This research study is being conducted to find out if certain individuals benefit from taking medication for their depression with a low dose of the antidepressant medication Zoloft.

Researchers at the University of Pittsburgh Medical Center Health System are currently recruiting men and women, ages 18 to 60, to examine the effectiveness of the FDA-approved medication sertraline (Zoloft) for major depression.

Participants will be randomly assigned to one of two groups. Each group will begin and continue taking Zoloft at different doses. A physician will follow eligible participants weekly for approximately 12 weeks

Inclusion Criteria:

• Male or female ages 18-60;
• Current diagnosis of major depression, and a rating of ³15 on the HRS-D-25; - -Presence of significant, co-existing panic-agoraphobic spectrum symptoms,
• Absence of ongoing therapy with psychotropic medications (except for intermittent use of nonbenzodiazepine hypnotics) or willingness to be withdrawn from an ineffective ongoing antidepressant medications
• Physically healthy,
• Female participants of childbearing potential must be practicing a medically acceptable form of double-barrier birth control or using oral contraceptives such as birth control pills, implants, or injections;

Exclusion Criteria:

• Females who are pregnant or breast-feeding;
• History of suicide attempt in the 6 months prior to entry, active suicidal ideation, or significant suicide risk;
• History of hypersensitivity to or current use of sertraline;
• Unstable or untreated medical conditions,
• Participants who do not wish to discontinue current, ineffective antidepressant treatment;
• Participants who have recently begun psychotherapy (less than 3 months prior to study entry);
• Diagnosis of current panic disorder, psychosis, substance or alcohol abuse, anorexia, bulimia, dissociative, bipolar disorder, or any other psychiatric or medical illness that would interfere with the best treatment strategy for the potential participant.