Depression
Conditions
Keywords
Depression, Major Depressive Disorder (MDD)
Brief summary
The investigators' hypotheses are: Low-dose testosterone augmentation improves depressive symptoms in women with Major Depressive Disorder (MDD) and antidepressant partial/nonresponse, adjunctive low-dose testosterone is safe and well-tolerated in women with MDD and antidepressant partial/nonresponse, and low-dose testosterone augmentation improves fatigue and sexual dysfunction.
Interventions
DRUGTestosterone
DRUGPlacebo
Sponsors
National Institutes of Health (NIH)
Lawley Pharmaceuticals
Massachusetts General Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
FEMALE
Age
21 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
1. Female, age 21-75 2. Major depressive disorder including MADRS\>/=12 3. Currently treated with an antidepressant monotherapy (1st, 2nd or 3rd trial in current episode), that has been taken at an adequate dose for at least six weeks.
Exclusion criteria
1. Serious suicide or homicide risk, as assessed by evaluating clinician 2. Unstable medical illness including cardiovascular, hepatic, renal, respiratory, endocrine, neurologic 3. Substance use disorder active within last six months, or clinical suspicion of ongoing substance use disorder at the discretion of the study clinician at time of screening based on history and/or laboratory results. 4. Any history of psychotic features, bipolar disorder, or primary obsessive compulsive disorder, as assessed by SCID 5. Currently treated with typical or atypical antipsychotic medications, or lithium 6. Untreated hypothyroidism. If treated hypothyroidism, change in levothyroxine dose within the prior 3 mos 7. Use of androgens, including testosterone, dehydroepiandrosterone (DHEA) and methyltestosterone, within the prior three months 8. Any investigational psychotropic drug within the last thirty days 9. In the judgment of the study clinician, unlikely to be able to participate safely throughout the study period (three or more episodes of self-harm in the past year, documented history of poor treatment adherence, or frequent missed appointments (\>50%) in the past year) 10. ALT \> 3x upper limit of normal or creatinine\> 3x upper limit 11. History of a hormone-responsive cancer
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Depressive Symptom Severity | Week 8 | Montgomery-Asberg Depression Rating Score (MADRS) Score: This scale measures depression symptom severity. Higher scores indicate more severe depression symptom severity. The score range is 0-60 units on a scale. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Fatigue | Week 8 | Brief Fatigue Inventory: This inventory measures fatigue severity. Higher scores indicate more severe fatigue. The range is 0-10 units on a scale. |
| Sexual Dysfunction | Week 8 | Derogatis Interview of Sexual Function (Total Score): This scale measures sexual function. Lower scores indicate worse sexual function. The score range for this questionnaire is 0-160. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Testosterone Testosterone cream will be applied to skin for 8 weeks. Starting dose is 10 mg daily and will be titrated based on blood levels.
Testosterone | 51 |
| Placebo Placebo cream will appear identical to the testosterone cream and will be applied to skin for 8 weeks.
Placebo | 50 |
| Total | 101 |
Baseline characteristics
| Characteristic | Testosterone | Total | Placebo |
|---|---|---|---|
| Age, Continuous | 46 years STANDARD_DEVIATION 14 | 47 years STANDARD_DEVIATION 14 | 48 years STANDARD_DEVIATION 14 |
| BMI | 28.2 kg/m2 STANDARD_DEVIATION 7.6 | 29.2 kg/m2 STANDARD_DEVIATION 7.8 | 30.3 kg/m2 STANDARD_DEVIATION 7.9 |
| Brief Fatigue Inventory | 6.2 units on a scale STANDARD_DEVIATION 1.9 | 5.9 units on a scale STANDARD_DEVIATION 2 | 5.6 units on a scale STANDARD_DEVIATION 2 |
| Derogatis Inventory of Sexual Function | 32.8 units on a scale STANDARD_DEVIATION 27.3 | 35.7 units on a scale STANDARD_DEVIATION 28.7 | 38.7 units on a scale STANDARD_DEVIATION 30.1 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 19 Participants | 40 Participants | 21 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 32 Participants | 61 Participants | 29 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Mean MADRS Score | 26.8 units on a scale STANDARD_DEVIATION 6.3 | 26.6 units on a scale STANDARD_DEVIATION 5.9 | 26.3 units on a scale STANDARD_DEVIATION 5.4 |
| Postmenopausal | 20 Participants | 46 Participants | 26 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 5 Participants | 5 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 | 3 Participants | 3 Participants |
| Race (NIH/OMB) White | 51 Participants | 92 Participants | 41 Participants |
| Region of Enrollment United States | 51 participants | 101 participants | 50 participants |
| Sex: Female, Male Female | 51 Participants | 101 Participants | 50 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 51 | 0 / 50 |
| other Total, other adverse events | 15 / 51 | 13 / 50 |
| serious Total, serious adverse events | 0 / 51 | 0 / 50 |
Outcome results
Primary
Depressive Symptom Severity
Montgomery-Asberg Depression Rating Score (MADRS) Score: This scale measures depression symptom severity. Higher scores indicate more severe depression symptom severity. The score range is 0-60 units on a scale.
Time frame: Week 8
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Testosterone | Depressive Symptom Severity | 15.3 units on a scale | Standard Error 1.4 |
| Placebo | Depressive Symptom Severity | 14.1 units on a scale | Standard Error 1.4 |
Secondary
Fatigue
Brief Fatigue Inventory: This inventory measures fatigue severity. Higher scores indicate more severe fatigue. The range is 0-10 units on a scale.
Time frame: Week 8
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Testosterone | Fatigue | 4.0 units on a scale | Standard Error 0.3 |
| Placebo | Fatigue | 3.7 units on a scale | Standard Error 0.4 |
Secondary
Sexual Dysfunction
Derogatis Interview of Sexual Function (Total Score): This scale measures sexual function. Lower scores indicate worse sexual function. The score range for this questionnaire is 0-160.
Time frame: Week 8
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Testosterone | Sexual Dysfunction | 45.1 units on a scale | Standard Error 4.7 |
| Placebo | Sexual Dysfunction | 47.5 units on a scale | Standard Error 5.4 |