Trial Outcomes & Findings for Influence of Escitalopram on Fear Conditioning (NCT NCT01398514)

Last Updated: 2014-06-11

Results Overview

Three-way interaction between group (active vs. placebo), CS (+ vs. -), and trials (1 - 4). CS+ refers to the conditioned stimulus associated with the unconditioned stimulus (electric shock). Higher numbers reflect higher skin conductance response to the CS+ (conditioned stimulus). CS- refers to the stimulus not associated with the unconditioned stimulus. Higher numbers reflect higher skin conductance response to a CS-. Square-root transformed skin conductance conditioned response are reported for trials 1 to 4 of the Early Extinction Phase.

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

65 participants

Primary outcome timeframe

Day 2 of Fear Conditioning Paradigm (15 to 18 days post medication initiation)

Results posted on

2014-06-11

Participant Flow

Participants free of DSM-IV Axis I disorders with varying levels of subsyndromal anxiety were recruited by advertisements (e.g., postings on Craigslist, postings on Massachusetts General Hospital research participation registry) from March 2009 through April 2011.

65 participants signed consent and were screened for enrollment. 10 participants did not meet study entry criteria due to exclusionary psychiatric conditions. Of the 55 eligible participants, 3 withdrew and 1 was lost to follow up. 52 participants were randomly assigned to a treatment arm. Fourteen were excluded from analyses.

Participant milestones

Participant milestones
Measure	Active Medication Escitalopram 10mg/day	Placebo Matched pill placebo
Overall Study STARTED	26	26
Overall Study COMPLETED	18	20
Overall Study NOT COMPLETED	8	6

Reasons for withdrawal

Reasons for withdrawal
Measure	Active Medication Escitalopram 10mg/day	Placebo Matched pill placebo
Overall Study Adverse Event	1	0
Overall Study Non-compliance with study procedures	2	0
Overall Study Physiologic non-responsiveness	1	3
Overall Study Failure to show a conditioned response	4	3

Baseline Characteristics

Influence of Escitalopram on Fear Conditioning

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Active Medication n=26 Participants Escitalopram 10mg/day	Placebo n=26 Participants Matched pill placebo	Total n=52 Participants Total of all reporting groups
Age, Categorical <=18 years	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	25 Participants n=5 Participants	26 Participants n=7 Participants	51 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Continuous	34.04 years STANDARD_DEVIATION 11.56 • n=5 Participants	30.46 years STANDARD_DEVIATION 11.46 • n=7 Participants	32.25 years STANDARD_DEVIATION 11.54 • n=5 Participants
Sex: Female, Male Female	14 Participants n=5 Participants	12 Participants n=7 Participants	26 Participants n=5 Participants
Sex: Female, Male Male	12 Participants n=5 Participants	14 Participants n=7 Participants	26 Participants n=5 Participants
Region of Enrollment United States	26 participants n=5 Participants	26 participants n=7 Participants	52 participants n=5 Participants

PRIMARY outcome

Timeframe: Day 2 of Fear Conditioning Paradigm (15 to 18 days post medication initiation)

Outcome measures

Outcome measures
Measure	Active Medication CS- n=16 Participants Escitalopram 10mg/day	Active Medication CS+ n=16 Participants Matched pill placebo	Placebo CS- n=18 Participants	Placebo CS+ n=18 Participants
Physiological Reactivity as Measured by Square-root Transformed Skin Conductance Conditioned Response in Early Extinction Trials 1 to 4 Trial 1	0.745 micro-Siemens (square rooted) Standard Error 0.130	0.853 micro-Siemens (square rooted) Standard Error 0.853	0.799 micro-Siemens (square rooted) Standard Error 0.122	0.717 micro-Siemens (square rooted) Standard Error 0.123
Physiological Reactivity as Measured by Square-root Transformed Skin Conductance Conditioned Response in Early Extinction Trials 1 to 4 Trial 2	0.496 micro-Siemens (square rooted) Standard Error 0.103	0.634 micro-Siemens (square rooted) Standard Error 0.114	0.386 micro-Siemens (square rooted) Standard Error 0.097	0.558 micro-Siemens (square rooted) Standard Error 0.108
Physiological Reactivity as Measured by Square-root Transformed Skin Conductance Conditioned Response in Early Extinction Trials 1 to 4 Trial 3	0.544 micro-Siemens (square rooted) Standard Error 0.111	0.520 micro-Siemens (square rooted) Standard Error 0.124	0.438 micro-Siemens (square rooted) Standard Error 0.105	0.787 micro-Siemens (square rooted) Standard Error 0.117
Physiological Reactivity as Measured by Square-root Transformed Skin Conductance Conditioned Response in Early Extinction Trials 1 to 4 Trial 4	0.374 micro-Siemens (square rooted) Standard Error 0.110	0.361 micro-Siemens (square rooted) Standard Error 0.116	0.309 micro-Siemens (square rooted) Standard Error 0.104	0.510 micro-Siemens (square rooted) Standard Error 0.109

PRIMARY outcome

Timeframe: Baseline on Day 1 of Fear Conditioning Paradigm (14 to 17 days post medication initiation)

Three-way interaction between group (active vs. placebo), CS (+ vs. -), and trials (1 - 5). CS+ refers to the conditioned stimulus associated with the unconditioned stimulus (electric shock). Higher numbers reflect higher skin conductance response to the CS+ (conditioned stimulus). CS- refers to the stimulus not associated with the unconditioned stimulus. Higher numbers reflect higher skin conductance response to a CS-. Square-root transformed skin conductance conditioned response are reported for trials 1 to 5 of the Acquisition Phase.

Outcome measures

Outcome measures
Measure	Active Medication CS- n=18 Participants Escitalopram 10mg/day	Active Medication CS+ n=18 Participants Matched pill placebo	Placebo CS- n=20 Participants	Placebo CS+ n=20 Participants
Physiological Reactivity as Measured by Square-root Transformed Skin Conductance Conditioned Response in Acquisition Trials 1 to 5 Trial 1	0.634 micro-Siemens (square rooted) Standard Error 0.093	0.574 micro-Siemens (square rooted) Standard Error 0.111	0.532 micro-Siemens (square rooted) Standard Error 0.088	0.634 micro-Siemens (square rooted) Standard Error 0.105
Physiological Reactivity as Measured by Square-root Transformed Skin Conductance Conditioned Response in Acquisition Trials 1 to 5 Trial 2	0.419 micro-Siemens (square rooted) Standard Error 0.122	0.870 micro-Siemens (square rooted) Standard Error 0.113	0.428 micro-Siemens (square rooted) Standard Error 0.116	0.817 micro-Siemens (square rooted) Standard Error 0.107
Physiological Reactivity as Measured by Square-root Transformed Skin Conductance Conditioned Response in Acquisition Trials 1 to 5 Trial 3	0.230 micro-Siemens (square rooted) Standard Error 0.119	0.685 micro-Siemens (square rooted) Standard Error 0.104	0.331 micro-Siemens (square rooted) Standard Error 0.112	0.856 micro-Siemens (square rooted) Standard Error 0.099
Physiological Reactivity as Measured by Square-root Transformed Skin Conductance Conditioned Response in Acquisition Trials 1 to 5 Trial 4	0.231 micro-Siemens (square rooted) Standard Error 0.086	0.626 micro-Siemens (square rooted) Standard Error 0.102	0.181 micro-Siemens (square rooted) Standard Error 0.082	0.677 micro-Siemens (square rooted) Standard Error 0.096
Physiological Reactivity as Measured by Square-root Transformed Skin Conductance Conditioned Response in Acquisition Trials 1 to 5 Trial 5	0.281 micro-Siemens (square rooted) Standard Error 0.071	0.543 micro-Siemens (square rooted) Standard Error 0.118	0.144 micro-Siemens (square rooted) Standard Error 0.067	0.714 micro-Siemens (square rooted) Standard Error 0.112

Adverse Events

Active Medication

Serious events: 0 serious events

Other events: 13 other events

Deaths: 0 deaths

Placebo

Serious events: 0 serious events

Other events: 7 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Additional Information

Dr. Naomi Simon

Massachusetts General Hospital

Phone: 617-726-7913

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The sponsor shall require the PI to furnish the sponsor with a copy of any proposed publication at least 60 days prior to submission. The sponsor shall be entitled to review such proposed publications. The PI shall give due regard to the sponsor's comments on the proposed publication. If the sponsor reasonably believes a patent application claiming an invention should be filed prior to such publication, such submission shall not be submitted until applicable patent applications have been filed.
Publication restrictions are in place

Restriction type: OTHER

Other adverse events
Measure	Active Medication n=25 participants at risk Escitalopram 10mg/day	Placebo n=26 participants at risk Matched pill placebo
Gastrointestinal disorders Appetite decrease	8.0% 2/25 • Number of events 2 • AEs were assessed in the period following randomization/medication initiation, through the experimental portion of the study (14-17 days post medication initiation), and 7 days following medication discontinuation. AEs were defined as any untoward or unfavorable medical occurrence in a human subject. SAEs event were defined as any event temporally associated with the subject's participation that: results in death, is life-threatening, results in inpatient hospitalization, results in significant disability, or results in a congenital anomaly or birth defect	0.00% 0/26 • AEs were assessed in the period following randomization/medication initiation, through the experimental portion of the study (14-17 days post medication initiation), and 7 days following medication discontinuation. AEs were defined as any untoward or unfavorable medical occurrence in a human subject. SAEs event were defined as any event temporally associated with the subject's participation that: results in death, is life-threatening, results in inpatient hospitalization, results in significant disability, or results in a congenital anomaly or birth defect
Nervous system disorders Tremor / Shakiness	4.0% 1/25 • Number of events 1 • AEs were assessed in the period following randomization/medication initiation, through the experimental portion of the study (14-17 days post medication initiation), and 7 days following medication discontinuation. AEs were defined as any untoward or unfavorable medical occurrence in a human subject. SAEs event were defined as any event temporally associated with the subject's participation that: results in death, is life-threatening, results in inpatient hospitalization, results in significant disability, or results in a congenital anomaly or birth defect	0.00% 0/26 • AEs were assessed in the period following randomization/medication initiation, through the experimental portion of the study (14-17 days post medication initiation), and 7 days following medication discontinuation. AEs were defined as any untoward or unfavorable medical occurrence in a human subject. SAEs event were defined as any event temporally associated with the subject's participation that: results in death, is life-threatening, results in inpatient hospitalization, results in significant disability, or results in a congenital anomaly or birth defect
Psychiatric disorders Anxiety / Nervousness	8.0% 2/25 • Number of events 2 • AEs were assessed in the period following randomization/medication initiation, through the experimental portion of the study (14-17 days post medication initiation), and 7 days following medication discontinuation. AEs were defined as any untoward or unfavorable medical occurrence in a human subject. SAEs event were defined as any event temporally associated with the subject's participation that: results in death, is life-threatening, results in inpatient hospitalization, results in significant disability, or results in a congenital anomaly or birth defect	0.00% 0/26 • AEs were assessed in the period following randomization/medication initiation, through the experimental portion of the study (14-17 days post medication initiation), and 7 days following medication discontinuation. AEs were defined as any untoward or unfavorable medical occurrence in a human subject. SAEs event were defined as any event temporally associated with the subject's participation that: results in death, is life-threatening, results in inpatient hospitalization, results in significant disability, or results in a congenital anomaly or birth defect
Nervous system disorders Jitteriness / Restlessness	4.0% 1/25 • Number of events 1 • AEs were assessed in the period following randomization/medication initiation, through the experimental portion of the study (14-17 days post medication initiation), and 7 days following medication discontinuation. AEs were defined as any untoward or unfavorable medical occurrence in a human subject. SAEs event were defined as any event temporally associated with the subject's participation that: results in death, is life-threatening, results in inpatient hospitalization, results in significant disability, or results in a congenital anomaly or birth defect	7.7% 2/26 • Number of events 2 • AEs were assessed in the period following randomization/medication initiation, through the experimental portion of the study (14-17 days post medication initiation), and 7 days following medication discontinuation. AEs were defined as any untoward or unfavorable medical occurrence in a human subject. SAEs event were defined as any event temporally associated with the subject's participation that: results in death, is life-threatening, results in inpatient hospitalization, results in significant disability, or results in a congenital anomaly or birth defect
General disorders Vivid or Disturbing Dreams	4.0% 1/25 • Number of events 1 • AEs were assessed in the period following randomization/medication initiation, through the experimental portion of the study (14-17 days post medication initiation), and 7 days following medication discontinuation. AEs were defined as any untoward or unfavorable medical occurrence in a human subject. SAEs event were defined as any event temporally associated with the subject's participation that: results in death, is life-threatening, results in inpatient hospitalization, results in significant disability, or results in a congenital anomaly or birth defect	3.8% 1/26 • Number of events 1 • AEs were assessed in the period following randomization/medication initiation, through the experimental portion of the study (14-17 days post medication initiation), and 7 days following medication discontinuation. AEs were defined as any untoward or unfavorable medical occurrence in a human subject. SAEs event were defined as any event temporally associated with the subject's participation that: results in death, is life-threatening, results in inpatient hospitalization, results in significant disability, or results in a congenital anomaly or birth defect
General disorders Fatigue	4.0% 1/25 • Number of events 1 • AEs were assessed in the period following randomization/medication initiation, through the experimental portion of the study (14-17 days post medication initiation), and 7 days following medication discontinuation. AEs were defined as any untoward or unfavorable medical occurrence in a human subject. SAEs event were defined as any event temporally associated with the subject's participation that: results in death, is life-threatening, results in inpatient hospitalization, results in significant disability, or results in a congenital anomaly or birth defect	0.00% 0/26 • AEs were assessed in the period following randomization/medication initiation, through the experimental portion of the study (14-17 days post medication initiation), and 7 days following medication discontinuation. AEs were defined as any untoward or unfavorable medical occurrence in a human subject. SAEs event were defined as any event temporally associated with the subject's participation that: results in death, is life-threatening, results in inpatient hospitalization, results in significant disability, or results in a congenital anomaly or birth defect
Nervous system disorders Headache	12.0% 3/25 • Number of events 3 • AEs were assessed in the period following randomization/medication initiation, through the experimental portion of the study (14-17 days post medication initiation), and 7 days following medication discontinuation. AEs were defined as any untoward or unfavorable medical occurrence in a human subject. SAEs event were defined as any event temporally associated with the subject's participation that: results in death, is life-threatening, results in inpatient hospitalization, results in significant disability, or results in a congenital anomaly or birth defect	3.8% 1/26 • Number of events 1 • AEs were assessed in the period following randomization/medication initiation, through the experimental portion of the study (14-17 days post medication initiation), and 7 days following medication discontinuation. AEs were defined as any untoward or unfavorable medical occurrence in a human subject. SAEs event were defined as any event temporally associated with the subject's participation that: results in death, is life-threatening, results in inpatient hospitalization, results in significant disability, or results in a congenital anomaly or birth defect
General disorders Sedation / Drowsiness	12.0% 3/25 • Number of events 3 • AEs were assessed in the period following randomization/medication initiation, through the experimental portion of the study (14-17 days post medication initiation), and 7 days following medication discontinuation. AEs were defined as any untoward or unfavorable medical occurrence in a human subject. SAEs event were defined as any event temporally associated with the subject's participation that: results in death, is life-threatening, results in inpatient hospitalization, results in significant disability, or results in a congenital anomaly or birth defect	0.00% 0/26 • AEs were assessed in the period following randomization/medication initiation, through the experimental portion of the study (14-17 days post medication initiation), and 7 days following medication discontinuation. AEs were defined as any untoward or unfavorable medical occurrence in a human subject. SAEs event were defined as any event temporally associated with the subject's participation that: results in death, is life-threatening, results in inpatient hospitalization, results in significant disability, or results in a congenital anomaly or birth defect
Gastrointestinal disorders Constipation	4.0% 1/25 • Number of events 1 • AEs were assessed in the period following randomization/medication initiation, through the experimental portion of the study (14-17 days post medication initiation), and 7 days following medication discontinuation. AEs were defined as any untoward or unfavorable medical occurrence in a human subject. SAEs event were defined as any event temporally associated with the subject's participation that: results in death, is life-threatening, results in inpatient hospitalization, results in significant disability, or results in a congenital anomaly or birth defect	0.00% 0/26 • AEs were assessed in the period following randomization/medication initiation, through the experimental portion of the study (14-17 days post medication initiation), and 7 days following medication discontinuation. AEs were defined as any untoward or unfavorable medical occurrence in a human subject. SAEs event were defined as any event temporally associated with the subject's participation that: results in death, is life-threatening, results in inpatient hospitalization, results in significant disability, or results in a congenital anomaly or birth defect
Psychiatric disorders Difficulty Concentrating	4.0% 1/25 • Number of events 1 • AEs were assessed in the period following randomization/medication initiation, through the experimental portion of the study (14-17 days post medication initiation), and 7 days following medication discontinuation. AEs were defined as any untoward or unfavorable medical occurrence in a human subject. SAEs event were defined as any event temporally associated with the subject's participation that: results in death, is life-threatening, results in inpatient hospitalization, results in significant disability, or results in a congenital anomaly or birth defect	0.00% 0/26 • AEs were assessed in the period following randomization/medication initiation, through the experimental portion of the study (14-17 days post medication initiation), and 7 days following medication discontinuation. AEs were defined as any untoward or unfavorable medical occurrence in a human subject. SAEs event were defined as any event temporally associated with the subject's participation that: results in death, is life-threatening, results in inpatient hospitalization, results in significant disability, or results in a congenital anomaly or birth defect
Reproductive system and breast disorders Sexual Dysfunction	8.0% 2/25 • Number of events 2 • AEs were assessed in the period following randomization/medication initiation, through the experimental portion of the study (14-17 days post medication initiation), and 7 days following medication discontinuation. AEs were defined as any untoward or unfavorable medical occurrence in a human subject. SAEs event were defined as any event temporally associated with the subject's participation that: results in death, is life-threatening, results in inpatient hospitalization, results in significant disability, or results in a congenital anomaly or birth defect	0.00% 0/26 • AEs were assessed in the period following randomization/medication initiation, through the experimental portion of the study (14-17 days post medication initiation), and 7 days following medication discontinuation. AEs were defined as any untoward or unfavorable medical occurrence in a human subject. SAEs event were defined as any event temporally associated with the subject's participation that: results in death, is life-threatening, results in inpatient hospitalization, results in significant disability, or results in a congenital anomaly or birth defect
General disorders Insomnia	12.0% 3/25 • Number of events 3 • AEs were assessed in the period following randomization/medication initiation, through the experimental portion of the study (14-17 days post medication initiation), and 7 days following medication discontinuation. AEs were defined as any untoward or unfavorable medical occurrence in a human subject. SAEs event were defined as any event temporally associated with the subject's participation that: results in death, is life-threatening, results in inpatient hospitalization, results in significant disability, or results in a congenital anomaly or birth defect	0.00% 0/26 • AEs were assessed in the period following randomization/medication initiation, through the experimental portion of the study (14-17 days post medication initiation), and 7 days following medication discontinuation. AEs were defined as any untoward or unfavorable medical occurrence in a human subject. SAEs event were defined as any event temporally associated with the subject's participation that: results in death, is life-threatening, results in inpatient hospitalization, results in significant disability, or results in a congenital anomaly or birth defect
General disorders Sweating / Hot Flashes	4.0% 1/25 • Number of events 1 • AEs were assessed in the period following randomization/medication initiation, through the experimental portion of the study (14-17 days post medication initiation), and 7 days following medication discontinuation. AEs were defined as any untoward or unfavorable medical occurrence in a human subject. SAEs event were defined as any event temporally associated with the subject's participation that: results in death, is life-threatening, results in inpatient hospitalization, results in significant disability, or results in a congenital anomaly or birth defect	0.00% 0/26 • AEs were assessed in the period following randomization/medication initiation, through the experimental portion of the study (14-17 days post medication initiation), and 7 days following medication discontinuation. AEs were defined as any untoward or unfavorable medical occurrence in a human subject. SAEs event were defined as any event temporally associated with the subject's participation that: results in death, is life-threatening, results in inpatient hospitalization, results in significant disability, or results in a congenital anomaly or birth defect
Nervous system disorders Lightheadedness	0.00% 0/25 • AEs were assessed in the period following randomization/medication initiation, through the experimental portion of the study (14-17 days post medication initiation), and 7 days following medication discontinuation. AEs were defined as any untoward or unfavorable medical occurrence in a human subject. SAEs event were defined as any event temporally associated with the subject's participation that: results in death, is life-threatening, results in inpatient hospitalization, results in significant disability, or results in a congenital anomaly or birth defect	3.8% 1/26 • Number of events 1 • AEs were assessed in the period following randomization/medication initiation, through the experimental portion of the study (14-17 days post medication initiation), and 7 days following medication discontinuation. AEs were defined as any untoward or unfavorable medical occurrence in a human subject. SAEs event were defined as any event temporally associated with the subject's participation that: results in death, is life-threatening, results in inpatient hospitalization, results in significant disability, or results in a congenital anomaly or birth defect
Gastrointestinal disorders Diarrhea	0.00% 0/25 • AEs were assessed in the period following randomization/medication initiation, through the experimental portion of the study (14-17 days post medication initiation), and 7 days following medication discontinuation. AEs were defined as any untoward or unfavorable medical occurrence in a human subject. SAEs event were defined as any event temporally associated with the subject's participation that: results in death, is life-threatening, results in inpatient hospitalization, results in significant disability, or results in a congenital anomaly or birth defect	3.8% 1/26 • Number of events 1 • AEs were assessed in the period following randomization/medication initiation, through the experimental portion of the study (14-17 days post medication initiation), and 7 days following medication discontinuation. AEs were defined as any untoward or unfavorable medical occurrence in a human subject. SAEs event were defined as any event temporally associated with the subject's participation that: results in death, is life-threatening, results in inpatient hospitalization, results in significant disability, or results in a congenital anomaly or birth defect
Gastrointestinal disorders Weightloss	4.0% 1/25 • Number of events 1 • AEs were assessed in the period following randomization/medication initiation, through the experimental portion of the study (14-17 days post medication initiation), and 7 days following medication discontinuation. AEs were defined as any untoward or unfavorable medical occurrence in a human subject. SAEs event were defined as any event temporally associated with the subject's participation that: results in death, is life-threatening, results in inpatient hospitalization, results in significant disability, or results in a congenital anomaly or birth defect	0.00% 0/26 • AEs were assessed in the period following randomization/medication initiation, through the experimental portion of the study (14-17 days post medication initiation), and 7 days following medication discontinuation. AEs were defined as any untoward or unfavorable medical occurrence in a human subject. SAEs event were defined as any event temporally associated with the subject's participation that: results in death, is life-threatening, results in inpatient hospitalization, results in significant disability, or results in a congenital anomaly or birth defect
Nervous system disorders Muscle cramping / spasm	0.00% 0/25 • AEs were assessed in the period following randomization/medication initiation, through the experimental portion of the study (14-17 days post medication initiation), and 7 days following medication discontinuation. AEs were defined as any untoward or unfavorable medical occurrence in a human subject. SAEs event were defined as any event temporally associated with the subject's participation that: results in death, is life-threatening, results in inpatient hospitalization, results in significant disability, or results in a congenital anomaly or birth defect	3.8% 1/26 • Number of events 1 • AEs were assessed in the period following randomization/medication initiation, through the experimental portion of the study (14-17 days post medication initiation), and 7 days following medication discontinuation. AEs were defined as any untoward or unfavorable medical occurrence in a human subject. SAEs event were defined as any event temporally associated with the subject's participation that: results in death, is life-threatening, results in inpatient hospitalization, results in significant disability, or results in a congenital anomaly or birth defect
General disorders Head cold	0.00% 0/25 • AEs were assessed in the period following randomization/medication initiation, through the experimental portion of the study (14-17 days post medication initiation), and 7 days following medication discontinuation. AEs were defined as any untoward or unfavorable medical occurrence in a human subject. SAEs event were defined as any event temporally associated with the subject's participation that: results in death, is life-threatening, results in inpatient hospitalization, results in significant disability, or results in a congenital anomaly or birth defect	3.8% 1/26 • Number of events 1 • AEs were assessed in the period following randomization/medication initiation, through the experimental portion of the study (14-17 days post medication initiation), and 7 days following medication discontinuation. AEs were defined as any untoward or unfavorable medical occurrence in a human subject. SAEs event were defined as any event temporally associated with the subject's participation that: results in death, is life-threatening, results in inpatient hospitalization, results in significant disability, or results in a congenital anomaly or birth defect
Psychiatric disorders Irritability	0.00% 0/25 • AEs were assessed in the period following randomization/medication initiation, through the experimental portion of the study (14-17 days post medication initiation), and 7 days following medication discontinuation. AEs were defined as any untoward or unfavorable medical occurrence in a human subject. SAEs event were defined as any event temporally associated with the subject's participation that: results in death, is life-threatening, results in inpatient hospitalization, results in significant disability, or results in a congenital anomaly or birth defect	3.8% 1/26 • Number of events 1 • AEs were assessed in the period following randomization/medication initiation, through the experimental portion of the study (14-17 days post medication initiation), and 7 days following medication discontinuation. AEs were defined as any untoward or unfavorable medical occurrence in a human subject. SAEs event were defined as any event temporally associated with the subject's participation that: results in death, is life-threatening, results in inpatient hospitalization, results in significant disability, or results in a congenital anomaly or birth defect
Gastrointestinal disorders Dry Mouth	4.0% 1/25 • Number of events 1 • AEs were assessed in the period following randomization/medication initiation, through the experimental portion of the study (14-17 days post medication initiation), and 7 days following medication discontinuation. AEs were defined as any untoward or unfavorable medical occurrence in a human subject. SAEs event were defined as any event temporally associated with the subject's participation that: results in death, is life-threatening, results in inpatient hospitalization, results in significant disability, or results in a congenital anomaly or birth defect	0.00% 0/26 • AEs were assessed in the period following randomization/medication initiation, through the experimental portion of the study (14-17 days post medication initiation), and 7 days following medication discontinuation. AEs were defined as any untoward or unfavorable medical occurrence in a human subject. SAEs event were defined as any event temporally associated with the subject's participation that: results in death, is life-threatening, results in inpatient hospitalization, results in significant disability, or results in a congenital anomaly or birth defect