Depressive Disorder Not Otherwise Specified, Dysthymia, Major Depression
Conditions
Keywords
Major Depression, Dysthymia, Depression Not Otherwise Specified, Dichotic Listening, Fluoxetine, Imipramine, Predictors
Brief summary
Depressed patients will have hearing tests and then be treated with up to three treatments (i.e., Fluoxetine, Imipramine) until remitted, to see whether test results predict specific outcomes.
Detailed description
100 depressed patients will be tested with verbal and nonverbal dichotic tests, and then treated sequentially with Fluoxetine and Imipramine until remitted. Preferential hemisphere for auditory processing will be correlated with treatment outcome.
Interventions
DRUGFluoxetine
Phase 1: Fluoxetine: wk 1: 10 mg/day; wks 2-3: 20 mg/day; wks 4-5: 40 mg/day; wk 6: 60 mg/day; wks 7-12: 80 mg/day \*All increases only if tolerated.
DRUGImipramine
Phase 2: Imipramine wk 1: 25 mg/day; wk 2: 50 mg/day; wk 3: 100 mg/day, 150 mg/day after 3 days; wk 4: 200 mg/day, 250 mg/day after 3 days; wks 5-6: 300 mg/day. \*All increases only if tolerated.
Sponsors
New York State Psychiatric Institute
Study design
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Ages between 18-65 * Meets Diagnostic and Statistical Manual, 4th Edition criteria for current Major Depression, Dysthymia or Depression Not Otherwise Specified
Exclusion criteria
* Known hearing impairment * Active suicidal ideation (history of suicide attempts will be evaluated on a case by case basis) * Hamilton Rating Scale for Depression, 17-item version \> 20 * Current (past six months) alcohol and/or drug abuse or dependence * Medical condition likely to require intervention contraindicated with study medication (e.g., known arrhythmia likely to be exacerbated by Imipramine) * Bipolar I * Psychosis * If currently taking antidepressants or mood stabilizers, cannot be off psychotropic medication for 7 weeks (10 weeks for Prozac) or felt to require other psychiatric medication (other than occasional sleep or Anxiety medication) * Premenopausal women not using known effective birth control * Not currently depressed (whether considered due to current treatment or not) * Nonresponse to adequate trial of both study medications (i.e., \> 4weeks on \> escitalopram 30 mg/d, and imipramine 200 mg/d); patients having an inadequate response to one study medication could be enrolled and receive the other; patients having responded to an adequate trial of either study medication would be offered a retrial; also excluded will be subjects having non responded to an adequate trial with citalopram (i.e., \> 4 weeks on \> citalopram 60 mg/d) * Left-handed
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Hamilton Depression Scale (HAM-D) | 6 weeks | The HAM-D is a commonly used measure of the severity of depression. While several versions exist consisting of different numbers of items, virtually all include the original 17. Each item is scored from on a 3 or 5 point scale (so, from 0-2 or 0-4), with 0 indicating the item is not present and the highest item score indicating it is present nearly all the time to the severest extent. Item scores are added to obtain a total HAM-D score. Minimum possible score is 0 (indicating none of the 17 items is present), maximal possible score is 52. By convention, scores of \<=7 are accepted as indicating remission and scores that have decreased \>= 50% from pre-treatment indicate positive response. Higher scores indicate worse depression, while lower scores indicate milder depression or lack of depressive symptoms. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Positive Response as Assessed by the Clinical Global Impression -Global Improvement Scale (CGI-I) | 6 weeks. | The CGI consists of two ratings: 1) Global Severity (CGI-S) and 2) Global Improvement (CGI-I), both having seven possible ratings, each from 1-7. Ratings on the CGI-S are: 1=No psychopathology 2=Minimal psychopathology 3=Mild psychopathology 4=Moderate psychopathology 5=Moderately severe psychopathology 6=Severe psychopathology 7 Extreme psychopathology. CGI-I ratings are rated for how the past week's psychopathology compares to the week immediately prior to start of treatment and includes: 1=Very much improved 2=much improved 3=minimally improved 4=Unchanged 5=minimally worse 6=much worse 7=very much worse. Scores on both thus range from 1-7 with lower scores indicating less psychopathology/greater improvement, respectively, and higher scores indicating more psychopathology/less improvement, respectively. We define response as a CGI-I of 1 or 2; nonresponse is all other ratings (i.e., CGI-I = 3 or higher. |
Countries
United States
Participant flow
Recruitment details
25 Screened. 4 did not return, 2 withdrew consent. Period 1 started with 17 participants available and eligible to participate in period I were treated with fluoxetine; 2 fluoxetine non-responders, 3 non-remiiters and 3/5 dropouts (n=8) continued to Period 2.
Pre-assignment details
17 participants available and eligible to participate in period I
Participants by arm
| Arm | Count |
|---|---|
| Fluoxetine / Imipramine Fluoxetine: wk 1: 10 mg/day; wks 2-3: 20 mg/day; wks 4-5: 40 mg/day; wk 6: 60 mg/day; wks 7-12: 80 mg/day \*All increases only if tolerated.
Imipramine: wk 1: 25 mg/day; wk 2: 50 mg/day; wk 3: 100 mg/day, 150 mg/day after 3 days; wk 4: 200 mg/day, 250 mg/day after 3 days; wks 5-6: 300 mg/day. \*All increases only if tolerated. | 25 |
| Total | 25 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Phase 1: Fluoxetine (1-12 Weeks) | Adverse Event | 4 |
| Phase 1: Fluoxetine (1-12 Weeks) | Lost to Follow-up | 1 |
| Phase 2: Imipramine (1-6 Weeks) | Lost to Follow-up | 1 |
Baseline characteristics
| Characteristic | Fluoxetine / Imipramine |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 25 Participants |
| Age, Continuous | 37 years STANDARD_DEVIATION 10 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 7 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 18 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 6 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 18 Participants |
| Sex: Female, Male Female | 13 Participants |
| Sex: Female, Male Male | 12 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 17 | 0 / 8 |
| other Total, other adverse events | 7 / 17 | 1 / 8 |
| serious Total, serious adverse events | 0 / 17 | 0 / 8 |
Outcome results
Primary
Hamilton Depression Scale (HAM-D)
The HAM-D is a commonly used measure of the severity of depression. While several versions exist consisting of different numbers of items, virtually all include the original 17. Each item is scored from on a 3 or 5 point scale (so, from 0-2 or 0-4), with 0 indicating the item is not present and the highest item score indicating it is present nearly all the time to the severest extent. Item scores are added to obtain a total HAM-D score. Minimum possible score is 0 (indicating none of the 17 items is present), maximal possible score is 52. By convention, scores of \<=7 are accepted as indicating remission and scores that have decreased \>= 50% from pre-treatment indicate positive response. Higher scores indicate worse depression, while lower scores indicate milder depression or lack of depressive symptoms.
Time frame: 6 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Fluoxetine | Hamilton Depression Scale (HAM-D) | 10 score on a scale | Standard Deviation 7 |
| Imipramine | Hamilton Depression Scale (HAM-D) | 9 score on a scale | Standard Deviation 7 |
Secondary
Number of Participants With Positive Response as Assessed by the Clinical Global Impression -Global Improvement Scale (CGI-I)
The CGI consists of two ratings: 1) Global Severity (CGI-S) and 2) Global Improvement (CGI-I), both having seven possible ratings, each from 1-7. Ratings on the CGI-S are: 1=No psychopathology 2=Minimal psychopathology 3=Mild psychopathology 4=Moderate psychopathology 5=Moderately severe psychopathology 6=Severe psychopathology 7 Extreme psychopathology. CGI-I ratings are rated for how the past week's psychopathology compares to the week immediately prior to start of treatment and includes: 1=Very much improved 2=much improved 3=minimally improved 4=Unchanged 5=minimally worse 6=much worse 7=very much worse. Scores on both thus range from 1-7 with lower scores indicating less psychopathology/greater improvement, respectively, and higher scores indicating more psychopathology/less improvement, respectively. We define response as a CGI-I of 1 or 2; nonresponse is all other ratings (i.e., CGI-I = 3 or higher.
Time frame: 6 weeks.
Population: Response Rate
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Fluoxetine | Number of Participants With Positive Response as Assessed by the Clinical Global Impression -Global Improvement Scale (CGI-I) | 7 Participants |
| Imipramine | Number of Participants With Positive Response as Assessed by the Clinical Global Impression -Global Improvement Scale (CGI-I) | 4 Participants |