Switching From Generic Selective Serotonin Reuptake Inhibitors (SSRIs) and Selective Serotonin and Norepinephrine Reuptake Inhibitors (SNRIs) to Three Different Dose Initiation Strategies With Vilazodone

Inclusion Criteria: 1. Age 18-65 years inclusive 2. DSM-IV Diagnosis of major depressive disorder 3. If female, nonpregnant/nonlactating 4. If a sexually active female of reproductive potential, must be using adequate contraception (i.e., oral contraceptives, barrier protection, or prior tubal ligation) 5. Inadequate response to antidepressants: having a score of ≥14 on the 17-item HAMD or a CGI-S score of ≥ 3 after a retrospective confirmation of an adequate trial of a single antidepressant (defined as an 6-week trial of acceptable therapeutic dose \[40 mg of fluoxetine, paroxetine 30 mg of citalopram, 20 mg of escitalopram, 37.5 mg of paroxetine CR, 150 mg of sertraline, 100 mg of fluvoxamine, 225 mg of venlafaxine XR) 6. Lack of tolerability of antidepressants: Patient reports of side effects that are judged to be clinically meaningful by the investigator 7. HAMD item 2 score ≥ 2 at screening 8. Duration of current MDD ≥ 4 weeks and \< 24 months Exclusion Criteria: 1. Any Axis I disorder within previous six months of screening except Generalized Anxiety Disorder, Social Anxiety Disorder, Panic Disorder and Simple Phobias 2. MDD with postpartum onset, psychotic features or seasonal features 3. DSM-IV substance abuse or dependence in the previous 6 months 4. Medically unstable as judged by study investigators on clinical and/or laboratory findings 5. Lack of capacity to provide informed, written, consent to investigators 6. Previous intolerance to vilazodone or current use of vilazodone at screening or within 3 months of study entry 7. Significant suicide risk as judged by the investigator based on information collected on the Columbia Suicide Severity Rating Scale (CSSRS) 8. History of augmentation with atypical antipsychotics, lithium, T3 or another antidepressant within 3 months of screening 9. Failure of ≥ 3 adequate trials of different antidepressants for the current episode of MDD 10. Concomitant medications: All medications for pre existing medical conditions will be permitted to continue unchanged provided subjects are on a stable dose of at least 12 weeks. Subjects on concomitant mood stabilizers or atypical antipsychotics will require a 2-week washout prior to screening visit. Subjects on a minimum of 3 month of stable dose of hypnotics (e.g. zolpidem 10 mg per day or benzodiazepine dose of ≤ 2 mg per day of lorazepam or trazodone ≤ 100 mg per day or quetiapine ≤ 100 mg per day) will be allowed to continue their hypnotic medication at the same dose. Quetiapine at doses ≤ 100 mg per day is appropriate only for hypnotic effects. Over the counter medications will be permitted if in the opinion of the investigator, they are not considered to have any significant impact on the study. Any medication that has the potential to cause a clinical significant drug interaction with vilazodone in the judgment of the investigator will require a washout.