Lamotrigine Therapy in Geriatric Bipolar Depression

Not Applicable

Completed

Conditions: Bipolar Depression

Interventions: Drug: Lamotrigine

Registration Number: NCT00720473

Lead Sponsor: Mclean Hospital

Brief Summary: We propose to study the efficacy and tolerability of lamotrigine in the treatment of older adults with bipolar depression and to compare measures of brain energy metabolism between older subjects with bipolar depression and healthy age-matched controls in order to better understand treatment response in geriatric bipolar depression.

Detailed Description: 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).

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 69

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
A: Other	Lamotrigine	Open Label Study

Primary Outcome Measures

Name	Time	Method
Mean Glutamine to Creatine Ratio by Diagnosis at Baseline	Baseline
Association of MADRS Changes With Glutamate to Creatine Ratio Changes From Baseline to Follow-up	8 Weeks	Estimated least squares mean metabolite ratio changes with a 10-point decrease in MADRS score. The MADRS minimum score is 0 and maximum is 60, with 60 being the most depressed score. Estimate was from linear regression models controlling for age and sex. The change is across regions, parieto-occipital and anterior cingulate cortex.
Mean Montgomery Asberg Depression Rating Scale (MADRS) Score at Baseline	Baseline	The minimum MADRS score is 0 and the maximum is 60, with 60 being the most depressed.
Means of MADRS Scores at 8 Weeks	8 Weeks	The minimum MADRS score is 0 and the maximum is 60, with 60 being the most depressed.
Mean Glutamate to Creatine Ratio by Diagnosis at Baseline	Baseline
Mean N-Acetyl Aspartate (NAA) to Creatine Ratio by Diagnosis at Baseline	Baseline
Associations Between Depression Symptom Severity and Glutamate to Creatine Ratio at Baseline	Baseline	Estimated changes in least squares mean in the metabolite ratio per 10-point increase in MADRS score. The minimum MADRS score is 0 and the maximum is 60, with 60 being the most depressed. Estimate was from linear regression models controlling for age and sex. The change is across regions, parieto-occipital and anterior cingulate cortex.
Estimated Change in Least Squares Mean in the Glutamine to Creatine Ratio Between Baseline and Follow-up	8 weeks	Follow-up Least Squares Mean - Baseline Least Squares Mean
Associations of MADRS Changes With Glutamine to Creatine Ratio Changes From Baseline to Follow-up	8 weeks	Estimated least squares mean metabolite ratio changes with a 10-point decrease in MADRS score. MADRS minimum score is 0 and maximum is 60, with 60 being most depressed. Estimate was from linear regression models controlling for age and sex. The change is across regions, parieto-occipital and anterior cingulate cortex.
Estimated Change in Least Squares Mean in the NAA to Creatine Ratio Between Baseline and Follow-up	8 weeks	Follow-up Least Squares Mean - Baseline Least Squares Mean
Estimated Change in Least Squares Mean in Glutamate to Creatine Ratio Between Baseline and Follow-up	8 Weeks	Follow-up Least Squares Mean - Baseline Least Squares Mean
Associations of MADRS Changes With NAA to Creatine Ratio Changes From Baseline to Follow-up	8 weeks	Estimated least squares mean metabolite ratio changes with a 10-point decrease in MADRS score. MADRS minimum score is 0 and maximum is 60, with 60 being most depressed. Estimate was from linear regression models controlling for age and sex. The change is across regions, parieto-occipital and anterior cingulate cortex.