Vilazodone for Treatment of Geriatric Depression

• Sponsor: University of California, Los Angeles (Other)
• Overall Status: Completed
• CT.gov ID: NCT01608295
• Collaborator: Forest Laboratories (Industry)
• Enrollment: 65
• Location: 1
• Arms: 2
• Duration (Months): 38
• Patients Per Site Per Month: 1.7

Study Details

Study Description

Brief Summary

The purpose of this study is to examine the effects of vilazodone for the treatment of depression in older adults.

Condition or Disease	Intervention/Treatment	Phase
Major Depressive Disorder	Drug: Vilazodone; Viibryd; Drug: Paroxetine; Paxil	Phase 4

Detailed Description

This is a 12-week double-blind comparison of a novel antidepressant, vilazodone, to the gold-standard drug, paroxetine, for the treatment of geriatric depression. We are interested in assessing the difference in response to vilazodone (VLZ) compared to paroxetine (PAR). We hope to detect difference in response in primary outcomes (depressed mood) and secondary outcomes cognition. We are seeking to examine this directly in 80 older adults (60 years of age or older) with major depression with anticipated 60 completers. This proposed trial will serve as a pilot study to estimate the efficacy and tolerability of the drug in older depressed adults, and use this project for dose-finding in this population.

Study Design

• Study Type: Interventional
• Actual Enrollment: 65 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: A Pilot Study of Double-blind Comparison of Vilazodone to Paroxetine in Geriatric Depression
• Study Start Date: Jul 1, 2012
• Actual Primary Completion Date: Sep 1, 2015
• Actual Study Completion Date: Sep 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Vilazodone; Viibryd After screening and baseline test results are reviewed and eligibility criteria are confirmed, medications will be dispensed if patients continue to meet eligibility criteria and sign the informed consent form. All eligible subjects will be randomized to vilazodone or paroxetine group using a computer-generated random assignment scheme, which assigned subjects in a 1:1 ratio to each group. Randomization will be done prior to subject's being assigned to the groups. Doses of the drugs will be adjusted according to individual tolerability and safety.	Drug: Vilazodone; Viibryd; Subjects randomized to receive vilazodone blindly will have incremental dose titration of 10mg per day for the 1st week; 20mg per day the 2nd week; 40mg per day for the 3rd-12th week. Doses of the drugs will be adjusted according to individual tolerability and safety.; Other Names: Vilazodone Viibryd Antidepressant
Experimental: Paroxetine; Paxil After screening and baseline test results are reviewed and eligibility criteria are confirmed, medications will be dispensed if patients continue to meet eligibility criteria and sign the informed consent form. All eligible subjects will be randomized to vilazodone or paroxetine group using a computer-generated random assignment scheme, which assigned subjects in a 1:1 ratio to each group. Randomization will be done prior to subject's being assigned to the groups. Doses of the drugs will be adjusted according to individual tolerability and safety.	Drug: Paroxetine; Paxil; Subjects randomized to receive paroxetine blindly will have incremental dose titration of paroxetine 10mg per day for the 1st week; 20mg per day for the 2nd week; and 30mg per day for the 3rd-12 week. Doses of the drugs will be adjusted according to individual tolerability and safety.; Other Names: Paroxetine Paxil Antidepressant

Outcome Measures

Primary Outcome Measures

1. Hamilton Depression Rating Scale (HDRS) [Baseline and 12 weeks]

   The HAMD measures the severity of depressive symptoms in participants with major depressive disorder (MDD). It is a checklist of 17 items that are ranked on a scale of 0-4 or 0-2. The range for the total score (which is the sum of the scores of all 17 items) is 0-52; a higher score indicates greater severity of symptoms.

Secondary Outcome Measures

1. UKU Side-effect Profile [Each visit for 12 weeks]

   Number of participants with each side-effect event.

2. Neurocognitive Measure: The Rey-Osterrieth Complex Figure Test [Baseline and Final Visit]

   The The Rey-Osterrieth Complex Figure Test (REY-O) is a neuropsychological assessment in which measures visual perception and long-term visual memory. Total raw scores range from 0 to 36 with higher scores representing better outcomes in recall. The total raw score represents a sum of subscales scored by 18 individual elements which are scored for both distortion and placement. Two points are awarded to elements that are accurately drawn and properly placed, one point is given to distorted or misplaced elements, 0.5 points are given if an element is both distorted and misplaced, and missing or unrecognizable elements receive zero points.

3. Changes in Proinflammatory Gene Expression From Baseline to Final Visit (up to 12 Weeks) [Baseline and Final Visit]

   Gene expression data were quantile-normalized and log2-transformed in RNA expression units. The measure included the promoter transcription factor binding motif prevalence ratio of the unit (log2 Vilazodone/Paroxetine) and ranging from a minimum of -3 to a maximum of 3 with higher scores indicating better outcomes.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 60 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• 60 years of age or older

• The presence of a major depressive disorder diagnosed according to the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) criteria

• A 24-item Hamilton Depression Rating Scale (HAMD) score of 17 or higher at baseline

• Mini-Mental State Exam (MMSE) score > 24.

Exclusion Criteria:

• Subjects will be excluded if they had any current and/or lifetime history of other psychiatric disorders (except unipolar depression with or without comorbid generalized anxiety disorder), or recent unstable medical or neurological disorders; any disabilities preventing their participation in the study; diagnosis of mild cognitive impairment (MCI)/dementia; those with known allergic reactions to paroxetine or vilazodone.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	UCLA Semel Institute	Los Angeles	California	United States	90095

Sponsors and Collaborators

• University of California, Los Angeles
• Forest Laboratories

Investigators

• Principal Investigator: Helen Lavretsky, M.D., University of California, Los Angeles

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Double-blind comparison of vilazodone to paroxetine in geriatric depression

Publications

None provided.

• Responsible Party: Helen Lavretsky, MD, Professor, University of California, Los Angeles
• ClinicalTrials.gov Identifier: NCT01608295
• Other Study ID Numbers: VII-IT-02
• First Posted: May 31, 2012
• Last Update Posted: May 11, 2018
• Last Verified: Apr 1, 2018

• Keywords provided by Helen Lavretsky, MD, Professor, University of California, Los Angeles: depressed; geriatric; older adults; antidepressants; depression; anxious; major depressive disorder; MDD
• Additional relevant MeSH terms: Depression; Depressive Disorder; Depressive Disorder, Major; Paroxetine; Antidepressive Agents; Vilazodone Hydrochloride

Study Results

Participant Flow

Recruitment Details	Single site outpatient clinic in the U.S.
Pre-assignment Detail	208 volunteers were assessed for eligibility, of which 100 declined to participate and 37 did not meet inclusion criteria. Seventy-one persons consented to participate, of which 65 passed screening and were enrolled; nine of 65 enrolled participants withdrew before randomization.

Arm/Group Title	Vilazodone; Viibryd	Paroxetine; Paxil
Arm/Group Description	After screening and baseline test results are reviewed and eligibility criteria are confirmed, medications will be dispensed if patients continue to meet eligibility criteria and sign the informed consent form. All eligible subjects will be randomized to vilazodone or paroxetine group using a computer-generated random assignment scheme, which assigned subjects in a 1:1 ratio to each group. Randomization will be done prior to subject's being assigned to the groups. Doses of the drugs will be adjusted according to individual tolerability and safety. Vilazodone; Viibryd: Subjects randomized to receive vilazodone blindly will have incremental dose titration of 10mg per day for the 1st week; 20mg per day the 2nd week; 40mg per day for the 3rd-12th week. Doses of the drugs will be adjusted according to individual tolerability and safety.	After screening and baseline test results are reviewed and eligibility criteria are confirmed, medications will be dispensed if patients continue to meet eligibility criteria and sign the informed consent form. All eligible subjects will be randomized to vilazodone or paroxetine group using a computer-generated random assignment scheme, which assigned subjects in a 1:1 ratio to each group. Randomization will be done prior to subject's being assigned to the groups. Doses of the drugs will be adjusted according to individual tolerability and safety. Paroxetine; Paxil: Subjects randomized to receive paroxetine blindly will have incremental dose titration of paroxetine 10mg per day for the 1st week; 20mg per day for the 2nd week; and 30mg per day for the 3rd-12 week. Doses of the drugs will be adjusted according to individual tolerability and safety.
Period Title: Overall Study
STARTED	26	30
COMPLETED	20	25
NOT COMPLETED	6	5

Baseline Characteristics

Arm/Group Title	Vilazodone; Viibryd	Paroxetine; Paxil	Total
Arm/Group Description	After screening and baseline test results are reviewed and eligibility criteria are confirmed, medications will be dispensed if patients continue to meet eligibility criteria and sign the informed consent form. All eligible subjects will be randomized to vilazodone or paroxetine group using a computer-generated random assignment scheme, which assigned subjects in a 1:1 ratio to each group. Randomization will be done prior to subject's being assigned to the groups. Doses of the drugs will be adjusted according to individual tolerability and safety. Vilazodone; Viibryd: Subjects randomized to receive vilazodone blindly will have incremental dose titration of 10mg per day for the 1st week; 20mg per day the 2nd week; 40mg per day for the 3rd-12th week. Doses of the drugs will be adjusted according to individual tolerability and safety.	After screening and baseline test results are reviewed and eligibility criteria are confirmed, medications will be dispensed if patients continue to meet eligibility criteria and sign the informed consent form. All eligible subjects will be randomized to vilazodone or paroxetine group using a computer-generated random assignment scheme, which assigned subjects in a 1:1 ratio to each group. Randomization will be done prior to subject's being assigned to the groups. Doses of the drugs will be adjusted according to individual tolerability and safety. Paroxetine; Paxil: Subjects randomized to receive paroxetine blindly will have incremental dose titration of paroxetine 10mg per day for the 1st week; 20mg per day for the 2nd week; and 30mg per day for the 3rd-12 week. Doses of the drugs will be adjusted according to individual tolerability and safety.	Total of all reporting groups
Overall Participants	26	30	56
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	5 19.2%	9 30%	14 25%
>=65 years	21 80.8%	21 70%	42 75%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	71.5 (7.2)	71.5 (7.7)	71.5 (7.4)
Sex: Female, Male (Count of Participants)
Female	13 50%	13 43.3%	26 46.4%
Male	13 50%	17 56.7%	30 53.6%
Region of Enrollment (participants) [Number]
United States	26 100%	30 100%	56 100%

Outcome Measures

1. Primary Outcome

Title	Hamilton Depression Rating Scale (HDRS)
Description	The HAMD measures the severity of depressive symptoms in participants with major depressive disorder (MDD). It is a checklist of 17 items that are ranked on a scale of 0-4 or 0-2. The range for the total score (which is the sum of the scores of all 17 items) is 0-52; a higher score indicates greater severity of symptoms.
Time Frame	Baseline and 12 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Vilazodone; Viibryd	Paroxetine; Paxil
Arm/Group Description	Vilazodone; Viibryd: Subjects randomized to receive vilazodone blindly received incremental dose titration of 10mg per day for the 1st week; 20mg per day the 2nd week; 40mg per day for the 3rd-12th week. Doses of the drugs will be adjusted according to individual tolerability and safety.	Paroxetine; Paxil: Subjects randomized to receive paroxetine blindly received incremental dose titration of paroxetine 10mg per day for the 1st week; 20mg per day for the 2nd week; and 30mg per day for the 3rd-12 week. Doses of the drugs were adjusted according to individual tolerability and safety.
Measure Participants	21	25
HDRS Baseline	17.2 (3.7)	16.6 (4.1)
HDRS Final Visit	7.6 (4.8)	7.5 (5.9)

2. Secondary Outcome

Title	UKU Side-effect Profile
Description	Number of participants with each side-effect event.
Time Frame	Each visit for 12 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Vilazodone; Viibryd	Paroxetine; Paxil
Arm/Group Description	Vilazodone; Viibryd: Subjects randomized to receive vilazodone blindly received incremental dose titration of 10mg per day for the 1st week; 20mg per day the 2nd week; 40mg per day for the 3rd-12th week. Doses of the drugs will be adjusted according to individual tolerability and safety.	Paroxetine; Paxil: Subjects randomized to receive paroxetine blindly received incremental dose titration of paroxetine 10mg per day for the 1st week; 20mg per day for the 2nd week; and 30mg per day for the 3rd-12 week. Doses of the drugs were adjusted according to individual tolerability and safety.
Measure Participants	25	30
Concentration Difficulties	3 11.5%	0 0%
Sedation	1 3.8%	3 10%
Increased dream activity	3 11.5%	3 10%
Reduced salivation	3 11.5%	1 3.3%
Diarrhea	3 11.5%	1 3.3%
Constipation	3 11.5%	5 16.7%
Orthostatic dizziness	3 11.5%	3 10%

3. Secondary Outcome

Title	Neurocognitive Measure: The Rey-Osterrieth Complex Figure Test
Description	The The Rey-Osterrieth Complex Figure Test (REY-O) is a neuropsychological assessment in which measures visual perception and long-term visual memory. Total raw scores range from 0 to 36 with higher scores representing better outcomes in recall. The total raw score represents a sum of subscales scored by 18 individual elements which are scored for both distortion and placement. Two points are awarded to elements that are accurately drawn and properly placed, one point is given to distorted or misplaced elements, 0.5 points are given if an element is both distorted and misplaced, and missing or unrecognizable elements receive zero points.
Time Frame	Baseline and Final Visit

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Vilazodone; Viibryd	Paroxetine; Paxil
Arm/Group Description	After screening and baseline test results are reviewed and eligibility criteria are confirmed, medications will be dispensed if patients continue to meet eligibility criteria and sign the informed consent form. All eligible subjects will be randomized to vilazodone or paroxetine group using a computer-generated random assignment scheme, which assigned subjects in a 1:1 ratio to each group. Randomization will be done prior to subject's being assigned to the groups. Doses of the drugs will be adjusted according to individual tolerability and safety. Vilazodone; Viibryd: Subjects randomized to receive vilazodone blindly will have incremental dose titration of 10mg per day for the 1st week; 20mg per day the 2nd week; 40mg per day for the 3rd-12th week. Doses of the drugs will be adjusted according to individual tolerability and safety.	After screening and baseline test results are reviewed and eligibility criteria are confirmed, medications will be dispensed if patients continue to meet eligibility criteria and sign the informed consent form. All eligible subjects will be randomized to vilazodone or paroxetine group using a computer-generated random assignment scheme, which assigned subjects in a 1:1 ratio to each group. Randomization will be done prior to subject's being assigned to the groups. Doses of the drugs will be adjusted according to individual tolerability and safety. Paroxetine; Paxil: Subjects randomized to receive paroxetine blindly will have incremental dose titration of paroxetine 10mg per day for the 1st week; 20mg per day for the 2nd week; and 30mg per day for the 3rd-12 week. Doses of the drugs will be adjusted according to individual tolerability and safety.
Measure Participants	20	25
REY-O 3 Minute Delay Baseline	13.3 (5.9)	13.3 (5.3)
REY-O 3 Minute Delay Final Visit	15.2 (7.4)	16.3 (4.8)

4. Secondary Outcome

Title	Changes in Proinflammatory Gene Expression From Baseline to Final Visit (up to 12 Weeks)
Description	Gene expression data were quantile-normalized and log2-transformed in RNA expression units. The measure included the promoter transcription factor binding motif prevalence ratio of the unit (log2 Vilazodone/Paroxetine) and ranging from a minimum of -3 to a maximum of 3 with higher scores indicating better outcomes.
Time Frame	Baseline and Final Visit

Outcome Measure Data

Analysis Population Description

The Arms/Groups are not combined, but results are presented as a ratio of Vilazodone/Paroxetine.

Arm/Group Title	Vilazodone and Paroxetine
Arm/Group Description	Subjects randomized to receive vilazodone relative to subjects randomized to receive paroxetine.
Measure Participants	46
AP-1, Activator Protein	-0.8 (0.5)
NF-kB, Nuclear Factor Kappa B	-1.25 (0.5)
GR, Glucocorticoid Receptor	0.2 (0.6)
CREB, cAMP response element binding protein	-2.1 (0.7)

Adverse Events

Arm/Group Title	Vilazodone; Viibryd		Paroxetine; Paxil
Arm/Group Description	Vilazodone; Viibryd: Subjects randomized to receive vilazodone blindly received incremental dose titration of 10mg per day for the 1st week; 20mg per day the 2nd week; 40mg per day for the 3rd-12th week. Doses of the drugs will be adjusted according to individual tolerability and safety.		Paroxetine; Paxil: Subjects randomized to receive paroxetine blindly received incremental dose titration of paroxetine 10mg per day for the 1st week; 20mg per day for the 2nd week; and 30mg per day for the 3rd-12 week. Doses of the drugs were adjusted according to individual tolerability and safety.
All Cause Mortality
	Vilazodone; Viibryd		Paroxetine; Paxil
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Vilazodone; Viibryd		Paroxetine; Paxil
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/26 (0%)		0/30 (0%)
Other (Not Including Serious) Adverse Events
	Vilazodone; Viibryd		Paroxetine; Paxil
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	19/26 (73.1%)		16/30 (53.3%)
Gastrointestinal disorders
Reduced salivation	3/26 (11.5%)		1/30 (3.3%)
Diarrhea	3/26 (11.5%)		1/30 (3.3%)
Constipation	3/26 (11.5%)		5/30 (16.7%)
Nervous system disorders
Sedation	1/26 (3.8%)		3/30 (10%)
Increased Dream Activity	3/26 (11.5%)		3/30 (10%)
Psychiatric disorders
Concentration Difficulties	3/26 (11.5%)		0/30 (0%)
Vascular disorders
Orthostatic dizziness	3/26 (11.5%)		3/30 (10%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT 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.