The major purpose of the study is to help determine whether giving the combination of Elzasonan with Zoloft to people with depression is a better treatment than taking Zoloft alone. This study will also compare the safety and tolerability of Elzasonan and Zoloft combination to Zoloft alone or placebo.

Inclusion Criteria:

• Adult subjects, 18 years of age or older with a diagnosis of recurrent, moderate-to-severe MDD without psychotic features (DSM-IV 296.3x, with a HAMD17 score >= to 22 and CGI-S >=4.
• MDD must be the primary psychiatric disorder that motivated the subject to seek treatment and the current episode must be at least 1 month in duration but no longer than 6 months in duration.

Exclusion Criteria:

• Subjects who, in the investigator's judgement, would require treatment with electroconvulsive therapy (ECT), or antipsychotics, or would require a change in intensity of psychotherapy, or subjects who would require treatment with any other psychotherapeutic drugs during the course of the trial.
• Subjects who have ever been diagnosed with Panic Disorder, Post-Traumatic Stress Disorder, Obsessive-Compulsive Disorder, Bipolar Affective Disorder, Schizophrenia, Schizoaffective Disorder or othe Psychotic Disorder, MDD with a seasonal pattern, or Dissociative Disorders per DSM-IV criteria.