This study will use pre-treatment positron emission topography and functional magnetic resonance imaging scans of the brain to predict the most effective antidepressant treatment for people with major depressive disorder.

Major depressive disorder (MDD) is characterized by a combination of symptoms that can interfere with a person's ability to work, study, sleep, eat, and enjoy activities that were once pleasurable. Studies have shown that as little as 50% to 60% of individuals with MDD may respond to the first antidepressant medication prescribed. Currently psychiatrists lack tools that allow them to select the treatment plan that is most likely to benefit a particular individual. Some of the chemical abnormalities in the brains of people with MDD are detectable on positron emission topography (PET) scans. There are distinct differences in the PET scans of people with MDD who respond to treatment with a selective serotonin reuptake inhibitor (SSRI), people with MDD who do not respond to SSRI treatment, and people who do not have MDD. This study will use pretreatment PET and functional magnetic resonance imaging (fMRI) scans of the brain to predict which antidepressants will be most effective in people with MDD. This may help to reduce the trial and error currently associated with antidepressant treatment.

Participants in this study will undergo one PET scan and one fMRI scan. Within 3 days of the scan, all participants will begin taking escitalopram, an SSRI, at a daily dose of 10 mg. After 4 weeks, participants who have responded to treatment will continue for an additional 4 weeks at a 10-mg daily dose. Participants who do not respond to the medication at the end of 4 weeks will begin taking 20 mg of escitalopram per day. After 8 weeks, participants for whom escitalopram does not succeed in relieving MDD symptoms will take desipramine, a norepinephrine reuptake inhibitor (NRI), for an additional 8 weeks. If desipramine is ineffective, participants may receive any treatment agreed upon by their treating physicians. Study visits will occur weekly for the first 4 weeks and then every other week for the remainder of the study. At visits, participants will meet with their psychiatrists to discuss how they have been feeling since the last visit, review medication side effects, and complete depression rating questionnaires. Outpatient participants will receive a total of 5 months of treatment for depression, and inpatient participants will receive treatment until they have achieved remission.

• Drug: Escitalopram
• Drug: Desipramine

• Experimental: Participants will take escitalopram.
• Active Comparator: Participants will take escitalopram plus desipramine.

Inclusion Criteria:

• Diagnosis of major depressive disorder
• Currently depressed

Exclusion Criteria:

• Current abuse of or dependence on alcohol or another substance
• Pregnant, breastfeeding, or planning to become pregnant during the study
• Any unstable medical conditions