Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT00961961 |
| Other study ID # |
R01MH080097 |
| Secondary ID |
R01MH080097R01MH |
| Status |
Completed |
| Phase |
Phase 4
|
| First received |
|
| Last updated |
|
| Start date |
July 1, 2009 |
| Est. completion date |
September 1, 2016 |
Study information
| Verified date |
September 2020 |
| Source |
University of Pennsylvania |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial 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.
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.
