The purpose of the study is to evaluate the efficacy and safety of flexible doses of escitalopram (Lexapro) compared to sertraline (Zoloft) for treatment of Dysthymic Disorder.

Dysthymic Disorder is a common, chronic type of depression that is often seen as a mild condition and is under-treated. Because of its chronic course, it is often complicated by episodes of major depression and may require long-term treatment.

This is a twelve week study during which daily doses of escitalopram (10-20 mg) or sertraline (50-200 mg) will be given to outpatients meeting criteria for Dysthymic Disorder or Double Depression. Medications will be assigned 1:1 and clinicians will be blinded to treatment. Efficacy will be based on scores for the Hamilton Depression Rating Scale, patient subjective reporting, and clinician observation. The study will have a total of 8 visits over 12 weeks, with a one-week medication taper period at the end. Subjects will have a physical exam, labs, and vital signs monitored at first visit and vital signs monitored at every subsequent visit. Women of childbearing potential must have a negative urine pregnancy test at screening. All subjects will remain on the lowest medication dose for the first four weeks of the study.

Inclusion Criteria:

• Primary diagnosis of Dysthymic Disorder or Major Depressive Disorder with Antecedent Dysthymia
• Women of childbearing potential must have negative pregnancy test at screen and agree to practice acceptable method of birth control
• Score of at least 12 on the 24-item Hamilton Depression Scale at study entry
• Initial screening labs grossly within normal limits
• Signed written informed consent

Exclusion Criteria:

• Other Axis-I diagnoses such as delirium, dementia, and substance dependence (active in last year) or any substance abuse including alcohol within the past six months
• Actively suicidal
• CNS neoplasm, demyelinization disease, degenerative neurological disorder, active CNS infection, or any progressive CNS disorder that may confound interpretation of study results
• History of seizure disorder, or EEG showing paroxysmal activity or head CT showing gross structural abnormality
• Acute systemic medical disorder
• Use of any psychotropic medications within 2 weeks prior to screen or 4 weeks prior to screen in the case of fluoxetine
• Current use of any herbal medication such as St. John's wort,
• Uncontrolled renal, hepatic, endocrine, cardiovascular, pulmonary, immunological, hematological or gastrointestinal disease
• Any other abnormal medical screening tests judged by the investigator to be clinically significant
• Received any experimental medication within 30 days prior to study entry
• Patients presently in or soon to be starting psychotherapy
• Prior treatment non-response to an adequate trial of citalopram, escitalopram, or sertraline
• History of allergy to citalopram, escitalopram or sertraline