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Lamotrigine Therapy in Geriatric Bipolar Depression

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Brent Forester, Mclean Hospital
ClinicalTrials.gov Identifier:
NCT00720473
First received: July 18, 2008
Last updated: June 7, 2016
Last verified: June 2016
  Purpose
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.

Condition Intervention
Bipolar Depression
Drug: Lamotrigine

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Basic Science
Official Title: Lamotrigine Therapy in the Treatment of Geriatric Bipolar Depression: An Evaluation of Markers of Cerebral Energy Metabolism

Resource links provided by NLM:


Further study details as provided by Mclean Hospital:

Primary Outcome Measures:
  • Mean Glutamine to Creatine Ratio by Diagnosis at Baseline [ Time Frame: Baseline ] [ Designated as safety issue: No ]
  • Mean Glutamate to Creatine Ratio by Diagnosis at Baseline [ Time Frame: Baseline ] [ Designated as safety issue: No ]
  • Mean N-Acetyl Aspartate (NAA) to Creatine Ratio by Diagnosis at Baseline [ Time Frame: Baseline ] [ Designated as safety issue: No ]
  • Associations Between Depression Symptom Severity and Glutamate to Creatine Ratio at Baseline [ Time Frame: Baseline ] [ Designated as safety issue: No ]
    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 Glutamate to Creatine Ratio Between Baseline and Follow-up [ Time Frame: 8 Weeks ] [ Designated as safety issue: No ]
    Follow-up Least Squares Mean - Baseline Least Squares Mean

  • Estimated Change in Least Squares Mean in the Glutamine to Creatine Ratio Between Baseline and Follow-up [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
    Follow-up Least Squares Mean - Baseline Least Squares Mean

  • Estimated Change in Least Squares Mean in the NAA to Creatine Ratio Between Baseline and Follow-up [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
    Follow-up Least Squares Mean - Baseline Least Squares Mean

  • Association of MADRS Changes With Glutamate to Creatine Ratio Changes From Baseline to Follow-up [ Time Frame: 8 Weeks ] [ Designated as safety issue: No ]
    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.

  • Associations of MADRS Changes With Glutamine to Creatine Ratio Changes From Baseline to Follow-up [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
    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.

  • Associations of MADRS Changes With NAA to Creatine Ratio Changes From Baseline to Follow-up [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
    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.

  • Mean Montgomery Asberg Depression Rating Scale (MADRS) Score at Baseline [ Time Frame: Baseline ] [ Designated as safety issue: No ]
    The minimum MADRS score is 0 and the maximum is 60, with 60 being the most depressed.

  • Means of MADRS Scores at 8 Weeks [ Time Frame: 8 Weeks ] [ Designated as safety issue: No ]
    The minimum MADRS score is 0 and the maximum is 60, with 60 being the most depressed.


Enrollment: 69
Study Start Date: April 2006
Study Completion Date: December 2011
Primary Completion Date: July 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
A: Other
Open Label Study
Drug: Lamotrigine
Lamotrigine with dosage range from 25 mg to 200 mg per day.
Other Name: Lamictal
No Intervention: B: Healthy Controls

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).
  Eligibility

Ages Eligible for Study:   60 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria (for Bipolar Subjects):

  • 60 years or older
  • Meet DSM-IV diagnostic criteria for Bipolar Disorder, Current Episode Depressed
  • First episode of mania before the age of 50 (early-onset bipolar disorder)
  • Montgomery-Asberg Depression Rating Scale (MADRS) Score of greater or equal to 20.
  • Young Mania Rating Scale (YMRS) of less than or equal to 6.
  • Able to provide informed consent
  • Must speak English
  • Must be able to visit McLean Hospital for the screening visit and six study visits during the 8-week duration of the study.
  • Subjects may be taking other medications for bipolar depression including antidepressants, mood stabilizers and antipsychotic mediations prior to lamotrigine therapy, but may not have any dosage adjustments of these medications in the week before lamotrigine is added.

Exclusion Criteria (for Bipolar Subjects):

  • Serious or unstable medical illness, including cardiovascular, hepatic, renal, respiratory, endocrine, neurologic or hematologic disease.
  • History of seizure disorder
  • History or current diagnosis of the following psychiatric illnesses: any organic mental disorder (including dementia), schizophrenia, schizoaffective disorder, delusional disorder, psychotic disorder not otherwise specified, unipolar major depressive disorder, patients with substance dependence disorders, including alcohol, active within the last 12 months.
  • First episode of mania after the age of 50 (to exclude late-onset bipolar disorder)
  • History of multiple adverse drug reactions or allergy to the study drugs.
  • Use of medications that are excluded in this study (benzodiazepines, barbiturates; however, the use of non-benzodiazepine sedative hypnotics (such as zolpidem (Ambien)) may be used as needed except within 48 hours of the MRI scan)
  • Any of the exclusion criteria mentioned in the MRI risks section below

Inclusion Criteria (for Controls):

  • 60 years or older
  • Able to provide informed consent
  • Must speak English
  • Women entering this study must be post-menopausal

Exclusion Criteria (for Controls):

- Same criteria for the Bipolar Depressed group with the exception of the "first episode of mania" which is not applicable.

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00720473

Locations
United States, Massachusetts
McLean Hospital
Belmont, Massachusetts, United States, 02478
Sponsors and Collaborators
Mclean Hospital
Investigators
Principal Investigator: Brent P Forester, MD Mclean Hospital
  More Information

Responsible Party: Brent Forester, Director, Mood Disorders Division, Geriatric Psychiatry Research Program, Mclean Hospital
ClinicalTrials.gov Identifier: NCT00720473     History of Changes
Other Study ID Numbers: 2005-P-002493 
Study First Received: July 18, 2008
Results First Received: November 26, 2013
Last Updated: June 7, 2016
Health Authority: United States: Food and Drug Administration

Keywords provided by Mclean Hospital:
Bipolar depression
Elderly
Lamotrigine
Brain energy metabolism

Additional relevant MeSH terms:
Depression
Depressive Disorder
Bipolar Disorder
Behavioral Symptoms
Mood Disorders
Mental Disorders
Bipolar and Related Disorders
Lamotrigine
Anticonvulsants
Calcium Channel Blockers
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Excitatory Amino Acid Antagonists
Excitatory Amino Acid Agents
Neurotransmitter Agents
Physiological Effects of Drugs
Voltage-Gated Sodium Channel Blockers
Sodium Channel Blockers

ClinicalTrials.gov processed this record on December 09, 2016