Lamotrigine Therapy in Geriatric Bipolar Depression

We will use MRI techniques and neuropsychological testing to investigate potential markers of treatment response in elderly bipolar depressed patients receiving lamotrigine and age-matched, non-depressed controls. We intend to test these hypotheses: 1. At least 50% of older subjects with bipolar depression will respond treatment with lamotrigine as evidenced by a 50% reduction on the Montgomery Asberg Rating Scale (MADRS). In addition, treatment with lamotrigine will be safe and well tolerated as evidenced by a drop-out rate of less than 10% due to adverse effects. 2. Compared with healthy age-matched, non-demented, non-depressed controls, subjects with geriatric bipolar depression will demonstrate abnormalities in cerebral energy metabolism as assessed by elevated levels of glutamate and lactate, and decreased levels of NAA, using 1H MRS at 4T. 3. Successful treatment with lamotrigine in geriatric bipolar depression will result in decreases in lactate and glutamate, and elevations in NAA. 4. Baseline measures of executive functioning and information processing speed (measured by performance on the Wisconsin Card Sorting Test (WCST), Trails A and B and Stroop tests) will be impaired in subjects with geriatric bipolar depression compared with healthy controls. These measures will improve with successful treatment with lamotrigine and correlate with improvements in markers of cerebral energy metabolism (lactate, glutamate, NAA).