This study will develop a new methodology to evaluate any treatment-emergent suicidal ideation that might occur when an antidepressant treatment has been started and/or during times when doses are increased in patients with major depressive disorder.

This is a pilot study to begin to develop a measurement procedure to help guide the clinical management of suicide risk in people beginning a type of antidepressant medication called a selective serotonin reuptake inhibitor (SSRI). The goals of the study are: 1) to identify the best method and assessment measures to evaluate the severity of suicidal ideation, 2) to determine the appropriate frequency and duration of assessment required to adequately evaluate this suicidal ideation, 3) to evaluate the presence of symptoms that are associated with suicidal ideation (such as anxiety, panic attacks, difficulty in sleeping) and 4) to identify the most critical time periods during which suicidal ideation appears or worsens (such as how long after initiation of treatment or dosage increase).

In all, 300 adult participants with major depressive disorder (MDD), between the ages of 18 and 75, may be enrolled at primary and psychiatric care sites across the US. All patients will be treated with an SSRI for eight weeks. The choice of SSRI used in treatment will be chosen by the study physician at each site. For this study, physicians will choose from the following six SSRIs: citalopram, escitalopram, sertraline, paroxetine, paroxetine-CR, and fluoxetine.

Patients beginning an SSRI for MDD in "real world" psychiatric and primary care settings, will have clinic visits and receive evaluations of their symptoms of depression, side effects, suicidal thinking and symptoms that are thought to be associated with suicidal risk, every other week for eight weeks. They will be evaluated by phone for symptoms and side effects each week they do not come to the clinic. They will also receive phone calls three times a week for the first two weeks of the study, after beginning the antidepressant, and after a dose increase to evaluate suicide risk.

Inclusion Criteria:

ONLY PATIENTS BEING TREATED AT THE PARTICIPATING CLINICS ARE ELIGIBLE FOR THIS STUDY

• Patients must be enrolled at the primary or specialty care site, and be planning to continue living in the area of that clinic throughout the study
• Patients must be 18-75 years old
• Patients must meet clinical criteria for MDD, based on clinical interview and DSM IV MDD checklist
• Screening HAM-D17 score greater than or equal to 14
• Patients must give written informed consent
• Patients with and without current suicidal ideation may be included in the study
• Patients must not have taken antidepressant medication for at least 2 weeks prior to screen (or 4 weeks in the case of fluoxetine).

Exclusion Criteria:

• Current substance abuse or dependence
• Two past SSRI treatment failures within the current episode, or last 2 years if chronic.
• Patients with a current Axis I diagnosis of Bipolar disorder or Schizophrenia
• Patients with a current Primary Axis I diagnosis of Obsessive-Compulsive disorder, Anorexia Nervosa or Bulimia.
• Women who are sexually active and who are not using adequate contraception, or who are pregnant, trying to become pregnant, or breast feeding.
• Patients with general medical conditions that contraindicate antidepressant medications
• Patients whose clinical status requires inpatient treatment at the time of baseline interview.
• Patients who cannot read and understand English since all research instruments are not yet translated and validated in Spanish or other languages.
• Some reports of SSRI-induced akathisia-like states have found them to be more highly correlated with either concurrent or previous treatment with a neuroleptic, even in patients with no history of movement disorders therefore, patients who have taken an anti-psychotic medication within 4 months of the screening visit will be excluded from the study.

Fifteen primary care and specialty care clinics across the country.