Dysthymic Disorder
Conditions
Keywords
Dysthymic Disorder, Dysthymia, Depression, Chronic Depression, Wellbutrin XL
Brief summary
This is a ten-week, double-blind study of Wellbutrin XL in outpatients with dysthymic disorder, a form of low-grade chronic depression. We hypothesize that patients taking Wellbutrin XL will show greater improvement in depression symptoms and psychosocial functioning than patients taking placebo.
Detailed description
This is a ten-week, double-blind, placebo-controlled study designed to evaluate the tolerability, dosing and efficacy of Wellbutrin XL in outpatients who meet Diagnostic and Statistical Manual-IV criteria for early onset, primary type dysthymic disorder (low-grade chronic depression). It is hypothesized that patients taking Wellbutrin XL will show greater improvement in depression symptoms and psychosocial functioning than patients taking placebo.
Interventions
DRUGbupropion XL
Antidepressant medication
OTHERPlacebo
Placebo
Sponsors
GlaxoSmithKline
St. Luke's-Roosevelt Hospital Center
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Male and female outpatients 18-65 years of age. * Patients with a Diagnostic and Statistical Manual Fourth Edition (DSM-IV) diagnosis of dysthymic disorder, early onset. * Patients will have a total score of 12 or higher on the Hamilton Depression Scale (24 items) at baseline.
Exclusion criteria
* Patients with a DSM-IV diagnosis of Delirium, Dementia, and Amnestic, and other Cognitive Disorders. * Patients who are pregnant or nursing women. * Patients with a principal diagnosis meeting DSM-IV criteria for: Major Depressive disorder, Bipolar Disorder or cyclothymia, Schizophrenia, Delusional (Paranoid) Disorders and Psychotic Disorders not elsewhere classified, Severe Borderline Personality Disorder * Patients who have a current or prior diagnosis of Anorexia Nervosa or Bulimia * Patients who, within the past 6 months, met DSM-IV criteria for abuse of or dependence on any drug, including alcohol. * Patients who would pose a serious risk for suicide during the course of the study, as evidenced by one of the following: * Report of having a specific plan for killing themselves, * A score of 3 or higher on the Hamilton Depression Rating Scale item #3 as rated by the treating clinician at Week 0, (indicative of active suicidal thoughts or behaviors), or * A suicide attempt within the past 12 months requiring emergency room visit, medical or psychiatric hospitalization, or otherwise deemed to be life-threatening (e.g. an overdose of \> 1 week's dose of medication). * Patients with a history of recurrent Grand Mal seizures or at risk of Grand Mal seizures, and those with other medical conditions in which Wellbutrin XL would be contraindicated, including a history of head trauma. * Use of any psychotropic medication within 1 week of starting study medication * Use of a monoamine oxidase inhibitor (a type of antidepressant) (MAOI) within the 14 days prior to the initial dose of study medication. * Use of fluoxetine within 28 days of the initial dose of study medication. * Use of Zyban® or other forms of bupropion hydrochloride (i.e. Wellbutrin immediate release or Wellbutrin Sustained Release (SR)) within 2 weeks of the initial dose of medication. * Patients who have failed to respond to adequate trials (minimum of six consecutive weeks) of two different classes of antidepressant medication (see Table 1 for definitions of an adequate trial.) * Patients with unstable medical conditions, such as acute hyperthyroidism, uncorrected hypothyroidism, undiagnosed fever, uncontrolled angina, or any other serious medical illness, including any cardiovascular, hepatic, respiratory, hematological, endocrinologic or neurologic disease, or any clinically significant laboratory abnormality. * Patients who have begun a course of psychotherapy within 3 months of starting the study, or who plan to terminate an ongoing psychotherapy prior to the end of the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Hamilton Depression Rating Scale, 24 Items (HDRS) | 10 weeks | Widely used depression rating scale, with higher scores reflecting greater level of depression. Assesses suicidality which is a safety issue. This study used the 24 item version of the Hamilton Depression Rating Scale; item scores range from 0 to 4 on some items, 0 to 2 or 0 to 3 on other items; range of total score = 0 to 75, with higher score indicating worse depression Response (\>50% decrease) Remission (score\<=7) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Cornell Dysthymia Rating Scale (CDRS) | 10 weeks | A 24 item scale assessing symptoms of chronic depression. Scores from 0 to 96 with higher score indicating worse depression |
| Beck Depression Inventory (BDI) | 10 weeks | 21 item patient rated assessment of depression symptoms, with item scores ranging from 0 to 3. Total BDI scores can range from 0 to 63, with higher scores indicating worse depression. |
| Clinical Global Improvement (CGI) | 10 weeks | A global assessment of patient improvement, ranging from 1 (very much improved) to 7 (very much worse) |
| Global Assessment of Functioning Scale (GAFS) | 10 weeks | A clinician rated assessment of patient's overall functioning, ranging from 0 (severely impaired) to 100 (excellent functioning) |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Bupropion XL Treatment with active medication (bupropion XL) dose ranging from 150 to 450 mg/day
bupropion XL: Antidepressant medication | 11 |
| Placebo Placebo comparator, matching appearance with active medication, taken from 1 to 3 tablets per day | 7 |
| Total | 18 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Withdrawal by Subject | 1 | 1 |
Baseline characteristics
| Characteristic | Bupropion XL | Total | Placebo |
|---|---|---|---|
| Age, Continuous | 40.6 years STANDARD_DEVIATION 11.5 | 40.3 years STANDARD_DEVIATION 11.3 | 40.0 years STANDARD_DEVIATION 10.9 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants | 4 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 8 Participants | 14 Participants | 6 Participants |
| Region of Enrollment United States | 11 participants | 18 participants | 7 participants |
| Sex: Female, Male Female | 7 Participants | 11 Participants | 4 Participants |
| Sex: Female, Male Male | 4 Participants | 7 Participants | 3 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 6 / 11 | 3 / 7 |
| serious Total, serious adverse events | 0 / 11 | 0 / 7 |
Outcome results
Primary
Hamilton Depression Rating Scale, 24 Items (HDRS)
Widely used depression rating scale, with higher scores reflecting greater level of depression. Assesses suicidality which is a safety issue. This study used the 24 item version of the Hamilton Depression Rating Scale; item scores range from 0 to 4 on some items, 0 to 2 or 0 to 3 on other items; range of total score = 0 to 75, with higher score indicating worse depression Response (\>50% decrease) Remission (score\<=7)
Time frame: 10 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Bupropion XL | Hamilton Depression Rating Scale, 24 Items (HDRS) | 14.4 units on a scale | Standard Deviation 6.9 |
| Placebo | Hamilton Depression Rating Scale, 24 Items (HDRS) | 13.3 units on a scale | Standard Deviation 8.4 |
p-value: <0.05t-test, 2 sided
Secondary
Beck Depression Inventory (BDI)
21 item patient rated assessment of depression symptoms, with item scores ranging from 0 to 3. Total BDI scores can range from 0 to 63, with higher scores indicating worse depression.
Time frame: 10 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Bupropion XL | Beck Depression Inventory (BDI) | 8 units on a scale | Standard Deviation 4.4 |
| Placebo | Beck Depression Inventory (BDI) | 12.3 units on a scale | Standard Deviation 10.1 |
Secondary
Clinical Global Improvement (CGI)
A global assessment of patient improvement, ranging from 1 (very much improved) to 7 (very much worse)
Time frame: 10 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Bupropion XL | Clinical Global Improvement (CGI) | 2.8 units on a scale | Standard Deviation 1 |
| Placebo | Clinical Global Improvement (CGI) | 2.43 units on a scale | Standard Deviation 1 |
Secondary
Cornell Dysthymia Rating Scale (CDRS)
A 24 item scale assessing symptoms of chronic depression. Scores from 0 to 96 with higher score indicating worse depression
Time frame: 10 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Bupropion XL | Cornell Dysthymia Rating Scale (CDRS) | 26.4 units on a scale | Standard Deviation 10.8 |
| Placebo | Cornell Dysthymia Rating Scale (CDRS) | 24 units on a scale | Standard Deviation 14 |
Secondary
Global Assessment of Functioning Scale (GAFS)
A clinician rated assessment of patient's overall functioning, ranging from 0 (severely impaired) to 100 (excellent functioning)
Time frame: 10 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Bupropion XL | Global Assessment of Functioning Scale (GAFS) | 64 units on a scale | Standard Deviation 8.6 |
| Placebo | Global Assessment of Functioning Scale (GAFS) | 67 units on a scale | Standard Deviation 9.6 |