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

August 1, 2005
August 5, 2014
August 2005
January 2010   (final data collection date for primary outcome measure)
  • 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.
  • MADRS overall and question-specific scores
  • neuropsychiatric assessment changes
  • hyperactivity measures
Complete list of historical versions of study NCT00125957 on ClinicalTrials.gov Archive Site
Not Provided
self-report
Not Provided
Not Provided
 
The Effects of Wellbutrin (Bupropion) on Residual and Cognitive Symptoms in SSRI-treated Depression
The Effects of Wellbutrin (Bupropion) on Residual and Cognitive Symptoms in SSRI-treated Depression

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).

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.

Interventional
Phase 3
Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
  • Depression
  • Major Depressive Disorder
  • Unipolar Depression
  • Drug: Wellbutrin
    Other Name: bupropion
  • Drug: Placebo
  • 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.
    Interventions:
    • Drug: Wellbutrin
    • 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.
    Interventions:
    • Drug: Wellbutrin
    • Drug: Placebo
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
32
December 2011
January 2010   (final data collection date for primary outcome measure)

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
Both
18 Years to 70 Years
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00125957
2005P-000502
No
Beth L. Murphy MD, PhD, Mclean Hospital
Mclean Hospital
National Association for Research on Schizophrenia and Affective Disorders.
Principal Investigator: Beth L Murphy, MD, PhD Mclean Hospital
Mclean Hospital
August 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP