Intervention: Vilazodone
Trial phase: Phase 3
ATC code: N06AX24
SMILES: N#Cc1ccc2[nH]cc(CCCCN3CCN(c4ccc5oc(C(N)=O)cc5c4)CC3)c2c1
Sex: All
Age groups: Adult | Older Adult
Healthy volunteers: No
Participants at risk: 22
Group description: vilazodone 40 mg/d arm (40 mg/d initiation and continuation dose for 8-week trial.

Vilazodone: All subjects will receive Vilazodone at 10, 20 or 40mg.
Eligibility criteria:
Inclusion Criteria:

Age 18-65 years inclusive
DSM-IV Diagnosis of major depressive disorder
If female, nonpregnant/nonlactating
If a sexually active female of reproductive potential, must be using adequate contraception (i.e., oral contraceptives, barrier protection, or prior tubal ligation)
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)
Lack of tolerability of antidepressants: Patient reports of side effects that are judged to be clinically meaningful by the investigator
HAMD item 2 score ≥ 2 at screening
Duration of current MDD ≥ 4 weeks and < 24 months

Exclusion Criteria:

Any Axis I disorder within previous six months of screening except Generalized Anxiety Disorder, Social Anxiety Disorder, Panic Disorder and Simple Phobias
MDD with postpartum onset, psychotic features or seasonal features
DSM-IV substance abuse or dependence in the previous 6 months
Medically unstable as judged by study investigators on clinical and/or laboratory findings
Lack of capacity to provide informed, written, consent to investigators
Previous intolerance to vilazodone or current use of vilazodone at screening or within 3 months of study entry
Significant suicide risk as judged by the investigator based on information collected on the Columbia Suicide Severity Rating Scale (CSSRS)
History of augmentation with atypical antipsychotics, lithium, T3 or another antidepressant within 3 months of screening
Failure of ≥ 3 adequate trials of different antidepressants for the current episode of MDD
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.