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Completed

NCT Number: NCT00720473

Lamotrigine Therapy in Geriatric Bipolar Depression

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.

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Key information

Conditions

Bipolar Depression Bipolar Disorder Bipolar and Related Disorders Mental Disorders Mood Disorders

Age range

60 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

McLean Hospital

Belmont, Massachusetts, 02478, United States

About this study

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:

  • 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.
  • 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.
  • Successful treatment with lamotrigine in geriatric bipolar depression will result in decreases in lactate and glutamate, and elevations in NAA.
  • 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).

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

Lamotrigine

Drug

Lamotrigine with dosage range from 25 mg to 200 mg per day.

Other names: Lamictal

Primary outcomes

  1. Mean Glutamine to Creatine Ratio by Diagnosis at Baseline

    Time frame: Baseline

  2. Mean Glutamate to Creatine Ratio by Diagnosis at Baseline

    Time frame: Baseline

  3. Mean N-Acetyl Aspartate (NAA) to Creatine Ratio by Diagnosis at Baseline

    Time frame: Baseline

  4. Associations Between Depression Symptom Severity and Glutamate to Creatine Ratio at Baseline

    Time frame: 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.

  5. Estimated Change in Least Squares Mean in Glutamate to Creatine Ratio Between Baseline and Follow-up

    Time frame: 8 Weeks

    Follow-up Least Squares Mean - Baseline Least Squares Mean

  6. Estimated Change in Least Squares Mean in the Glutamine to Creatine Ratio Between Baseline and Follow-up

    Time frame: 8 weeks

    Follow-up Least Squares Mean - Baseline Least Squares Mean

  7. Estimated Change in Least Squares Mean in the NAA to Creatine Ratio Between Baseline and Follow-up

    Time frame: 8 weeks

    Follow-up Least Squares Mean - Baseline Least Squares Mean

  8. Association of MADRS Changes With Glutamate to Creatine Ratio Changes From Baseline to Follow-up

    Time frame: 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.

  9. Associations of MADRS Changes With Glutamine to Creatine Ratio Changes From Baseline to Follow-up

    Time frame: 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.

  10. Associations of MADRS Changes With NAA to Creatine Ratio Changes From Baseline to Follow-up

    Time frame: 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.

  11. Mean Montgomery Asberg Depression Rating Scale (MADRS) Score at Baseline

    Time frame: Baseline

    The minimum MADRS score is 0 and the maximum is 60, with 60 being the most depressed.

  12. Means of MADRS Scores at 8 Weeks

    Time frame: 8 Weeks

    The minimum MADRS score is 0 and the maximum is 60, with 60 being the most depressed.

Sponsors and collaborators

Lead sponsor

Mclean Hospital

Other

Registry information

Official study title

Lamotrigine Therapy in the Treatment of Geriatric Bipolar Depression: An Evaluation of Markers of Cerebral Energy Metabolism

Important dates

Study start
2006
Primary completion
2011
Study completion
2011
First posted
Jul 22, 2008
Registry last updated
Feb 1, 2017

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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