Sert2: A Trial of Sertraline in Young Children With Autism Spectrum Disorder

• Sponsor: Randi J. Hagerman, MD (Other)
• Overall Status: Completed
• CT.gov ID: NCT02385799
• Collaborator: Health Resources and Services Administration (HRSA) (U.S. Fed)
• Enrollment: 58
• Location: 1
• Arms: 2
• Actual Duration (Months): 39
• Patients Per Site Per Month: 1.5

Study Details

Study Description

Brief Summary

This study is a control trial of sertraline (Zoloft) in children aged 2 to 5 years old inclusive with Autism Spectrum Disorder. The trial is six months long, and each participant will receive a series of tests at both the beginning and end of the study. The researchers hope to show improvements in language and social deficits.

Condition or Disease	Intervention/Treatment	Phase
Autism Spectrum Disorder	Drug: Sertraline Liquid Placebo; Drug: Sertraline	Phase 2

Detailed Description

This is a single center study and the UC Davis MIND Institute for Autism Spectrum Disorder (ASD) patients aged between 2 years and 5 years old inclusive funded by the Health Resources and Services Administration (HRSA). It is a double-blind control trial of sertraline (Zoloft), an anti-depressant typically used in the treatment of depression, obsessive-compulsive disorder, panic disorder, and other conditions. The researchers are investigating the use of this selective serotonin reuptake inhibitor (SSRI) in ASD because a retrospective study has shown significant improvements in language and social deficits. There is also emerging evidence regarding the stimulation of brain-derived neurotrophic factor (BDNF) and the stimulation of neurogenesis when an SSRI is given early on in the development of animal models of Down syndrome. The researchers hope to see improvements in language stimulation, social gaze and social reciprocity, spatial attention, and a decrease in autistic behaviors.

The aim of this study is to carry out a double-blind placebo controlled trial of sertraline in children with ASD who are between the ages of 2 years and 5 years old inclusive. At baseline, the researchers will assess behavioral and cognitive development. Each participant will be involved in this trial for a period of six months. This will include three visits to the UC Davis MIND Institute and eight phone calls. The researchers will also assess the side effects of the sertraline treatment throughout the study.

Study Design

• Study Type: Interventional
• Actual Enrollment: 58 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Treatment
• Official Title: A Controlled Trial of Sertraline in Young Children With Autism Spectrum Disorder
• Actual Study Start Date: Apr 1, 2015
• Actual Primary Completion Date: Jul 1, 2018
• Actual Study Completion Date: Jul 1, 2018

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: Sertraline Liquid Placebo The placebo will be dosed in an age depended manner. Participants aged 2-3 years of age will be given 2.5 mg of liquid placebo once per day for a period of six months. Participants aged 4 years to 6 years will be given 5 mg of liquid placebo once per day for a period of six months.	Drug: Sertraline Liquid Placebo; Liquid placebo given in parallel to active medication; Other Names: Placebo
Active Comparator: Sertraline Active Medication Liquid sertraline (20 mg/cc) will be dosed in an age depended manner. Participants aged 2-3 years of age will be given 2.5 mg of liquid sertraline once per day for a period of six months. Participants aged 4 years to 6 years will be given 5 mg of liquid sertraline once per day for a period of six months.	Drug: Sertraline; Active medication; Other Names: Zoloft

Outcome Measures

Primary Outcome Measures

1. Change in Mullen Scales of Early Learning - Expressive Language Raw Score [From baseline visit to six-month visit]

   The Mullen Scales of Early Learning (MSEL) is a cognitive test to measure cognitive ability and language development. The test has five scales: gross motor, visual reception, fine motor, receptive language, and expressive language. Shown here are the baseline and 6-month follow-up raw scores from the expressive language scale. This scale's raw scores range from 0 to 50. The lower the score on this scale, the weaker the ability; the higher the score, the greater the ability. The MSEL was administered at the baseline visit and at the 6-month follow-up visit.

2. Change in Mullen Scales of Early Learning - Combined Age Equivalent Score [From baseline visit to six-month visit]

   The Mullen Scales of Early Learning (MSEL) is a cognitive test to measure cognitive ability and language development. The test has five scales: gross motor, visual reception, fine motor, receptive language, and expressive language. Shown here are the baseline and 6-month follow-up combined age equivalent scores, calculated as the sum of the age equivalent scores from each scale. The combined score ranges from 0 to 280. The lower the score on this scale, the weaker the ability; the higher the score, the greater the ability. The MSEL was administered at the baseline visit and at the 6-month follow-up visit.

Secondary Outcome Measures

1. Vineland Adaptive Behavior Scales, Second Edition (Vineland-II) Adaptive Behavior Composite Standard Score [At baseline visit]

   The Vineland-II measures the personal and social skills of individuals from birth through adulthood. It was designed to assess handicapped and non-handicapped persons in their personal and social functioning and is appropriate for individuals of all ages. The Vineland-II is a survey that is administered to a parent or caregiver using a semi-structured interview format and is organized around four Behavior Domains: Communication, Daily Living Skills, Socialization, and Motor Skills. Each subtest is scored with a standard score X=100 ± 15 and summed to calculate the Adaptive Behavior Composite (ABC) using age-adjusted scoring tables. Reported here are the ABC mean standard scores for the placebo and treatment groups at baseline. The ABC ranges from 20 to 160 and indicates low (20-70), moderately low (70-85), adequate (85-115), moderately high (115-130), or high (130-160) overall adaptive functioning.

2. Vineland Adaptive Behavior Scales, Second Edition (Vineland-II) Adaptive Behavior Composite Standard Score [At six-month visit]

   The Vineland-II measures the personal and social skills of individuals from birth through adulthood. It was designed to assess handicapped and non-handicapped persons in their personal and social functioning and is appropriate for individuals of all ages. The Vineland-II is a survey that is administered to a parent or caregiver using a semi-structured interview format and is organized around four Behavior Domains: Communication, Daily Living Skills, Socialization, and Motor Skills. Each subtest is scored with a standard score X=100 ± 15 and summed to calculate the Adaptive Behavior Composite (ABC) using age-adjusted scoring tables. Reported here are the ABC mean standard scores for the placebo and treatment groups at the six-month visit. The ABC ranges from 20 to 160 and indicates low (20-70), moderately low (70-85), adequate (85-115), moderately high (115-130), or high (130-160) overall adaptive functioning.

3. Preschool Anxiety Scale-Revised - Total Score [At baseline visit]

   Preschool Anxiety Scale-Revised (PAS-R) is a questionnaire designed to assess symptoms of anxiety and fears in young children aged 6 and below as reported by their parents. The PAS-R consists of 34 questions, each with a rating option of 0 to 4 where 0=not true at all, 1=seldom true, 2=sometimes true, 3=quite often true, and 4=very often true. The total score is calculated as the sum of all responses and therefore ranges from 0 to 136. Lower scores indicate less anxiety/fear; higher scores indicate more anxiety/fear. Reported here are the mean total scores for the placebo and treatment groups at baseline.

4. Preschool Anxiety Scale-Revised - Total Score [At six-month visit]

   Preschool Anxiety Scale-Revised (PAS-R) is a questionnaire designed to assess symptoms of anxiety and fears in young children aged 6 and below as reported by their parents. The PAS-R consists of 34 questions, each with a rating option of 0 to 4 where 0=not true at all, 1=seldom true, 2=sometimes true, 3=quite often true, and 4=very often true. The total score is calculated as the sum of all responses and therefore ranges from 0 to 136. Lower scores indicate less anxiety/fear; higher scores indicate more anxiety/fear. Reported here are the mean total scores for the placebo and treatment groups at the six-month visit.

5. Preschool Language Scale-Fifth Edition - Total Language Raw Score [At baseline visit]

   The Preschool Language Scale-Fifth Edition (PLS-5) is designed to measure auditory comprehension (AC) and expressive communication (EC) for children from birth to 7 years 11 months. The measure examines the child's attention, play, gestures, social communication, semantics, language structure, integrative language skills and emergent literacy skills. The PLS-5 has expanded coverage of early play behaviors, concepts, theory of mind, and emergent literacy skills. The PLS-5 yields norm-referenced scores including standard scores, percentile ranks and age equivalents for the AC and EC scales as well as for Total Language (TL). Raw score ranges are 0 to 65 in AC, 0 to 67 in EC, and therefore 0 to 132 in TL (calculated by summing AC+EC raw scores). The higher the scores, the greater the language ability. Shown here are the mean TL raw scores from the baseline visit.

6. Preschool Language Scale-Fifth Edition - Total Language Raw Score [At six-month visit]

   The Preschool Language Scale-Fifth Edition (PLS-5) is designed to measure auditory comprehension (AC) and expressive communication (EC) for children from birth to 7 years 11 months. The measure examines the child's attention, play, gestures, social communication, semantics, language structure, integrative language skills and emergent literacy skills. The PLS-5 has expanded coverage of early play behaviors, concepts, theory of mind, and emergent literacy skills. The PLS-5 yields norm-referenced scores including standard scores, percentile ranks and age equivalents for the AC and EC scales as well as for Total Language (TL). Raw score ranges are 0 to 65 in AC, 0 to 67 in EC, and therefore 0 to 132 in TL (calculated by summing AC+EC raw scores). The higher the scores, the greater the language ability. Shown here are the mean TL raw scores from the six-month visit.

7. Sensory Processing Measure-Preschool - Social Participation Raw Score [At baseline visit]

   The Sensory Processing Measure-Preschool (SPM-P) is a questionnaire measuring specific problems, including under- and over-responsiveness, sensory-seeking behavior, and perceptual problems in multiple environments (at home, at school, and in the community) for children aged 2 to 5 years old, as reported by the parent/caregiver. The SPM-P provides norm-referenced standard scores for two higher-level integrative functions (praxis and social participation) and five sensor sensory systems (visual, auditory, tactile, proprioceptive, and vestibular functioning). Reported here is the Social Participation subscale mean raw score at baseline, which ranges from 8 to 32. The lower the raw score, the more limited the child's level of social participation. The higher the score, the greater the child's level of social participation.

8. Sensory Processing Measure-Preschool - Social Participation Raw Score [At six-month visit]

   The Sensory Processing Measure-Preschool (SPM-P) is a questionnaire measuring specific problems, including under- and over-responsiveness, sensory-seeking behavior, and perceptual problems in multiple environments (at home, at school, and in the community) for children aged 2 to 5 years old, as reported by the parent/caregiver. The SPM-P provides norm-referenced standard scores for two higher-level integrative functions (praxis and social participation) and five sensor sensory systems (visual, auditory, tactile, proprioceptive, and vestibular functioning). Reported here is the Social Participation subscale mean raw score at the six-month visit, which ranges from 8 to 32. The lower the raw score, the more limited the child's level of social participation. The higher the score, the greater the child's level of social participation.

9. Clinical Global Impression Scale-Severity (CGI-S) [At baseline visit]

   The Clinical Global Impression-Severity (CGI-S) is a 7-point scale completed by a clinician that yields a rating of the patient's illness severity at the time of assessment, relative to the clinician's past experience with patients who have the same diagnosis. The 7-point scale ranges from: 1 = Normal; 2 = Borderline Ill; 3 = Mildly Ill; 4 = Moderately Ill; 5 = Markedly Ill; 6 = Severely Ill; and 7 = Extremely Ill. Therefore, the higher the score, the greater the severity of the patient's illness. The CGI-S was administered at baseline only for the purpose of characterizing the study population. Shown here are the CGI-S mean scores from the baseline visit.

10. Clinical Global Impression Scale-Improvement (CGI-I) [At three-month visit]

    The Clinical Global Impression-Improvement (CGI-I) is a 7-point scale completed by a clinician that yields a score measuring the overall behavioral change of an individual and their therapeutic response. The 7-point scale ranges from: 1 = Very much improved; 2 = Much improved; 3 = Minimally improved; 4 = No change; 5 = Minimally worse; 6 = Much worse; and 7 = Very much worse. Therefore, the lower the score, the greater the behavioral improvement as rated by the clinician. The CGI-I was administered at the three-month and six-month visits. Shown here are the CGI-I mean scores from the 3-month follow-up visit.

11. Clinical Global Impression Scale-Improvement (CGI-I) [At six-month visit]

    The Clinical Global Impression-Improvement (CGI-I) is a 7-point scale completed by a clinician that yields a score measuring the overall behavioral change of an individual and their therapeutic response. The 7-point scale ranges from: 1 = Very much improved; 2 = Much improved; 3 = Minimally improved; 4 = No change; 5 = Minimally worse; 6 = Much worse; and 7 = Very much worse. Therefore, the lower the score, the greater the behavioral improvement as rated by the clinician. The CGI-I was administered at the three-month and six-month visits. Shown here are the CGI-I mean scores from the 6-month follow-up visit.

12. Visual Analog Scale - Language/Communication Score [At baseline visit]

    The Visual Analog Scale measures the severity of three specific behavioral symptoms as reported by the parent/caregiver: Language/Communication, Anxiety/Obsessive Compulsive Behaviors, and Aggression/Hyperactivity/Hyperarousal. Caregivers mark on a visual line measuring 10 cm with "worst behavior" at 0 cm and "best behavior" at 10 cm. For each behavior the caregiver is instructed to mark their impression of the behavior at baseline visit and again at the six-month visit. The calculated distance in cm between the marks drawn at the baseline and six-month visits thereby demonstrates whether each behavior improved, worsened, or stayed the same during the study, and by how much. Shown here is the mean distance in cm from the "worst behavior" side for the Language/Communication scale, at baseline. The smaller the value, the worse the behavior. The range is minimum 0 cm to maximum 10 cm.

13. Visual Analog Scale - Language/Communication Score [At six-month visit]

    The Visual Analog Scale measures the severity of three specific behavioral symptoms as reported by the parent/caregiver: Language/Communication, Anxiety/Obsessive Compulsive Behaviors, and Aggression/Hyperactivity/Hyperarousal. Caregivers mark on a visual line measuring 10 cm with "worst behavior" at 0 cm and "best behavior" at 10 cm. For each behavior the caregiver is instructed to mark their impression of the behavior at baseline visit and again at the six-month visit. The calculated distance in cm between the marks drawn at the baseline and six-month visits thereby demonstrates whether each behavior improved, worsened, or stayed the same during the study, and by how much. Shown here is the mean distance in cm from the "worst behavior" side for the Language/Communication scale, at the six-month visit. The smaller the value, the worse the behavior. The range is minimum 0 cm to maximum 10 cm.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 24 Months to 72 Months
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Documentation of Autism Spectrum Disorder with Diagnostic and Statistical Manual for Mental Disorders-Fifth edition, criteria as well as a standardized autism assessment such as the Autism Diagnostic Observation Schedule or the Autism Diagnostic Interview-Revised.

• Subject between the ages of 24-72 months of age.

• A reliable parent or caregiver who can report the side effects and communicate effectively with the research team.

• Stable medications during the two months prior to enrollment.

• Currently receiving interventions in the community or school for Autism Spectrum Disorder

Exclusion Criteria:

• Current or past Selective Serotonin Reuptake Inhibitor treatment.

• Other serious co-morbid medical disorders affecting brain function and behavior, including uncontrolled seizures.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	UC Davis MIND Institute	Sacramento	California	United States	95817

Sponsors and Collaborators

• Randi J. Hagerman, MD
• Health Resources and Services Administration (HRSA)

Investigators

• Principal Investigator: Randi J Hagerman, M.D., UC Davis MIND Institute

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Jun 15, 2017

More Information

Publications

None provided.

• Responsible Party: Randi J. Hagerman, MD, UC Davis MIND Institute Medical Director, University of California, Davis
• ClinicalTrials.gov Identifier: NCT02385799
• Other Study ID Numbers: 663866
• First Posted: Mar 11, 2015
• Last Update Posted: Oct 22, 2019
• Last Verified: Oct 1, 2019

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Keywords provided by Randi J. Hagerman, MD, UC Davis MIND Institute Medical Director, University of California, Davis: Autism Spectrum Disorder; Behavior; sertraline; treatment
• Additional relevant MeSH terms: Disease; Autistic Disorder; Autism Spectrum Disorder; Child Development Disorders, Pervasive; Sertraline

Study Results

Participant Flow

Arm/Group Title	Sertraline Liquid Placebo	Sertraline Active Medication
Arm/Group Description	The placebo will be dosed in an age depended manner. Participants aged 2-3 years of age at enrollment will be given 2.5 mg of liquid placebo once per day for a period of six months. Participants aged 4-5 years at enrollment will be given 5 mg of liquid placebo once per day for a period of six months. Sertraline Liquid Placebo: Liquid placebo given in parallel to active medication	Liquid sertraline (20 mg/cc) will be dosed in an age depended manner. Participants aged 2-3 years of age at enrollment will be given 2.5 mg of liquid sertraline once per day for a period of six months. Participants aged 4-5 years at enrollment will be given 5 mg of liquid sertraline once per day for a period of six months. Sertraline: Active medication
Period Title: Overall Study
STARTED	26	32
Completed End-of-Treatment Visit	21	26
COMPLETED	21	24
NOT COMPLETED	5	8

Baseline Characteristics

Arm/Group Title	Sertraline Liquid Placebo	Sertraline Active Medication	Total
Arm/Group Description	The placebo will be dosed in an age depended manner. Participants aged 2-3 years of age at enrollment will be given 2.5 mg of liquid placebo once per day for a period of six months. Participants aged 4-5 years at enrollment will be given 5 mg of liquid placebo once per day for a period of six months. Sertraline Liquid Placebo: Liquid placebo given in parallel to active medication	Liquid sertraline (20 mg/cc) will be dosed in an age depended manner. Participants aged 2-3 years of age at enrollment will be given 2.5 mg of liquid sertraline once per day for a period of six months. Participants aged 4-5 years at enrollment will be given 5 mg of liquid sertraline once per day for a period of six months. Sertraline: Active medication	Total of all reporting groups
Overall Participants	26	32	58
Age (Count of Participants)
<=18 years	26 100%	32 100%	58 100%
Between 18 and 65 years	0 0%	0 0%	0 0%
>=65 years	0 0%	0 0%	0 0%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	3.70 (1.10)	4.31 (0.90)	4.005 (1.00)
Sex: Female, Male (Count of Participants)
Female	5 19.2%	7 21.9%	12 20.7%
Male	21 80.8%	25 78.1%	46 79.3%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	8 30.8%	3 9.4%	11 19%
Not Hispanic or Latino	18 69.2%	29 90.6%	47 81%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	4 15.4%	7 21.9%	11 19%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	2 7.7%	5 15.6%	7 12.1%
White	18 69.2%	19 59.4%	37 63.8%
More than one race	2 7.7%	1 3.1%	3 5.2%
Unknown or Not Reported	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
United States	26 100%	32 100%	58 100%
The Autism Diagnostic Observation Schedule-Second Edition (ADOS-2) (units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on a scale]	7.88 (1.62)	7.34 (1.58)	7.58 (1.60)

Outcome Measures

1. Primary Outcome

Title	Change in Mullen Scales of Early Learning - Expressive Language Raw Score
Description	The Mullen Scales of Early Learning (MSEL) is a cognitive test to measure cognitive ability and language development. The test has five scales: gross motor, visual reception, fine motor, receptive language, and expressive language. Shown here are the baseline and 6-month follow-up raw scores from the expressive language scale. This scale's raw scores range from 0 to 50. The lower the score on this scale, the weaker the ability; the higher the score, the greater the ability. The MSEL was administered at the baseline visit and at the 6-month follow-up visit.
Time Frame	From baseline visit to six-month visit

Outcome Measure Data

Analysis Population Description

Placebo group: 5 discontinued treatment, 0 of whom returned to complete follow-up assessments, so 21 subjects were analyzed at follow-up. Sertraline group: 8 discontinued treatment, 2 of whom returned voluntarily to complete follow-up assessments, so 26 subjects were analyzed at follow-up.

Arm/Group Title	Sertraline Liquid Placebo	Sertraline Active Medication
Arm/Group Description	The placebo will be dosed in an age depended manner. Participants aged 2-3 years of age at enrollment will be given 2.5 mg of liquid placebo once per day for a period of six months. Participants aged 4-5 years at enrollment will be given 5 mg of liquid placebo once per day for a period of six months. Sertraline Liquid Placebo: Liquid placebo given in parallel to active medication	Liquid sertraline (20 mg/cc) will be dosed in an age depended manner. Participants aged 2-3 years of age at enrollment will be given 2.5 mg of liquid sertraline once per day for a period of six months. Participants aged 4-5 years at enrollment will be given 5 mg of liquid sertraline once per day for a period of six months. Sertraline: Active medication
Measure Participants	26	32
Baseline	19.69 (11.69)	18.19 (10.39)
Follow-up	21.81 (14.29)	20.31 (11.70)

2. Primary Outcome

Title	Change in Mullen Scales of Early Learning - Combined Age Equivalent Score
Description	The Mullen Scales of Early Learning (MSEL) is a cognitive test to measure cognitive ability and language development. The test has five scales: gross motor, visual reception, fine motor, receptive language, and expressive language. Shown here are the baseline and 6-month follow-up combined age equivalent scores, calculated as the sum of the age equivalent scores from each scale. The combined score ranges from 0 to 280. The lower the score on this scale, the weaker the ability; the higher the score, the greater the ability. The MSEL was administered at the baseline visit and at the 6-month follow-up visit.
Time Frame	From baseline visit to six-month visit

Outcome Measure Data

Analysis Population Description

Placebo group: 5 discontinued treatment, 0 of whom returned to complete follow-up assessments, so 21 subjects were analyzed at follow-up. Sertraline group: 8 discontinued treatment, 2 of whom returned voluntarily to complete follow-up assessments, so 26 subjects were analyzed at follow-up.

Arm/Group Title	Sertraline Liquid Placebo	Sertraline Active Medication
Arm/Group Description	The placebo will be dosed in an age depended manner. Participants aged 2-3 years of age at enrollment will be given 2.5 mg of liquid placebo once per day for a period of six months. Participants aged 4-5 years at enrollment will be given 5 mg of liquid placebo once per day for a period of six months. Sertraline Liquid Placebo: Liquid placebo given in parallel to active medication	Liquid sertraline (20 mg/cc) will be dosed in an age depended manner. Participants aged 2-3 years of age at enrollment will be given 2.5 mg of liquid sertraline once per day for a period of six months. Participants aged 4-5 years at enrollment will be given 5 mg of liquid sertraline once per day for a period of six months. Sertraline: Active medication
Measure Participants	26	32
Baseline	25.61 (11.73)	24.98 (12.79)
Follow-up	30.30 (15.58)	28.16 (14.15)

3. Secondary Outcome

Title	Vineland Adaptive Behavior Scales, Second Edition (Vineland-II) Adaptive Behavior Composite Standard Score
Description	The Vineland-II measures the personal and social skills of individuals from birth through adulthood. It was designed to assess handicapped and non-handicapped persons in their personal and social functioning and is appropriate for individuals of all ages. The Vineland-II is a survey that is administered to a parent or caregiver using a semi-structured interview format and is organized around four Behavior Domains: Communication, Daily Living Skills, Socialization, and Motor Skills. Each subtest is scored with a standard score X=100 ± 15 and summed to calculate the Adaptive Behavior Composite (ABC) using age-adjusted scoring tables. Reported here are the ABC mean standard scores for the placebo and treatment groups at baseline. The ABC ranges from 20 to 160 and indicates low (20-70), moderately low (70-85), adequate (85-115), moderately high (115-130), or high (130-160) overall adaptive functioning.
Time Frame	At baseline visit

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Sertraline Liquid Placebo	Sertraline Active Medication
Arm/Group Description	The placebo will be dosed in an age depended manner. Participants aged 2-3 years of age at enrollment will be given 2.5 mg of liquid placebo once per day for a period of six months. Participants aged 4-5 years at enrollment will be given 5 mg of liquid placebo once per day for a period of six months. Sertraline Liquid Placebo: Liquid placebo given in parallel to active medication	Liquid sertraline (20 mg/cc) will be dosed in an age depended manner. Participants aged 2-3 years of age at enrollment will be given 2.5 mg of liquid sertraline once per day for a period of six months. Participants aged 4-5 years at enrollment will be given 5 mg of liquid sertraline once per day for a period of six months. Sertraline: Active medication
Measure Participants	26	32
Mean (Standard Deviation) [score on a scale]	68.50 (11.14)	60.03 (12.15)

4. Secondary Outcome

Title	Vineland Adaptive Behavior Scales, Second Edition (Vineland-II) Adaptive Behavior Composite Standard Score
Description	The Vineland-II measures the personal and social skills of individuals from birth through adulthood. It was designed to assess handicapped and non-handicapped persons in their personal and social functioning and is appropriate for individuals of all ages. The Vineland-II is a survey that is administered to a parent or caregiver using a semi-structured interview format and is organized around four Behavior Domains: Communication, Daily Living Skills, Socialization, and Motor Skills. Each subtest is scored with a standard score X=100 ± 15 and summed to calculate the Adaptive Behavior Composite (ABC) using age-adjusted scoring tables. Reported here are the ABC mean standard scores for the placebo and treatment groups at the six-month visit. The ABC ranges from 20 to 160 and indicates low (20-70), moderately low (70-85), adequate (85-115), moderately high (115-130), or high (130-160) overall adaptive functioning.
Time Frame	At six-month visit

Outcome Measure Data

Analysis Population Description

Placebo group: 5 discontinued treatment, 0 of whom returned to complete follow-up assessments, so 21 subjects were analyzed at follow-up. Sertraline group: 8 discontinued treatment, 2 of whom returned for an end-of-treatment visit, but due to time limitations only 1 of these 2 completed this assessment, so 25 subjects were analyzed at follow-up.

Arm/Group Title	Sertraline Liquid Placebo	Sertraline Active Medication
Arm/Group Description	The placebo will be dosed in an age depended manner. Participants aged 2-3 years of age at enrollment will be given 2.5 mg of liquid placebo once per day for a period of six months. Participants aged 4-5 years at enrollment will be given 5 mg of liquid placebo once per day for a period of six months. Sertraline Liquid Placebo: Liquid placebo given in parallel to active medication	Liquid sertraline (20 mg/cc) will be dosed in an age depended manner. Participants aged 2-3 years of age at enrollment will be given 2.5 mg of liquid sertraline once per day for a period of six months. Participants aged 4-5 years at enrollment will be given 5 mg of liquid sertraline once per day for a period of six months. Sertraline: Active medication
Measure Participants	21	25
Mean (Standard Deviation) [score on a scale]	71.52 (15.47)	69.68 (15.14)

5. Secondary Outcome

Title	Preschool Anxiety Scale-Revised - Total Score
Description	Preschool Anxiety Scale-Revised (PAS-R) is a questionnaire designed to assess symptoms of anxiety and fears in young children aged 6 and below as reported by their parents. The PAS-R consists of 34 questions, each with a rating option of 0 to 4 where 0=not true at all, 1=seldom true, 2=sometimes true, 3=quite often true, and 4=very often true. The total score is calculated as the sum of all responses and therefore ranges from 0 to 136. Lower scores indicate less anxiety/fear; higher scores indicate more anxiety/fear. Reported here are the mean total scores for the placebo and treatment groups at baseline.
Time Frame	At baseline visit

Outcome Measure Data

Analysis Population Description

Placebo group: staff inadvertently neglected to administer this questionnaire to the 2 subjects' caregivers at baseline, so only 24 were completed.

Arm/Group Title	Sertraline Liquid Placebo	Sertraline Active Medication
Arm/Group Description	The placebo will be dosed in an age depended manner. Participants aged 2-3 years of age at enrollment will be given 2.5 mg of liquid placebo once per day for a period of six months. Participants aged 4-5 years at enrollment will be given 5 mg of liquid placebo once per day for a period of six months. Sertraline Liquid Placebo: Liquid placebo given in parallel to active medication	Liquid sertraline (20 mg/cc) will be dosed in an age depended manner. Participants aged 2-3 years of age at enrollment will be given 2.5 mg of liquid sertraline once per day for a period of six months. Participants aged 4-5 years at enrollment will be given 5 mg of liquid sertraline once per day for a period of six months. Sertraline: Active medication
Measure Participants	24	32
Mean (Standard Deviation) [score on a scale]	15.38 (12.51)	14.75 (11.58)

6. Secondary Outcome

Title	Preschool Anxiety Scale-Revised - Total Score
Description	Preschool Anxiety Scale-Revised (PAS-R) is a questionnaire designed to assess symptoms of anxiety and fears in young children aged 6 and below as reported by their parents. The PAS-R consists of 34 questions, each with a rating option of 0 to 4 where 0=not true at all, 1=seldom true, 2=sometimes true, 3=quite often true, and 4=very often true. The total score is calculated as the sum of all responses and therefore ranges from 0 to 136. Lower scores indicate less anxiety/fear; higher scores indicate more anxiety/fear. Reported here are the mean total scores for the placebo and treatment groups at the six-month visit.
Time Frame	At six-month visit

Outcome Measure Data

Analysis Population Description

Placebo group: 5 discontinued treatment, 0 of whom returned to complete follow-up assessments, so 21 subjects were analyzed at follow-up. Sertraline group: 8 discontinued treatment, 2 of whom returned voluntarily to complete follow-up assessments, so 26 subjects were analyzed at follow-up.

Arm/Group Title	Sertraline Liquid Placebo	Sertraline Active Medication
Arm/Group Description	The placebo will be dosed in an age depended manner. Participants aged 2-3 years of age at enrollment will be given 2.5 mg of liquid placebo once per day for a period of six months. Participants aged 4-5 years at enrollment will be given 5 mg of liquid placebo once per day for a period of six months. Sertraline Liquid Placebo: Liquid placebo given in parallel to active medication	Liquid sertraline (20 mg/cc) will be dosed in an age depended manner. Participants aged 2-3 years of age at enrollment will be given 2.5 mg of liquid sertraline once per day for a period of six months. Participants aged 4-5 years at enrollment will be given 5 mg of liquid sertraline once per day for a period of six months. Sertraline: Active medication
Measure Participants	21	26
Mean (Standard Deviation) [score on a scale]	11.43 (10.04)	14.77 (14.45)

7. Secondary Outcome

Title	Preschool Language Scale-Fifth Edition - Total Language Raw Score
Description	The Preschool Language Scale-Fifth Edition (PLS-5) is designed to measure auditory comprehension (AC) and expressive communication (EC) for children from birth to 7 years 11 months. The measure examines the child's attention, play, gestures, social communication, semantics, language structure, integrative language skills and emergent literacy skills. The PLS-5 has expanded coverage of early play behaviors, concepts, theory of mind, and emergent literacy skills. The PLS-5 yields norm-referenced scores including standard scores, percentile ranks and age equivalents for the AC and EC scales as well as for Total Language (TL). Raw score ranges are 0 to 65 in AC, 0 to 67 in EC, and therefore 0 to 132 in TL (calculated by summing AC+EC raw scores). The higher the scores, the greater the language ability. Shown here are the mean TL raw scores from the baseline visit.
Time Frame	At baseline visit

Outcome Measure Data

Analysis Population Description

Sertraline group: 2 subjects were completely nonverbal at baseline, so the rater determined that their assessments could not be completed; therefore, only 30 subjects in this arm were analyzed at baseline.

Arm/Group Title	Sertraline Liquid Placebo	Sertraline Active Medication
Arm/Group Description	The placebo will be dosed in an age depended manner. Participants aged 2-3 years of age at enrollment will be given 2.5 mg of liquid placebo once per day for a period of six months. Participants aged 4-5 years at enrollment will be given 5 mg of liquid placebo once per day for a period of six months. Sertraline Liquid Placebo: Liquid placebo given in parallel to active medication	Liquid sertraline (20 mg/cc) will be dosed in an age depended manner. Participants aged 2-3 years of age at enrollment will be given 2.5 mg of liquid sertraline once per day for a period of six months. Participants aged 4-5 years at enrollment will be given 5 mg of liquid sertraline once per day for a period of six months. Sertraline: Active medication
Measure Participants	26	30
Mean (Standard Deviation) [score on a scale]	48.65 (25.57)	43.03 (23.35)

8. Secondary Outcome

Title	Preschool Language Scale-Fifth Edition - Total Language Raw Score
Description	The Preschool Language Scale-Fifth Edition (PLS-5) is designed to measure auditory comprehension (AC) and expressive communication (EC) for children from birth to 7 years 11 months. The measure examines the child's attention, play, gestures, social communication, semantics, language structure, integrative language skills and emergent literacy skills. The PLS-5 has expanded coverage of early play behaviors, concepts, theory of mind, and emergent literacy skills. The PLS-5 yields norm-referenced scores including standard scores, percentile ranks and age equivalents for the AC and EC scales as well as for Total Language (TL). Raw score ranges are 0 to 65 in AC, 0 to 67 in EC, and therefore 0 to 132 in TL (calculated by summing AC+EC raw scores). The higher the scores, the greater the language ability. Shown here are the mean TL raw scores from the six-month visit.
Time Frame	At six-month visit

Outcome Measure Data

Analysis Population Description

Placebo group: 5 discontinued treatment, 0 of whom returned to complete follow-up assessments, so 21 subjects were analyzed at follow-up. Sertraline group: 8 discontinued treatment, 2 of whom returned for an end-of-treatment visit, but due to time limitations only 1 of these 2 completed this assessment, so 25 subjects were analyzed at follow-up.

Arm/Group Title	Sertraline Liquid Placebo	Sertraline Active Medication
Arm/Group Description	The placebo will be dosed in an age depended manner. Participants aged 2-3 years of age at enrollment will be given 2.5 mg of liquid placebo once per day for a period of six months. Participants aged 4-5 years at enrollment will be given 5 mg of liquid placebo once per day for a period of six months. Sertraline Liquid Placebo: Liquid placebo given in parallel to active medication	Liquid sertraline (20 mg/cc) will be dosed in an age depended manner. Participants aged 2-3 years of age at enrollment will be given 2.5 mg of liquid sertraline once per day for a period of six months. Participants aged 4-5 years at enrollment will be given 5 mg of liquid sertraline once per day for a period of six months. Sertraline: Active medication
Measure Participants	21	25
Mean (Standard Deviation) [score on a scale]	57.24 (26.26)	51.40 (23.56)

9. Secondary Outcome

Title	Sensory Processing Measure-Preschool - Social Participation Raw Score
Description	The Sensory Processing Measure-Preschool (SPM-P) is a questionnaire measuring specific problems, including under- and over-responsiveness, sensory-seeking behavior, and perceptual problems in multiple environments (at home, at school, and in the community) for children aged 2 to 5 years old, as reported by the parent/caregiver. The SPM-P provides norm-referenced standard scores for two higher-level integrative functions (praxis and social participation) and five sensor sensory systems (visual, auditory, tactile, proprioceptive, and vestibular functioning). Reported here is the Social Participation subscale mean raw score at baseline, which ranges from 8 to 32. The lower the raw score, the more limited the child's level of social participation. The higher the score, the greater the child's level of social participation.
Time Frame	At baseline visit

Outcome Measure Data

Analysis Population Description

Placebo group: staff inadvertently neglected to administer this questionnaire to 1 subject's caregiver at baseline, so only 25 were completed. Sertraline group: staff inadvertently neglected to administer this questionnaire to 1 subject's caregiver at baseline, so only 31 were completed.

Arm/Group Title	Sertraline Liquid Placebo	Sertraline Active Medication
Arm/Group Description	The placebo will be dosed in an age depended manner. Participants aged 2-3 years of age at enrollment will be given 2.5 mg of liquid placebo once per day for a period of six months. Participants aged 4-5 years at enrollment will be given 5 mg of liquid placebo once per day for a period of six months. Sertraline Liquid Placebo: Liquid placebo given in parallel to active medication	Liquid sertraline (20 mg/cc) will be dosed in an age depended manner. Participants aged 2-3 years of age at enrollment will be given 2.5 mg of liquid sertraline once per day for a period of six months. Participants aged 4-5 years at enrollment will be given 5 mg of liquid sertraline once per day for a period of six months. Sertraline: Active medication
Measure Participants	25	31
Mean (Standard Deviation) [score on a scale]	21.96 (3.81)	22.39 (5.10)

10. Secondary Outcome

Title	Sensory Processing Measure-Preschool - Social Participation Raw Score
Description	The Sensory Processing Measure-Preschool (SPM-P) is a questionnaire measuring specific problems, including under- and over-responsiveness, sensory-seeking behavior, and perceptual problems in multiple environments (at home, at school, and in the community) for children aged 2 to 5 years old, as reported by the parent/caregiver. The SPM-P provides norm-referenced standard scores for two higher-level integrative functions (praxis and social participation) and five sensor sensory systems (visual, auditory, tactile, proprioceptive, and vestibular functioning). Reported here is the Social Participation subscale mean raw score at the six-month visit, which ranges from 8 to 32. The lower the raw score, the more limited the child's level of social participation. The higher the score, the greater the child's level of social participation.
Time Frame	At six-month visit

Outcome Measure Data

Analysis Population Description

Placebo group: 5 discontinued treatment, 0 of whom returned to complete follow-up assessments, so 21 subjects were analyzed at follow-up. Sertraline group: 8 discontinued treatment, 2 of whom returned for an end-of-treatment visit, but due to time limitations only 1 of these 2 completed this assessment, so 25 subjects were analyzed at follow-up.

Arm/Group Title	Sertraline Liquid Placebo	Sertraline Active Medication
Arm/Group Description	The placebo will be dosed in an age depended manner. Participants aged 2-3 years of age at enrollment will be given 2.5 mg of liquid placebo once per day for a period of six months. Participants aged 4-5 years at enrollment will be given 5 mg of liquid placebo once per day for a period of six months. Sertraline Liquid Placebo: Liquid placebo given in parallel to active medication	Liquid sertraline (20 mg/cc) will be dosed in an age depended manner. Participants aged 2-3 years of age at enrollment will be given 2.5 mg of liquid sertraline once per day for a period of six months. Participants aged 4-5 years at enrollment will be given 5 mg of liquid sertraline once per day for a period of six months. Sertraline: Active medication
Measure Participants	21	25
Mean (Standard Deviation) [score on a scale]	20.86 (4.07)	21.16 (5.04)

11. Secondary Outcome

Title	Clinical Global Impression Scale-Severity (CGI-S)
Description	The Clinical Global Impression-Severity (CGI-S) is a 7-point scale completed by a clinician that yields a rating of the patient's illness severity at the time of assessment, relative to the clinician's past experience with patients who have the same diagnosis. The 7-point scale ranges from: 1 = Normal; 2 = Borderline Ill; 3 = Mildly Ill; 4 = Moderately Ill; 5 = Markedly Ill; 6 = Severely Ill; and 7 = Extremely Ill. Therefore, the higher the score, the greater the severity of the patient's illness. The CGI-S was administered at baseline only for the purpose of characterizing the study population. Shown here are the CGI-S mean scores from the baseline visit.
Time Frame	At baseline visit

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Sertraline Liquid Placebo	Sertraline Active Medication
Arm/Group Description	The placebo will be dosed in an age depended manner. Participants aged 2-3 years of age at enrollment will be given 2.5 mg of liquid placebo once per day for a period of six months. Participants aged 4-5 years at enrollment will be given 5 mg of liquid placebo once per day for a period of six months. Sertraline Liquid Placebo: Liquid placebo given in parallel to active medication	Liquid sertraline (20 mg/cc) will be dosed in an age depended manner. Participants aged 2-3 years of age at enrollment will be given 2.5 mg of liquid sertraline once per day for a period of six months. Participants aged 4-5 years at enrollment will be given 5 mg of liquid sertraline once per day for a period of six months. Sertraline: Active medication
Measure Participants	26	32
Mean (Standard Deviation) [score on a scale]	4.38 (0.98)	4.66 (0.94)

12. Secondary Outcome

Title	Clinical Global Impression Scale-Improvement (CGI-I)
Description	The Clinical Global Impression-Improvement (CGI-I) is a 7-point scale completed by a clinician that yields a score measuring the overall behavioral change of an individual and their therapeutic response. The 7-point scale ranges from: 1 = Very much improved; 2 = Much improved; 3 = Minimally improved; 4 = No change; 5 = Minimally worse; 6 = Much worse; and 7 = Very much worse. Therefore, the lower the score, the greater the behavioral improvement as rated by the clinician. The CGI-I was administered at the three-month and six-month visits. Shown here are the CGI-I mean scores from the 3-month follow-up visit.
Time Frame	At three-month visit

Outcome Measure Data

Analysis Population Description

Placebo group: 3 discontinued treatment/become lost to follow-up prior to reaching 3-month visit, so 23 subjects were analyzed at this timepoint. Sertraline group: 5 discontinued treatment/become lost to follow-up prior to reaching 3-month visit, so 27 subjects were analyzed at this timepoint.

Arm/Group Title	Sertraline Liquid Placebo	Sertraline Active Medication
Arm/Group Description	The placebo will be dosed in an age depended manner. Participants aged 2-3 years of age at enrollment will be given 2.5 mg of liquid placebo once per day for a period of six months. Participants aged 4-5 years at enrollment will be given 5 mg of liquid placebo once per day for a period of six months. Sertraline Liquid Placebo: Liquid placebo given in parallel to active medication	Liquid sertraline (20 mg/cc) will be dosed in an age depended manner. Participants aged 2-3 years of age at enrollment will be given 2.5 mg of liquid sertraline once per day for a period of six months. Participants aged 4-5 years at enrollment will be given 5 mg of liquid sertraline once per day for a period of six months. Sertraline: Active medication
Measure Participants	23	27
Mean (Standard Deviation) [score on a scale]	2.65 (1.11)	2.70 (1.03)

13. Secondary Outcome

Title	Clinical Global Impression Scale-Improvement (CGI-I)
Description	The Clinical Global Impression-Improvement (CGI-I) is a 7-point scale completed by a clinician that yields a score measuring the overall behavioral change of an individual and their therapeutic response. The 7-point scale ranges from: 1 = Very much improved; 2 = Much improved; 3 = Minimally improved; 4 = No change; 5 = Minimally worse; 6 = Much worse; and 7 = Very much worse. Therefore, the lower the score, the greater the behavioral improvement as rated by the clinician. The CGI-I was administered at the three-month and six-month visits. Shown here are the CGI-I mean scores from the 6-month follow-up visit.
Time Frame	At six-month visit

Outcome Measure Data

Analysis Population Description

Placebo group: 5 discontinued treatment, 0 of whom returned to complete follow-up assessments, so 21 subjects were analyzed at follow-up. Sertraline group: 8 discontinued treatment, 2 of whom returned voluntarily to complete follow-up assessments, so 26 subjects were analyzed at follow-up.

Arm/Group Title	Sertraline Liquid Placebo	Sertraline Active Medication
Arm/Group Description	The placebo will be dosed in an age depended manner. Participants aged 2-3 years of age at enrollment will be given 2.5 mg of liquid placebo once per day for a period of six months. Participants aged 4-5 years at enrollment will be given 5 mg of liquid placebo once per day for a period of six months. Sertraline Liquid Placebo: Liquid placebo given in parallel to active medication	Liquid sertraline (20 mg/cc) will be dosed in an age depended manner. Participants aged 2-3 years of age at enrollment will be given 2.5 mg of liquid sertraline once per day for a period of six months. Participants aged 4-5 years at enrollment will be given 5 mg of liquid sertraline once per day for a period of six months. Sertraline: Active medication
Measure Participants	21	26
Mean (Standard Deviation) [score on a scale]	1.14 (0.96)	1.23 (1.11)

14. Secondary Outcome

Title	Visual Analog Scale - Language/Communication Score
Description	The Visual Analog Scale measures the severity of three specific behavioral symptoms as reported by the parent/caregiver: Language/Communication, Anxiety/Obsessive Compulsive Behaviors, and Aggression/Hyperactivity/Hyperarousal. Caregivers mark on a visual line measuring 10 cm with "worst behavior" at 0 cm and "best behavior" at 10 cm. For each behavior the caregiver is instructed to mark their impression of the behavior at baseline visit and again at the six-month visit. The calculated distance in cm between the marks drawn at the baseline and six-month visits thereby demonstrates whether each behavior improved, worsened, or stayed the same during the study, and by how much. Shown here is the mean distance in cm from the "worst behavior" side for the Language/Communication scale, at baseline. The smaller the value, the worse the behavior. The range is minimum 0 cm to maximum 10 cm.
Time Frame	At baseline visit

Outcome Measure Data

Analysis Population Description

Placebo group: staff inadvertently neglected to administer this assessment to 1 subject's caregiver at baseline, so only 25 were completed. Sertraline group: staff inadvertently neglected to administer this assessment to 1 subject's caregiver at baseline, so only 31 were completed.

Arm/Group Title	Sertraline Liquid Placebo	Sertraline Active Medication
Arm/Group Description	The placebo will be dosed in an age depended manner. Participants aged 2-3 years of age at enrollment will be given 2.5 mg of liquid placebo once per day for a period of six months. Participants aged 4-5 years at enrollment will be given 5 mg of liquid placebo once per day for a period of six months. Sertraline Liquid Placebo: Liquid placebo given in parallel to active medication	Liquid sertraline (20 mg/cc) will be dosed in an age depended manner. Participants aged 2-3 years of age at enrollment will be given 2.5 mg of liquid sertraline once per day for a period of six months. Participants aged 4-5 years at enrollment will be given 5 mg of liquid sertraline once per day for a period of six months. Sertraline: Active medication
Measure Participants	25	31
Mean (Standard Deviation) [centimeters]	2.84 (2.04)	2.03 (1.70)

15. Secondary Outcome

Title	Visual Analog Scale - Language/Communication Score
Description	The Visual Analog Scale measures the severity of three specific behavioral symptoms as reported by the parent/caregiver: Language/Communication, Anxiety/Obsessive Compulsive Behaviors, and Aggression/Hyperactivity/Hyperarousal. Caregivers mark on a visual line measuring 10 cm with "worst behavior" at 0 cm and "best behavior" at 10 cm. For each behavior the caregiver is instructed to mark their impression of the behavior at baseline visit and again at the six-month visit. The calculated distance in cm between the marks drawn at the baseline and six-month visits thereby demonstrates whether each behavior improved, worsened, or stayed the same during the study, and by how much. Shown here is the mean distance in cm from the "worst behavior" side for the Language/Communication scale, at the six-month visit. The smaller the value, the worse the behavior. The range is minimum 0 cm to maximum 10 cm.
Time Frame	At six-month visit

Outcome Measure Data

Analysis Population Description

Placebo group: 5 discontinued treatment, 0 of whom returned to complete follow-up assessments, so 21 subjects were analyzed at follow-up. Sertraline group: 8 discontinued treatment, 2 of whom returned for an end-of-treatment visit, but due to time limitations only 1 of these 2 completed this assessment, so 25 subjects were analyzed at follow-up.

Arm/Group Title	Sertraline Liquid Placebo	Sertraline Active Medication
Arm/Group Description	The placebo will be dosed in an age depended manner. Participants aged 2-3 years of age at enrollment will be given 2.5 mg of liquid placebo once per day for a period of six months. Participants aged 4-5 years at enrollment will be given 5 mg of liquid placebo once per day for a period of six months. Sertraline Liquid Placebo: Liquid placebo given in parallel to active medication	Liquid sertraline (20 mg/cc) will be dosed in an age depended manner. Participants aged 2-3 years of age at enrollment will be given 2.5 mg of liquid sertraline once per day for a period of six months. Participants aged 4-5 years at enrollment will be given 5 mg of liquid sertraline once per day for a period of six months. Sertraline: Active medication
Measure Participants	21	25
Mean (Standard Deviation) [centimeters]	5.53 (2.95)	4.70 (2.73)

Adverse Events

Time Frame	From baseline to follow-up (6 months).
Arm/Group Title	Sertraline Liquid Placebo		Sertraline Active Medication
Arm/Group Description	The placebo will be dosed in an age depended manner. Participants aged 2-3 years of age at enrollment will be given 2.5 mg of liquid placebo once per day for a period of six months. Participants aged 4-5 years at enrollment will be given 5 mg of liquid placebo once per day for a period of six months. Sertraline Liquid Placebo: Liquid placebo given in parallel to active medication		Liquid sertraline (20 mg/cc) will be dosed in an age depended manner. Participants aged 2-3 years of age at enrollment will be given 2.5 mg of liquid sertraline once per day for a period of six months. Participants aged 4-5 years at enrollment will be given 5 mg of liquid sertraline once per day for a period of six months. Sertraline: Active medication
All Cause Mortality
	Sertraline Liquid Placebo		Sertraline Active Medication
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/26 (0%)		0/32 (0%)
Serious Adverse Events
	Sertraline Liquid Placebo		Sertraline Active Medication
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/26 (0%)		1/32 (3.1%)
Infections and infestations
Hospitalization for dehydration	0/26 (0%)	0	1/32 (3.1%)	1
Other (Not Including Serious) Adverse Events
	Sertraline Liquid Placebo		Sertraline Active Medication
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	26/26 (100%)		30/32 (93.8%)
Congenital, familial and genetic disorders
Tuberous sclerosis	1/26 (3.8%)	1	0/32 (0%)	0
Ear and labyrinth disorders
PE tube surgery	1/26 (3.8%)	1	0/32 (0%)	0
Eye disorders
Dilated pupils	1/26 (3.8%)	2	0/32 (0%)	0
Eye redness	2/26 (7.7%)	2	0/32 (0%)	0
Gastrointestinal disorders
Diarrhea	15/26 (57.7%)	17	8/32 (25%)	11
Vomiting	3/26 (11.5%)	3	7/32 (21.9%)	9
Gastroenteritis	5/26 (19.2%)	7	7/32 (21.9%)	7
Constipation	3/26 (11.5%)	3	1/32 (3.1%)	2
Decreased appetite	1/26 (3.8%)	1	3/32 (9.4%)	3
Encopresis	0/26 (0%)	0	2/32 (6.3%)	2
Gas	0/26 (0%)	0	1/32 (3.1%)	1
Increased frequency of bowel movements	0/26 (0%)	0	1/32 (3.1%)	1
Immune system disorders
Seasonal allergies	2/26 (7.7%)	3	1/32 (3.1%)	1
Localized left leg swelling	1/26 (3.8%)	1	0/32 (0%)	0
Infections and infestations
Upper respiratory infection	19/26 (73.1%)	39	23/32 (71.9%)	48
Fever	7/26 (26.9%)	8	6/32 (18.8%)	10
Otitis media	2/26 (7.7%)	2	5/32 (15.6%)	7
Hand Foot Mouth Disease	1/26 (3.8%)	1	0/32 (0%)	0
Staph infection	1/26 (3.8%)	1	0/32 (0%)	0
Chicken pox	0/26 (0%)	0	1/32 (3.1%)	1
Flu	0/26 (0%)	0	1/32 (3.1%)	1
Injury, poisoning and procedural complications
Cut	1/26 (3.8%)	1	0/32 (0%)	0
Sprained ankle	1/26 (3.8%)	1	0/32 (0%)	0
Musculoskeletal and connective tissue disorders
Tooth pain	0/26 (0%)	0	1/32 (3.1%)	1
Nervous system disorders
Tic	0/26 (0%)	0	2/32 (6.3%)	4
Excessive drooling	1/26 (3.8%)	1	0/32 (0%)	0
Headaches	1/26 (3.8%)	1	0/32 (0%)	0
Gray matter heterotopia	1/26 (3.8%)	1	0/32 (0%)	0
Possible seizure/syncope	1/26 (3.8%)	1	0/32 (0%)	0
Psychiatric disorders
Hyperactivity	9/26 (34.6%)	13	12/32 (37.5%)	14
Sleep disturbance	3/26 (11.5%)	3	10/32 (31.3%)	14
Irritability/Aggression	10/26 (38.5%)	11	7/32 (21.9%)	9
Lethargy	4/26 (15.4%)	5	3/32 (9.4%)	3
Obsessive behaviors	2/26 (7.7%)	2	0/32 (0%)	0
Self-injurious behavior	1/26 (3.8%)	2	1/32 (3.1%)	1
Increased stimming	1/26 (3.8%)	1	2/32 (6.3%)	2
Mouthing/chewing objects	0/26 (0%)	0	2/32 (6.3%)	2
Regression	0/26 (0%)	0	2/32 (6.3%)	2
Teeth grinding	1/26 (3.8%)	1	2/32 (6.3%)	2
Increase in pica	1/26 (3.8%)	1	0/32 (0%)	0
Separation anxiety	1/26 (3.8%)	1	1/32 (3.1%)	1
Hoarding	0/26 (0%)	0	1/32 (3.1%)	1
Inappropriate laughing	0/26 (0%)	0	1/32 (3.1%)	1
Inattention	0/26 (0%)	0	1/32 (3.1%)	1
Renal and urinary disorders
Enuresis	1/26 (3.8%)	1	1/32 (3.1%)	1
Urinary retention	1/26 (3.8%)	1	0/32 (0%)	0
Skin and subcutaneous tissue disorders
Rash	4/26 (15.4%)	6	1/32 (3.1%)	1
Itching	1/26 (3.8%)	1	1/32 (3.1%)	1
Burned feet	0/26 (0%)	0	1/32 (3.1%)	1

Limitations/Caveats

Not having minimum or maximum verbal or other developmental requirements to qualify for inclusion in this study. Sample size is small due to significant recruitment/retention challenges. Study power threshold was not met.

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.