Clinical trial NCT00961961: Prevention of Relapse & Recurrence of Bipolar Depression
Official title: Prevention of Relapse & Recurrence of Bipolar Depression
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Bipolar Disorder
Keywords: Bipolar Disorder
Manic Depression
Major Depressive Episode
Mania
Hypomania
Long Term Treatment
Lead sponsor: University of Pennsylvania
Sponsor class: OTHER
Collaborators: name: National Institute of Mental Health (NIMH)
First posted: 2009-08-19
Enrollment: 177
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to determine whether the long-term use of combined antidepressant plus mood stabilizer therapy is superior to mood stabilizer therapy alone in preventing the relapse and recurrence of bipolar depression.

Detailed description: Recurrence of Bipolar I (BP I) major depressive episode (MDE), is now recognized as a major mental health problem. Recurrent BP I MDE is a disorder with no satisfactory therapy, and its treatment remains a challenge to clinicians. To date, initial and long-term therapy of BP I MDE has been based on un-validated practice guidelines. These guidelines recommend limiting antidepressant drug (AD) use during initial therapy of BP I MDE, and completely avoiding AD use during long-term therapy. There is, however, no empirical evidence to suggest that mood stabilizer (MS) monotherapy is superior to combined MS plus AD therapy in preventing recurrent BP I MDE. Nor is there evidence to suggest that long-term MS plus AD therapy results in more manic switch episodes. We present evidence that AD-induced mania during long-term therapy of BP I MDE has been over-estimated, and that long-term use of MS plus AD therapy may be superior to MS therapy alone in preventing recurrent BP I MDE. In this study, we will ask: "Does continuation therapy with combined lithium plus fluoxetine result in fewer MDE relapses and recurrences vs. lithium monotherapy?" To answer this question, patients with BP I MDE will receive combined lithium plus fluoxetine therapy for 8 weeks. Responders who stay well for an additional 4 weeks of consolidation therapy will then be randomized to double-blind continuation therapy with either (i) combined lithium plus fluoxetine, or (ii) lithium alone (following fluoxetine taper and discontinuation) for an additional 50 weeks. We hypothesize that long-term lithium plus fluoxetine therapy will result in fewer MDE relapses and recurrences vs. lithium monotherapy. We will also ask: "What is the relative safety, tolerability, and frequency of syndromal and sub-syndromal manic, hypomanic, and mixed state conversions during continuation treatment with combined lithium plus fluoxetine vs. lithium monotherapy?" To answer this question, we will measure: the frequency, severity, and duration of syndromal and sub-syndromal manic, hypomanic, and mixed state conversions; frequency, severity, and duration of treatment-emergent adverse events; frequency of treatment discontinuation; time to onset of first syndromal and sub-syndromal conversion event; time to first treatment intervention of each syndromal and sub-syndromal conversion event; and, time to onset of increase in suicidal ideation event. We hypothesize that lithium plus fluoxetine therapy will result in a similar frequency of syndromal and sub-syndromal conversion events, and a similar frequency of treatment-emergent adverse events. We further hypothesize that lithium plus fluoxetine therapy will result in fewer suicide ideation events and fewer study discontinuations vs. lithium monotherapy. We believe that the results of this trial may have an important public health impact on the current practice guidelines for treating BP I MDE.

Eligibility criteria: Inclusion Criteria:

* Men/women (all races and ethnicity)
* Age at least 18 years old
* Bipolar Type I Disorder
* Current Major Depressive Episode
* Able to understand and provide signed informed consent

Exclusion Criteria:

* Current alcohol or drug abuse
* Alcohol or drug dependence within 3 months
* Allergic to Fluoxetine or Lithium
* Unstable medical condition (e.g., uncontrolled thyroid, renal, cardiovascular disease)
* Pregnant or nursing women
* Women of child-bearing potential unwilling to use a medically acceptable form of contraception
* Actively suicidal
* Requiring hospitalization
* Use of medication contraindicated with lithium or fluoxetine
* Unable to participate in a year-long trial

Primary outcomes:
measure: Number of Participants With Relapse of Major Depressive Episode Within 1 Year
timeFrame: 1 year
Secondary outcomes:
measure: Number of Participants With an Onset of a Manic Episode Within 1 Year
timeFrame: 1 Year
measure: Number of Participants With an Onset of a Hypomanic Episode Within 1 Year
timeFrame: 1 Year
measure: Number of Participants With the Onset of a Sub-Syndromal Mood Conversion Episode Within 1 Year
timeFrame: 1 Year
Other outcomes:
Locations:
city: Chicago
country: United States
facility: Rush University Medical Center
state: Illinois
city: Philadelphia
country: United States
facility: Depression Research Unit
state: Pennsylvania
Study officials:
affiliation: University of Pennsylvania
name: Robert J. DeRubeis, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Rush University Medical Center
name: John M Zajecka, MD
role: PRINCIPAL_INVESTIGATOR
References: