Trial Outcomes & Findings for Identifying Factors That Predict Antidepressant Treatment Response (NCT NCT00360399)

Last Updated: 2016-08-30

Results Overview

The percentage of participants who achieved remission from a major depressive episode, using a last observation carried forward (LOCF) dataset, defined as all randomized patients who initiated treatment and had at least one follow-up rating assessment. A score of equal to or greater than 7 on the Hamilton Depression Rating Scale (HDRS) at the last observation was considered to be remission from depression.

Recruitment status

COMPLETED

Study phase

Target enrollment

344 participants

Primary outcome timeframe

Up to 12 Weeks

Results posted on

2016-08-30

Participant Flow

Participants were recruited through the Emory University Mood and Anxiety Disorders Program. Men and women, aged 18-65, meeting DSM-IV criteria for a current major depressive disorder, and who had not received prior treatment for a mood disorder were eligible. 515 consented to participate in the trial and 344 were randomized to a treatment arm.

A total of 344 participants were randomized as follows: 114 randomized to the Escitalopram arm 115 randomized to the Duloxetine arm 115 randomized to the Cognitive behavioral therapy (CBT) arm 28 participants did not return for a post-randomization assessment, resulting in 316 participants with data to analyze.

Participant milestones

Participant milestones
Measure	Escitalopram Participants were randomized to receive treatment with escitalopram for 12 weeks, at a dose of 10 to 20 mg per day	Duloxetine Participants were randomized to receive treatment with duloxetine for 12 weeks, at a dose of 30 to 60 mg per day	Cognitive Behavioral Therapy (CBT) Participants were randomized to receive 16 one-hour sessions of cognitive behavioral therapy (CBT) delivered over 12 weeks
Overall Study STARTED	114	115	115
Overall Study Had Post-randomization Assessment	105	106	105
Overall Study COMPLETED	86	79	69
Overall Study NOT COMPLETED	28	36	46

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Identifying Factors That Predict Antidepressant Treatment Response

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Escitalopram n=114 Participants Participants were randomized to receive treatment with escitalopram for 12 weeks, at a dose of 10 to 20 mg per day	Duloxetine n=115 Participants Participants were randomized to receive treatment with duloxetine for 12 weeks, at a dose of 30 to 60 mg per day	Cognitive Behavioral Therapy (CBT) n=115 Participants Participants were randomized to receive 16 one-hour sessions of cognitive behavioral therapy (CBT) delivered over 12 weeks	Total n=344 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	0 Participants n=483 Participants
Age, Categorical Between 18 and 65 years	114 Participants n=93 Participants	115 Participants n=4 Participants	115 Participants n=27 Participants	344 Participants n=483 Participants
Age, Categorical >=65 years	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	0 Participants n=483 Participants
Age, Continuous	41.6 years STANDARD_DEVIATION 12.1 • n=93 Participants	38.3 years STANDARD_DEVIATION 11.4 • n=4 Participants	40.0 years STANDARD_DEVIATION 11.3 • n=27 Participants	40.0 years STANDARD_DEVIATION 11.7 • n=483 Participants
Sex: Female, Male Female	64 Participants n=93 Participants	68 Participants n=4 Participants	64 Participants n=27 Participants	196 Participants n=483 Participants
Sex: Female, Male Male	50 Participants n=93 Participants	47 Participants n=4 Participants	51 Participants n=27 Participants	148 Participants n=483 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	36 Participants n=93 Participants	34 Participants n=4 Participants	32 Participants n=27 Participants	102 Participants n=483 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	78 Participants n=93 Participants	81 Participants n=4 Participants	83 Participants n=27 Participants	242 Participants n=483 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	0 Participants n=483 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	0 Participants n=483 Participants
Race (NIH/OMB) Asian	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	0 Participants n=483 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	0 Participants n=483 Participants
Race (NIH/OMB) Black or African American	28 Participants n=93 Participants	23 Participants n=4 Participants	13 Participants n=27 Participants	64 Participants n=483 Participants
Race (NIH/OMB) White	47 Participants n=93 Participants	56 Participants n=4 Participants	61 Participants n=27 Participants	164 Participants n=483 Participants
Race (NIH/OMB) More than one race	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	0 Participants n=483 Participants
Race (NIH/OMB) Unknown or Not Reported	39 Participants n=93 Participants	36 Participants n=4 Participants	41 Participants n=27 Participants	116 Participants n=483 Participants
Region of Enrollment United States	114 participants n=93 Participants	115 participants n=4 Participants	115 participants n=27 Participants	344 participants n=483 Participants
Current Anxiety Disorder Yes	67 participants n=93 Participants	67 participants n=4 Participants	71 participants n=27 Participants	205 participants n=483 Participants
Current Anxiety Disorder No	47 participants n=93 Participants	48 participants n=4 Participants	44 participants n=27 Participants	139 participants n=483 Participants
Previous Episode(s) of Depression One	59 participants n=93 Participants	51 participants n=4 Participants	67 participants n=27 Participants	177 participants n=483 Participants
Previous Episode(s) of Depression Two	20 participants n=93 Participants	26 participants n=4 Participants	17 participants n=27 Participants	63 participants n=483 Participants
Previous Episode(s) of Depression Three or more	33 participants n=93 Participants	38 participants n=4 Participants	28 participants n=27 Participants	99 participants n=483 Participants
Previous Episode(s) of Depression None	2 participants n=93 Participants	0 participants n=4 Participants	3 participants n=27 Participants	5 participants n=483 Participants
Chronic Episode of Depression (2 or More Years) Yes	31 participants n=93 Participants	37 participants n=4 Participants	38 participants n=27 Participants	106 participants n=483 Participants
Chronic Episode of Depression (2 or More Years) No	83 participants n=93 Participants	78 participants n=4 Participants	77 participants n=27 Participants	238 participants n=483 Participants
History of Suicide Attempt Yes	4 participants n=93 Participants	13 participants n=4 Participants	8 participants n=27 Participants	25 participants n=483 Participants
History of Suicide Attempt No	110 participants n=93 Participants	102 participants n=4 Participants	107 participants n=27 Participants	319 participants n=483 Participants

PRIMARY outcome

Timeframe: Up to 12 Weeks

Population: This population consists of all participants who were randomized and returned for at least one study visit. This population was used for the intent to treat analyses and not all of these individuals completed the study.

Outcome measures

Outcome measures
Measure	Escitalopram n=105 Participants Participants were randomized to receive treatment with escitalopram for 12 weeks, at a dose of 10 to 20 mg per day	Duloxetine n=106 Participants Participants were randomized to receive treatment with duloxetine for 12 weeks, at a dose of 30 to 60 mg per day	Cognitive Behavioral Therapy (CBT) n=105 Participants Participants were randomized to receive 16 one-hour sessions of cognitive behavioral therapy (CBT) delivered over 12 weeks
Remission From Major Depressive Episode in Intent to Treat Sample	46.7 percentage of participants	54.7 percentage of participants	41.9 percentage of participants

PRIMARY outcome

Timeframe: Measured at Weeks 10 and 12

Population: This population includes participants who completed the trial, per study protocol.

The percentage of participants who achieved remission from a major depressive episode. A score of equal to or greater than 7 on the Hamilton Depression Rating Scale (HDRS) after 10 weeks and 12 weeks of the assigned study treatment was considered to be remission from depression.

Outcome measures

Outcome measures
Measure	Escitalopram n=86 Participants Participants were randomized to receive treatment with escitalopram for 12 weeks, at a dose of 10 to 20 mg per day	Duloxetine n=79 Participants Participants were randomized to receive treatment with duloxetine for 12 weeks, at a dose of 30 to 60 mg per day	Cognitive Behavioral Therapy (CBT) n=69 Participants Participants were randomized to receive 16 one-hour sessions of cognitive behavioral therapy (CBT) delivered over 12 weeks
Remission From Major Depressive Episode Among Participants Who Completed the Intervention	44.2 percentage of participants	51.9 percentage of participants	43.5 percentage of participants

SECONDARY outcome

Timeframe: Up to 12 Weeks

Population: The population is defined as all randomized patients who initiated treatment and had at least one follow-up rating assessment.

Four mutually exclusive categorical outcomes were defined based on the last valid Hamilton Depression Rating Scale (HDRS) rating at the last observation: 1. Non-response: \<30% reduction from baseline 2. Partial Response: 30-49% reduction from baseline 3. Response without remission: ≥50% reduction from baseline, but HDRS-17 score \>7 4. Remission: HDRS score ≤7

Outcome measures

Outcome measures
Measure	Escitalopram n=105 Participants Participants were randomized to receive treatment with escitalopram for 12 weeks, at a dose of 10 to 20 mg per day	Duloxetine n=106 Participants Participants were randomized to receive treatment with duloxetine for 12 weeks, at a dose of 30 to 60 mg per day	Cognitive Behavioral Therapy (CBT) n=105 Participants Participants were randomized to receive 16 one-hour sessions of cognitive behavioral therapy (CBT) delivered over 12 weeks
Number of Participants in Each Category of Response to Treatment of Depressive Symptoms, in Intent to Treat Sample Non-Response	26 participants	21 participants	32 participants
Number of Participants in Each Category of Response to Treatment of Depressive Symptoms, in Intent to Treat Sample Partial Response	12 participants	16 participants	19 participants
Number of Participants in Each Category of Response to Treatment of Depressive Symptoms, in Intent to Treat Sample Response without remission	18 participants	11 participants	10 participants
Number of Participants in Each Category of Response to Treatment of Depressive Symptoms, in Intent to Treat Sample Remission	49 participants	58 participants	44 participants

SECONDARY outcome

Timeframe: Measured at Weeks 10 and 12

Population: This population includes participants who completed the trial, per study protocol.

Four mutually exclusive categorical outcomes were defined based on the last valid Hamilton Depression Rating Scale (HDRS) rating at the Week 10 and Week 12 visits: 1. Non-response: \<30% reduction from baseline 2. Partial Response: 30-49% reduction from baseline 3. Response without remission: ≥50% reduction from baseline, but HDRS-17 score \>7 4. Remission: HDRS score ≤7

Outcome measures

Outcome measures
Measure	Escitalopram n=86 Participants Participants were randomized to receive treatment with escitalopram for 12 weeks, at a dose of 10 to 20 mg per day	Duloxetine n=79 Participants Participants were randomized to receive treatment with duloxetine for 12 weeks, at a dose of 30 to 60 mg per day	Cognitive Behavioral Therapy (CBT) n=69 Participants Participants were randomized to receive 16 one-hour sessions of cognitive behavioral therapy (CBT) delivered over 12 weeks
Number of Participants in Each Category of Response to Treatment of Depressive Symptoms, Among Participants Who Completed the Intervention Non-Response	15 participants	10 participants	15 participants
Number of Participants in Each Category of Response to Treatment of Depressive Symptoms, Among Participants Who Completed the Intervention Partial Response	10 participants	12 participants	13 participants
Number of Participants in Each Category of Response to Treatment of Depressive Symptoms, Among Participants Who Completed the Intervention Response without remission	23 participants	16 participants	11 participants
Number of Participants in Each Category of Response to Treatment of Depressive Symptoms, Among Participants Who Completed the Intervention Remission	38 participants	41 participants	30 participants

SECONDARY outcome

Timeframe: Measured at 6, 9, 12, 15, 18, 21, and 24 months

Population: This population is comprised of participants who completed 12 weeks of treatment, achieved remission, and participated in a follow-up phase that lasted for up to 21 months or until recurrence occurred.

The number of participants experiencing a recurrence of depression after they had been in remission with the monotherapy treatment they were randomized to receive.

Outcome measures

Outcome measures
Measure	Escitalopram n=34 Participants Participants were randomized to receive treatment with escitalopram for 12 weeks, at a dose of 10 to 20 mg per day	Duloxetine n=38 Participants Participants were randomized to receive treatment with duloxetine for 12 weeks, at a dose of 30 to 60 mg per day	Cognitive Behavioral Therapy (CBT) n=24 Participants Participants were randomized to receive 16 one-hour sessions of cognitive behavioral therapy (CBT) delivered over 12 weeks
Number of Participants Experiencing Depression Recurrence Following Remission to Monotherapy Treatment 6 Months	0 participants	0 participants	1 participants
Number of Participants Experiencing Depression Recurrence Following Remission to Monotherapy Treatment 9 Months	1 participants	2 participants	1 participants
Number of Participants Experiencing Depression Recurrence Following Remission to Monotherapy Treatment 12 Months	1 participants	2 participants	3 participants
Number of Participants Experiencing Depression Recurrence Following Remission to Monotherapy Treatment 15 Months	1 participants	4 participants	5 participants
Number of Participants Experiencing Depression Recurrence Following Remission to Monotherapy Treatment 18 Months	2 participants	4 participants	5 participants
Number of Participants Experiencing Depression Recurrence Following Remission to Monotherapy Treatment 21 Months	3 participants	5 participants	5 participants
Number of Participants Experiencing Depression Recurrence Following Remission to Monotherapy Treatment 24 Months	3 participants	5 participants	5 participants

SECONDARY outcome

Timeframe: Measured after 12 weeks of combined treatment

Population: Participants who did not achieve remission during monotherapy were offered 12 weeks of combination therapy. This sample consists of those participants who consented for the combination therapy part of the trial and who completed the 12 weeks of treatment.

The number of participants achieving remission from major depressive episode after 12 weeks of combined treatment consisting of antidepressant plus cognitive behavioral therapy (CBT) treatments. Those originally randomized to receive one of the antidepressants remained on that medication and had CBT sessions added. Participants originally randomized to CBT had escitalopram added at a dose of 10 to 20 mg per day for 12 weeks

Outcome measures

Outcome measures
Measure	Escitalopram n=41 Participants Participants were randomized to receive treatment with escitalopram for 12 weeks, at a dose of 10 to 20 mg per day	Duloxetine n=25 Participants Participants were randomized to receive treatment with duloxetine for 12 weeks, at a dose of 30 to 60 mg per day	Cognitive Behavioral Therapy (CBT) n=31 Participants Participants were randomized to receive 16 one-hour sessions of cognitive behavioral therapy (CBT) delivered over 12 weeks
Number of Participants Achieving Remission From Major Depressive Episode After 12 Weeks of Combined Treatment, for Those Patients Who do Not Achieve Remission With Monotherapy	22 participants	10 participants	18 participants

Adverse Events

Escitalopram

Serious events: 6 serious events

Other events: 100 other events

Deaths: 0 deaths

Duloxetine

Serious events: 3 serious events

Other events: 108 other events

Deaths: 0 deaths

Cognitive Behavioral Therapy (CBT)

Serious events: 1 serious events

Other events: 70 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Escitalopram n=114 participants at risk Participants were randomized to receive treatment with escitalopram for 12 weeks, at a dose of 10 to 20 mg per day	Duloxetine n=115 participants at risk Participants were randomized to receive treatment with duloxetine for 12 weeks, at a dose of 30 to 60 mg per day	Cognitive Behavioral Therapy (CBT) n=115 participants at risk Participants were randomized to receive 16 one-hour sessions of cognitive behavioral therapy (CBT) delivered over 12 weeks
Respiratory, thoracic and mediastinal disorders Hospitalization for asthma attack	0.00% 0/114 • Adverse events will be collected during the entire time a participant remains in the trial (up to 24 weeks)	0.00% 0/115 • Adverse events will be collected during the entire time a participant remains in the trial (up to 24 weeks)	0.87% 1/115 • Number of events 1 • Adverse events will be collected during the entire time a participant remains in the trial (up to 24 weeks)
Skin and subcutaneous tissue disorders Laceration	0.88% 1/114 • Number of events 1 • Adverse events will be collected during the entire time a participant remains in the trial (up to 24 weeks)	0.00% 0/115 • Adverse events will be collected during the entire time a participant remains in the trial (up to 24 weeks)	0.00% 0/115 • Adverse events will be collected during the entire time a participant remains in the trial (up to 24 weeks)
General disorders Motor Vehicle Accident	1.8% 2/114 • Number of events 2 • Adverse events will be collected during the entire time a participant remains in the trial (up to 24 weeks)	0.87% 1/115 • Number of events 1 • Adverse events will be collected during the entire time a participant remains in the trial (up to 24 weeks)	0.00% 0/115 • Adverse events will be collected during the entire time a participant remains in the trial (up to 24 weeks)
Renal and urinary disorders Urinary retention	0.88% 1/114 • Number of events 1 • Adverse events will be collected during the entire time a participant remains in the trial (up to 24 weeks)	0.00% 0/115 • Adverse events will be collected during the entire time a participant remains in the trial (up to 24 weeks)	0.00% 0/115 • Adverse events will be collected during the entire time a participant remains in the trial (up to 24 weeks)
Vascular disorders Deep vein thrombosis	0.88% 1/114 • Number of events 1 • Adverse events will be collected during the entire time a participant remains in the trial (up to 24 weeks)	0.00% 0/115 • Adverse events will be collected during the entire time a participant remains in the trial (up to 24 weeks)	0.00% 0/115 • Adverse events will be collected during the entire time a participant remains in the trial (up to 24 weeks)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lung cancer	0.88% 1/114 • Number of events 1 • Adverse events will be collected during the entire time a participant remains in the trial (up to 24 weeks)	0.00% 0/115 • Adverse events will be collected during the entire time a participant remains in the trial (up to 24 weeks)	0.00% 0/115 • Adverse events will be collected during the entire time a participant remains in the trial (up to 24 weeks)
Psychiatric disorders AttemptedSuicide by Overdose	0.00% 0/114 • Adverse events will be collected during the entire time a participant remains in the trial (up to 24 weeks)	1.7% 2/115 • Number of events 2 • Adverse events will be collected during the entire time a participant remains in the trial (up to 24 weeks)	0.00% 0/115 • Adverse events will be collected during the entire time a participant remains in the trial (up to 24 weeks)

Other adverse events

Additional Information

Helen Mayberg

Emory University

Phone: 404-727-6740

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Escitalopram n=114 participants at risk Participants were randomized to receive treatment with escitalopram for 12 weeks, at a dose of 10 to 20 mg per day	Duloxetine n=115 participants at risk Participants were randomized to receive treatment with duloxetine for 12 weeks, at a dose of 30 to 60 mg per day	Cognitive Behavioral Therapy (CBT) n=115 participants at risk Participants were randomized to receive 16 one-hour sessions of cognitive behavioral therapy (CBT) delivered over 12 weeks
General disorders Headache	31.6% 36/114 • Adverse events will be collected during the entire time a participant remains in the trial (up to 24 weeks)	33.0% 38/115 • Adverse events will be collected during the entire time a participant remains in the trial (up to 24 weeks)	16.5% 19/115 • Adverse events will be collected during the entire time a participant remains in the trial (up to 24 weeks)
Gastrointestinal disorders Nausea	25.4% 29/114 • Adverse events will be collected during the entire time a participant remains in the trial (up to 24 weeks)	32.2% 37/115 • Adverse events will be collected during the entire time a participant remains in the trial (up to 24 weeks)	7.0% 8/115 • Adverse events will be collected during the entire time a participant remains in the trial (up to 24 weeks)
Respiratory, thoracic and mediastinal disorders Upper Respiratory Tract Infection	12.3% 14/114 • Adverse events will be collected during the entire time a participant remains in the trial (up to 24 weeks)	27.0% 31/115 • Adverse events will be collected during the entire time a participant remains in the trial (up to 24 weeks)	23.5% 27/115 • Adverse events will be collected during the entire time a participant remains in the trial (up to 24 weeks)
Gastrointestinal disorders Diarrhea	20.2% 23/114 • Adverse events will be collected during the entire time a participant remains in the trial (up to 24 weeks)	19.1% 22/115 • Adverse events will be collected during the entire time a participant remains in the trial (up to 24 weeks)	9.6% 11/115 • Adverse events will be collected during the entire time a participant remains in the trial (up to 24 weeks)
General disorders Fatigue	19.3% 22/114 • Adverse events will be collected during the entire time a participant remains in the trial (up to 24 weeks)	23.5% 27/115 • Adverse events will be collected during the entire time a participant remains in the trial (up to 24 weeks)	1.7% 2/115 • Adverse events will be collected during the entire time a participant remains in the trial (up to 24 weeks)
General disorders Insomnia	17.5% 20/114 • Adverse events will be collected during the entire time a participant remains in the trial (up to 24 weeks)	22.6% 26/115 • Adverse events will be collected during the entire time a participant remains in the trial (up to 24 weeks)	2.6% 3/115 • Adverse events will be collected during the entire time a participant remains in the trial (up to 24 weeks)
General disorders Dry Mouth	15.8% 18/114 • Adverse events will be collected during the entire time a participant remains in the trial (up to 24 weeks)	24.3% 28/115 • Adverse events will be collected during the entire time a participant remains in the trial (up to 24 weeks)	1.7% 2/115 • Adverse events will be collected during the entire time a participant remains in the trial (up to 24 weeks)
General disorders Dizziness	14.0% 16/114 • Adverse events will be collected during the entire time a participant remains in the trial (up to 24 weeks)	18.3% 21/115 • Adverse events will be collected during the entire time a participant remains in the trial (up to 24 weeks)	3.5% 4/115 • Adverse events will be collected during the entire time a participant remains in the trial (up to 24 weeks)
General disorders Sedation	13.2% 15/114 • Adverse events will be collected during the entire time a participant remains in the trial (up to 24 weeks)	15.7% 18/115 • Adverse events will be collected during the entire time a participant remains in the trial (up to 24 weeks)	3.5% 4/115 • Adverse events will be collected during the entire time a participant remains in the trial (up to 24 weeks)
Gastrointestinal disorders Abdominal Pain	6.1% 7/114 • Adverse events will be collected during the entire time a participant remains in the trial (up to 24 weeks)	11.3% 13/115 • Adverse events will be collected during the entire time a participant remains in the trial (up to 24 weeks)	6.1% 7/115 • Adverse events will be collected during the entire time a participant remains in the trial (up to 24 weeks)
Gastrointestinal disorders Dyspepsia	7.9% 9/114 • Adverse events will be collected during the entire time a participant remains in the trial (up to 24 weeks)	8.7% 10/115 • Adverse events will be collected during the entire time a participant remains in the trial (up to 24 weeks)	5.2% 6/115 • Adverse events will be collected during the entire time a participant remains in the trial (up to 24 weeks)
Reproductive system and breast disorders Decreased Libido	10.5% 12/114 • Adverse events will be collected during the entire time a participant remains in the trial (up to 24 weeks)	9.6% 11/115 • Adverse events will be collected during the entire time a participant remains in the trial (up to 24 weeks)	1.7% 2/115 • Adverse events will be collected during the entire time a participant remains in the trial (up to 24 weeks)
Gastrointestinal disorders Constipation	7.9% 9/114 • Adverse events will be collected during the entire time a participant remains in the trial (up to 24 weeks)	11.3% 13/115 • Adverse events will be collected during the entire time a participant remains in the trial (up to 24 weeks)	1.7% 2/115 • Adverse events will be collected during the entire time a participant remains in the trial (up to 24 weeks)
Psychiatric disorders Anxiety	7.9% 9/114 • Adverse events will be collected during the entire time a participant remains in the trial (up to 24 weeks)	8.7% 10/115 • Adverse events will be collected during the entire time a participant remains in the trial (up to 24 weeks)	2.6% 3/115 • Adverse events will be collected during the entire time a participant remains in the trial (up to 24 weeks)
Reproductive system and breast disorders Anorgasmia	10.5% 12/114 • Adverse events will be collected during the entire time a participant remains in the trial (up to 24 weeks)	6.1% 7/115 • Adverse events will be collected during the entire time a participant remains in the trial (up to 24 weeks)	1.7% 2/115 • Adverse events will be collected during the entire time a participant remains in the trial (up to 24 weeks)
General disorders Yawning	6.1% 7/114 • Adverse events will be collected during the entire time a participant remains in the trial (up to 24 weeks)	8.7% 10/115 • Adverse events will be collected during the entire time a participant remains in the trial (up to 24 weeks)	1.7% 2/115 • Adverse events will be collected during the entire time a participant remains in the trial (up to 24 weeks)
Metabolism and nutrition disorders Decreased Appetite	6.1% 7/114 • Adverse events will be collected during the entire time a participant remains in the trial (up to 24 weeks)	7.8% 9/115 • Adverse events will be collected during the entire time a participant remains in the trial (up to 24 weeks)	0.87% 1/115 • Adverse events will be collected during the entire time a participant remains in the trial (up to 24 weeks)
General disorders Bruxism	7.0% 8/114 • Adverse events will be collected during the entire time a participant remains in the trial (up to 24 weeks)	5.2% 6/115 • Adverse events will be collected during the entire time a participant remains in the trial (up to 24 weeks)	0.87% 1/115 • Adverse events will be collected during the entire time a participant remains in the trial (up to 24 weeks)
Musculoskeletal and connective tissue disorders Back Pain	3.5% 4/114 • Adverse events will be collected during the entire time a participant remains in the trial (up to 24 weeks)	6.1% 7/115 • Adverse events will be collected during the entire time a participant remains in the trial (up to 24 weeks)	2.6% 3/115 • Adverse events will be collected during the entire time a participant remains in the trial (up to 24 weeks)
Gastrointestinal disorders Flatulence	5.3% 6/114 • Adverse events will be collected during the entire time a participant remains in the trial (up to 24 weeks)	4.3% 5/115 • Adverse events will be collected during the entire time a participant remains in the trial (up to 24 weeks)	2.6% 3/115 • Adverse events will be collected during the entire time a participant remains in the trial (up to 24 weeks)
General disorders Somnolence	7.0% 8/114 • Adverse events will be collected during the entire time a participant remains in the trial (up to 24 weeks)	4.3% 5/115 • Adverse events will be collected during the entire time a participant remains in the trial (up to 24 weeks)	0.87% 1/115 • Adverse events will be collected during the entire time a participant remains in the trial (up to 24 weeks)
General disorders Feeling Jittery	5.3% 6/114 • Adverse events will be collected during the entire time a participant remains in the trial (up to 24 weeks)	6.1% 7/115 • Adverse events will be collected during the entire time a participant remains in the trial (up to 24 weeks)	0.00% 0/115 • Adverse events will be collected during the entire time a participant remains in the trial (up to 24 weeks)
Skin and subcutaneous tissue disorders Hyperhidrosis	3.5% 4/114 • Adverse events will be collected during the entire time a participant remains in the trial (up to 24 weeks)	7.8% 9/115 • Adverse events will be collected during the entire time a participant remains in the trial (up to 24 weeks)	0.00% 0/115 • Adverse events will be collected during the entire time a participant remains in the trial (up to 24 weeks)
Reproductive system and breast disorders Abnormal Orgasm	2.6% 3/114 • Adverse events will be collected during the entire time a participant remains in the trial (up to 24 weeks)	7.8% 9/115 • Adverse events will be collected during the entire time a participant remains in the trial (up to 24 weeks)	0.87% 1/115 • Adverse events will be collected during the entire time a participant remains in the trial (up to 24 weeks)
Eye disorders Blurred Vision	5.3% 6/114 • Adverse events will be collected during the entire time a participant remains in the trial (up to 24 weeks)	3.5% 4/115 • Adverse events will be collected during the entire time a participant remains in the trial (up to 24 weeks)	1.7% 2/115 • Adverse events will be collected during the entire time a participant remains in the trial (up to 24 weeks)
Psychiatric disorders Emotional Poverty	7.9% 9/114 • Adverse events will be collected during the entire time a participant remains in the trial (up to 24 weeks)	0.87% 1/115 • Adverse events will be collected during the entire time a participant remains in the trial (up to 24 weeks)	0.00% 0/115 • Adverse events will be collected during the entire time a participant remains in the trial (up to 24 weeks)
Metabolism and nutrition disorders Increased Appetite	6.1% 7/114 • Adverse events will be collected during the entire time a participant remains in the trial (up to 24 weeks)	0.87% 1/115 • Adverse events will be collected during the entire time a participant remains in the trial (up to 24 weeks)	0.87% 1/115 • Adverse events will be collected during the entire time a participant remains in the trial (up to 24 weeks)
Cardiac disorders Palpitations	1.8% 2/114 • Adverse events will be collected during the entire time a participant remains in the trial (up to 24 weeks)	5.2% 6/115 • Adverse events will be collected during the entire time a participant remains in the trial (up to 24 weeks)	0.00% 0/115 • Adverse events will be collected during the entire time a participant remains in the trial (up to 24 weeks)