Trial Outcomes & Findings for Prevention of Relapse & Recurrence of Bipolar Depression (NCT NCT00961961)

NCT ID: NCT00961961

Last Updated: 2020-10-19

Results Overview

Patients who were randomized to one of the Phase II conditions were interviewed once each month. If they met criteria for a relapse of a Major Depressive Episode, this was considered the study outcome. If they participated for the full year of Phase II without a documented relapse, they were considered a completer.

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

177 participants

Primary outcome timeframe

1 year

Results posted on

2020-10-19

Participant Flow

Phase I was an open label treatment, of Lithium and Fluoxetine, of all enrolled patients. Those who met criteria for response after 12 weeks were randomized to one of two Phase II (double-blinded) arms: Lithium plus Fluoxetine Lithium plus Placebo

Participant milestones

Participant milestones
Measure	Lithium Plus Fluoxetine Phase I Lithium / Fluoxetine: Individualized Daily Dosage	Lithium Plus Fluoxetine Phase II One of the two randomly assigned groups, each of which continued on Lithium Double-blind assignment to continue on Fluoxetine (this group)	Lithium Plus Placebo Phase II One of the two randomly assigned groups, each of which continued on Lithium Double-blind assignment to switch from Fluoxetine to Placebo (this group)
Phase I STARTED	177	0	0
Phase I COMPLETED	51	0	0
Phase I NOT COMPLETED	126	0	0
Phase II STARTED	0	29	22
Phase II COMPLETED	0	17	14
Phase II NOT COMPLETED	0	12	8

Reasons for withdrawal

Reasons for withdrawal
Measure	Lithium Plus Fluoxetine Phase I Lithium / Fluoxetine: Individualized Daily Dosage	Lithium Plus Fluoxetine Phase II One of the two randomly assigned groups, each of which continued on Lithium Double-blind assignment to continue on Fluoxetine (this group)	Lithium Plus Placebo Phase II One of the two randomly assigned groups, each of which continued on Lithium Double-blind assignment to switch from Fluoxetine to Placebo (this group)
Phase I Withdrawal by Subject	7	0	0
Phase I Lost to Follow-up	10	0	0
Phase I Lack of Efficacy	94	0	0
Phase I Adverse Event	7	0	0
Phase I Physician Decision	8	0	0
Phase II Lost to Follow-up	0	10	7
Phase II Adverse Event	0	0	1
Phase II Physician Decision	0	1	0
Phase II Withdrawal by Subject	0	1	0

Baseline Characteristics

Prevention of Relapse & Recurrence of Bipolar Depression

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Lithium Plus Fluoxetine Phase I n=177 Participants All eligible and consenting participants began in this open phase. Therefore baseline characteristics are only relevant for this category.	Lithium Plus Placebo Phase I No participant was begun on Placebo. Lithium Plus Placebo was a real condition only after randomization, in Phase II. Baseline characteristics for all participants are listed under Lithium plus Fluoxetine Phase I.	Lithium Plus Fluoxetine Phase II This is a subset of patients whose baseline characteristics are listed under Lithium plus Fluoxetine Phase I.	Lithium Plus Placebo Phase II This is a subset of patients whose baseline characteristics are listed under Lithium plus Fluoxetine Phase I.	Total n=177 Participants Total of all reporting groups
Sex: Female, Male Female	90 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	0 Participants n=483 Participants	90 Participants n=36 Participants
Sex: Female, Male Male	87 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	0 Participants n=483 Participants	87 Participants n=36 Participants
Region of Enrollment United States	177 participants n=93 Participants	—	—	—	177 participants n=36 Participants
Age, Categorical <=18 years	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	0 Participants n=483 Participants	0 Participants n=36 Participants
Age, Categorical Between 18 and 65 years	175 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	0 Participants n=483 Participants	175 Participants n=36 Participants
Age, Categorical >=65 years	2 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	0 Participants n=483 Participants	2 Participants n=36 Participants

PRIMARY outcome

Timeframe: 1 year

Population: The analyses are relevant only during Phase II. The comparisons are between those assigned to one of the two randomized Phase II conditions.

Outcome measures

Outcome measures
Measure	Lithium Plus Fluoxetine Phase I The outcome measures, including this one, are only relevant in Phase II. Thus there will be zeroes in this category.	Lithium Plus Placebo Phase I The outcome measures, including this one, are only relevant in Phase II. Thus there will be zeroes in this category.	Lithium Plus Fluoxetine Phase II n=29 Participants Participants randomized to this condition remained on active medications. However, the fluoxetine pills were made to look like the placebo pills, to maintain the double-blind.	Lithium Plus Placebo Phase II n=22 Participants Participants randomized to this condition were switched from fluoxetine to placebo. However, the placebo pills were made to look like the fluoxetine pills, to maintain the double-blind.
Number of Participants With Relapse of Major Depressive Episode Within 1 Year	—	—	4 Participants	5 Participants

SECONDARY outcome

Timeframe: 1 Year

Population: This and other outcomes are only relevant in the double-blind Phase II of the study.

Onsets of a manic episodes were ascertained with the clinician-rated Young Mania Rating Scale (YMRS). The YMRS covers 11 symptom groups over the previous 48 hours. Four of the items are rated on a scale from 0 to 4; the other 4 are rated on a scale of 0 to 8. A score of 12 or above indicates a manic episode.

Outcome measures

Outcome measures
Measure	Lithium Plus Fluoxetine Phase I The outcome measures, including this one, are only relevant in Phase II. Thus there will be zeroes in this category.	Lithium Plus Placebo Phase I The outcome measures, including this one, are only relevant in Phase II. Thus there will be zeroes in this category.	Lithium Plus Fluoxetine Phase II n=29 Participants Participants randomized to this condition remained on active medications. However, the fluoxetine pills were made to look like the placebo pills, to maintain the double-blind.	Lithium Plus Placebo Phase II n=22 Participants Participants randomized to this condition were switched from fluoxetine to placebo. However, the placebo pills were made to look like the fluoxetine pills, to maintain the double-blind.
Number of Participants With an Onset of a Manic Episode Within 1 Year	0 Participants	0 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: 1 Year

Population: These are the patients who were randomly assigned, after responding to the medications provided in Phase I, to either remain on the same regime or have their fluoxetine switched to placebo.

Onsets of a hypomanic episodes were ascertained with the clinician-rated Hypomania Interview Guide and associated scoring rules.

Outcome measures

Outcome measures
Measure	Lithium Plus Fluoxetine Phase I The outcome measures, including this one, are only relevant in Phase II. Thus there will be zeroes in this category.	Lithium Plus Placebo Phase I The outcome measures, including this one, are only relevant in Phase II. Thus there will be zeroes in this category.	Lithium Plus Fluoxetine Phase II n=29 Participants Participants randomized to this condition remained on active medications. However, the fluoxetine pills were made to look like the placebo pills, to maintain the double-blind.	Lithium Plus Placebo Phase II n=22 Participants Participants randomized to this condition were switched from fluoxetine to placebo. However, the placebo pills were made to look like the fluoxetine pills, to maintain the double-blind.
Number of Participants With an Onset of a Hypomanic Episode Within 1 Year	0 Participants	0 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: 1 Year

Population: This was not a diagnosis that was recognized widely in the profession. Procedures for ascertaining such episodes were not consistent across the two performance sites. As a consequence the data obtained to document this outcome were unreliable.

Outcome measures

Outcome data not reported

Adverse Events

Lithium Plus Fluoxetine Phase I

Serious events: 20 serious events

Other events: 0 other events

Deaths: 0 deaths

Lithium Plus Placebo Phase I

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Lithium Plus Fluoxetine Phase II

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Lithium Plus Placebo Phase II

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Lithium Plus Fluoxetine Phase I n=177 participants at risk This is the condition that all participants started in. They were given Lithium plus Fluoxetine and, if they responded, they were asked to accept random assignment to Phase II.	Lithium Plus Placebo Phase I No one was on placebo in Phase I.	Lithium Plus Fluoxetine Phase II n=29 participants at risk These are the patients randomly assigned to stay on the fluoxetine in Phase II.	Lithium Plus Placebo Phase II n=22 participants at risk These are the patients randomly assigned to switch to placebo from fluoxetine in Phase II.
Psychiatric disorders Suicide ideation	1.1% 2/177 • Number of events 2 • 15 months All events were noted during the first phase of the study.	— 0/0 • 15 months All events were noted during the first phase of the study.	0.00% 0/29 • 15 months All events were noted during the first phase of the study.	0.00% 0/22 • 15 months All events were noted during the first phase of the study.
Psychiatric disorders Acute mood disturbance	1.1% 2/177 • Number of events 2 • 15 months All events were noted during the first phase of the study.	— 0/0 • 15 months All events were noted during the first phase of the study.	0.00% 0/29 • 15 months All events were noted during the first phase of the study.	0.00% 0/22 • 15 months All events were noted during the first phase of the study.
Gastrointestinal disorders Elevated Creatinine	0.56% 1/177 • Number of events 1 • 15 months All events were noted during the first phase of the study.	— 0/0 • 15 months All events were noted during the first phase of the study.	0.00% 0/29 • 15 months All events were noted during the first phase of the study.	0.00% 0/22 • 15 months All events were noted during the first phase of the study.
Gastrointestinal disorders Unable to swallow pills	0.56% 1/177 • Number of events 1 • 15 months All events were noted during the first phase of the study.	— 0/0 • 15 months All events were noted during the first phase of the study.	0.00% 0/29 • 15 months All events were noted during the first phase of the study.	0.00% 0/22 • 15 months All events were noted during the first phase of the study.
General disorders Hospitalized for dehydration	0.56% 1/177 • Number of events 1 • 15 months All events were noted during the first phase of the study.	— 0/0 • 15 months All events were noted during the first phase of the study.	0.00% 0/29 • 15 months All events were noted during the first phase of the study.	0.00% 0/22 • 15 months All events were noted during the first phase of the study.
Psychiatric disorders Hospitalized for overdose of benzodiazepines	1.1% 2/177 • Number of events 2 • 15 months All events were noted during the first phase of the study.	— 0/0 • 15 months All events were noted during the first phase of the study.	0.00% 0/29 • 15 months All events were noted during the first phase of the study.	0.00% 0/22 • 15 months All events were noted during the first phase of the study.
Psychiatric disorders Hospitalized for acute alcohol abuse	0.56% 1/177 • Number of events 1 • 15 months All events were noted during the first phase of the study.	— 0/0 • 15 months All events were noted during the first phase of the study.	0.00% 0/29 • 15 months All events were noted during the first phase of the study.	0.00% 0/22 • 15 months All events were noted during the first phase of the study.
Psychiatric disorders Hospitalized for acute substance abuse	0.56% 1/177 • Number of events 2 • 15 months All events were noted during the first phase of the study.	— 0/0 • 15 months All events were noted during the first phase of the study.	0.00% 0/29 • 15 months All events were noted during the first phase of the study.	0.00% 0/22 • 15 months All events were noted during the first phase of the study.
Nervous system disorders Lethargy, cognitive dulling	1.7% 3/177 • Number of events 3 • 15 months All events were noted during the first phase of the study.	— 0/0 • 15 months All events were noted during the first phase of the study.	0.00% 0/29 • 15 months All events were noted during the first phase of the study.	0.00% 0/22 • 15 months All events were noted during the first phase of the study.
Gastrointestinal disorders Nausea	0.56% 1/177 • Number of events 1 • 15 months All events were noted during the first phase of the study.	— 0/0 • 15 months All events were noted during the first phase of the study.	0.00% 0/29 • 15 months All events were noted during the first phase of the study.	0.00% 0/22 • 15 months All events were noted during the first phase of the study.
Musculoskeletal and connective tissue disorders Muscle stiffness	0.56% 1/177 • Number of events 1 • 15 months All events were noted during the first phase of the study.	— 0/0 • 15 months All events were noted during the first phase of the study.	0.00% 0/29 • 15 months All events were noted during the first phase of the study.	0.00% 0/22 • 15 months All events were noted during the first phase of the study.
Skin and subcutaneous tissue disorders Skin rash	0.56% 1/177 • Number of events 1 • 15 months All events were noted during the first phase of the study.	— 0/0 • 15 months All events were noted during the first phase of the study.	0.00% 0/29 • 15 months All events were noted during the first phase of the study.	0.00% 0/22 • 15 months All events were noted during the first phase of the study.
Nervous system disorders Tremors	1.7% 3/177 • Number of events 3 • 15 months All events were noted during the first phase of the study.	— 0/0 • 15 months All events were noted during the first phase of the study.	0.00% 0/29 • 15 months All events were noted during the first phase of the study.	0.00% 0/22 • 15 months All events were noted during the first phase of the study.

Other adverse events

Adverse event data not reported

Additional Information

Dr. Robert J. DeRubeis

UPenn

Phone: 215-573-5804

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place