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

Bipolar Disorder Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00194129
• Other study ID #: R01MH050165
• Secondary ID: R01MH050165
• Status: Completed
• Phase: Phase 3
• First received: September 13, 2005
• Last updated: January 22, 2018
• Start date: November 1997
• Est. completion date: September 2006

Study information

• Verified date: January 2018
• Source: University Hospitals Cleveland Medical Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 31
• Est. completion date: September 2006
• Est. primary completion date: September 2006
• Accepts healthy volunteers: No
• Gender: All
• Age group: 16 Years to 65 Years

Eligibility

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.

Related Conditions & MeSH terms

• Bipolar Disorder
• Disease
• Substance-Related Disorders

Intervention

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.
• Divalproex
Divalproex was then initiated at 250 mg twice daily and increased over 3-6 weeks to minimum blood levels of 50 ug/ml.
• Placebo
Placebo pills that looked exact to divaloproex were provided to subjects and take twice daily.

Locations

Country	Name	City	State
United States	University Hospitals of Cleveland	Cleveland	Ohio

Sponsors (3)

Lead Sponsor	Collaborator
University Hospitals Cleveland Medical Center	Abbott, National Institute of Mental Health (NIMH)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	Up to 6 months
Secondary	Time to Treatment for Emerging Symptoms of a Manic/Hypomanic/Mixed Episode		Up to 6 months
Secondary	Time to Treatment for Emerging Symptoms of a Depressive Episode		Up to 6 months
Secondary	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	Baseline to Month 6
Secondary	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	Baseline to Month 6
Secondary	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	Baseline to Month 6