Our goal is to study pharmacogenetics in Mexican-Americans, using depression treatments as a proof of the concept that pharmacogenetic approaches can be used to optimize treatment strategies for common and complex disorders in this population.

This is a single site, 8-week, double-blinded, placebo lead-in trial with fluoxetine or desipramine. All subjects have a comprehensive psychiatric and medical assessment, and if enrolled, continued with two consecutive phases of the study: 1) A one-week, single-blind placebo lead-in phase to eliminate placebo responders. 2) Subsequent random assignment to one of two treatment groups: fluoxetine 10-40 mg/day or desipramine 50-200 mg/day. Given the proven efficacy of these antidepressant medications, a placebo lead-in period followed by active treatment for all patients has been utilized in order to minimize human subjects at risk.

Inclusion Criteria: 1) At least 3 out of 4 grandparents born in Mexico [12]. 2) DSM-IV diagnosis of current, unipolar major depressive episode [13]. 3) 21-Item Hamilton Depression Rating Scale (HAM-D) [14] score of 18 or greater with item #1 (depressed mood) rated 2 or greater. 4) Age between 18-70 years.

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Exclusion Criteria: 1) Any axis I disorder other than major depressive disorder (e.g. dementia, psychotic illness, bipolar disorder, adjustment disorder) or primary anxiety disorders. 2) Active medical illnesses that could be related to the ongoing depression (e.g. untreated hypothyroidism, recent myocardial infarction or cerebrovascular accident within the past six months, uncontrolled hypertension or diabetes). 3) Current suicidal ideation with a plan and strong intent, or recent serious suicide attempt. 4) Pregnant or lactating women, or women of childbearing age not using contraception. 5) History of electroconvulsive therapy in the last six months. 6) Current use of medications with central nervous system activity which interfere with EEG activity (e.g. benzodiazepines) or any other antidepressant treatment within the 2 weeks prior to enrollment. 7) History of poor response to therapeutic treatment with desipramine or fluoxetine. 8) Illicit drug use and/or alcohol abuse in the last three months. 9) Current enrollment in counseling or psychotherapies.

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