Antidepressant Therapy in Treating Bipolar Type II Major Depression

• Sponsor: University of Pennsylvania (Other)
• Overall Status: Completed
• CT.gov ID: NCT00602537
• Collaborator: National Institute of Mental Health (NIMH) (NIH)
• Enrollment: 140
• Location: 1
• Arms: 2
• Duration (Months): 66
• Patients Per Site Per Month: 2.1

Study Details

Study Description

Brief Summary

This study will compare the safety and effectiveness of antidepressant therapy versus mood stabilizing therapy in treating people with bipolar type II major depression.

Condition or Disease	Intervention/Treatment	Phase
Bipolar Disorder; Depression	Drug: Venlafaxine; Drug: Lithium Carbonate	Phase 4

Detailed Description

Bipolar type II (BP II) depression affects 2.5% of the U.S. adult population. People with BP II disorder do not experience the manic episodes that are characteristic of BP I disorder, but rather they experience more modest mood swings with a greater number of major depressive episodes (MDEs). These MDEs are associated with high rates of disease and death. The treatment of BP II depression remains a challenge for clinicians. Mood stabilizer (MS) monotherapy is the current recommended treatment for BD II MDE, but there is reason to believe that antidepressant drug (AD) monotherapy could also be an effective treatment. However, concerns over AD-induced manic switch episodes have limited the use of this treatment option. Preliminary studies using the ADs fluoxetine or venlafaxine have shown success in treating and lowering the manic switch rate of those with BP II MDE. This study will compare the safety and effectiveness of AD monotherapy versus MS monotherapy in treating people with BP II major depression.

Participation in this double-blind study will last up to 9 months. After screening, which includes a medical and psychiatric history review, a physical exam, an electrocardiogram (EKG) test, clinical laboratory tests, a urine-based drug test, and a pregnancy test if applicable, participants will be randomly placed into one of two treatment groups. Participants in the AD monotherapy group will be treated with venlafaxine, and participants in the MS monotherapy group will be treated with lithium. During the first 12 weeks, there will be a total of nine study visits lasting between 45 and 60 minutes. In these visits, participants will receive their study drug and will undergo various assessments, including a review of medication history and side effects, vital sign measurements, and questionnaires about depression and daily functioning. Blood samples will be taken at most visits.

Participants who respond well during the initial 12 weeks of therapy with either drug will have the option to continue treatment for 6 additional months. During this time, participants will continue their assigned treatment and will attend five monthly study visits that will repeat previous assessments and procedures.

For information on a related study, please follow this link:

http://clinicaltrials.gov/show/NCT00044616

Study Design

• Study Type: Interventional
• Actual Enrollment: 140 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Treatment of Bipolar Type II Major Depression
• Study Start Date: Dec 1, 2007
• Actual Primary Completion Date: Jun 1, 2013
• Actual Study Completion Date: Jun 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Experimental: I Antidepressant therapy	Drug: Venlafaxine; 75 to 375 mg
Active Comparator: II Mood stabilizer therapy	Drug: Lithium Carbonate; 300 to 2400 mg

Outcome Measures

Primary Outcome Measures

1. Depressive Relapse [Weeks 16, 20, 24, 30, 36]

   These subjects must be responders. Outcome measures were obtained at continuation weeks. Participant would be considered "depressive relapse" if relapsed by any of these times.

Secondary Outcome Measures

1. Treatment-Emergent Mood Symptoms [Measured at Weeks 12 and 36]

   These subjects must be responders.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Meets DSM-IV criteria for Axis I bipolar II disorder

• Meets DSM-IV criteria for Axis I major depressive episode

• Score of 16 on 17-item HAM-D rating scale

• Not taking monoamine oxidase inhibitors (MAOI) for more than 2 weeks prior to study entry

• Willing to use an effective form of birth control throughout the study

Exclusion Criteria:

• History of mania

• Current primary Axis I diagnosis other than bipolar II disorder

• Alcohol or drug dependence within 3 months prior to study entry

• Contraindication to treatment with venlafaxine or lithium

• Unstable medical condition (e.g., thyroid disease, hypertension, or angina pectoris)

• Pregnant or breastfeeding

• Experiencing suicidal thoughts

• Requires hospitalization

• Requires concurrent neuroleptic or MS therapy

• Requires concurrent AD therapy

• Current psychotic features

• Inadequate trial of therapy at the time of initial screening visit

• History of intolerance to either venlafaxine or lithium

• Unlikely to participate in a 36-week trial

• Presence of apparent secondary gain

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Depression Research Unit - University of Pennsylvania	Philadelphia	Pennsylvania	United States	19104-3309

Sponsors and Collaborators

• University of Pennsylvania
• National Institute of Mental Health (NIMH)

Investigators

• Principal Investigator: Robert J. DeRubeis, PhD, University of Pennsylvania

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: University of Pennsylvania
• ClinicalTrials.gov Identifier: NCT00602537
• Other Study ID Numbers: R01MH060353-02; R01MH060353-02; 2R01MH060353-06A2
• First Posted: Jan 28, 2008
• Last Update Posted: Apr 25, 2017
• Last Verified: Apr 1, 2017

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Keywords provided by University of Pennsylvania: Bipolar Type II Disorder; Hypomania; Antidepressant; Mood Stabilizer; Venlafaxine; Lithium Carbonate; Major Depressive Episode; Hypomanic Episodes; Prevention of Depression Relapse
• Additional relevant MeSH terms: Depression; Depressive Disorder; Bipolar Disorder; Lithium Carbonate; Venlafaxine Hydrochloride

Study Results

Participant Flow

Arm/Group Title	Antidepressant Therapy	Mood Stabilizer Therapy
Arm/Group Description	Venlafaxine: 75 to 375 mg	Lithium Carbonate: 300 to 2400 mg
Period Title: 12 Week Double Blind Comparison
STARTED	65	64
Responded	44	22
COMPLETED	42	17
NOT COMPLETED	23	47
Period Title: 12 Week Double Blind Comparison
STARTED	42	17
COMPLETED	31	14
NOT COMPLETED	11	3

Baseline Characteristics

Arm/Group Title	Antidepressant Therapy	Mood Stabilizer Therapy	Total
Arm/Group Description	Venlafaxine: 75 to 375 mg	Lithium Carbonate: 300 to 2400 mg	Total of all reporting groups
Overall Participants	42	17	59
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	41.8 (11.4)	43.1 (15.2)	42.2 (12.5)
Sex: Female, Male (Count of Participants)
Female	24 57.1%	8 47.1%	32 54.2%
Male	18 42.9%	9 52.9%	27 45.8%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	1 2.4%	0 0%	1 1.7%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	4 9.5%	5 29.4%	9 15.3%
White	37 88.1%	12 70.6%	49 83.1%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%
Inter-episode recovery (Count of Participants)
Count of Participants [Participants]	14 33.3%	2 11.8%	16 27.1%
Age 1st major depressive episode (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	19.0 (7.7)	17.4 (5.4)	18.5 (7.1)
Age 1st hypomanic episode (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	20.7 (7.6)	16.2 (10.0)	19.4 (8.5)
Number of lifetime major depressive episodes (Episodes) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Episodes]	28.4 (50.4)	33.3 (49.7)	29.9 (11.0)
Number of lifetime hypomanic episodes (Episodes) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Episodes]	45.8 (66.4)	32.2 (47.3)	41.9 (61.4)
Baseline HRSD score (units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on a scale]	19.4 (3.6)	18.8 (3.3)	19.2 (3.5)
Baseline YMRS score (units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on a scale]	0.8 (1.7)	0.6 (1.4)	0.8 (1.6)
Duration major depressive episode (months) [Median (Full Range) ]
Median (Full Range) [months]	4.5	4.0	4
Baseline HRSD Score for Follow-Up study (units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on a scale]	4.3 (2.8)	4.4 (3.4)	4.3 (2.9)

Outcome Measures

1. Primary Outcome

Title	Depressive Relapse
Description	These subjects must be responders. Outcome measures were obtained at continuation weeks. Participant would be considered "depressive relapse" if relapsed by any of these times.
Time Frame	Weeks 16, 20, 24, 30, 36

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Antidepressant Therapy	Mood Stabilizer Therapy
Arm/Group Description	Venlafaxine: 75 to 375 mg	Lithium Carbonate: 300 to 2400 mg
Measure Participants	40	15
Count of Participants [Participants]	3 7.1%	4 23.5%

2. Secondary Outcome

Title	Treatment-Emergent Mood Symptoms
Description	These subjects must be responders.
Time Frame	Measured at Weeks 12 and 36

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Antidepressant Therapy	Mood Stabilizer Therapy
Arm/Group Description	Venlafaxine: 75 to 375 mg	Lithium Carbonate: 300 to 2400 mg
Measure Participants	40	15
Any depression	15 35.7%	11 64.7%
Any subsyndromal hypomania	3 7.1%	3 17.6%

Adverse Events

Arm/Group Title	Antidepressant Therapy		Mood Stabilizer Therapy
Arm/Group Description	Venlafaxine: 75 to 375 mg		Lithium Carbonate: 300 to 2400 mg
All Cause Mortality
	Antidepressant Therapy		Mood Stabilizer Therapy
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Antidepressant Therapy		Mood Stabilizer Therapy
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/65 (0%)		0/64 (0%)
Other (Not Including Serious) Adverse Events
	Antidepressant Therapy		Mood Stabilizer Therapy
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/65 (0%)		0/64 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.