By Padmaja Kandula, MD

Assistant Professor of Neurology and Neuroscience, Comprehensive Epilepsy Center, Weill Cornell Medical College

Dr. Kandula reports no financial relationships relevant to this field of study.

SYNOPSIS: Epileptic patients with major depression were randomized to either cognitive behavioral therapy (CBT) or sertraline. Depression and related secondary health outcomes were analyzed in both groups. Sertraline and CBT were found to be equally efficacious with improvement in mood in more than half of patients.

SOURCE: Gilliam F, Black KJ, Carter J, et al. A trial of sertraline or cognitive behavioral therapy for depression in epilepsy. Ann Neurol 2019;86:552-560.

Depression has been a long-standing comorbidity for patients with many neurologic conditions, including epilepsy. The risk of suicidality is 30 times greater in those with combined epilepsy and depression vs. the general population. In recent years, the prevalence and global use of healthcare resources to treat both conditions continues to increase, yet optimal treatment is not clearly defined in this subpopulation. In addition, there are potential safety concerns regarding selective serotonin reuptake inhibitors (SSRIs), including the risk of lowering of seizure threshold or induction of suicidal ideation.

Gilliam et al randomized epileptic patients with major depression to either sertraline treatment or cognitive behavioral treatment (CBT). Primary outcome measures included depression severity. Secondary outcomes included seizure counts, side effects, quality of life, and suicidality. Subjects were recruited from either general neurology or epilepsy clinics at two major institutions. Patients were included in the study if they were between 21 and 75 years of age; carried a diagnosis of epilepsy as confirmed by an epileptologist; experienced a clinically recognized seizure within the last 12 months on approved anticonvulsant; scored > 14 on the Centers for Epidemiological Studies Depression Scale (CES-D); were diagnosed with major depressive episode on the Mini International Neuropsychiatric Interview (MINI); and could read and understand the study protocol and documents. A computer-generated code randomized patients to either CBT or sertraline therapy. Subjects were re-evaluated with the Beck Depression Inventory (BDI), CES-D, seizure counts, and side effects between office visits and monthly at scheduled follow-up. Sertraline was titrated by 50 mg increments every two weeks as needed for a CES-D score > 14, up to a maximum daily dose of 200 mg per day. Standardized CBT was performed by a licensed therapist for one-hour increments weekly during the 16-week study period. Primary outcome measures included the proportion of patients achieving depression remission as gauged by the MINI. Secondary endpoints included depression severity using BDI and CES-D, suicidality (suicide subsections of MINI), quality of life (QOLIE, or Quality of Life in Epilepsy Inventory), medication side effects (adverse events profile), and seizure severity and rate via standardized seizure calendars and based on International League Against Epilepsy classification.

Researchers randomized 140 patients to either treatment arm. Nearly 90% of patients had not received depression treatment. There was a similar treatment cessation dropout rate (5.6% vs. 7.3%) for both the sertraline and CBT groups, respectively, However, both groups completed outcome assessments. In the final analysis, 52.8% of patients assigned to sertraline achieved depression remission as defined by the MINI. Thirty-seven percent of patients achieved remission with an average sertraline dosage of 100 mg per day; 60.3% of patients achieved depression remission with CBT. The difference in time to remission between both groups was 2.8 days. Overall, there was an improvement in quality of life scores of 28% in the sertraline group vs. 27% in the CBT group. The principal seizure outcome assessment was similar between both arms as well. The occurrence of a convulsion (in those who experienced convulsion six months prior to enrollment) was low, at 7.8% and 7.5% in the sertraline vs. CBT group. No significant difference in mean adverse events was noted between groups. Depression remission was associated with lower adverse event profile scores compared to those with continued depression for both groups.


This randomized, naturalistic study carries several important implications. Depression can remit in 50% of epilepsy patients with major depression by using effective medical or behavioral therapy. Surprisingly, modest doses of SSRIs (100 mg) or one-hour weekly CBT sessions efficiently and effectively treated depression. The difference in time to remission was less than three days between both treatment modalities. The convulsion rate between both groups was similarly low. Remission of depression resulted in improved quality of life scores. Adverse events were similar between both groups, and decreased over time in both groups as depression remitted. Lastly, the persistence of depression was the only statistically significant predictor of suicidality. Why are clinicians not treating depression aggressively? As the global health burden of chronic disease continues to rise and access to mental health resources declines, early identification and treatment of comorbidities will become inevitable. This study shows how simple therapeutic techniques can significantly affect various psychosocial aspects of epilepsy.