Brain Aging and Treatment Response in Geriatric Depression

• Sponsor: University of California, Los Angeles (Other)
• Overall Status: Completed
• CT.gov ID: NCT01902004
• Collaborator: National Institute of Mental Health (NIMH) (NIH)
• Enrollment: 115
• Location: 1
• Arms: 2
• Actual Duration (Months): 63.7
• Patients Per Site Per Month: 1.8

Study Details

Study Description

Brief Summary

The proposed project will evaluate the role of neuroimaging biomarkers of brain aging (i.e., neurodegenerative and vascular brain changes) and mild cognitive impairment in the patterns of treatment response to memantine combined with escitalopram compared to escitalopram and placebo.

Condition or Disease	Intervention/Treatment	Phase
Mild Cognitive Impairment (MCI); Depression	Drug: Escitalopram; Drug: Memantine; Drug: Placebo	Phase 4

Detailed Description

This study is designed to conduct a double-blind placebo-controlled trial of Namenda (Memantine) as an augmentation to Lexapro (Escitalopram) in depressed older adults 60 years of age and older. Throughout the course of the study, the investigators anticipate screening about 400 subjects to recruit 134 participants in the first four years. This study will require that the subjects complete up to 20 (twenty) visits in 12 (twelve) months to the study site during their participation. The purpose of this study is to determine whether Namenda (memantine) when taken in combination with Lexapro (escitalopram), may improve the quality of treatment response by making it faster and more complete, and also by improving thinking and memory in comparison to Lexapro taken with a placebo. Enrolled subjects will be provided with 10-20 mg of escitalopram for 12 months, and concurrently randomly assigned to either memantine or placebo groups. The investigators will also examine the safety and tolerability (how well the treatment works and the side effects) of a combination of Namenda and Lexapro as compared to placebo and Lexapro in subjects with major depressive disorder and mild cognitive impairment who are at least 60 years of age. Memantine is likely to accelerate and enhance antidepressant response to escitalopram and improve cognitive performance. Subjects with amnestic mild cognitive impairment or biomarkers of brain aging at baseline are likely to have preferential response to the combination of memantine and escitalopram compared to escitalopram and placebo, thus identifying a more personalized treatment approach in the high-risk subgroups for poor clinical outcomes.

Study Design

• Study Type: Interventional
• Actual Enrollment: 115 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Treatment of Geriatric Depression With Mild Cognitive Impairment: A Double-blind Placebo-Controlled Trial of Namenda (Memantine) Augmentation of Lexapro (Escitalopram) in Depressed Patients at Least 60 Years of Age
• Actual Study Start Date: Oct 1, 2013
• Actual Primary Completion Date: Jan 23, 2019
• Actual Study Completion Date: Jan 23, 2019

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Escitalopram and Memantine Participants will take a combination of Escitalopram and Memantine for 12 months	Drug: Escitalopram; All subjects will receive 10 to 20mg of escitalopram open-label throughout the trial. Participants will begin taking one 10mg capsule once per day, and this dosage may be increased or decreased depending on the participant's response to the medication. Participants will continue on their assigned dosage of escitalopram until treatment completion.; Other Names: Lexapro ; Drug: Memantine; Memantine dosage will be 5 to 20mg a day. Participants will initially take one 5mg capsule once a day, which will be gradually increased to a maximum of 10mg capsules twice per day.; Other Names: Namenda
Active Comparator: Escitalopram and placebo Participants will take a combination of Escitalopram and placebo for 12 months	Drug: Escitalopram; All subjects will receive 10 to 20mg of escitalopram open-label throughout the trial. Participants will begin taking one 10mg capsule once per day, and this dosage may be increased or decreased depending on the participant's response to the medication. Participants will continue on their assigned dosage of escitalopram until treatment completion.; Other Names: Lexapro ; Drug: Placebo; Placebo pills will be taken in combination with the active Namenda (Memantine) pills. Participants will initially take 1 capsule per day, which will be increased to a maximum of 1 capsule twice per day.; Other Names: inactive substance

Outcome Measures

Primary Outcome Measures

1. Change in Hamilton Depression Rating Scale [Measured at 3 months; 6 months and 12 months]

   Clinician administered scale measures severity of depressive symptoms. This measure includes 24 items. Response options vary item to item and include the following ranges: [0-2], [0-3], and [0-4]. A score of 0 suggests absence of symptoms and/or difficulties and higher scores represent more severe difficulties. Possible overall score range [0-74], higher scores representing more severe difficulties.

Secondary Outcome Measures

1. Change in Montgomery Asberg Depression Rating Scale [Measured at 3 months; 6 months and 12 months]

   Clinician administered item scale measures severity of depressive symptoms. The 10 items are measured on a 7-point scale ranging from 0 to 6; creating a total range of 0-60. A score of 0 suggests absence of symptoms and higher scores represent greater severity of depression.Severity gradations for the MADRS have been proposed (9-17 = mild, 18-34 = moderate, and ≥ 35 = severe). Treatment remission is defined as an endpoint total score ≤ 10.

2. Change in Cognitive Domain Scores [Measured at 6 months and 12 months]

   Neuropsychological battery of tests which included the following domains: learning, delayed recall, and executive functioning. Raw scores were transformed to z-scores for each test score of interest for each participant, and then averaged. These z-scores were averaged within each neuropsychological domain to produce composite scores and then averaged over all tests to calculate a global performance score. Higher scores are indicative of better performance.

Other Outcome Measures

1. Number of Participants With Adverse Events [Measured at 3, 6 months and 12 months]

   The UKU (Udvalg for Kliniske Undersogelser) Side Effect Rating Scale organizes symptoms into 4 categories (i.e., Psychic, Neurologic, Autonomic, Other) containing 8-19 symptoms each. Each symptom receives a score for degree and causal relationship. Degree is scored between 0-3 with higher scores being more severe. Causal relationship is scored as improbable, possible, or probable.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Meets the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) criteria for major depressive disorder (recurrent and nonrecurrent course will be identified)

• Score of 16 or higher on the 24-item Hamilton Rating Scale for Depression (HDRS) at study entry

• Score of 24 or higher on the Mini-Mental State Exam (MMSE)

• Age 60 years old or older

Exclusion Criteria:

• History of psychiatric illness or a substance abuse disorder other than unipolar depression, diagnosed prior to the onset of the first depressive episode

• Presence of psychotic symptoms

• Severe or acute medical illness (e.g., major surgery, metastatic cancer, stroke, heart attack) 6 months prior to study entry

• Acute suicidal or violent behavior or history of suicide attempt within the year prior to study entry

• Presence of delirium, neurodegenerative dementia, Parkinson's disease, or any other central nervous system (CNS) diseases

• Toxic or metabolic abnormalities on laboratory examination

• Medications taken or medical illnesses present that could account for depression

• Active heart failure categorized as Class III or greater according to New York Heart Association criteria

• Heart attack or crescendo angina within the 3 months prior to study entry

• Symptomatic cardiac arrhythmias or symptomatic, hemodynamically significant mitral or aortic valvular disease

• Resting heart rate less than 50 beats per minute and a corrected QT (QTc) interval greater than 0.45 seconds

• Second or third degree atrioventricular block

• Systolic blood pressure greater than 180 mmHg or less than 90 mmHg and diastolic blood pressure greater than 105 mmHg or less than 50 mmHg at study entry

• Treated with depot neuroleptic therapy within 6 months prior to study entry

• Treated with any neuroleptic, antidepressant, anxiolytic medication (other than lorazepam), or over-the-counter CNS-active medications used for treatment of depression (e.g, St. John's Wort, kava-kava, melatonin) within 2 weeks (4 weeks for fluoxetine or monoamine-oxidase inhibitors [MAOIs]) prior to the first administration of study medication

• Known allergy to escitalopram or memantine or history of ineffective treatment with escitalopram or memantine for current depressive episode

• Requires concomitant therapy with any prescription or over-the-counter medications that have potentially dangerous interactions with either escitalopram or memantine

• Requires electroconvulsive therapy (ECT) or received ECT within 3 months prior to study entry

• Initiated psychotherapy within 3 months prior to study entry or will be initiating or terminating psychotherapy during the study

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	UCLA Semel Institute - Neuropsychiatric Institute (NPI)	Los Angeles	California	United States	90095

Sponsors and Collaborators

• University of California, Los Angeles
• National Institute of Mental Health (NIMH)

Investigators

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

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Sep 19, 2018

More Information

Publications

None provided.

• Responsible Party: Helen Lavretsky, MD, Professor, University of California, Los Angeles
• ClinicalTrials.gov Identifier: NCT01902004
• Other Study ID Numbers: R-01 MH097892; R01MH097892
• First Posted: Jul 17, 2013
• Last Update Posted: Oct 15, 2019
• Last Verified: Oct 1, 2019

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Keywords provided by Helen Lavretsky, MD, Professor, University of California, Los Angeles: Major Depression; Geriatric Major Depression; Executive Cognitive Dysfunction; Mild Cognitive Impairment; Older Adults; Geriatric; Executive Cognitive Impairment; Quality of Life; Disability; Comorbidity; Medical Burden; Safety; Candidate Genes
• Additional relevant MeSH terms: Depression; Depressive Disorder; Cognitive Dysfunction; Memantine; Citalopram

Study Results

Participant Flow

Pre-assignment Detail	A total of 20 participants were excluded after being consented and prior to randomization. 5 were determined to be ineligible after completing the in-person screen visit in which they were consented. 15 withdrew consent before being randomized.

Arm/Group Title	Escitalopram and Memantine	Escitalopram and Placebo
Arm/Group Description	Participants will take a combination of Escitalopram and Memantine for 12 months Escitalopram: All subjects will receive 10 to 20mg of escitalopram open-label throughout the trial. Participants will begin taking one 10mg capsule once per day, and this dosage may be increased or decreased depending on the participant's response to the medication. Participants will continue on their assigned dosage of escitalopram until treatment completion. Memantine: Memantine dosage will be 5 to 20mg a day. Participants will initially take one 5mg capsule once a day, which will be gradually increased to a maximum of 10mg capsules twice per day.	Participants will take a combination of Escitalopram and placebo for 12 months Escitalopram: All subjects will receive 10 to 20mg of escitalopram open-label throughout the trial. Participants will begin taking one 10mg capsule once per day, and this dosage may be increased or decreased depending on the participant's response to the medication. Participants will continue on their assigned dosage of escitalopram until treatment completion. Placebo: Placebo pills will be taken in combination with the active Namenda (Memantine) pills. Participants will initially take 1 capsule per day, which will be increased to a maximum of 1 capsule twice per day.
Period Title: Overall Study
STARTED	48	47
COMPLETED	33	29
NOT COMPLETED	15	18

Baseline Characteristics

Arm/Group Title	Escitalopram and Memantine	Escitalopram and Placebo	Total
Arm/Group Description	Participants will take a combination of Escitalopram and Memantine for 12 months Escitalopram: All subjects will receive 10 to 20mg of escitalopram open-label throughout the trial. Participants will begin taking one 10mg capsule once per day, and this dosage may be increased or decreased depending on the participant's response to the medication. Participants will continue on their assigned dosage of escitalopram until treatment completion. Memantine: Memantine dosage will be 5 to 20mg a day. Participants will initially take one 5mg capsule once a day, which will be gradually increased to a maximum of 10mg capsules twice per day.	Participants will take a combination of Escitalopram and placebo for 12 months Escitalopram: All subjects will receive 10 to 20mg of escitalopram open-label throughout the trial. Participants will begin taking one 10mg capsule once per day, and this dosage may be increased or decreased depending on the participant's response to the medication. Participants will continue on their assigned dosage of escitalopram until treatment completion. Placebo: Placebo pills will be taken in combination with the active Namenda (Memantine) pills. Participants will initially take 1 capsule per day, which will be increased to a maximum of 1 capsule twice per day.	Total of all reporting groups
Overall Participants	48	47	95
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	14 29.2%	8 17%	22 23.2%
>=65 years	34 70.8%	39 83%	73 76.8%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	71 (6.9)	72.8 (6.8)	71.9 (6.8)
Sex: Female, Male (Count of Participants)
Female	26 54.2%	25 53.2%	51 53.7%
Male	22 45.8%	22 46.8%	44 46.3%
Race/Ethnicity, Customized (Count of Participants)
Caucasian	37 77.1%	33 70.2%	70 73.7%
African American	4 8.3%	2 4.3%	6 6.3%
Hispanic	3 6.3%	8 17%	11 11.6%
Other	4 8.3%	2 4.3%	6 6.3%
Region of Enrollment (participants) [Number]
United States	48 100%	47 100%	95 100%
Hamilton Depression Rating Scale Score (units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on a scale]	17.8 (2.3)	17.7 (2.4)	17.8 (2.3)

Outcome Measures

1. Primary Outcome

Title	Change in Hamilton Depression Rating Scale
Description	Clinician administered scale measures severity of depressive symptoms. This measure includes 24 items. Response options vary item to item and include the following ranges: [0-2], [0-3], and [0-4]. A score of 0 suggests absence of symptoms and/or difficulties and higher scores represent more severe difficulties. Possible overall score range [0-74], higher scores representing more severe difficulties.
Time Frame	Measured at 3 months; 6 months and 12 months

Outcome Measure Data

Analysis Population Description

The number of participants with available data at each time point differs due to participant dropout over the course of the study.

Arm/Group Title	Escitalopram and Memantine	Escitalopram and Placebo
Arm/Group Description	Participants will take a combination of Escitalopram and Memantine for 12 months Escitalopram: All subjects will receive 10 to 20mg of escitalopram open-label throughout the trial. Participants will begin taking one 10mg capsule once per day, and this dosage may be increased or decreased depending on the participant's response to the medication. Participants will continue on their assigned dosage of escitalopram until treatment completion. Memantine: Memantine dosage will be 5 to 20mg a day. Participants will initially take one 5mg capsule once a day, which will be gradually increased to a maximum of 10mg capsules twice per day.	Participants will take a combination of Escitalopram and placebo for 12 months Escitalopram: All subjects will receive 10 to 20mg of escitalopram open-label throughout the trial. Participants will begin taking one 10mg capsule once per day, and this dosage may be increased or decreased depending on the participant's response to the medication. Participants will continue on their assigned dosage of escitalopram until treatment completion. Placebo: Placebo pills will be taken in combination with the active Namenda (Memantine) pills. Participants will initially take 1 capsule per day, which will be increased to a maximum of 1 capsule twice per day.
Measure Participants	48	47
Baseline	17.8 (2.3)	17.7 (2.4)
3 Months	6.0 (4.5)	6.7 (4.7)
6 Months	5.9 (5.2)	6.9 (5.1)
12 Months	7.2 (5.8)	5.4 (5.3)

2. Secondary Outcome

Title	Change in Montgomery Asberg Depression Rating Scale
Description	Clinician administered item scale measures severity of depressive symptoms. The 10 items are measured on a 7-point scale ranging from 0 to 6; creating a total range of 0-60. A score of 0 suggests absence of symptoms and higher scores represent greater severity of depression.Severity gradations for the MADRS have been proposed (9-17 = mild, 18-34 = moderate, and ≥ 35 = severe). Treatment remission is defined as an endpoint total score ≤ 10.
Time Frame	Measured at 3 months; 6 months and 12 months

Outcome Measure Data

Analysis Population Description

The number of participants with available data at each time point differs due to participant dropout over the course of the study.

Arm/Group Title	Escitalopram and Memantine	Escitalopram and Placebo
Arm/Group Description	Participants will take a combination of Escitalopram and Memantine for 12 months Escitalopram: All subjects will receive 10 to 20mg of escitalopram open-label throughout the trial. Participants will begin taking one 10mg capsule once per day, and this dosage may be increased or decreased depending on the participant's response to the medication. Participants will continue on their assigned dosage of escitalopram until treatment completion. Memantine: Memantine dosage will be 5 to 20mg a day. Participants will initially take one 5mg capsule once a day, which will be gradually increased to a maximum of 10mg capsules twice per day.	Participants will take a combination of Escitalopram and placebo for 12 months Escitalopram: All subjects will receive 10 to 20mg of escitalopram open-label throughout the trial. Participants will begin taking one 10mg capsule once per day, and this dosage may be increased or decreased depending on the participant's response to the medication. Participants will continue on their assigned dosage of escitalopram until treatment completion. Placebo: Placebo pills will be taken in combination with the active Namenda (Memantine) pills. Participants will initially take 1 capsule per day, which will be increased to a maximum of 1 capsule twice per day.
Measure Participants	48	47
Baseline	16.7 (3.2)	14.8 (3.5)
3 Months	7.1 (5.9)	8.7 (5.5)
6 Months	6.0 (5.5)	8.6 (4.5)
12 Months	8.8 (7.3)	8.0 (6.5)

3. Secondary Outcome

Title	Change in Cognitive Domain Scores
Description	Neuropsychological battery of tests which included the following domains: learning, delayed recall, and executive functioning. Raw scores were transformed to z-scores for each test score of interest for each participant, and then averaged. These z-scores were averaged within each neuropsychological domain to produce composite scores and then averaged over all tests to calculate a global performance score. Higher scores are indicative of better performance.
Time Frame	Measured at 6 months and 12 months

Outcome Measure Data

Analysis Population Description

The number of participants with available data at each time point differs due to participant dropout over the course of the study.

Arm/Group Title	Escitalopram and Memantine	Escitalopram and Placebo
Arm/Group Description	Participants will take a combination of Escitalopram and Memantine for 12 months Escitalopram: All subjects will receive 10 to 20mg of escitalopram open-label throughout the trial. Participants will begin taking one 10mg capsule once per day, and this dosage may be increased or decreased depending on the participant's response to the medication. Participants will continue on their assigned dosage of escitalopram until treatment completion. Memantine: Memantine dosage will be 5 to 20mg a day. Participants will initially take one 5mg capsule once a day, which will be gradually increased to a maximum of 10mg capsules twice per day.	Participants will take a combination of Escitalopram and placebo for 12 months Escitalopram: All subjects will receive 10 to 20mg of escitalopram open-label throughout the trial. Participants will begin taking one 10mg capsule once per day, and this dosage may be increased or decreased depending on the participant's response to the medication. Participants will continue on their assigned dosage of escitalopram until treatment completion. Placebo: Placebo pills will be taken in combination with the active Namenda (Memantine) pills. Participants will initially take 1 capsule per day, which will be increased to a maximum of 1 capsule twice per day.
Measure Participants	48	47
Baseline	.02 (.62)	-.04 (0.7)
6 Months	0.03 (.53)	-.1 (.67)
12 Months	.15 (.67)	-.26 (.71)

4. Other Pre-specified Outcome

Title	Number of Participants With Adverse Events
Description	The UKU (Udvalg for Kliniske Undersogelser) Side Effect Rating Scale organizes symptoms into 4 categories (i.e., Psychic, Neurologic, Autonomic, Other) containing 8-19 symptoms each. Each symptom receives a score for degree and causal relationship. Degree is scored between 0-3 with higher scores being more severe. Causal relationship is scored as improbable, possible, or probable.
Time Frame	Measured at 3, 6 months and 12 months

Outcome Measure Data

Analysis Population Description

The number of participants with available data at each time point differs due to participant dropout over the course of the study.

Arm/Group Title	Escitalopram and Memantine	Escitalopram and Placebo
Arm/Group Description	Participants will take a combination of Escitalopram and Memantine for 12 months Escitalopram: All subjects will receive 10 to 20mg of escitalopram open-label throughout the trial. Participants will begin taking one 10mg capsule once per day, and this dosage may be increased or decreased depending on the participant's response to the medication. Participants will continue on their assigned dosage of escitalopram until treatment completion. Memantine: Memantine dosage will be 5 to 20mg a day. Participants will initially take one 5mg capsule once a day, which will be gradually increased to a maximum of 10mg capsules twice per day.	Participants will take a combination of Escitalopram and placebo for 12 months Escitalopram: All subjects will receive 10 to 20mg of escitalopram open-label throughout the trial. Participants will begin taking one 10mg capsule once per day, and this dosage may be increased or decreased depending on the participant's response to the medication. Participants will continue on their assigned dosage of escitalopram until treatment completion. Placebo: Placebo pills will be taken in combination with the active Namenda (Memantine) pills. Participants will initially take 1 capsule per day, which will be increased to a maximum of 1 capsule twice per day.
Measure Participants	48	47
3 Months	3 6.3%	2 4.3%
6 Months	3 6.3%	5 10.6%
12 Months	1 2.1%	0 0%

Adverse Events

Time Frame	1 year
Arm/Group Title	Escitalopram and Memantine		Escitalopram and Placebo
Arm/Group Description	Participants will take a combination of Escitalopram and Memantine for 12 months Escitalopram: All subjects will receive 10 to 20mg of escitalopram open-label throughout the trial. Participants will begin taking one 10mg capsule once per day, and this dosage may be increased or decreased depending on the participant's response to the medication. Participants will continue on their assigned dosage of escitalopram until treatment completion. Memantine: Memantine dosage will be 5 to 20mg a day. Participants will initially take one 5mg capsule once a day, which will be gradually increased to a maximum of 10mg capsules twice per day.		Participants will take a combination of Escitalopram and placebo for 12 months Escitalopram: All subjects will receive 10 to 20mg of escitalopram open-label throughout the trial. Participants will begin taking one 10mg capsule once per day, and this dosage may be increased or decreased depending on the participant's response to the medication. Participants will continue on their assigned dosage of escitalopram until treatment completion. Placebo: Placebo pills will be taken in combination with the active Namenda (Memantine) pills. Participants will initially take 1 capsule per day, which will be increased to a maximum of 1 capsule twice per day.
All Cause Mortality
	Escitalopram and Memantine		Escitalopram and Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/48 (0%)		0/47 (0%)
Serious Adverse Events
	Escitalopram and Memantine		Escitalopram and Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/48 (0%)		0/47 (0%)
Other (Not Including Serious) Adverse Events
	Escitalopram and Memantine		Escitalopram and Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	41/48 (85.4%)		41/47 (87.2%)
Cardiac disorders
Palpitations/Tachycardia	0/48 (0%)		1/47 (2.1%)
Eye disorders
Accomodation Disturbance	1/48 (2.1%)		0/47 (0%)
Gastrointestinal disorders
Nausea/Vomiting	2/48 (4.2%)		5/47 (10.6%)
Diarrhea	1/48 (2.1%)		1/47 (2.1%)
Constipation	3/48 (6.3%)		4/47 (8.5%)
General disorders
Increased Salivation	0/48 (0%)		1/47 (2.1%)
Reduced Salivation	4/48 (8.3%)		7/47 (14.9%)
Orthostatic Dizziness	3/48 (6.3%)		4/47 (8.5%)
Increased Tendancy to Sweating	1/48 (2.1%)		0/47 (0%)
Metabolism and nutrition disorders
Weight Gain	1/48 (2.1%)		2/47 (4.3%)
Nervous system disorders
Failing Memory	2/48 (4.2%)		2/47 (4.3%)
Headache	5/48 (10.4%)		2/47 (4.3%)
Psychiatric disorders
Concentration Difficulties	4/48 (8.3%)		5/47 (10.6%)
Asthenia/Lassitude/Increased Fatigability	3/48 (6.3%)		2/47 (4.3%)
Sleepiness/Sedation	11/48 (22.9%)		11/47 (23.4%)
Depression	0/48 (0%)		1/47 (2.1%)
Tension/Inner Unrest	4/48 (8.3%)		3/47 (6.4%)
Increased Duration of Sleep	1/48 (2.1%)		3/47 (6.4%)
Reduced Duration of Sleep	1/48 (2.1%)		3/47 (6.4%)
Increased Dream Activity	1/48 (2.1%)		1/47 (2.1%)
Renal and urinary disorders
Micturtion Disturbances	1/48 (2.1%)		3/47 (6.4%)
Polyuria/Polydipsia	3/48 (6.3%)		3/47 (6.4%)
Reproductive system and breast disorders
Diminished Sexual Drive	4/48 (8.3%)		4/47 (8.5%)
Erectile Dysfunction	2/48 (4.2%)		2/47 (4.3%)
Ejaculatory Dysfunction	1/48 (2.1%)		1/47 (2.1%)
Orgastic Dysfunction	0/48 (0%)		1/47 (2.1%)
Skin and subcutaneous tissue disorders
Rash	0/48 (0%)		2/47 (4.3%)
Pruritus	0/48 (0%)		2/47 (4.3%)

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.