Depression, Major Depressive Disorder, Unipolar Depression
Conditions
Keywords
depression, serotonin, norepinephrine, SSRI, Wellbutrin, bupropion, executive function, residual symptoms
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).
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.
Interventions
DRUGWellbutrin
DRUGPlacebo
Sponsors
National Association for Research on Schizophrenia and Affective Disorders.
Mclean Hospital
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Wellbutrin-Placebo 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. | 15 |
| Placebo-Wellbutrin 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. | 17 |
| Total | 32 |
Baseline characteristics
| Characteristic | Wellbutrin-Placebo | Placebo-Wellbutrin | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 1 Participants | 0 Participants | 1 Participants |
| Age, Categorical Between 18 and 65 years | 14 Participants | 17 Participants | 31 Participants |
| Age, Continuous | 49 years | 47 years | 48 years |
| Region of Enrollment United States | 15 participants | 17 participants | 32 participants |
| Sex: Female, Male Female | 9 Participants | 8 Participants | 17 Participants |
| Sex: Female, Male Male | 6 Participants | 9 Participants | 15 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 15 | 0 / 17 |
| serious Total, serious adverse events | 0 / 15 | 0 / 17 |
Outcome results
Primary
Hamilton Depression Rating Scale (HAM-D)
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
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Wellbutrin First, Then Placebo | Hamilton Depression Rating Scale (HAM-D) | Baseline | 21.5 units on a scale |
| Wellbutrin First, Then Placebo | Hamilton Depression Rating Scale (HAM-D) | Follow-up at week 4 | 13.5 units on a scale |
| Placebo First, Then Wellbutrin | Hamilton Depression Rating Scale (HAM-D) | Baseline | 14 units on a scale |
| Placebo First, Then Wellbutrin | Hamilton Depression Rating Scale (HAM-D) | Follow-up at week 4 | 14 units on a scale |
Comparison: Null Hypothesis: There is no difference in the median HAM-D score between Wellbutrin-Placebo and Placebo-Wellbutrin treatment groupsp-value: 0.09Wilcoxon (Mann-Whitney)
Primary
Montgomery-Asberg Depression Rating Scale (MADRS)
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
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Wellbutrin First, Then Placebo | Montgomery-Asberg Depression Rating Scale (MADRS) | Baseline | 22.0 units on a scale |
| Wellbutrin First, Then Placebo | Montgomery-Asberg Depression Rating Scale (MADRS) | Follow-up at week 4 | 12.0 units on a scale |
| Placebo First, Then Wellbutrin | Montgomery-Asberg Depression Rating Scale (MADRS) | Baseline | 18.0 units on a scale |
| Placebo First, Then Wellbutrin | Montgomery-Asberg Depression Rating Scale (MADRS) | Follow-up at week 4 | 14.0 units on a scale |
Comparison: Null Hypothesis: There is no difference in the mean change MADRS score between Wellbutrin-Placebo and Placebo-Wellbutrin treatment groupsp-value: 0.04Wilcoxon (Mann-Whitney)