Depressive Disorder, Major
Conditions
Brief summary
We hypothesize that AndroGel may offer some relief to subjects with low or borderline testosterone levels who suffer from depression and have failed to respond to a trial of a standard antidepressant. During this nine week, outpatient, double-blind study, male subjects between the ages of 30 and 65 years with treatment-refractory depression and low or borderline low testosterone levels will be treated with either AndroGel or placebo. Following this nine week, double-blind phase, eligible subjects will have the option to continue into a six month, open-label phase during which time all subjects will receive the AndroGel patch.
Detailed description
We will recruit 100 men between the ages of 30 and 65 years who have treatment-refractory depression and low or borderline low testosterone levels for participation in this study. For a period of nine weeks subjects will receive double-blind treatment with either AndroGel (testosterone gel) or placebo. During this double-blind treatment phase subjects will come to McLean Hospital for a total of seven visits. Both clinical assessments (including ratings of your levels of depression and anxiety, quality of life, and visuospatial memory)and laboratory tests will be performed at these visits. Following the nine week, double-blind phase, eligible subjects may enter into a six month, open-label treatment phase in which all subject receive AndroGel. If you participate in the open-label phase, you will be asked to return to the site for 8 visits during the six month period.
Interventions
DRUGTestosterone gel
AndroGel 2.5g and 5g sachets at doses ranging from 10g/day for duration of trial.
DRUGPlacebo
Placebo
Sponsors
Solvay Pharmaceuticals
Mclean Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
MALE
Age
30 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Male * 30-65 years old * Taking at least one serotonergic antidepressant at adequate dose for at least six weeks but still meeting DSM-IV criteria for major depressive disorder within the past year * HAM-D score \>12
Exclusion criteria
* Current suicidal ideation * Substance abuse or dependence within the past year * Current or past psychotic symptoms * A history of bipolar disorder * A prostate-specific antigen (PSA) level greater than 4.0 ng/ml * Other clinically significant medical condition * A history of failing to show any clinically significant response to two or more adequate trials of different antidepressants.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 21-item Hamilton Depression Rating Scale Score (HAM-D) | 9 weeks (1-week placebo lead-in and 8 weeks of blinded medication treatment) | The HAM-D generates a score ranging from 0 (no depressive symptoms) to 64 (most severe depression). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Montgomery Asberg Depression Rating Scale (MADRS) | 9 weeks (1 week of placebo lead-in and 8 weeks of blinded medication treatment) | The Montgomery Asberg Depression Rating Scale (MADRS) is a clinician-assessed scale that rates depressive symptoms on a scale from 0 (no depressive symptoms) to 60 (maximal depressive symptoms). |
Countries
Israel, United States
Participant flow
Recruitment details
The study was conducted at two sites - McLean Hospital in Belmont Massachusetts, USA and the Chaim Sheba Medical Center in Tel Hashomer, Israel. Using advertisements at each site, we recruited men age 30-65 with major depressive disorder incompletely responsive to a serotonergic antidepressant, and showing a total testosterone level ≤ 350 ng/dL.
Pre-assignment details
At baseline, participants began a 1-week, single-blind placebo lead-in of one packet of placebo gel daily. Men exhibiting ≥ 50% improvement on either the Hamilton Depression Rating Scale (HAM-D) or Montgomery-Asberg Depression Rating Scale (MADRS) after placebo lead-in were withdrawn; all others were randomized to study medication.
Participants by arm
| Arm | Count |
|---|---|
| Testosterone Gel AndroGel, (1% testosterone transdermal gel), 2.5 g - 10 g daily | 50 |
| Placebo Gel Placebo gel identical in appearance to the testosterone gel | 50 |
| Total | 100 |
Baseline characteristics
| Characteristic | Testosterone Gel | Placebo Gel | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 50 Participants | 50 Participants | 100 Participants |
| Age Continuous | 50.6 years STANDARD_DEVIATION 8.2 | 49.9 years STANDARD_DEVIATION 7.1 | 50.3 years STANDARD_DEVIATION 7.7 |
| Region of Enrollment Israel | 21 participants | 26 participants | 47 participants |
| Region of Enrollment United States | 29 participants | 24 participants | 53 participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 50 Participants | 50 Participants | 100 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 3 / 50 | 0 / 50 |
| serious Total, serious adverse events | 0 / 50 | 0 / 50 |
Outcome results
Primary
21-item Hamilton Depression Rating Scale Score (HAM-D)
The HAM-D generates a score ranging from 0 (no depressive symptoms) to 64 (most severe depression).
Time frame: 9 weeks (1-week placebo lead-in and 8 weeks of blinded medication treatment)
Population: All of the 100 randomized participants are included in the Last Observation Carried Forward (LOCF) analysis presented here online, which provides the mean and SD of this outcome measure for each study arm. Full details of all analyses are provided in the published paper presenting the results of the study.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Testosterone Gel | 21-item Hamilton Depression Rating Scale Score (HAM-D) | 13.5 units on a scale | Standard Deviation 7.1 |
| Placebo Gel | 21-item Hamilton Depression Rating Scale Score (HAM-D) | 15.6 units on a scale | Standard Deviation 6.2 |
Comparison: Our primary analysis of efficacy was a mixed effects linear regression analysis comparing the rate of change of score on the HAM-D during the blinded treatment phase between groups. Our model for the mean of the outcome variable included terms for treatment, time (modeled as a continuous variable), and treatment-by-time. The measure of effect was the treatment-by-time interaction, which can be interpreted as the difference in slope with respect to time, of the outcome measure.p-value: 0.71mixed effects linear regression analysis
Secondary
Montgomery Asberg Depression Rating Scale (MADRS)
The Montgomery Asberg Depression Rating Scale (MADRS) is a clinician-assessed scale that rates depressive symptoms on a scale from 0 (no depressive symptoms) to 60 (maximal depressive symptoms).
Time frame: 9 weeks (1 week of placebo lead-in and 8 weeks of blinded medication treatment)
Population: All of the 100 randomized participants are included in the Last Observation Carried Forward (LOCF) analysis presented here online, which provides the mean and SD of this outcome measure for each study arm. Full details of all analyses are provided in the published paper presenting the results of the study.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Testosterone Gel | Montgomery Asberg Depression Rating Scale (MADRS) | 17.9 units on a scale | Standard Deviation 9 |
| Placebo Gel | Montgomery Asberg Depression Rating Scale (MADRS) | 19.9 units on a scale | Standard Deviation 8.4 |