Buspirone for Anxiety in Autistic Youth

A Randomized Controlled Trial of Buspirone for Anxiety in Autistic Youth

The purpose of the study is to do a preliminary trial to determine if buspirone is effective, safe, and tolerable in autistic youth with anxiety.

Study Overview

• Status: Not yet recruiting
• Conditions: Anxiety; Autism Spectrum Disorder
• Intervention / Treatment: Drug: buspirone; Drug: Placebo

Detailed Description

After being informed about the study and potential risks, all patients or their legal guardians giving written informed consent will be screened for study eligibility. Patients who meet the eligibility requirements will participate in a 16-week, flexibly-dosed, randomized controlled trial of buspirone versus placebo. The dose of buspirone will be adjusted over the first 12 weeks of the study and a stable dose will be maintained for the final four weeks of the trial. Adverse effects will be reviewed at each visit and standardized measures of anxiety will be conducted at weeks 4, 8, 12, and 16.

• Study Type: Interventional
• Enrollment (Estimated): 20
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Robyn P. Thom, MD; Phone Number: 781-860-1711; Email: luriecenterresearch@mgb.org

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Age 7-17 years
2. Diagnosis of Autism Spectrum Disorder (ASD) confirmed by the study clinician using the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) criteria and Social Communication Questionnaire (SCQ)
3. Diagnosis of social phobia, separation anxiety disorder, or generalized anxiety disorder of at least moderate severity based on the Anxiety and Related Disorders Interview Schedule (ADIS), 5-item Pediatric Anxiety Rating Scale (PARS) score ≥10, and Clinical Global Impression Severity subscale (CGI-S) ≥4
4. IQ ≥50 based on Stanford Binet, 5th Edition Abbreviated IQ test or the Kaufman Brief Intelligence Test, 2nd Edition (KBIT-2)
5. Stable medications for ≥30 days
6. English speaking
7. Ability to swallow buspirone capsules or liquid suspension

Exclusion Criteria:

1. Known diagnosis of a genetic syndrome associated with ASD (e.g. Fragile X syndrome, Angelman syndrome) based on parent report
2. Known cardiac arrythmia based on parent report
3. Current primary diagnosis of bipolar disorder, psychosis, substance use disorder, posttraumatic stress disorder, eating disorder, or major depressive disorder in the opinion of the PI
4. Any past or present conditions that would make treatment with buspirone unsafe
5. Current use of any of the following psychotropic medications: SSRIs, SNRIs, mirtazapine, benzodiazepines, tricyclic antidepressants, monoamine oxidase inhibitors, mood stabilizers, or antipsychotics
6. Previous adequate trial of buspirone (≥20 mg/day for at least 4 weeks) or significant adverse effects
7. Aberrant Behavior Checklist Irritability subscale score (ABC-I) ≥18
8. Pregnancy or sexual activity without the use of an acceptable form of birth control in females of childbearing age
9. Acutely unstable medical/psychiatric condition (e.g. self-injury, suicidality) that would preclude study participation in the opinion of the PI
10. Inability to tolerate Bittium Faros device in the opinion of the parent or a known allergy to adhesives

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Placebo; Matching placebo capsules/liquid formulation will be prepared.
Active Comparator: Buspirone	Drug: buspirone; Buspirone, an anxiety medication that is FDA approved for generalized anxiety disorder in adults, will be the active comparator for this trial.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean 16-Week Change in Pediatric Anxiety Rating Scale (PARS) 5-Item Total Score	The PARS, a clinician-administered measure of child anxiety symptom severity based on both patient and parent-report will be the primary outcome measure. It has demonstrated inter-rater and test-retest reliability, and has previously been used by our group as the primary outcome measure in a RCT of mirtazapine for anxiety in youth with ASD, demonstrating sensitivity to change. The 5-item PARS score will be the primary outcome measure for this trial. Scaled score ranges from 0-25 with higher scores indicating more severe anxiety symptoms.	Baseline, Week 4, Week 8, Week 2, Week 16; Change from Baseline to Week 16 reported

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of Participants who Responded to Treatment at 16 Weeks According to the Improvement Item of the Clinical Global Impression-Improvement (CGI-I) (Response Defined as CGI-I = 1 or 2)	The Clinical Global Impressions Global Improvement (CGI-I) is designed to take into account all factors to arrive at an assessment of response to treatment. The CGI-I scale ranges from 1 to 7 (1=very much improved; 2=much improved; 3=minimally improved; 4=no change; 5=minimally worse; 6=much worse; 7=very much worse), with lower scales indicating improvement (1=very much improved; 2=much improved). In this study, the CGI-I will be focused on the target symptom of anxiety. Participants with a CGI-I score of 1 or 2 will be classified as responders.	Week 4, Week 8, Week 12, Week 16. Week 16 score reported.
Mean 16-Week Change in Clinical Global Impression Severity Subscale (CGI-S)	The CGI-S is rated on a scale from 1 to 7, where 1 = normal, not at all ill; 3 = mildly ill; 5 = markedly ill; 7 = among the most extremely ill patients. The CGI-S will be rated based on the severity of anxiety symptoms.	Baseline, Week 4, Week 8, Week 12, Week 16. Change from Baseline to Week 16 reported.
Mean 16-Week Change in Parent-Rated Anxiety Scale for Autism Spectrum Disorder (PRAS-ASD) Score	The PRAS-ASD is a novel parent-rated 25-item scale with demonstrated reliability and validity. Scores range from 0-75, with higher scores indicating more severe parent-rated anxiety.	Baseline, Week 8, Week 16. Change from Baseline to Week 16 reported.

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean 16-Week Change in Aberrant Behavior Checklist (ABC-2) Irritability Subscale Score	The ABC-2 is a 58-item questionnaire with 5 subscales derived by factor analysis. It has been extensively used in psychopharmacological studies of ASD and assesses many symptoms that are either central to autism or frequently a target of treatment. The Irritability Subscale is derived from 15 items, with a score range from 0-45, where higher scores indicate more severe irritability.	Baseline, Week 8, Week 16; Change from Baseline to Week 16 reported
Mean 16-Week Change in Aberrant Behavior Checklist (ABC-2) Lethargy/Social Withdrawal Subscale Score	The ABC-2 is a 58-item questionnaire with 5 subscales derived by factor analysis. It has been extensively used in psychopharmacological studies of ASD and assesses many symptoms that are either central to autism or frequently a target of treatment. The Lethargy/Withdrawal Subscale is derived from 16 items, with a score range from 0-48 where higher scores indicate more severe Lethargy/Withdrawal symptoms.	Baseline, Week 8, Week 16; Change from Baseline to Week 16 reported
Mean 16-Week Change in Aberrant Behavior Checklist (ABC-2) Stereotypic Behavior Subscale Score	The ABC-2 is a 58-item questionnaire with 5 subscales derived by factor analysis. It has been extensively used in psychopharmacological studies of ASD and assesses many symptoms that are either central to autism or frequently a target of treatment. The Stereotypic Behavior Subscale is derived from 7 items, with a score range of 0-21 where higher scores indicate more severe stereotypic behaviors.	Baseline, Week 8, Week 16; Change from Baseline to Week 16 reported
Mean 16-Week Change in Aberrant Behavior Checklist (ABC-2) Hyperactivity Subscale Score	The ABC-2 is a 58-item questionnaire with 5 subscales derived by factor analysis. It has been extensively used in psychopharmacological studies of ASD and assesses many symptoms that are either central to autism or frequently a target of treatment. The Hyperactivity Subscale is derived from 16 items with a score range of 0-48, where severe scores indicate more severe hyperactivity symptoms.	Baseline, Week 8, Week 16; Change from Baseline to Week 16 reported
Mean 16-Week Change in Aberrant Behavior Checklist (ABC-2) Inappropriate Speech Subscale Score	The ABC-2 is a 58-item questionnaire with 5 subscales derived by factor analysis. It has been extensively used in psychopharmacological studies of ASD and assesses many symptoms that are either central to autism or frequently a target of treatment. The Inappropriate Speech Subscale is derived from 4 items with a score range of 0-12, where higher scores indicate more severe Inappropriate Speech symptoms.	Baseline, Week 8, Week 16; Change from Baseline to Week 16 reported
Mean 16-Week Change in Attention Deficit Hyperactivity Disorder Rating Scale (ADHD-RS) Score	The ADHD-RS is an 18-question, parent-rated assessment reflecting DSM symptoms of ADHD. The score range is 0-54, with higher scores indicating more severe ADHD symptoms.	Baseline, Week 16; Change from Baseline to Week 16 reported
Mean 16-Week Change in Children's Sleep Habits Questionnaire (CSHQ) Total Score	The CSHQ is a 52-question parent survey used to assess sleep difficulties. 33 items are used to generate the total score, which ranges from 33-99, with a cutoff of >41 suggesting clinically significant sleep problems. Higher scores are indicative of more severe sleep problems.	Baseline, Week 16; Change from Baseline to Week 16 is reported
Mean 16-Week Change in Heart Rate Variability (HRV) at Rest	The log[root mean square of successive differences (RMSSD)] will be utilized as the primary HRV measure. It will be measured at rest in the laboratory setting pre- and post-treatment.	Baseline, Week 16; Change from Baseline to Week 16 reported
Mean 16-Week Change in Heart Rate Variability (HRV) with Startle	The log[root mean square of successive differences (RMSSD)] will be utilized as the primary HRV measure. It will be measured during a startle tone in the laboratory setting pre- and post-treatment.	Baseline, Week 16; Change from Baseline to Week 16 reported
Mean 16-Week Change in Heart Rate Variability (HRV) During a Working Memory Task	The log[root mean square of successive differences (RMSSD)] will be utilized as the primary HRV measure. It will be measured during a working memory task in the laboratory setting pre- and post-treatment.	Baseline, Week 16; Change from Baseline to Week 16 reported
Mean 16-Week Change in Heart Rate Variability (HRV) During Cold Pressor Task	The log[root mean square of successive differences (RMSSD)] will be utilized as the primary HRV measure. It will be measured during the Cold Pressor Task in the laboratory setting pre- and post-treatment.	Baseline, Week 16; Change from Baseline to Week 16 reported
Mean 16-Week Change in Blood Pressure	Blood pressure will be measured at rest in the laboratory setting pre- and post-treatment.	Baseline, Week 16; Change from Baseline to Week 16 reported
Mean 16-Week Change in Skin Conductance Level at Rest	Skin conductance level will be measured at rest in the laboratory setting pre- and post-treatment.	Baseline, Week 16; Change from Baseline to Week 16 reported
Mean 16-Week Change in Skin Conductance Level with Startle	Skin conductance level will be measured during a startle tone in the laboratory setting pre- and post-treatment.	Baseline, Week 16; Change from Baseline to Week 16 reported
Mean 16-Week Change in Skin Conductance Level During Working Memory Task	Skin conductance level will be measured during a working memory task in the laboratory setting pre- and post-treatment.	Baseline, Week 16; Change from Baseline to Week 16 reported
Mean 16-Week Change in Skin Conductance Level During Cold Pressor Task	Skin conductance level will be measured during the Cold Pressor Task in the laboratory setting pre- and post-treatment.	Baseline, Week 16; Change from Baseline to Week 16 reported
Mean 16-Week Change in Ambulatory Heart Rate Variability	Heart rate variability (HRV) will be assessed remotely throughout the 16-week trial using the Bittium Faros holter monitor. Change in log[root mean square of successive differences (RMSSD)] over the course of the trial will be quantified.	Baseline, Week 16; Change from Baseline to Week 16 reported
Mean 16-Week Change in Ambulatory Accelerometry Magnitude	Accelerometry magnitude will be assessed remotely throughout the 16-week trial using the Bittium Faros holter monitor, which records acceleration vector components (x, y, and z). Accelerometry magnitude (m/s^2) will be calculated using the vector sum of the acceleration vector components. Change in accelerometry magnitude over the course of the trial will be quantified.	Baseline, Week 16; Change from Baseline to Week 16 reported

Collaborators and Investigators

• Sponsor: Massachusetts General Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): August 1, 2026
• Primary Completion (Estimated): February 1, 2029
• Study Completion (Estimated): June 1, 2029

Study Registration Dates

• First Submitted: February 13, 2026
• First Submitted That Met QC Criteria: February 24, 2026
• First Posted (Actual): February 27, 2026

Study Record Updates

• Last Update Posted (Actual): February 27, 2026
• Last Update Submitted That Met QC Criteria: February 24, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Keywords: randomized controlled trial; autism; autism spectrum disorder; anxiety; buspirone
• Additional Relevant MeSH Terms: Mental Disorders; Neurodevelopmental Disorders; Child Development Disorders, Pervasive; Autism Spectrum Disorder; Anxiety Disorders; Autistic Disorder; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Hydrocarbons; Hydrocarbons, Cyclic; Polycyclic Compounds; Pyrimidines; Piperazines; Spiro Compounds; Buspirone
• Other Study ID Numbers: 2025P003437

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No