Double-Blind Treatment of Major Depressive Disorder With Vilazodone

• Sponsor: University of Chicago (Other)
• Overall Status: Completed
• CT.gov ID: NCT01742832
• Collaborator: (none)
• Enrollment: 79
• Location: 1
• Arms: 2
• Duration (Months): 34
• Patients Per Site Per Month: 2.3

Study Details

Study Description

Brief Summary

The purpose of this study is to evaluate the safety and effectiveness of vilazodone for the treatment of major depressive disorder versus citalopram. Doctors want to determine if vilazodone is effective for the treatment of major depressive disorder in those who have not responded to generic selective serotonin reuptake inhibitors (SSRI), which is a class of anti-depressant drugs such as Prozac, Lexapro, Paxil, or Zoloft. Both vilazodone and citalopram have been approved for the treatment of major depressive disorder. This research is being done because the researchers want to find out if vilazodone works in reducing the symptoms of depression significantly more than a generic SSRI.

Condition or Disease	Intervention/Treatment	Phase
Major Depressive Disorder	Drug: Vilazodone; Drug: Citalopram	Phase 2

Detailed Description

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 79 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Triple (Participant, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Double-Blind Switch Study of Vilazodone in the Treatment of Major Depressive Disorder Following Partial Response to or Inability to Tolerate a Generic SSRI
• Study Start Date: May 1, 2013
• Actual Primary Completion Date: Mar 1, 2016
• Actual Study Completion Date: Mar 1, 2016

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Vilazodone A fixed dose titration (with doses ranging from 10mg to 40mg/day) will be used. Subjects will take 10mg/day for 1 week, 20mg/day for 1 week and then 40mg/day.	Drug: Vilazodone; A fixed dose titration (with doses ranging from 10mg to 40mg/day) will be used. Subjects will take 10mg/day for 1 week, 20mg/day for 1 week and then 40mg/day.
Placebo Comparator: Citalopram For those assigned to citalopram, the dose of citalopram will be maximized to 40mg/day. For those assigned to vilazodone, their citalopram dose will be maintained at 20mg/day for 1 week, then reduced to 10mg/day for 1 week, then switched to vilazodone 10mg/day.	Drug: Citalopram; For those assigned to citalopram, the dose of citalopram will be maximized to 40mg/day. For those assigned to vilazodone, their citalopram dose will be maintained at 20mg/day for 1 week, then reduced to 10mg/day for 1 week, then switched to vilazodone 10mg/day.

Outcome Measures

Primary Outcome Measures

1. Montgomery-Åsberg Depression Rating Scale (MADRS) [Baseline and final MADRS scores during the double-blind phase.]

   The entire study will last 18 weeks. For the first 6 weeks, subjects will come in once every 2 weeks. For the next 4 weeks, subjects will come in once per week. For the next 6 weeks, subjects will come in once every 2 weeks. The final visit will come 2 weeks later for a total of 11 visits where the MADRS will be administered. Only the baseline and final (last observation) assessments for the outcome measure was used in determining results, thus these are the only values included. MADRS scores range from 0-60, with higher scores indicating a greater level of severity. No subscales were used.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 60 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Chicago	Chicago	Illinois	United States	60615

Sponsors and Collaborators

• University of Chicago

Investigators

• Principal Investigator: Jon Grant, MD,JD,MPH, University of Chicago

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Jon Grant, Professor of Psychiatry, University of Chicago
• ClinicalTrials.gov Identifier: NCT01742832
• Other Study ID Numbers: 2012MDDVilaz
• First Posted: Dec 5, 2012
• Last Update Posted: May 30, 2017
• Last Verified: Apr 1, 2017

• Keywords provided by Jon Grant, Professor of Psychiatry, University of Chicago: Vilazodone; Citalopram; Major Depressive Disorder
• Additional relevant MeSH terms: Disease; Depressive Disorder; Depression; Depressive Disorder, Major; Citalopram; Vilazodone Hydrochloride

Study Results

Participant Flow

Recruitment Details	The Enrollment number in the Protocol Section (79) conflicts with the number of participants Started in the Participant Flow module (48) because the assessment of interested was the double-blind portion of the study. Only 48 subjects were enrolled in this phase of the study, while 79 were enrolled in the preliminary open-label phase.
Pre-assignment Detail	The results reported are for the double-blind phase, not the open label citalopram phase of the study.

Arm/Group Title	Vilazodone	Citalopram
Arm/Group Description	A fixed dose titration (with doses ranging from 10mg to 40mg/day) will be used. Subjects will take 10mg/day for 1 week, 20mg/day for 1 week and then 40mg/day. Vilazodone: A fixed dose titration (with doses ranging from 10mg to 40mg/day) will be used. Subjects will take 10mg/day for 1 week, 20mg/day for 1 week and then 40mg/day.	For those assigned to citalopram, the dose of citalopram will be maximized to 40mg/day. For those assigned to vilazodone, their citalopram dose will be maintained at 20mg/day for 1 week, then reduced to 10mg/day for 1 week, then switched to vilazodone 10mg/day. Citalopram: For those assigned to citalopram, the dose of citalopram will be maximized to 40mg/day. For those assigned to vilazodone, their citalopram dose will be maintained at 20mg/day for 1 week, then reduced to 10mg/day for 1 week, then switched to vilazodone 10mg/day.
Period Title: Overall Study
STARTED	20	28
COMPLETED	19	23
NOT COMPLETED	1	5

Baseline Characteristics

Arm/Group Title	Vilazodone	Citalopram	Total
Arm/Group Description	A fixed dose titration (with doses ranging from 10mg to 40mg/day) will be used. Subjects will take 10mg/day for 1 week, 20mg/day for 1 week and then 40mg/day. Vilazodone: A fixed dose titration (with doses ranging from 10mg to 40mg/day) will be used. Subjects will take 10mg/day for 1 week, 20mg/day for 1 week and then 40mg/day.	For those assigned to citalopram, the dose of citalopram will be maximized to 40mg/day. For those assigned to vilazodone, their citalopram dose will be maintained at 20mg/day for 1 week, then reduced to 10mg/day for 1 week, then switched to vilazodone 10mg/day. Citalopram: For those assigned to citalopram, the dose of citalopram will be maximized to 40mg/day. For those assigned to vilazodone, their citalopram dose will be maintained at 20mg/day for 1 week, then reduced to 10mg/day for 1 week, then switched to vilazodone 10mg/day.	Total of all reporting groups
Overall Participants	19	23	42
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	19 100%	23 100%	42 100%
>=65 years	0 0%	0 0%	0 0%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	31.7 (11.3)	38.6 (11.1)	35.4 (11.6)
Sex: Female, Male (Count of Participants)
Female	11 57.9%	10 43.5%	21 50%
Male	8 42.1%	13 56.5%	21 50%
Region of Enrollment (Count of Participants)
United States	19 100%	23 100%	42 100%

Outcome Measures

1. Primary Outcome

Title	Montgomery-Åsberg Depression Rating Scale (MADRS)
Description	The entire study will last 18 weeks. For the first 6 weeks, subjects will come in once every 2 weeks. For the next 4 weeks, subjects will come in once per week. For the next 6 weeks, subjects will come in once every 2 weeks. The final visit will come 2 weeks later for a total of 11 visits where the MADRS will be administered. Only the baseline and final (last observation) assessments for the outcome measure was used in determining results, thus these are the only values included. MADRS scores range from 0-60, with higher scores indicating a greater level of severity. No subscales were used.
Time Frame	Baseline and final MADRS scores during the double-blind phase.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Vilazodone	Citalopram
Arm/Group Description	A fixed dose titration (with doses ranging from 10mg to 40mg/day) will be used. Subjects will take 10mg/day for 1 week, 20mg/day for 1 week and then 40mg/day. Vilazodone: A fixed dose titration (with doses ranging from 10mg to 40mg/day) will be used. Subjects will take 10mg/day for 1 week, 20mg/day for 1 week and then 40mg/day.	For those assigned to citalopram, the dose of citalopram will be maximized to 40mg/day. For those assigned to vilazodone, their citalopram dose will be maintained at 20mg/day for 1 week, then reduced to 10mg/day for 1 week, then switched to vilazodone 10mg/day. Citalopram: For those assigned to citalopram, the dose of citalopram will be maximized to 40mg/day. For those assigned to vilazodone, their citalopram dose will be maintained at 20mg/day for 1 week, then reduced to 10mg/day for 1 week, then switched to vilazodone 10mg/day.
Measure Participants	19	23
First Randomized Visit (Visit 8)	13.9 (5.3)	12.7 (8.4)
Second Randomized Visit (Visit 9)	14.5 (4.4)	13.2 (8.5)
Third Randomized Visit (Visit 10)	13.9 (5.1)	13.5 (8.5)
Fourth Randomized Visit (Visit 11)	13.9 (5.3)	12.7 (8.4)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Vilazodone, Citalopram
	Comments
	Type of Statistical Test	Other
	Comments	Linear repeated measures regression models were constructed to assess trends over time between groups where the dependent variable was outcome measure (MADRS score) and independent variables included visit, treatment group, visit by treatment group interaction, and any baseline variables that were significant between groups.
Statistical Test of Hypothesis	p-Value	0.342
	Comments	P-value for linear regression assessing outcome measure (MADRS score) and treatment group.
	Method	Regression, Linear
	Comments

Adverse Events

Time Frame	The adverse events reported were during the double-blind phase of the study
Arm/Group Title	Vilazodone		Citalopram
Arm/Group Description	A fixed dose titration (with doses ranging from 10mg to 40mg/day) will be used. Subjects will take 10mg/day for 1 week, 20mg/day for 1 week and then 40mg/day. Vilazodone: A fixed dose titration (with doses ranging from 10mg to 40mg/day) will be used. Subjects will take 10mg/day for 1 week, 20mg/day for 1 week and then 40mg/day.		For those assigned to citalopram, the dose of citalopram will be maximized to 40mg/day. For those assigned to vilazodone, their citalopram dose will be maintained at 20mg/day for 1 week, then reduced to 10mg/day for 1 week, then switched to vilazodone 10mg/day. Citalopram: For those assigned to citalopram, the dose of citalopram will be maximized to 40mg/day. For those assigned to vilazodone, their citalopram dose will be maintained at 20mg/day for 1 week, then reduced to 10mg/day for 1 week, then switched to vilazodone 10mg/day.
All Cause Mortality
	Vilazodone		Citalopram
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Vilazodone		Citalopram
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/19 (0%)		0/23 (0%)
Other (Not Including Serious) Adverse Events
	Vilazodone		Citalopram
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/19 (15.8%)		1/23 (4.3%)
Gastrointestinal disorders
Nausea	0/19 (0%)		1/23 (4.3%)
Diarrhea	1/19 (5.3%)		0/23 (0%)
General disorders
Dry Mouth	1/19 (5.3%)		0/23 (0%)
Sexual side effects	1/19 (5.3%)		0/23 (0%)

Limitations/Caveats

The sample size was likely too small to make comments about predictors of outcome and generally the study was under-powered, which would make differences difficult to detect. The study design enrolled only non-responders into the double-blind phase.

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.