• MINI [ Time Frame: completed at screen and 16 weeks ] [ Designated as safety issue: No ]
• Health Related Quality of life as measured by the QOILIE-89 [ Time Frame: completed every 4 weeks during the 16 week intervention period and at 6 month and 1 year follow ups ] [ Designated as safety issue: No ]
• antiepileptic medication compliance [ Time Frame: assessed at 16 weeks ] [ Designated as safety issue: No ]
• antiepileptic medication toxicity as measured by the AEP [ Time Frame: assessed every 2 weeks during the 16 week intervention period ] [ Designated as safety issue: No ]
• seizure frequency and seizure severity [ Time Frame: assessed every 2 weeks during the 16 week intervention period ] [ Designated as safety issue: No ]

To define the benefits of antidepressant treatment or cognitive behavior therapy on mood, function, and quality of life in persons with depression and refractory epilepsy.

This randomized clinical trial will be conducted to compare the drug sertraline to cognitive behavioral therapy on symptoms of depression, antiepileptic medication compliance, seizure frequency, and quality of life outcomes in persons with depression and a seizure disorder or epilepsy. Approximately 140 persons will be enrolled in this study over a period of five years. Individual participation will last approximately 16 weeks. Study participants will be chosen randomly to receive either the study medication (sertraline) or cognitive behavior therapy for 16 weeks. Sertraline is approved by the Food and Drug Administration (FDA). Subjects who receive cognitive behavior therapy will be provided with a one-hour individual session with a licensed clinical psychologist each week for 15 weeks. All study participants will attend scheduled clinic visits every 4 weeks for 16 weeks.

• Depression
• Epilepsy

• Drug: sertraline
• Behavioral: cognitive behavior therapy

INCLUSION:

• Must have a seizure disorder.
• Must meet the DSM-IV criteria for major depression.
• Must be willing to provide written informed consent.
• Must be age 21 to 75 years old.
• Must be compliant, cooperative, reliable, and able to follow instructions, and to visit the clinic on schedule.

EXCLUSION:

• Have active suicidal or homicidal ideation.
• Have current alcohol or other substance abuse disorders or a history of bipolar depression or any psychotic disorder.
• Are pregnant or lactating.
• Are known to be hypersensitive to sertraline.
• Have a progressive central nervous system disorder (such as a tumor or multiple sclerosis), or severe hepatic or renal disease (serum creatinine >3 mg/dl).
• Currently taking an antidepressant medication or seeing a therapist regularly.