The Effects of Wellbutrin (Bupropion) on Residual and Cognitive Symptoms in SSRI-treated Depression
|Depression Major Depressive Disorder Unipolar Depression||Drug: Wellbutrin Drug: Placebo||Phase 3|
|Study Design:||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|
- Montgomery-Asberg Depression Rating Scale (MADRS) [ Time Frame: 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.
- Hamilton Depression Rating Scale (HAM-D) [ Time Frame: 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.
|Study Start Date:||August 2005|
|Study Completion Date:||December 2011|
|Primary Completion Date:||January 2010 (Final data collection date for primary outcome measure)|
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.
Other Name: bupropionDrug: 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.
Other Name: bupropionDrug: Placebo
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00125957
|United States, Massachusetts|
|Belmont, Massachusetts, United States, 02478|
|Principal Investigator:||Beth L Murphy, MD, PhD||Mclean Hospital|