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Combination Therapy in Dual Diagnosis Bipolar Rapid Cycling

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Joseph Calabrese, MD, University Hospital Case Medical Center
ClinicalTrials.gov Identifier:
NCT00221975
First received: September 13, 2005
Last updated: December 1, 2014
Last verified: December 2014
  Purpose

Combination Therapy in Dual Diagnosis Bipolar Rapid Cycling: This study recruits males and females age 18 and older who currently meet diagnostic criteria for rapid cycling bipolar disorder (type I or II) and who have met the criteria for substance abuse or dependence of cocaine, marijuana and/or alcohol within the past six months. Patients begin treatment with a combination of lithium and divalproex. Once these medications are tolerated, they are randomly assigned to double-blind treatment with lamotrigine or placebo. Patients remain in this study until they experience a marked bimodal response for four consecutive weeks. This study is sponsored by the Stanley Foundation.


Condition Intervention Phase
Bipolar Disorder
Drug: Divalproex
Drug: Lamotrigine
Drug: Lithium
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator, Outcomes Assessor)
Primary Purpose: Diagnostic
Official Title: Combination Therapy in Dual Diagnosis Rapid Cycling Bipolar Disorder

Resource links provided by NLM:


Further study details as provided by University Hospital Case Medical Center:

Primary Outcome Measures:
  • Proportion of patients who experience a marked and persistent bimodal response [ Time Frame: Phase 1: Baseline - Week 16 ] [ Designated as safety issue: No ]

Enrollment: 98
Study Start Date: July 2002
Study Completion Date: December 2007
Primary Completion Date: June 2007 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Lithium + Divalproex + Lamictal
Lithium monotherapy was initiated at 450 mg once daily and titrated slowly over 3 weeks to a minimum blood level of 0.5 mEqlL. Divalproex was then initiated at 250 mg twice daily and increased slowly over 5 weeks to a minimum blood level of 50 μg/mL. Patients meeting the criteria of being non-responsive to lithium plus divalproex were randomly assigned to receive lamotrigine or placebo. Patients randomized to the lamotrigine group were titrated up to a minimum dose of 150 mg and maximum dose of 200 mg per day.
Drug: Divalproex
Once a therapeutic blood level of lithium was achieved, Divalproex was initiated at 250 mg twice daily and increased slowly over 5 weeks to a minimum blood level of 50 μg/mL.
Other Name: Depakote
Drug: Lamotrigine
Lithium monotherapy was initiated at 450 mg once daily and titrated slowly over 3 weeks to a minimum blood level of 0.5 mEqlL.
Other Name: Lamictal
Drug: Lithium
Subjects who did not respond to the combination of Lithium and Divalproex were then randomly assigned in a 1:1 ratio to adjunctive lamotrigine versus placebo after stratification by illness type (bipolar I versus bipolar II), historical response to lithium (response versus oon-response), and the length of current exposure to the combination treatment with lithium and divalproex (<2 months versus ≥2 months).
Other Name: Eskalith
Placebo Comparator: Lithium + Divalproex + Placebo
Lithium monotherapy was initiated at 450 mg once daily and titrated slowly over 3 weeks to a minimum blood level of 0.5 mEqlL. Divalproex was then initiated at 250 mg twice daily and increased slowly over 5 weeks to a minimum blood level of 50 μg/mL. Patients meeting the criteria of being non-responsive to lithium plus divalproex were randomly assigned to receive lamotrigine or placebo. Patients randomized to the placebo group were giving matching placebo.
Drug: Divalproex
Once a therapeutic blood level of lithium was achieved, Divalproex was initiated at 250 mg twice daily and increased slowly over 5 weeks to a minimum blood level of 50 μg/mL.
Other Name: Depakote
Drug: Lithium
Subjects who did not respond to the combination of Lithium and Divalproex were then randomly assigned in a 1:1 ratio to adjunctive lamotrigine versus placebo after stratification by illness type (bipolar I versus bipolar II), historical response to lithium (response versus oon-response), and the length of current exposure to the combination treatment with lithium and divalproex (<2 months versus ≥2 months).
Other Name: Eskalith

  Eligibility

Ages Eligible for Study:   16 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Has given written informed consent.
  • Males or females 16 years of age and older. For patients less than 18 years old, concurrent written informed consent will also be required from the parents or legal guardians.
  • Must meet Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) criteria for major depression at the time of study entry.
  • Must meet DSM-IV criteria for rapid-cycling bipolar disorder in the last 12 months.
  • Must meet DSM-IV criteria for alcohol or drug abuse within the past 3 months or dependence in the last 6 months (unless most recent period of abstinence occurred while in a controlled environment).
  • Must have no medical illness precluding the use of lithium, divalproex sodium and/or lamotrigine.
  • Regardless of treatment response, patients who have been exposed to lithium or divalproex sodium will be included as long as the medication was adequately tolerated and all three medications were not administered concurrently.

Exclusion Criteria:

  • Patients who have had intolerable side effects to lamotrigine, lithium at levels of 0.6 mEq/L or divalproex sodium at levels of 50ug/ml.
  • Patients who have previously been treated with lithium, divalproex sodium and lamotrigine concurrently.
  • Patients who have previously been treated with an adequate trial of lamotrigine, which was considered to be a treatment failure.
  • Patients who do not have a recent history of, or are not currently abusing or dependent on alcohol or drugs.
  • Patients with a prior history of seizure disorder, cerebral vascular disease, structural brain damage from trauma, clinically significant focal neurological abnormalities, closed head injury, EEG abnormalities with frank paroxysmal activity or a previous CT/MRI scan of the brain with gross structural abnormalities.
  • Patients who have clinically significant gastrointestinal, renal, hepatic, endocrine, cardiovascular, pulmonary, immunologic, hematologic, or oncologic diseases. Clinically significant evidence of thyroid failure will be defined as a decreased free thyroxine index with several clinical signs and symptoms of overt failure.
  • Patients who are pregnant, at-risk of becoming pregnant or intend to become pregnant during the study. Patients who are not at risk of becoming pregnant are females who are post menopausal, who have undergone a hysterectomy, bilateral oophorectomy or sterilization, who agree to use an IUD, barrier protection, a contraceptive implantation system (e.g., Norplant), oral contraceptive pills, or who, in the investigator's judgment, will continue to be sexually inactive.
  • Patients who have received haloperidol decanoate or fluphenazine decanoate within the last 10 weeks.
  • Patients who have a central nervous system (CNS) neoplasm, uncontrolled metabolic, demyelinating or progressive degenerative disorder, active CNS infection, or any progressive neurological disorder.
  • Patients who are taking exogenous steroids.
  • Patients who have ultra-fast rapid-cycling bipolar disorder, but do not formally meet DSM-IV criteria for bipolar disorder. This is designed to exclude patients with episode frequencies too high to permit objective quantification.
  • Patients who are currently suicidal in the opinion of the investigator or have a score of greater than 4 on the suicide item of the (Montgomery-Asberg Rating Scale (MADRS).
  • Patients who have been treated with any dose or duration of a tricyclic antidepressant within the last three months.
  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: NCT00221975

Locations
United States, Ohio
University Hospitals of Cleveland
Cleveland, Ohio, United States, 44106
Sponsors and Collaborators
University Hospital Case Medical Center
Investigators
Principal Investigator: Keming Gao, MD, PhD Case Western Reserve University / University Hospitals of Cleveland
  More Information

No publications provided by University Hospital Case Medical Center

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Joseph Calabrese, MD, Director, Mood Disorders Program, University Hospital Case Medical Center
ClinicalTrials.gov Identifier: NCT00221975     History of Changes
Other Study ID Numbers: 02T 183
Study First Received: September 13, 2005
Last Updated: December 1, 2014
Health Authority: United States: Institutional Review Board

Additional relevant MeSH terms:
Bipolar Disorder
Affective Disorders, Psychotic
Mental Disorders
Mood Disorders
Lamotrigine
Lithium
Lithium Carbonate
Anticonvulsants
Antidepressive Agents
Antimanic Agents
Antipsychotic Agents
Calcium Channel Blockers
Cardiovascular Agents
Central Nervous System Agents
Central Nervous System Depressants
Enzyme Inhibitors
Excitatory Amino Acid Agents
Excitatory Amino Acid Antagonists
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents
Pharmacologic Actions
Physiological Effects of Drugs
Psychotropic Drugs
Sodium Channel Blockers
Therapeutic Uses
Tranquilizing Agents
Voltage-Gated Sodium Channel Blockers

ClinicalTrials.gov processed this record on March 03, 2015