Clinical trial NCT00194129: 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
Overall status: COMPLETED
Phase: PHASE3
Conditions: Bipolar Disorder
Lead sponsor: University Hospitals Cleveland Medical Center
Sponsor class: OTHER
Collaborators: name: National Institute of Mental Health (NIMH)
name: Abbott
First posted: 2005-09-19
Enrollment: 31
Sex: ALL
Minimum age (years): 16
Maximum age (years): 65
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Time to Treatment for Emerging Symptoms of a Mood Relapse
timeFrame: Up to 6 months
Secondary outcomes:
measure: Time to Treatment for Emerging Symptoms of a Manic/Hypomanic/Mixed Episode
timeFrame: Up to 6 months
measure: Time to Treatment for Emerging Symptoms of a Depressive Episode
timeFrame: Up to 6 months
measure: Change in Rate of Alcohol Use Disorders After Open-label Treatment With Lithium and Divalproex
timeFrame: Baseline to Month 6
measure: Change in Rate of Cannabis Use Disorders After Open-label Treatment With Lithium and Divalproex
timeFrame: Baseline to Month 6
measure: Change in Rate of Cocaine Use Disorders After Open-label Treatment With Lithium and Divalproex
timeFrame: Baseline to Month 6
Other outcomes:
Locations:
city: Cleveland
country: United States
facility: University Hospitals of Cleveland
state: Ohio
Study officials:
affiliation: Case Western Reserve University / University Hospitals of Cleveland
name: Joseph R Calabrese, MD
role: PRINCIPAL_INVESTIGATOR
References:
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.
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.