This study will examine how brain activity is affected by antidepressant treatment and how changes in brain activity relate to treatment response in people with depression.

Depression is a serious medical illness that is characterized by a persistent sad, anxious, or empty mood. Many treatments have been shown to relieve depression, including both medications and behavioral therapies. No single treatment, however, works for everyone. Approximately half of the people being treated for depression do not respond to the first medication they try. Studies have shown that some people with depression show changes in brain activity within 2 weeks of starting treatment, even though symptoms do not change until later. People who do not respond to treatment, however, do not exhibit these changes in brain activity. More information is needed to understand the different ways in which people with depression respond to medication. This study will examine how brain activity is affected by antidepressant treatment and how changes in brain activity relate to treatment response in people with depression. It will also determine whether the brain testing involved in this study is burdensome to the participants.

Individuals interested in taking part in this 1-year study will first attend one screening visit to determine their eligibility for participation. Before beginning treatment, all participants will have an electroencephalogram (EEG) to determine baseline brain activity. Participants will then receive up to 12 weeks of treatment with escitalopram, an antidepressant medication. Study visits will be held every 2 to 3 weeks during this phase. At the Week 2 visit, participants will have another EEG. Participants who respond to escitalopram by the end of the treatment phase will be asked to participate in a 6-month follow-up phase, in which participants will be followed by their own personal physicians, but will have the option to continue treatment with escitalopram. Follow-up visits will be held at Months 3 and 6. Participants who do not respond to escitalopram by the end of the treatment phase will have another EEG, and will then receive up to 12 weeks of treatment with sertraline, another antidepressant medication. Study visits will be held every 2 to 3 weeks, and participants will have a fourth EEG at Week 2. Participants who respond to sertraline will then enter the 6-month follow-up phase, and may continue receiving sertraline. Participants who do not improve with sertraline will receive referrals for additional care outside of the study.

Inclusion Criteria:

• Currently an outpatient with nonpsychotic, unipolar major depressive disorder (MDD)
• Score of 14 or greater on the 17-item Hamilton Rating Scale for Depression (HAM-D17)
• Antidepressant treatment is deemed appropriate by the study clinician
• Willing to use an effective form of contraception throughout the study

Exclusion Criteria:

• Mentally or legally incapacitated
• Lifetime history of bipolar disorder, schizophrenia, schizoaffective disorder, MDD with psychotic features, or dementia
• Patients currently suffering from anorexia nervosa, bulimia nervosa, or obsessive compulsive disorder
• History of substance abuse disorder within 6 months prior to study entry
• Current suicidal ideation that would make outpatient treatment unsafe
• Past medication response that may make escitalopram or sertraline treatment unsafe or inappropriate (e.g., previous intolerance or lack of response to either medication)
• History of a failed treatment with escitalopram (40 mg or more) or sertraline (200 mg or more) during the current depressive episode
• Any medical conditions that would make treatment with escitalopram or sertraline medically inadvisable
• Unstable medical illness
• Unstable psychiatric illness likely to require inpatient treatment within the 6 months following study entry
• History of seizures, brain surgery, skull fracture, significant head trauma, or previous abnormal EEG
• Pregnant or plans to become pregnant within the 12 months following study entry
• Breastfeeding