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

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ClinicalTrials.gov Identifier: NCT00834652
Recruitment Status : Completed
First Posted : February 3, 2009
Last Update Posted : August 10, 2015
Information provided by (Responsible Party):

Study Description
Brief Summary:
This study will determine whether the drug metformin improves the effects of traditional antidepressant medications in people who are overweight.

Condition or disease Intervention/treatment Phase
Depression Drug: Sertraline Drug: Metformin Phase 4

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 be divided into two phases lasting a total of 40 weeks. Phase 1 will last 16 weeks and include baseline testing and seven scheduled study visits. During this phase, 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, 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. At the end of Phase 1, participants will undergo repeat baseline testing.

Participants whose depression has improved after Phase 1 will be eligible to continue to Phase 2 of the study, which will determine the longer term effects of taking metformin with sertraline. Phase 2 of the study will last 24 weeks, with study visits occurring monthly. During the study visits, participants will complete questionnaires again, and medication will be collected and handed out. At Weeks 24 and 32, participants will provide blood samples by finger stick. After completing Phase 2, participants will again undergo repeat baseline testing.

Study Design

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 255 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Improving Depression Treatment Outcomes With an Insulin-Sensitizing Agent
Study Start Date : September 2007
Primary Completion Date : May 2013
Study Completion Date : May 2013

Resource links provided by the National Library of Medicine

U.S. FDA Resources

Arms and Interventions

Arm Intervention/treatment
Experimental: 1
Participants will receive sertraline and metformin.
Drug: Sertraline
50 mg once a day, which may be increased to 200 mg once a day
Other Name: Zoloft
Drug: Metformin
Starting dose of 500 mg daily and increasing by 500 mg every 2 weeks to a total of 2,000 mg daily
Placebo Comparator: 2
Participants will receive sertraline and placebo.
Drug: Sertraline
50 mg once a day, which may be increased to 200 mg once a day
Other Name: Zoloft

Outcome Measures

Primary Outcome Measures :
  1. Treatment of major depressive disorder (MDD) (acute phase) and prevention of MDD recurrence (maintenance phase) [ Time Frame: Measured over 40 weeks ]

Secondary Outcome Measures :
  1. Insulin resistance (IR), glycemic control, anthropometrics and body composition, and cortisol levels [ Time Frame: Measured over 40 weeks ]
  2. Value of reducing IR for predicting reduction in depression symptoms and time-to-recurrence (TTR) [ Time Frame: Measured over 40 weeks ]
  3. Sustained IR reduction during the depression-free interval following treatment [ Time Frame: Measured over 40 weeks ]

Eligibility Criteria

Information from the National Library of Medicine

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Ages Eligible for Study:   20 Years to 60 Years   (Adult)
Sexes Eligible for Study:   All
Accepts 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
Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00834652

United States, Missouri
Washington University School of Medicine
St. Louis, Missouri, United States, 63110
Sponsors and Collaborators
Washington University School of Medicine
National Institute of Mental Health (NIMH)
Principal Investigator: Patrick J. Lustman, PhD Washington University School of Medicine
More Information

Responsible Party: Washington University School of Medicine
ClinicalTrials.gov Identifier: NCT00834652     History of Changes
Other Study ID Numbers: R01MH081150 ( U.S. NIH Grant/Contract )
First Posted: February 3, 2009    Key Record Dates
Last Update Posted: August 10, 2015
Last Verified: August 2015

Keywords provided by Washington University School of Medicine:
Metabolic Diseases
Depressive Disorder, Major
Depressive Disorder
Glucose Metabolism Disorders
Depression Recurrence

Additional relevant MeSH terms:
Depressive Disorder
Behavioral Symptoms
Mood Disorders
Mental Disorders
Hypoglycemic Agents
Physiological Effects of Drugs
Antidepressive Agents
Psychotropic Drugs
Serotonin Uptake Inhibitors
Neurotransmitter Uptake Inhibitors
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents
Serotonin Agents