Back to resultsLithium and Divalproex for the Treatment of Comorbid Rapid Cycling Bipolar Disorder and Substance Abuse Disorder
Primary Purpose
Bipolar Disorder
Status
Completed
Phase
Phase 3
Locations
United States
Study Type
Interventional
Intervention
Lithium
Divalproex
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Bipolar Disorder
Eligibility 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.
Sites / Locations
- University Hospitals of Cleveland
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
Lithium plus Divalproex
Lithium plus placebo
Arm Description
Patients assigned to the combination group were continued on lithium and blinded divalproex.
Patients assigned to lithium monotherapy underwent divalproex-placebo substitution at a rate of 250 mg decrements every week until discontinued.
Outcomes
Primary Outcome Measures
Time to Treatment for Emerging Symptoms of a Mood Relapse
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
Time to Treatment for Emerging Symptoms of a Manic/Hypomanic/Mixed Episode
Time to Treatment for Emerging Symptoms of a Depressive Episode
Change in Rate of Alcohol Use Disorders After Open-label Treatment With Lithium and Divalproex
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
Change in Rate of Cannabis Use Disorders After Open-label Treatment With Lithium and Divalproex
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
Change in Rate of Cocaine Use Disorders After Open-label Treatment With Lithium and Divalproex
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
Full Information
NCT ID
NCT00194129
First Posted
September 13, 2005
Last Updated
January 22, 2018
Sponsor
University Hospitals Cleveland Medical Center
Collaborators
National Institute of Mental Health (NIMH), Abbott
1. Study Identification
Unique Protocol Identification Number
NCT00194129
Brief Title
Lithium and Divalproex for the Treatment of Comorbid Rapid Cycling Bipolar Disorder and Substance Abuse Disorder
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 Type
Interventional
2. Study Status
Record Verification Date
January 2018
Overall Recruitment Status
Completed
Study Start Date
November 1997 (undefined)
Primary Completion Date
September 2006 (Actual)
Study Completion Date
September 2006 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University Hospitals Cleveland Medical Center
Collaborators
National Institute of Mental Health (NIMH), Abbott
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
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.
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Bipolar Disorder
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
31 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Lithium plus Divalproex
Arm Type
Experimental
Arm Description
Patients assigned to the combination group were continued on lithium and blinded divalproex.
Arm Title
Lithium plus placebo
Arm Type
Placebo Comparator
Arm Description
Patients assigned to lithium monotherapy underwent divalproex-placebo substitution at a rate of 250 mg decrements every week until discontinued.
Intervention Type
Drug
Intervention Name(s)
Lithium
Other Intervention Name(s)
Lithium Carbonate
Intervention Description
Lithium monotherapy was initiated at 300 mg twice daily and titrated over 3-6 weeks to minimum blood levels of 0.8 meq/L.
Intervention Type
Drug
Intervention Name(s)
Divalproex
Other Intervention Name(s)
Valproic Acid, Depakote
Intervention Description
Divalproex was then initiated at 250 mg twice daily and increased over 3-6 weeks to minimum blood levels of 50 ug/ml.
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Placebo pills that looked exact to divaloproex were provided to subjects and take twice daily.
Primary Outcome Measure Information:
Title
Time to Treatment for Emerging Symptoms of a Mood Relapse
Description
A relapse is a return to either a depressive, manic, hypomanic or mixed episode after a period of not have any symptoms.
Time Frame
Up to 6 months
Secondary Outcome Measure Information:
Title
Time to Treatment for Emerging Symptoms of a Manic/Hypomanic/Mixed Episode
Time Frame
Up to 6 months
Title
Time to Treatment for Emerging Symptoms of a Depressive Episode
Time Frame
Up to 6 months
Title
Change in Rate of Alcohol Use Disorders After Open-label Treatment With Lithium and Divalproex
Description
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
Time Frame
Baseline to Month 6
Title
Change in Rate of Cannabis Use Disorders After Open-label Treatment With Lithium and Divalproex
Description
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
Time Frame
Baseline to Month 6
Title
Change in Rate of Cocaine Use Disorders After Open-label Treatment With Lithium and Divalproex
Description
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
Time Frame
Baseline to Month 6
10. Eligibility
Sex
All
Minimum Age & Unit of Time
16 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Joseph R Calabrese, MD
Organizational Affiliation
Case Western Reserve University / University Hospitals of Cleveland
Official's Role
Principal Investigator
Facility Information:
Facility Name
University Hospitals of Cleveland
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44106
Country
United States
12. IPD Sharing Statement
Citations:
PubMed Identifier
19192457
Citation
Kemp DE, Gao K, Ganocy SJ, Elhaj O, Bilali SR, Conroy C, Findling RL, Calabrese JR. A 6-month, double-blind, maintenance trial of lithium monotherapy versus the combination of lithium and divalproex for rapid-cycling bipolar disorder and Co-occurring substance abuse or dependence. J Clin Psychiatry. 2009 Jan;70(1):113-21. doi: 10.4088/jcp.07m04022. Epub 2008 Dec 30.
Results Reference
derived
PubMed Identifier
18588360
Citation
Gao K, Verduin ML, Kemp DE, Tolliver BK, Ganocy SJ, Elhaj O, Bilali S, Brady KT, Findling RL, Calabrese JR. Clinical correlates of patients with rapid-cycling bipolar disorder and a recent history of substance use disorder: a subtype comparison from baseline data of 2 randomized, placebo-controlled trials. J Clin Psychiatry. 2008 Jul;69(7):1057-63. doi: 10.4088/jcp.v69n0703.
Results Reference
derived
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Lithium and Divalproex for the Treatment of Comorbid Rapid Cycling Bipolar Disorder and Substance Abuse Disorder
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