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

NCT00194129 | Completed Phase 3 Results DMC

• 1 other identifier: R01MH050165
• Study Type: interventional
• Target: 31
• Locations: 1 country
• Sites: 1

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.

Conditions

Bipolar Disorder

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (5)

• Time to Treatment for Emerging Symptoms of a Manic/Hypomanic/Mixed Episode

  Up to 6 months

• Time to Treatment for Emerging Symptoms of a Depressive Episode

  Up to 6 months

• Change in Rate of Alcohol Use Disorders After Open-label Treatment With Lithium and Divalproex

  Baseline to Month 6

• Change in Rate of Cannabis Use Disorders After Open-label Treatment With Lithium and Divalproex

  Baseline to Month 6

• Change in Rate of Cocaine Use Disorders After Open-label Treatment With Lithium and Divalproex

  Baseline to Month 6

Study Arms (2)

Lithium plus Divalproex

EXPERIMENTAL

Patients assigned to the combination group were continued on lithium and blinded divalproex.

Drug: Lithium; Drug: Divalproex

Lithium plus placebo

PLACEBO COMPARATOR

Patients assigned to lithium monotherapy underwent divalproex-placebo substitution at a rate of 250 mg decrements every week until discontinued.

Drug: Lithium; Drug: Placebo

Interventions

Lithium DRUG

Lithium monotherapy was initiated at 300 mg twice daily and titrated over 3-6 weeks to minimum blood levels of 0.8 meq/L.

Also known as: Lithium Carbonate

Lithium plus Divalproex; Lithium plus placebo

Divalproex DRUG

Divalproex was then initiated at 250 mg twice daily and increased over 3-6 weeks to minimum blood levels of 50 ug/ml.

Also known as: Valproic Acid, Depakote

Lithium plus Divalproex

Placebo DRUG

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

Lithium plus placebo

Eligibility Criteria

• Age: 16 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• University Hospitals Cleveland Medical Center: lead
• National Institute of Mental Health (NIMH): collaborator
• Abbott: collaborator

Study Sites (1)

University Hospitals of Cleveland

Cleveland, Ohio, 44106, United States

Location

Related Publications (2)

• 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.

  PMID: 19192457 DERIVED

• 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.

  PMID: 18588360 DERIVED

MeSH Terms

Conditions

Bipolar Disorder

Interventions

Lithium; Lithium Carbonate; Valproic Acid

Condition Hierarchy (Ancestors)

Bipolar and Related Disorders; Mood Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Metals, Alkali; Elements; Inorganic Chemicals; Metals, Light; Metals; Carbonates; Alkalies; Carbonic Acid; Carbon Compounds, Inorganic; Lithium Compounds; Pentanoic Acids; Valerates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Fatty Acids, Volatile; Fatty Acids; Lipids

Results Point of Contact

• Title: David Kemp, MD
• Organization: UHCMC Mood Disorders Program

David.Kemp@UHhospitals.org

216-844-2865

Study Officials

• Joseph R Calabrese, MD

  Case Western Reserve University / University Hospitals of Cleveland

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director, Mood Disorders Program

Study Record Dates

• First Submitted: September 13, 2005
• First Posted: September 19, 2005
• Study Start: November 1, 1997
• Primary Completion: September 1, 2006
• Study Completion: September 1, 2006
• Last Updated: February 20, 2018
• Results First Posted: December 23, 2013

Record last verified: 2018-01

Locations

US (1)