Depression
Conditions
Keywords
Metabolic Diseases, Depressive Disorder, Major, Depressive Disorder, Glucose Metabolism Disorders, Depression Recurrence
Brief summary
This study will determine whether the drug metformin improves the effects of traditional antidepressant medications in people who are overweight.
Detailed description
Current depression treatments are not effective for approximately one-half of overweight people, and depression eventually returns in approximately one-third of those overweight people whose initial treatment is effective. One possible reason for these treatment failures is that overweight people often experience a condition called insulin resistance (IR), which can lead to type 2 diabetes, an associated disease that might also affect depression treatment. IR results in elevated blood sugar levels that may interfere with medications used to treat depression. Metformin, a medication commonly used to treat diabetes, reduces blood sugar levels. This study will examine whether taking metformin with the antidepressant medication sertraline will enhance the effectiveness of sertraline in people who are overweight and depressed. Participation in this study will last a total of 16 weeks and will include baseline testing and ten scheduled study visits. Participants will be randomly assigned to receive either sertraline and metformin or sertraline and placebo on a daily basis. The baseline visit will include the following tests and measures: an electrocardiogram (EKG), which will measure the electrical activity in the heart; an oral glucose tolerance test (OGTT), which will measure how a person's body breaks down glucose; a blood test, which will measure lipids, glycosylated hemoglobin (A1C), and other cardiometabolic risk factors; a dual energy x-ray absorptimetry (DEXA) scan, which will measure body fat; a pregnancy test for women; measurements of vital signs, height, weight, waist-to-hip ratio, and waist circumference; and questionnaires concerning health, medication use, physical activity, diet, and mood. Some of the questionnaires will be administered through interviews with a researcher. During the study visits, which will occur every 2 weeks, participants will complete questionnaires, unused medication will be collected, and new medication will be handed out. At Week 8, participants will provide an additional blood sample by finger stick.
Interventions
DRUGSertraline
50 mg once a day, which may be increased to 200 mg once a day
DRUGMetformin
Starting dose of 500 mg daily and increasing by 500 mg every 2 weeks to a total of 2,000 mg daily
Sponsors
National Institute of Mental Health (NIMH)
Washington University School of Medicine
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
20 Years to 60 Years
Healthy volunteers
No
Inclusion criteria
* Body mass index (BMI) greater than 28.7 * Positive screening for depression * Must live within 100 miles of the St. Louis metropolitan area
Exclusion criteria
* Pregnant or breastfeeding * Known hypersensitivity to sertraline or metformin * Recent history of heart attack or unstable heart disease * Severe liver disease or kidney impairment, defined by a serum creatine level above 3 mg/dL * Psychiatric disorder thought to affect management, such as schizophrenia, or alcohol or drug dependence
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change of Beck Depression Inventory-II Scores Over 16 Weeks | Measured at Baseline and 16 Weeks | Beck Depression Inventory-II (BDI) scores 0-63, minimum score =0, maximum score =63, Higher scores represent worse outcome. Baseline scores are compared to scores after treatment. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Sertraline Plus Metformin Participants will receive sertraline and metformin for 16 weeks.
Sertraline: 50 mg once a day, which may be increased to 200 mg once a day
Metformin: Starting dose of 500 mg daily and increasing by 500 mg every 2 weeks to a total of 2,000 mg daily | 104 |
| Sertraline Plus Placebo Participants will receive sertraline and placebo for 16 weeks.
Sertraline: 50 mg once a day, which may be increased to 200 mg once a day | 102 |
| Total | 206 |
Baseline characteristics
| Characteristic | Sertraline Plus Metformin | Sertraline Plus Placebo | Total |
|---|---|---|---|
| Age, Continuous | 43.67 years | 42.15 years | 42.91 years |
| Baseline Body Mass Index (BMI) | 38.53 kg/m^2 | 38.07 kg/m^2 | 38.30 kg/m^2 |
| Education | 14.64 years | 14.60 years | 14.62 years |
| Marital Status (married) | 48 participants | 45 participants | 93 participants |
| Region of Enrollment United States | 104 participants | 102 participants | 206 participants |
| Sex: Female, Male Female | 86 Participants | 85 Participants | 171 Participants |
| Sex: Female, Male Male | 18 Participants | 17 Participants | 35 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 44 / 104 | 41 / 102 |
| serious Total, serious adverse events | 0 / 104 | 1 / 102 |
Outcome results
Primary
Change of Beck Depression Inventory-II Scores Over 16 Weeks
Beck Depression Inventory-II (BDI) scores 0-63, minimum score =0, maximum score =63, Higher scores represent worse outcome. Baseline scores are compared to scores after treatment.
Time frame: Measured at Baseline and 16 Weeks
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Sertraline Plus Metformin | Change of Beck Depression Inventory-II Scores Over 16 Weeks | BDI Change Scores | 18.82 units on a scale | Standard Deviation 8.78 |
| Sertraline Plus Metformin | Change of Beck Depression Inventory-II Scores Over 16 Weeks | BDI at Baseline | 22.68 units on a scale | Standard Deviation 8 |
| Sertraline Plus Metformin | Change of Beck Depression Inventory-II Scores Over 16 Weeks | BDI at Week 16 | 3.86 units on a scale | Standard Deviation 4.57 |
| Sertraline Plus Placebo | Change of Beck Depression Inventory-II Scores Over 16 Weeks | BDI Change Scores | 17.50 units on a scale | Standard Deviation 7.94 |
| Sertraline Plus Placebo | Change of Beck Depression Inventory-II Scores Over 16 Weeks | BDI at Baseline | 22.03 units on a scale | Standard Deviation 7.71 |
| Sertraline Plus Placebo | Change of Beck Depression Inventory-II Scores Over 16 Weeks | BDI at Week 16 | 4.53 units on a scale | Standard Deviation 4.1 |
p-value: <0.05t-test, 2 sided