Levomilnacipran ER vs. Adjunctive Quetiapine for Adults With Inadequate Relief With SSRIs in MDD

• Sponsor: Duke University (Other)
• Overall Status: Completed
• CT.gov ID: NCT02720198
• Collaborator: Forest Laboratories (Industry), Institute for Advanced Medical Research, Alpharetta, GA (Other)
• Enrollment: 60
• Location: 1
• Arms: 2
• Actual Duration (Months): 16.6
• Patients Per Site Per Month: 3.6

Study Details

Study Description

Brief Summary

This study's primary objective is to compare the efficacy and tolerability of switching patients with inadequate relief on generic SSRIs to levomilnacipran versus adding a new treatment (quetiapine) to the participants' existing treatment with people diagnosed with depression (major depression disorder).

The secondary objective is to examine the response and remission rates following the switch from a generic SSRI to levomilnacipran ER and augmentation with quetiapine along with examining changes in neurocognitive and apathy measures after the switch.

Condition or Disease	Intervention/Treatment	Phase
Major Depressive Disorder	Drug: Levomilnacipran; Drug: Quetiapine	Phase 3

Detailed Description

1. Study Design 1) An 8-week, randomized rater blinded parallel group, 2-arm trial 2) Trial duration - 9 weeks 3) Drug doses

• Levomilnacipran ER; Switching to a flexible dose regime of levomilnacipran ER 40-120 mg/day after initial dose of 20mg.

• Quetiapine XR; Adjunct a flexible dose regimen of quetiapine XR 150-300 mg/day after initial dose of 50mg.

1. Objective 1) To compare the efficacy and tolerability of switching to levomilnacipran ER (40-120 mg/d) versus augmentation with quetiapine XR 150-300 mg/day to the patients' existing treatment for patients with inadequate relief on generic SSRIs in patients with MDD.

1. To examine the response following the switch from generic SSRI to levomilnacipran ER and augmentation with quetiapine XR.

2. To examine changes in neurocognitive and apathy measures after switching from SSRI to levomilnacipran ER and after augmentation with quetiapine XR in MDD

Study Design

• Study Type: Interventional
• Actual Enrollment: 60 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Randomized Trial Comparing Efficacy and Tolerability of Levomilnacipran Switch Versus Adjunctive Quetiapine in Major Depressive Disorder (MDD) With Inadequate Response to SSRIs
• Actual Study Start Date: Jan 23, 2017
• Actual Primary Completion Date: Jun 12, 2018
• Actual Study Completion Date: Jun 12, 2018

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Levomilnacipran Levomilnacipran ER is switched from SSRI.	Drug: Levomilnacipran; treating major depression. A flexible dose regime of levomilnacipran ER 20-120 mg/d mg per day starting at 20 mg/d on Days 1-2, increasing to 40 mg/d on Days 3-7 in week 1, then flexibly dosed between 40 mg/d -120 mg/d during weeks 2 through 8; Other Names: Fetzima
Active Comparator: Quetiapine Quetiapine XR is added in addition to current SSRI.	Drug: Quetiapine; Quetiapine will be started at 50 mg/d on Day 1-2, increasing to 150 mg/d on Days 3-7 in Week 1 and then flexibly dosed between 150-300 mg/d during Weeks 1 through 8 along with their current antidepressant.; Other Names: Seroquel

Outcome Measures

Primary Outcome Measures

1. Changes of Montgomery-Åsberg Depression Rating Scale (MADRS) Total Score [Baseline to Week 8]

   A ten-item diagnostic questionnaire used to measure the severity of depressive episodes in patients with mood disorders. Total scores will range from 0 to 60. Higher scores indicate greater severity of depressive episodes.

Secondary Outcome Measures

1. Response Rate [Week 8]

   Remission was defined as [>or=50% reduction in MADRS score with MADRS <or=10] and response was defined as [>or=50% reduction in MADRS with MADRS >10]. Response rate included remission and response.

2. Remission Rate [Week 8]

   Remission was defined as [>or=50% reduction in MADRS score with MADRS <or=10]

3. Changes in Neurocognition by Changes in Scores on Reyes Verbal Learning Test [Baseline to Week 8]

   Number of words correctly recalled by the respondent is recorded. 1 point for each word correctly recalled. Total score range of 0-40. Higher scores mean better cognitive function.

4. Changes in Neurocognition by Changes in Scores on Scores on Digit Symbol Substitution Test (DSST) [Baseline to Week 8]

   DSST measures working memory and visuospatial processing. 1 point for each object correctly substituted from number to each matched symbol. Total score range of 0-89. Higher scores mean better cognitive function.

5. Number of Subjects With Global Improvement in Scores on Clinical Global Impression Scale- Severity (CGI-S) [Baseline to Week 8]

   CGI-S is a 7 point scale that assess the severity of illness and requires the clinician to assess how much the patient's illness has improved or worsened relative to a baseline state at the beginning of the intervention. It is used to assess the clinician's view of the patient's global functioning. Total score range of 0-7.

6. Number of Subjects With General Improvement in Scores on Clinical Global Impression Scale- Improvement (CGI-I) [Baseline to Week 8]

   CGI-I a 7 point scale that requires the clinician to assess how much the patient's illness has improved or worsened relative to a baseline state at the beginning of the intervention. It is used to assess the clinician's view of the patient's global functioning. Total score range of 0-7.

7. Changes of Anxiety Symptoms in Scores on Hamilton Anxiety Rating Scale (HAM-A) [Baseline to Week 8]

   A questionnaire used by clinicians to rate the severity of a patient's anxiety. Total score range of 0-48. A higher score indicates greater anxiety.

8. Changes of Quality of Life in Scores on Sheehan Disability Scale (SDS) Total [Baseline to Week 8]

   A self-reported brief scale to assess impairment of work/school, social life and family and home. Total score range of 0-30. A higher score indicates greater impairment.

9. Changes in Scores on Apathy Evaluation Scale (AES). [Baseline to Week 8]

   Self-Administered assessment measuring lack of motivation not attributable to diminished level of consciousness, cognitive impairment, or emotional distress. Total scores range from 0-54. Higher scores indicate greater apathy.

10. Changes in Sexual Dysfunction by Changes in Scores on Arizona Sexual Experience Scale (ASEX) [Baseline to Week 8]

    ASEX is scale for sexual dysfunction to assess safety and tolerability of medication. Total scores range from 5-30. Higher scores indicate greater sexual dysfunction.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 65 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Age 18-65 years inclusive

• Current diagnosis of MDD based on DSM-IV criteria

• Able to understand study rules and procedures and willing to sign written informed consent for study participation

• Inadequate response to antidepressants: having a score of ≥14 on the 17-item Hamilton Anxiety Scale (HAMD) and not having a ≥ 50% reduction in HAMD or CGI-S scores from baseline after a retrospective confirmation of an adequate trial of a single antidepressant (defined as a minimum 6-week trial of acceptable therapeutic dose (daily dose ≥ 40 mg of fluoxetine, 40 mg of paroxetine, 20 mg of citalopram, 10 mg of escitalopram, 37.5 mg of paroxetine CR, 150 mg of sertraline, 100 mg of fluvoxamine).

• If female, nonpregnant/nonlactating status

• Duration of current MDD ≥ 4 weeks and < 24 months

• Not more than 2 treatment failures of adequate antidepressant trials for current episode of MDD

Exclusion Criteria:

• Has previously participated in a levomilnacipran ER or quetiapine XR or quetiapine clinical study in previous 12 months

Has 1 or more the following:

• Current or past history of: manic or hypomanic episode, schizophrenia or any other psychotic disorder defined in the DSM- 5

• Diagnosis of alcohol or other substance use disorder (except nicotine and caffeine) as defined in the DSM-5 that has not been in sustained full remission for at least 6 months prior to screening (participant must also have negative urine drug screen prior to baseline).

• Presence or history of a clinically significant neurological disorder (including epilepsy)

• Poorly controlled Hypertension or Diabetes

• uncontrolled narrow-angle glaucoma

• hypersensitivity to levomilnacipran, milnacipran , quetiapine or quetiapine XR

• Neurodegenerative disorder.

• Has a thyroid stimulating hormone value outside the normal range at the Screening Visit that is deemed clinically significant by the investigator.

• Has clinically significant abnormal vital signs as determined by the investigator.

• Has a clinical significant abnormal electrocardiogram.

• Has screening laboratory values greater than 2.5 times the upper or lower limits of normal range or judged to be clinically significant

• Has a disease or takes medication that, in the opinion of the investigator, could interfere with the assessments of safety, tolerability, or efficacy or prevent the individual from completing the study.

• Female subjects of childbearing potential not on adequate contraception methods in the opinion of the investigator

o If the female is childbearing, she must agree to use appropriate contraceptive measures for the duration of the study and for one month afterwards. Medically acceptable contraceptives include: (1) surgical sterilization (such as tubal ligation of hysterectomy), (2) approved hormonal contraceptives (such as birth control pills, patches, implants, or injections), (3) barrier methods (such as condom or diaphragm) used with a spermicide, or (4) an intrauterine device (IUD). Contraceptive measures such as Plan B ™, sold for emergency use after unprotected sex, are not acceptable methods for routine use. If the female does become pregnant during this study she must inform the study physician immediately.

• Has a significant risk of suicide according to Columbia Suicide Severity Rating Scale (CSSRS) or in the clinical judgment of the investigator

• History of suicide attempt in the previous 12 months

• MDD with postpartum onset, psychotic features or seasonal features

• Hamilton Anxiety Scale (HAM-A) baseline score ≥ 24

• Failure of ≥ 3 adequate trials of different antidepressants for the current episode of MDD

• ≥ 3 episodes major depression in previous 12 months or ≥ 8 lifetime episodes of MDD

• Current or previous use of an atypical or typical antipsychotic agent for augmentation of major depression or treatment of psychotic depression, mania psychosis, or agitation. Previous use of antipsychotics for insomnia will be permitted.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Institute for Advanced Medical Research	Alpharetta	Georgia	United States	30005

Sponsors and Collaborators

• Duke University
• Forest Laboratories
• Institute for Advanced Medical Research, Alpharetta, GA

Investigators

• Principal Investigator: Ashwin A Patkar, MD, Duke Universtiy Medical Center

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Jul 18, 2017

More Information

Publications

None provided.

• Responsible Party: Duke University
• ClinicalTrials.gov Identifier: NCT02720198
• Other Study ID Numbers: Pro00064983
• First Posted: Mar 25, 2016
• Last Update Posted: Aug 14, 2019
• Last Verified: Aug 1, 2019

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Depressive Disorder; Depression; Depressive Disorder, Major; Milnacipran; Quetiapine Fumarate; Levomilnacipran

Study Results

Participant Flow

Recruitment Details	Potential participants were identified by self-referral via the printed ad, phone script, the patients' physicians, local health providers, mental health providers, or Duke providers. Others were recommended by PI or Study Coordinator. They assessed and screened at 2 sites, an university hospital and a clinic of the research institute.
Pre-assignment Detail	One subject was lost to follow up after screening.

Arm/Group Title	Levomilnacipran	Quetiapine
Arm/Group Description	Levomilnacipran ER is switched from SSRI. Levomilnacipran ER: A flexible dose regime of levomilnacipran ER 20-120 mg/d mg per day, starting at 20 mg/d on Days 1-2, increasing to 40 mg/d on Days 3-7 in week 1, then flexibly dosed between 40 mg/d -120 mg/d during weeks 2 through 8.	Quetiapine XR was added in addition to current SSRI. Quetiapine XR: Quetiapine XR was started at 50 mg/d on Day 1-2, increasing to 150 mg/d on Days 3-7 in Week 1 and then flexibly dosed between 150-300 mg/d during Weeks 1 through 8 along with their current SSRI.
Period Title: Overall Study
STARTED	29	31
COMPLETED	29	30
NOT COMPLETED	0	1

Baseline Characteristics

Arm/Group Title	Levomilnacipran	Quetiapine	Total
Arm/Group Description	Levomilnacipran ER is switched from SSRI. Levomilnacipran ER: A flexible dose regime of levomilnacipran ER 20-120 mg/d mg per day, starting at 20 mg/d on Days 1-2, increasing to 40 mg/d on Days 3-7 in week 1, then flexibly dosed between 40 mg/d -120 mg/d during weeks 2 through 8.	Quetiapine XR was added in addition to current SSRI. Quetiapine XR: Quetiapine XR was started at 50 mg/d on Day 1-2, increasing to 150 mg/d on Days 3-7 in Week 1 and then flexibly dosed between 150-300 mg/d during Weeks 1 through 8 along with their current SSRI.	Total of all reporting groups
Overall Participants	29	31	60
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	28 96.6%	30 96.8%	58 96.7%
>=65 years	1 3.4%	1 3.2%	2 3.3%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	45.34 (14.28)	46.13 (11.17)	45.75 (12.67)
Sex: Female, Male (Count of Participants)
Female	20 69%	20 64.5%	40 66.7%
Male	9 31%	11 35.5%	20 33.3%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%	1 3.2%	1 1.7%
Not Hispanic or Latino	29 100%	30 96.8%	59 98.3%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	20 69%	25 80.6%	45 75%
White	9 31%	4 12.9%	13 21.7%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	2 6.5%	2 3.3%
Region of Enrollment (participants) [Number]
United States	29 100%	31 100%	60 100%
Baseline SSRI (Count of Participants)
Escitalopram	9 31%	3 9.7%	12 20%
Fluoxetine	3 10.3%	10 32.3%	13 21.7%
Sertraline	5 17.2%	6 19.4%	11 18.3%
Citalopram	8 27.6%	5 16.1%	13 21.7%
Paroxetine	3 10.3%	7 22.6%	10 16.7%
Unknown	1 3.4%	0 0%	1 1.7%
Baseline Dose of SSRI (dose of medication, mg) [Mean (Standard Deviation) ]
mg(Escitalopram)	18.89 (3.333)	16.67 (5.774)	18.33 (3.892)
mg(Fluoxetine)	53.33 (23.094)	42.00 (6.325)	44.62 (11.983)
mg(Sertraline)	170.00 (27.386)	150.00 (31.623)	159.09 (30.151)
mg(Citalopram)	21.25 (8.345)	28.00 (10.954)	23.85 (9.608)
mg(Paroxetine)	40.00 (0.000)	51.43 (15.736)	48.00 (13.984)

Outcome Measures

1. Primary Outcome

Title	Changes of Montgomery-Åsberg Depression Rating Scale (MADRS) Total Score
Description	A ten-item diagnostic questionnaire used to measure the severity of depressive episodes in patients with mood disorders. Total scores will range from 0 to 60. Higher scores indicate greater severity of depressive episodes.
Time Frame	Baseline to Week 8

Outcome Measure Data

Analysis Population Description

Data not available on some participants.

Arm/Group Title	Levomilnacipran	Quetiapine
Arm/Group Description	Levomilnacipran ER is switched from SSRI. Levomilnacipran ER: A flexible dose regime of levomilnacipran ER 20-120 mg/d mg per day, starting at 20 mg/d on Days 1-2, increasing to 40 mg/d on Days 3-7 in week 1, then flexibly dosed between 40 mg/d -120 mg/d during weeks 2 through 8.	Quetiapine XR was added in addition to current SSRI. Quetiapine XR: Quetiapine XR was started at 50 mg/d on Day 1-2, increasing to 150 mg/d on Days 3-7 in Week 1 and then flexibly dosed between 150-300 mg/d during Weeks 1 through 8 along with their current SSRI.
Measure Participants	26	30
Mean (Standard Deviation) [score on a scale]	-5.81 (6.080)	-6.97 (7.632)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Levomilnacipran, Quetiapine
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.53
	Comments
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	1.159
	Confidence Interval	(2-Sided) 95%; -2.518 to 4.836
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.834
	Estimation Comments

2. Secondary Outcome

Title	Response Rate
Description	Remission was defined as [>or=50% reduction in MADRS score with MADRS <or=10] and response was defined as [>or=50% reduction in MADRS with MADRS >10]. Response rate included remission and response.
Time Frame	Week 8

Outcome Measure Data

Analysis Population Description

Data not available on some participants.

Arm/Group Title	Levomilnacipran	Quetiapine
Arm/Group Description	Levomilnacipran ER is switched from SSRI. Levomilnacipran ER: A flexible dose regime of levomilnacipran ER 20-120 mg/d mg per day, starting at 20 mg/d on Days 1-2, increasing to 40 mg/d on Days 3-7 in week 1, then flexibly dosed between 40 mg/d -120 mg/d during weeks 2 through 8.	Quetiapine XR was added in addition to current SSRI. Quetiapine XR: Quetiapine XR was started at 50 mg/d on Day 1-2, increasing to 150 mg/d on Days 3-7 in Week 1 and then flexibly dosed between 150-300 mg/d during Weeks 1 through 8 along with their current SSRI.
Measure Participants	26	30
Count of Participants [Participants]	3 10.3%	7 22.6%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Levomilnacipran, Quetiapine
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.428
	Comments
	Method	Mantel Haenszel
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.492
	Confidence Interval	(2-Sided) 95%; 0.101 to 2.388
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.806
	Estimation Comments

3. Secondary Outcome

Title	Remission Rate
Description	Remission was defined as [>or=50% reduction in MADRS score with MADRS <or=10]
Time Frame	Week 8

Outcome Measure Data

Analysis Population Description

Data not available on some participants.

Arm/Group Title	Levomilnacipran	Quetiapine
Arm/Group Description	Levomilnacipran ER is switched from SSRI. Levomilnacipran ER: A flexible dose regime of levomilnacipran ER 20-120 mg/d mg per day, starting at 20 mg/d on Days 1-2, increasing to 40 mg/d on Days 3-7 in week 1, then flexibly dosed between 40 mg/d -120 mg/d during weeks 2 through 8.	Quetiapine XR was added in addition to current SSRI. Quetiapine XR: Quetiapine XR was started at 50 mg/d on Day 1-2, increasing to 150 mg/d on Days 3-7 in Week 1 and then flexibly dosed between 150-300 mg/d during Weeks 1 through 8 along with their current SSRI.
Measure Participants	26	30
Count of Participants [Participants]	2 6.9%	3 9.7%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Levomilnacipran, Quetiapine
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.272
	Comments
	Method	Mantel Haenszel
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.451
	Confidence Interval	(2-Sided) 95%; 0.109 to 1.866
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.724
	Estimation Comments

4. Secondary Outcome

Title	Changes in Neurocognition by Changes in Scores on Reyes Verbal Learning Test
Description	Number of words correctly recalled by the respondent is recorded. 1 point for each word correctly recalled. Total score range of 0-40. Higher scores mean better cognitive function.
Time Frame	Baseline to Week 8

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Levomilnacipran	Quetiapine
Arm/Group Description	Levomilnacipran ER is switched from SSRI. Levomilnacipran ER: A flexible dose regime of levomilnacipran ER 20-120 mg/d mg per day, starting at 20 mg/d on Days 1-2, increasing to 40 mg/d on Days 3-7 in week 1, then flexibly dosed between 40 mg/d -120 mg/d during weeks 2 through 8.	Quetiapine XR was added in addition to current SSRI. Quetiapine XR: Quetiapine XR was started at 50 mg/d on Day 1-2, increasing to 150 mg/d on Days 3-7 in Week 1 and then flexibly dosed between 150-300 mg/d during Weeks 1 through 8 along with their current SSRI.
Measure Participants	29	30
Mean (Standard Deviation) [score on a scale]	2.28 (5.694)	2.90 (5.255)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Levomilnacipran, Quetiapine
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.664
	Comments
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.624
	Confidence Interval	(2-Sided) 95%; -3.484 to 2.236
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.428
	Estimation Comments

5. Secondary Outcome

Title	Changes in Neurocognition by Changes in Scores on Scores on Digit Symbol Substitution Test (DSST)
Description	DSST measures working memory and visuospatial processing. 1 point for each object correctly substituted from number to each matched symbol. Total score range of 0-89. Higher scores mean better cognitive function.
Time Frame	Baseline to Week 8

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Levomilnacipran	Quetiapine
Arm/Group Description	Levomilnacipran ER is switched from SSRI. Levomilnacipran ER: A flexible dose regime of levomilnacipran ER 20-120 mg/d mg per day, starting at 20 mg/d on Days 1-2, increasing to 40 mg/d on Days 3-7 in week 1, then flexibly dosed between 40 mg/d -120 mg/d during weeks 2 through 8.	Quetiapine XR was added in addition to current SSRI. Quetiapine XR: Quetiapine XR was started at 50 mg/d on Day 1-2, increasing to 150 mg/d on Days 3-7 in Week 1 and then flexibly dosed between 150-300 mg/d during Weeks 1 through 8 along with their current SSRI.
Measure Participants	29	30
Mean (Standard Deviation) [score on a scale]	3.21 (9.321)	0.87 (7.431)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Levomilnacipran, Quetiapine
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.292
	Comments
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	2.34
	Confidence Interval	(2-Sided) 95%; -2.070 to 6.750
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 2.199
	Estimation Comments

6. Secondary Outcome

Title	Number of Subjects With Global Improvement in Scores on Clinical Global Impression Scale- Severity (CGI-S)
Description	CGI-S is a 7 point scale that assess the severity of illness and requires the clinician to assess how much the patient's illness has improved or worsened relative to a baseline state at the beginning of the intervention. It is used to assess the clinician's view of the patient's global functioning. Total score range of 0-7.
Time Frame	Baseline to Week 8

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Levomilnacipran	Quetiapine
Arm/Group Description	Levomilnacipran ER is switched from SSRI. Levomilnacipran ER: A flexible dose regime of levomilnacipran ER 20-120 mg/d mg per day, starting at 20 mg/d on Days 1-2, increasing to 40 mg/d on Days 3-7 in week 1, then flexibly dosed between 40 mg/d -120 mg/d during weeks 2 through 8.	Quetiapine XR was added in addition to current SSRI. Quetiapine XR: Quetiapine XR was started at 50 mg/d on Day 1-2, increasing to 150 mg/d on Days 3-7 in Week 1 and then flexibly dosed between 150-300 mg/d during Weeks 1 through 8 along with their current SSRI.
Measure Participants	29	30
Count of Participants [Participants]	13 44.8%	13 41.9%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Levomilnacipran, Quetiapine
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.884
	Comments
	Method	Mantel Haenszel
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.063
	Confidence Interval	(2-Sided) 95%; 0.380 to 2.971
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.525
	Estimation Comments

7. Secondary Outcome

Title	Number of Subjects With General Improvement in Scores on Clinical Global Impression Scale- Improvement (CGI-I)
Description	CGI-I a 7 point scale that requires the clinician to assess how much the patient's illness has improved or worsened relative to a baseline state at the beginning of the intervention. It is used to assess the clinician's view of the patient's global functioning. Total score range of 0-7.
Time Frame	Baseline to Week 8

Outcome Measure Data

Analysis Population Description

Data not available for some participants.

Arm/Group Title	Levomilnacipran	Quetiapine
Arm/Group Description	Levomilnacipran ER is switched from SSRI. Levomilnacipran ER: A flexible dose regime of levomilnacipran ER 20-120 mg/d mg per day, starting at 20 mg/d on Days 1-2, increasing to 40 mg/d on Days 3-7 in week 1, then flexibly dosed between 40 mg/d -120 mg/d during weeks 2 through 8.	Quetiapine XR was added in addition to current SSRI. Quetiapine XR: Quetiapine XR was started at 50 mg/d on Day 1-2, increasing to 150 mg/d on Days 3-7 in Week 1 and then flexibly dosed between 150-300 mg/d during Weeks 1 through 8 along with their current SSRI.
Measure Participants	27	30
Count of Participants [Participants]	21 72.4%	24 77.4%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Levomilnacipran, Quetiapine
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.905
	Comments
	Method	Mantel Haenszel
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.875
	Confidence Interval	(2-Sided) 95%; 0.245 to 3.129
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.650
	Estimation Comments

8. Secondary Outcome

Title	Changes of Anxiety Symptoms in Scores on Hamilton Anxiety Rating Scale (HAM-A)
Description	A questionnaire used by clinicians to rate the severity of a patient's anxiety. Total score range of 0-48. A higher score indicates greater anxiety.
Time Frame	Baseline to Week 8

Outcome Measure Data

Analysis Population Description

Data not available for all subjects.

Arm/Group Title	Levomilnacipran	Quetiapine
Arm/Group Description	Levomilnacipran ER is switched from SSRI. Levomilnacipran ER: A flexible dose regime of levomilnacipran ER 20-120 mg/d mg per day, starting at 20 mg/d on Days 1-2, increasing to 40 mg/d on Days 3-7 in week 1, then flexibly dosed between 40 mg/d -120 mg/d during weeks 2 through 8.	Quetiapine XR was added in addition to current SSRI. Quetiapine XR: Quetiapine XR was started at 50 mg/d on Day 1-2, increasing to 150 mg/d on Days 3-7 in Week 1 and then flexibly dosed between 150-300 mg/d during Weeks 1 through 8 along with their current SSRI.
Measure Participants	28	30
Mean (Standard Deviation) [score on a scale]	-3.89 (4.969)	-5.53 (5.859)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Levomilnacipran, Quetiapine
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.254
	Comments
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	1.64
	Confidence Interval	(2-Sided) 95%; -1.211 to 4.492
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.423
	Estimation Comments

9. Secondary Outcome

Title	Changes of Quality of Life in Scores on Sheehan Disability Scale (SDS) Total
Description	A self-reported brief scale to assess impairment of work/school, social life and family and home. Total score range of 0-30. A higher score indicates greater impairment.
Time Frame	Baseline to Week 8

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Levomilnacipran	Quetiapine
Arm/Group Description	Levomilnacipran ER is switched from SSRI. Levomilnacipran ER: A flexible dose regime of levomilnacipran ER 20-120 mg/d mg per day, starting at 20 mg/d on Days 1-2, increasing to 40 mg/d on Days 3-7 in week 1, then flexibly dosed between 40 mg/d -120 mg/d during weeks 2 through 8.	Quetiapine XR was added in addition to current SSRI. Quetiapine XR: Quetiapine XR was started at 50 mg/d on Day 1-2, increasing to 150 mg/d on Days 3-7 in Week 1 and then flexibly dosed between 150-300 mg/d during Weeks 1 through 8 along with their current SSRI.
Measure Participants	29	30
Mean (Standard Deviation) [score on a scale]	-3.79 (6.477)	-0.10 (8.126)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Levomilnacipran, Quetiapine
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.058
	Comments
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-3.693
	Confidence Interval	(2-Sided) 95%; -7.520 to 0.134
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.910
	Estimation Comments

10. Secondary Outcome

Title	Changes in Scores on Apathy Evaluation Scale (AES).
Description	Self-Administered assessment measuring lack of motivation not attributable to diminished level of consciousness, cognitive impairment, or emotional distress. Total scores range from 0-54. Higher scores indicate greater apathy.
Time Frame	Baseline to Week 8

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Levomilnacipran	Quetiapine
Arm/Group Description	Levomilnacipran ER is switched from SSRI. Levomilnacipran ER: A flexible dose regime of levomilnacipran ER 20-120 mg/d mg per day, starting at 20 mg/d on Days 1-2, increasing to 40 mg/d on Days 3-7 in week 1, then flexibly dosed between 40 mg/d -120 mg/d during weeks 2 through 8.	Quetiapine XR was added in addition to current SSRI. Quetiapine XR: Quetiapine XR was started at 50 mg/d on Day 1-2, increasing to 150 mg/d on Days 3-7 in Week 1 and then flexibly dosed between 150-300 mg/d during Weeks 1 through 8 along with their current SSRI.
Measure Participants	29	30
Mean (Standard Deviation) [score on a scale]	-2.07 (8.689)	-1.83 (7.852)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Levomilnacipran, Quetiapine
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.913
	Comments
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.236
	Confidence Interval	(2-Sided) 95%; -4.559 to 4.088
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 2.158
	Estimation Comments

11. Secondary Outcome

Title	Changes in Sexual Dysfunction by Changes in Scores on Arizona Sexual Experience Scale (ASEX)
Description	ASEX is scale for sexual dysfunction to assess safety and tolerability of medication. Total scores range from 5-30. Higher scores indicate greater sexual dysfunction.
Time Frame	Baseline to Week 8

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Levomilnacipran	Quetiapine
Arm/Group Description	Levomilnacipran ER is switched from SSRI. Levomilnacipran ER: A flexible dose regime of levomilnacipran ER 20-120 mg/d mg per day, starting at 20 mg/d on Days 1-2, increasing to 40 mg/d on Days 3-7 in week 1, then flexibly dosed between 40 mg/d -120 mg/d during weeks 2 through 8.	Quetiapine XR was added in addition to current SSRI. Quetiapine XR: Quetiapine XR was started at 50 mg/d on Day 1-2, increasing to 150 mg/d on Days 3-7 in Week 1 and then flexibly dosed between 150-300 mg/d during Weeks 1 through 8 along with their current SSRI.
Measure Participants	29	30
Mean (Standard Deviation) [score on a scale]	-0.76 (2.923)	-0.30 (4.829)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Levomilnacipran, Quetiapine
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.660
	Comments
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.459
	Confidence Interval	(2-Sided) 95%; -2.540 to 1.623
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.035
	Estimation Comments

Adverse Events

Time Frame	Screening to Week 9
Arm/Group Title	Levomilnacipran		Quetiapine
Arm/Group Description	Levomilnacipran ER is switched from SSRI. Levomilnacipran ER: A flexible dose regime of levomilnacipran ER 20-120 mg/d mg per day, starting at 20 mg/d on Days 1-2, increasing to 40 mg/d on Days 3-7 in week 1, then flexibly dosed between 40 mg/d -120 mg/d during weeks 2 through 8.		Quetiapine XR was added in addition to current SSRI. Quetiapine XR: Quetiapine XR was started at 50 mg/d on Day 1-2, increasing to 150 mg/d on Days 3-7 in Week 1 and then flexibly dosed between 150-300 mg/d during Weeks 1 through 8 along with their current SSRI.
All Cause Mortality
	Levomilnacipran		Quetiapine
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/29 (0%)		0/31 (0%)
Serious Adverse Events
	Levomilnacipran		Quetiapine
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/29 (0%)		0/31 (0%)
Other (Not Including Serious) Adverse Events
	Levomilnacipran		Quetiapine
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	16/29 (55.2%)		22/31 (71%)
Gastrointestinal disorders
Nausea	4/29 (13.8%)		4/31 (12.9%)
General disorders
Increase Appetite	0/29 (0%)		3/31 (9.7%)
Weight Gain	1/29 (3.4%)		3/31 (9.7%)
Weight Loss	1/29 (3.4%)		0/31 (0%)
Dry Mouth	0/29 (0%)		1/31 (3.2%)
Sweating	3/29 (10.3%)		0/31 (0%)
Nervous system disorders
Headache	6/29 (20.7%)		2/31 (6.5%)
Drowsiness	2/29 (6.9%)		12/31 (38.7%)
Dizziness	0/29 (0%)		1/31 (3.2%)
Confusion	0/29 (0%)		2/31 (6.5%)
Renal and urinary disorders
Dysuria	2/29 (6.9%)		0/31 (0%)

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.