The Effects of Wellbutrin (Bupropion) on Residual and Cognitive Symptoms in SSRI-treated Depression

• Sponsor: Mclean Hospital (Other)
• Overall Status: Completed
• CT.gov ID: NCT00125957
• Collaborator: National Association for Research on Schizophrenia and Affective Disorders. (Other)
• Enrollment: 32
• Location: 1
• Arms: 2
• Duration (Months): 76
• Patients Per Site Per Month: 0.4

Study Details

Study Description

Brief Summary

Many people with depression are treated with a serotonin-specific reuptake inhibitor anti-depressant (SSRI) and feel 'better'. Although many people feel 'better', they do not feel completely 'well'. Often, individuals continue to complain of cognitive problems such as lack of attention, diminished motivation, and impaired problem-solving. This study looks at whether residual and cognitive symptoms of depression in individuals are affected by the addition of Wellbutrin (bupropion).

Condition or Disease	Intervention/Treatment	Phase
Depression; Major Depressive Disorder; Unipolar Depression	Drug: Wellbutrin; Drug: Placebo	Phase 3

Detailed Description

As many as 65-75% of treated patients continue to experience residual symptoms of depression. Cognitive impairments feature frontal cognitive dysfunction. Many experts believe that executive functions are better predictors of functional level than psychiatric diagnoses.

Frontal cognitive impairment and changes in neuroimaging are seen in individuals depleted of tryptophan, a serotonin precursor. These cognitive changes do not improve following serotonin-specific reuptake inhibitor treatment and at least one study has found that executive dysfunction predicts non-response to fluoxetine. In many patients, remission of mood symptoms in depression requires medications to target non-serotonergic neurotransmitter systems. Brain areas mediating executive functions receive rich noradrenergic inputs, and norepinephrine is known to be intimately involved in many of the executive functions.

A better understanding of serotonergic and catecholaminergic interactions would enable evidence-based treatment of depression which maximizes executive cognitive functions. This study examines the hypothesis that individuals treated with Wellbutrin will have higher scores on tests of executive functions and lower scores on depression indices.

Study Design

• Study Type: Interventional
• Actual Enrollment: 32 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Triple (Participant, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: The Effects of Wellbutrin (Bupropion) on Residual and Cognitive Symptoms in SSRI-treated Depression
• Study Start Date: Aug 1, 2005
• Actual Primary Completion Date: Jan 1, 2010
• Actual Study Completion Date: Dec 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Wellbutrin first, then Placebo Subjects randomly assigned to the Wellbutrin then Placebo group will receive 100mg BID of Wellbutrin at the first visit following intake (Week 0).Subjects will be increased to 150mg Wellbutrin BID at Week 1 unless moderate/severe side effects are reported. If subject and rater classify 1+ symptom as severe or 2+ symptoms as moderate, subject will continue on 100mg of bupropion qAM. If subject and rater classify 1+ symptom as moderate or 2+ mild as moderate, subject will continue on Wellbutrin 100mg BID. At Week 4, subjects will cross-over to placebo and will continue to take placebo until Week 8.	Drug: Wellbutrin; Other Names: bupropion ; Drug: Placebo
Experimental: Placebo first, then Wellbutrin Subjects randomly assigned to the Placebo then Wellbutrin group will receive placebo until Week 4 when they will cross-over to active drug. At Week 4, subjects will be assigned 100mg Wellbutrin BID. At Week 5, Subjects will be increased to 150mg Wellbutrin BID unless moderate/severe side effects are reported. If subject and rater classify 1+ symptom as severe or 2+ symptoms as moderate, subject will continue on 100mg of Wellbutrin qAM. If subject and rater classify 1+ symptom as moderate or 2+ mild as moderate, subject will continue on bupropion 100mg BID. Subject will continue on the assigned dosage until Week 8 of study.	Drug: Wellbutrin; Other Names: bupropion ; Drug: Placebo

Outcome Measures

Primary Outcome Measures

1. Montgomery-Asberg Depression Rating Scale (MADRS) [Baseline and follow-up]

   Median total depression symptoms rating at baseline and follow-up visits. The MADRS consists o 10 questions assessing depression symptoms. All questions are scored on a 0-6 severity scale, with 0 being absent and 4 being most severe. Total scores can range from 0-60.

2. Hamilton Depression Rating Scale (HAM-D) [Baseline and follow-up]

   Median total depression ratings at baseline and follow-up using the HAM-D. The scale consists of 21 questions that assess depression symptoms. Questions 1-3, 7-11, 15, and 19 are rated on a scale of 0-4, with 0 being not present to and 4 being severe. Questions 4, 5, 12 - 14, 16-18 and 21 are rated from 0-2 with a score of 0 signifying the symptom is absent and a score of 2 as most severe. Item 20 is score on a scale of 0-3 with the same pattern of severity as all other questions. The total score for the HAM-D ranges from 0-63.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 70 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Depression

• SSRI-treated

Exclusion Criteria:

• Bipolar disorder

• Serotonin-norepinephrine reuptake inhibitor (SNRI) or bupropion treatment

• Treatment-resistant depression

• Seizure disorder

• Bulimia or anorexia nervosa

• Pregnancy

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	McLean Hospital	Belmont	Massachusetts	United States	02478

Sponsors and Collaborators

• Mclean Hospital
• National Association for Research on Schizophrenia and Affective Disorders.

Investigators

• Principal Investigator: Beth L Murphy, MD, PhD, Mclean Hospital

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Web site for McLean hospital with links to research.

Publications

None provided.

• Responsible Party: Beth L. Murphy MD, PhD, Principal Investigator, Mclean Hospital
• ClinicalTrials.gov Identifier: NCT00125957
• Other Study ID Numbers: 2005P-000502
• First Posted: Aug 2, 2005
• Last Update Posted: Aug 6, 2014
• Last Verified: Aug 1, 2014

• Keywords provided by Beth L. Murphy MD, PhD, Principal Investigator, Mclean Hospital: depression; serotonin; norepinephrine; SSRI; Wellbutrin; bupropion; executive function; residual symptoms
• Additional relevant MeSH terms: Neurobehavioral Manifestations; Depression; Depressive Disorder; Depressive Disorder, Major; Bupropion

Study Results

Participant Flow

Arm/Group Title	Wellbutrin First, Then Placebo	Placebo First, Then Wellbutrin
Arm/Group Description	Subjects randomly assigned to the Wellbutrin first, then Placebo group will receive 100mg BID of Wellbutrin at the first visit following intake (Week 0).Subjects will be increased to 150mg Wellbutrin BID at Week 1 unless moderate/severe side effects are reported. If subject and rater classify 1+ symptom as severe or 2+ symptoms as moderate, subject will continue on 100mg of bupropion qAM. If subject and rater classify 1+ symptom as moderate or 2+ mild as moderate, subject will continue on Wellbutrin 100mg BID. At Week 4, subjects will cross-over to placebo and will continue to take placebo until Week 8.	Subjects randomly assigned to the Placebo first, then Wellbutrin group will receive placebo until Week 4 when they will cross-over to active drug. At Week 4, subjects will be assigned 100mg Wellbutrin BID. At Week 5, Subjects will be increased to 150mg Wellbutrin BID unless moderate/severe side effects are reported. If subject and rater classify 1+ symptom as severe or 2+ symptoms as moderate, subject will continue on 100mg of Wellbutrin qAM. If subject and rater classify 1+ symptom as moderate or 2+ mild as moderate, subject will continue on bupropion 100mg BID. Subject will continue on the assigned dosage until Week 8 of study.
Period Title: First Intervention (3 Weeks)
STARTED	15	17
COMPLETED	15	17
NOT COMPLETED	0	0
Period Title: First Intervention (3 Weeks)
STARTED	15	17
COMPLETED	15	17
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Wellbutrin-Placebo	Placebo-Wellbutrin	Total
Arm/Group Description	Study subjects randomly assigned to this arm of the study will begin on active drug (100 mg twice daily (BID) of Wellbutrin) at week 1. At week 2, active drug is increased to 150mg BID unless subject reports one or more symptoms that are classified as moderate-severe. At week 4, subjects cross over to placebo for remainder of study. Subjects continue on placebo until end of study at week 8.	Subjects randomly assigned to this arm are given placebo at week 1. They will continue on placebo until week 4, at which time they will cross-over to Wellbutrin 100 mg twice daily (BID). At week 5, active drug is increased to 150mg BID unless subject reports one or more symptoms that are classified as moderate-severe. Subjects continue on active drug until end of study at week 8.	Total of all reporting groups
Overall Participants	15	17	32
Age (years) [Mean (Full Range) ]
Mean (Full Range) [years]	49	47	48
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	14 93.3%	17 100%	31 96.9%
>=65 years	1 6.7%	0 0%	1 3.1%
Sex: Female, Male (Count of Participants)
Female	9 60%	8 47.1%	17 53.1%
Male	6 40%	9 52.9%	15 46.9%
Region of Enrollment (participants) [Number]
United States	15 100%	17 100%	32 100%

Outcome Measures

1. Primary Outcome

Title	Montgomery-Asberg Depression Rating Scale (MADRS)
Description	Median total depression symptoms rating at baseline and follow-up visits. The MADRS consists o 10 questions assessing depression symptoms. All questions are scored on a 0-6 severity scale, with 0 being absent and 4 being most severe. Total scores can range from 0-60.
Time Frame	Baseline and follow-up

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Wellbutrin First, Then Placebo	Placebo First, Then Wellbutrin
Arm/Group Description	Subjects randomly assigned to Treatment A will receive Wellbutrin or placebo at Week 1 and will cross over to Wellbutrin or placebo at week 4.	Subjects randomly assigned to Treatment B will receive Wellbutrin or placebo at Week 1 and will cross over to Wellbutrin or placebo at week 4.
Measure Participants	15	17
Baseline	22.0	18.0
Follow-up at week 4	12.0	14.0

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Wellbutrin First, Then Placebo, Placebo First, Then Wellbutrin
	Comments	Null Hypothesis: There is no difference in the mean change MADRS score between Wellbutrin-Placebo and Placebo-Wellbutrin treatment groups
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	.04
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

2. Primary Outcome

Title	Hamilton Depression Rating Scale (HAM-D)
Description	Median total depression ratings at baseline and follow-up using the HAM-D. The scale consists of 21 questions that assess depression symptoms. Questions 1-3, 7-11, 15, and 19 are rated on a scale of 0-4, with 0 being not present to and 4 being severe. Questions 4, 5, 12 - 14, 16-18 and 21 are rated from 0-2 with a score of 0 signifying the symptom is absent and a score of 2 as most severe. Item 20 is score on a scale of 0-3 with the same pattern of severity as all other questions. The total score for the HAM-D ranges from 0-63.
Time Frame	Baseline and follow-up

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Wellbutrin First, Then Placebo	Placebo First, Then Wellbutrin
Arm/Group Description	Subjects randomly assigned to Treatment A will receive Wellbutrin or placebo at Week 1 and will cross over to Wellbutrin or placebo at week 4.	Subjects randomly assigned to Treatment B will receive Wellbutrin or placebo at Week 1 and will cross over to Wellbutrin or placebo at week 4.
Measure Participants	15	17
Baseline	21.5	14
Follow-up at week 4	13.5	14

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Wellbutrin First, Then Placebo, Placebo First, Then Wellbutrin
	Comments	Null Hypothesis: There is no difference in the median HAM-D score between Wellbutrin-Placebo and Placebo-Wellbutrin treatment groups
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.09
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

Adverse Events

Arm/Group Title	Bupropion-Placebo		Placebo-Bupropion
Arm/Group Description	Study subjects randomly assigned to this arm of the study will begin on active drug (100 mg BID bupropion) at week 1. At week 2, active drug is increased to 150mg BID unless subject reports one or more symptoms that are classified as moderate-severe. At week 4, subjects cross over to placebo for remainder of study. Subjects continue on placebo until end of study at week 8.		Subjects randomly assigned to this arm are given placebo at week 1. They will continue on placebo until week 4, at which time they will cross-over to bupropion 100 mg BID. At week 5, active drug is increased to 150mg BID unless subject reports one or more symptoms that are classified as moderate-severe. Subjects continue on active drug until end of study at week 8.
All Cause Mortality
	Bupropion-Placebo		Placebo-Bupropion
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Bupropion-Placebo		Placebo-Bupropion
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/15 (0%)		0/17 (0%)
Other (Not Including Serious) Adverse Events
	Bupropion-Placebo		Placebo-Bupropion
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/15 (0%)		0/17 (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.