Double-Blind Treatment of Major Depressive Disorder With Vilazodone

The goal of the proposed study is to evaluate the efficacy and safety of switching to
Vilazodone in patients with major depressive disorder (MDD) who are unresponsive to, only
partially responsive to, or cannot tolerate a trial of the generic SSRI, citalopram (e.g.,
"partially responsive" means patients who report that their depressive symptoms have
improved through the use of citalopram but that significant depressive symptoms persist;
"cannot tolerate" refers to patient report of intolerable side effects that result in a
desire to discontinue the medication). Seventy-two subjects with major depressive disorder
who are still symptomatic or report intolerable side effects after a 6-week open-label trial
of citalopram 20mg/day ( i.e. who are not classified as responders) will be randomized to
receive a higher maximum dose of citalopram (40mg/day) or switch to vilazodone during the
randomization phase of the trial for 6 weeks. The hypothesis to be tested is that vilazodone
will result in greater rates of treatment response and be better tolerated compared to being
titrated up to a higher maximum dose (40mg/day) of citalopram. The proposed study will
provide needed data on the efficacy of switching antidepressants when individuals do not
fully respond to previous treatment or have intolerable side effects with a generic SSRI.

Inclusion Criteria:

1. Men and women age 18-60;

2. Primary diagnosis of MDD. Diagnosis of MDD will be made with the Structured Clinical
Interview for DSM-IV

3. Score of at least 23 on the Montgomery-Åsberg Depression Rating Scale

4. Treatment with citalopram at a dose no higher than 20mg/day for no longer than 4
weeks (subjects not currently taking an antidepressant will be started on citalopram
20mg/day for the 6-week open-label phase)

5. Ability to understand and sign the consent form.

Exclusion Criteria:

1. Unstable medical illness based on history or clinically significant abnormalities on
baseline physical examination (e.g., congestive heart failure, bradyarrhythmias).

2. Current pregnancy or lactation, or inadequate contraception in women of childbearing
potential

3. Subjects considered an immediate suicide risk based on the Columbia Suicide Severity
rating Scale (C-SSRS)

4. Past 3-month DSM-IV substance abuse or dependence

5. Illegal substance use based on urine toxicology screening

6. Initiation of psychotherapy or behavior therapy specifically for MDD from a mental
health professional within 3 months prior to study baseline

7. Initiation of any other psychotropic medication within 2 months prior to study
inclusion

8. Concomitant use of any antidepressant (except low dose doxepin, amitriptyline,
trazodone when used PRN as a hypnotic).

9. Concomitant use of medications that prolong the QT interval or are CYP2C19 inhibitors
(e.g., cimetidine)

10. Previous treatment with vilazodone

11. Diagnosis of bipolar I or II disorder or any psychotic disorder (anxiety disorders
will be allowed as long as MDD is considered the primary psychiatric disorder)

12. Cognitive impairment that interferes with the capacity to understand and
self-administer medication or provide written informed consent