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Lithium and Divalproex for the Treatment of Comorbid Rapid Cycling Bipolar Disorder and Substance Abuse Disorder

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00194129
Recruitment Status : Completed
First Posted : September 19, 2005
Results First Posted : December 23, 2013
Last Update Posted : February 20, 2018
Sponsor:
Collaborators:
National Institute of Mental Health (NIMH)
Abbott
Information provided by (Responsible Party):
Joseph Calabrese, MD, University Hospitals Cleveland Medical Center

Brief Summary:
This study will determine the efficacy and safety of combination therapy with divalproex and lithium for treating mania in people with rapid cycling bipolar disorder and a substance abuse disorder.

Condition or disease Intervention/treatment Phase
Bipolar Disorder Drug: Lithium Drug: Divalproex Drug: Placebo Phase 3

Detailed Description:
Longitudinal Evaluation of the Efficacy and Safety of Divalproex and Lithium 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 are initially stabilized on dual therapy of lithium and depakote and then randomly assigned to double-blind treatment with either lithium monotherapy or continued dual therapy. Patients remain in the study for six months or until they experience a relapse. Patients in this study are required to bring a friend or family member to all study visits as well as attend chemical dependency services. This study is sponsored by the NIMH. Subjects receive study-related care at no cost.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 31 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Randomized, Double Blind Comparison of Lithium Monotherapy Versus Lithium Plus Divalproex for the Outpatient Management of Hypomania/Mania in Patients With Rapid Cycling Bipolar Disorder Comorbid With Substance Abuse/Dependence
Study Start Date : November 1997
Actual Primary Completion Date : September 2006
Actual Study Completion Date : September 2006

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Bipolar Disorder

Arm Intervention/treatment
Experimental: Lithium plus Divalproex
Patients assigned to the combination group were continued on lithium and blinded divalproex.
Drug: Lithium
Lithium monotherapy was initiated at 300 mg twice daily and titrated over 3-6 weeks to minimum blood levels of 0.8 meq/L.
Other Name: Lithium Carbonate

Drug: Divalproex
Divalproex was then initiated at 250 mg twice daily and increased over 3-6 weeks to minimum blood levels of 50 ug/ml.
Other Names:
  • Valproic Acid
  • Depakote

Placebo Comparator: Lithium plus placebo
Patients assigned to lithium monotherapy underwent divalproex-placebo substitution at a rate of 250 mg decrements every week until discontinued.
Drug: Lithium
Lithium monotherapy was initiated at 300 mg twice daily and titrated over 3-6 weeks to minimum blood levels of 0.8 meq/L.
Other Name: Lithium Carbonate

Drug: Placebo
Placebo pills that looked exact to divaloproex were provided to subjects and take twice daily.




Primary Outcome Measures :
  1. Time to Treatment for Emerging Symptoms of a Mood Relapse [ Time Frame: Up to 6 months ]
    A relapse is a return to either a depressive, manic, hypomanic or mixed episode after a period of not have any symptoms.


Secondary Outcome Measures :
  1. Time to Treatment for Emerging Symptoms of a Manic/Hypomanic/Mixed Episode [ Time Frame: Up to 6 months ]
  2. Time to Treatment for Emerging Symptoms of a Depressive Episode [ Time Frame: Up to 6 months ]
  3. Change in Rate of Alcohol Use Disorders After Open-label Treatment With Lithium and Divalproex [ Time Frame: Baseline to Month 6 ]
    Number of subjects who no longer met criteria for active abuse or had entered into early full remission after receiving up to 6 months of open-label treatment with lithium and divalproex

  4. Change in Rate of Cannabis Use Disorders After Open-label Treatment With Lithium and Divalproex [ Time Frame: Baseline to Month 6 ]
    Number of subjects who no longer met criteria for active cannabis abuse or had entered into early full remission after receiving up to 6 months of open-label treatment with lithium and divalproex

  5. Change in Rate of Cocaine Use Disorders After Open-label Treatment With Lithium and Divalproex [ Time Frame: Baseline to Month 6 ]
    Number of subjects who no longer met criteria for active cocaine abuse or had entered into early full remission after receiving up to 6 months of open-label treatment with lithium and divalproex



Information from the National Library of Medicine

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Ages Eligible for Study:   16 Years to 65 Years   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • To be included in this study, patients will be required to be either acutely hypomanic or manic as defined by the Diagnostic and Statistical Manual -IV (DSM-IV) and meet criteria for current substance abuse and/or dependence disorder within the last six months.
  • Must have 4 or more episodes in the immediate 12 months prior to study entry.
  • Males or females 16 - 65 years of age.
  • A score of 60 or less on the Global Assessment Scale.
  • Have no medical illness precluding the use of lithium or divalproex.

Exclusion Criteria:

  • Patients who have had intolerable side effects to lithium levels 0.8 meq/L or divalproex levels of 50 ug/ml. Patients who have been completely non-responsive to lithium in the past will be excluded, whereas patients who have had partial responses to lithium will be permitted into the study.
  • Patients with a prior history of seizure disorder, cerebral vascular disease, structural brain damage from trauma, clinically significant focal neurological abnormalities, EEG abnormalities with frank paroxysmal activity or a previous CT/MRI scan of the brain with gross structural abnormalities.
  • Patients who require anticoagulant drug therapy.
  • Patients who have uncontrolled gastrointestinal, renal, hepatic, endocrine, cardiovascular, pulmonary, immunological or hematological disease. Patients with alcohol-related liver disease as reflected by diffuse elevations in liver functions tests exceeding the upper limits of the normal range by 50% will be excluded.
  • Patients who are pregnant or plan to become pregnant during the study.
  • 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 disorder; active CNS infection; or any progressive neurological disorder.
  • Patients who are taking exogenous steroids.
  • Patients who do not meet criteria for substance abuse or dependence.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00194129


Locations
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United States, Ohio
University Hospitals of Cleveland
Cleveland, Ohio, United States, 44106
Sponsors and Collaborators
University Hospitals Cleveland Medical Center
National Institute of Mental Health (NIMH)
Abbott
Investigators
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Principal Investigator: Joseph R Calabrese, MD Case Western Reserve University / University Hospitals of Cleveland

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Joseph Calabrese, MD, Director, Mood Disorders Program, University Hospitals Cleveland Medical Center
ClinicalTrials.gov Identifier: NCT00194129    
Other Study ID Numbers: R01MH050165 ( U.S. NIH Grant/Contract )
R01MH050165 ( U.S. NIH Grant/Contract )
First Posted: September 19, 2005    Key Record Dates
Results First Posted: December 23, 2013
Last Update Posted: February 20, 2018
Last Verified: January 2018
Additional relevant MeSH terms:
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Disease
Substance-Related Disorders
Bipolar Disorder
Pathologic Processes
Bipolar and Related Disorders
Mental Disorders
Chemically-Induced Disorders
Lithium Carbonate
Antidepressive Agents
Psychotropic Drugs
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antimanic Agents
Tranquilizing Agents
Central Nervous System Depressants
Physiological Effects of Drugs