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

This study has been completed.
Sponsor:
Collaborator:
National Association for Research on Schizophrenia and Affective Disorders.
Information provided by (Responsible Party):
Beth L. Murphy MD, PhD, Mclean Hospital
ClinicalTrials.gov Identifier:
NCT00125957
First received: August 1, 2005
Last updated: August 5, 2014
Last verified: August 2014
  Purpose

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 Intervention Phase
Depression
Major Depressive Disorder
Unipolar Depression
Drug: Wellbutrin
Drug: Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: The Effects of Wellbutrin (Bupropion) on Residual and Cognitive Symptoms in SSRI-treated Depression

Resource links provided by NLM:


Further study details as provided by Mclean Hospital:

Primary Outcome Measures:
  • Montgomery-Asberg Depression Rating Scale (MADRS) [ Time Frame: Baseline and follow-up ] [ Designated as safety issue: No ]
    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.

  • Hamilton Depression Rating Scale (HAM-D) [ Time Frame: Baseline and follow-up ] [ Designated as safety issue: No ]
    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.


Enrollment: 32
Study Start Date: August 2005
Study Completion Date: December 2011
Primary Completion Date: January 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: 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 Name: bupropion
Drug: Placebo

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.

  Eligibility

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00125957

Locations
United States, Massachusetts
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
  More Information

Additional Information:
No publications provided

Responsible Party: Beth L. Murphy MD, PhD, Principal Investigator, Mclean Hospital
ClinicalTrials.gov Identifier: NCT00125957     History of Changes
Other Study ID Numbers: 2005P-000502
Study First Received: August 1, 2005
Results First Received: June 11, 2014
Last Updated: August 5, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by Mclean Hospital:
depression
serotonin
norepinephrine
SSRI
Wellbutrin
bupropion
executive function
residual symptoms

Additional relevant MeSH terms:
Depression
Depressive Disorder
Depressive Disorder, Major
Neurobehavioral Manifestations
Behavioral Symptoms
Mental Disorders
Mood Disorders
Nervous System Diseases
Neurologic Manifestations
Signs and Symptoms
Bupropion
Antidepressive Agents
Antidepressive Agents, Second-Generation
Central Nervous System Agents
Dopamine Agents
Dopamine Uptake Inhibitors
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents
Neurotransmitter Uptake Inhibitors
Pharmacologic Actions
Physiological Effects of Drugs
Psychotropic Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on November 27, 2014