克/千克），持续42天，在雄性瑞士白化小鼠中诱导点燃（一种诱导慢性癫痫的动物模型）。癫痫动物接受生理盐水、丙咪嗪（20毫克/千克/天，腹腔注射）、氟西汀（20毫克/千克/天，腹腔注射）、文拉法辛（10毫克/千克/天，腹腔注射）和米氮平（10毫克/千克/天，腹腔注射）治疗15天。除未处理的动物外，每隔5天用亚惊厥剂量的戊四氮（35毫克/千克，腹腔注射）对动物进行刺激，以确定惊厥严重程度评分、首次肌阵挛抽搐潜伏期、首次强直阵挛惊厥潜伏期和强直阵挛惊厥次数。在戊四氮亚惊厥剂量后2小时，每隔5天采用悬尾试验评估抑郁症。
所有抗抑郁药均具有显著的抗抑郁潜力，然而，关于它们在癫痫动物中的惊厥安全性，获得了不同的结果。发现长期给予文拉法辛和米氮平在癫痫动物中具有显著的抗惊厥作用。神经化学研究结果进一步证实了行为学数据。
文拉法辛和米氮平治疗癫痫伴发的抑郁症可能是安全的，并且作为辅助治疗可能增强抗癫痫药物的抗惊厥潜力。然而，在将这些发现应用于癫痫患者之前，有必要进行药代动力学研究。
