Adding an Insulin-Sensitizing Medication to Depression Treatment for People Who Are Depressed and Overweight

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.

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