Abstract: Objective：To observe the clinical effect of lamotrigine in the treatment of epilepsy with depression and the influence on the cognitive function of the patients.Methods：68 patients with epilepsy and depression in our hospital were randomly divided into observation group (n=34) and control group (n=34). The control group patients were treated with topiramate.The observation group was treated with lamotrigine.After 12 weeks of treatment，therapeutic effect of 2 groups were evaluated.Depressive symptom score was evaluated in 2 groups of patients before and after treatment using Hamilton Depression Scale (HAMD) respectively，and patients′ cognitive function were evaluated with concise mental state examination scale (MMSE).Results：The clinical total effective rate was 91.17% in observation group, and 88.24% in the control group.There was no statistically significant difference(P>0.05).On the average HAMD score, there was no significant difference between the two groups before the treatment (P>0.05). After 8 weeks and 12 weeks, the HAMD scores of the observation group were lower than that of the control group (P<0.05).In group comparison, the 2 groups decreased after treatment 8 weeks and 12 weeks after treatment (P<0.05). After 12 weeks of treatment, the average MMSE score of the patients in both groups was higher than that before treatment (P<0.05), and the average MMSE score of the observation group was higher than that of the control group (P<0.05). Conclusion：The clinical curative effect of lamotrigine in the treatment of epilepsy with depression is significant， and can effectively improve the symptoms of depression and cognitive dysfunction.