Fluoxetine Treatment of Depression in Down Syndrome

NCT05458479 | Completed Phase 4 Results FDA Drug

• 1 other identifier: 2022P000858
• Study Type: interventional
• Target: 4
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of the study is to do a preliminary assessment of whether fluoxetine is effective, safe, and tolerable for the treatment of depression in adults with Down syndrome.

Conditions

Down Syndrome; Depression

Outcome Measures

Primary Outcomes (1)

• Proportion of Participants Who Responded to Treatment at 16 Weeks According to Improvement Item of the Clinical Global Impression-Scale (Response Defined as CGI-I=1 or CGI-I=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 scores indicating improvement (1=very much improved; 2=much improved). In this study, the CGI-I will be focused on the treatment target of depression symptom severity. Participants with a CGI-I score of 1 or 2 will be classified as responders.

  Week 16

Secondary Outcomes (4)

• Mean 16-Week Change in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score

  Baseline, Week 16

• Mean 16-Week Change in Hamilton Depression Rating Scale (HAM-D) Total Score

  Baseline, Week 16

• Mean 16-Week Change in Glasgow Depression Scale for People With a Learning Disability (GDS-LD) Total Score

  Baseline, Week 16

• Mean 16-Week Change in Glasgow Depression Scale for People With a Learning Disability Carer Supplement (GDS-CS) Total Score

  Baseline, Week 16

Study Arms (1)

Fluoxetine

EXPERIMENTAL

Subjects will receive fluoxetine 5 mg each morning at the start of the trial. The dose will be increased by 5 mg every 2 weeks depending on effectiveness and tolerability. The optimal dose will be reached by week 12 of treatment. The minimum starting dose will be 5 mg and the maximum total daily dose will be 30 mg.

Drug: Fluoxetine

Interventions

Fluoxetine DRUG

All participants in the study will receive open-label treatment with orally administered fluoxetine for the full duration of the 16-week trial. Fluoxetine is a selective serotonin reuptake inhibitor. It is approved for the management of major depressive disorder in adults.

Fluoxetine

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Age 18-45 years.
• Diagnosis of DS confirmed via genetic testing or a clinical diagnosis made by a clinician with significant experience treating patients with DS.
• Diagnosis of major depressive disorder based on Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) criteria, confirmed through the Structured Clinical Interview for DSM-5 (SCID-5).
• A Clinical Global Impression Severity Item score \> 4 (moderate) for depression symptoms at Screen and Baseline.

You may not qualify if:

• Current or previous diagnosis of dementia, or use of medication to treat dementia. Given the potential overlap between depression and dementia symptoms, we want to ensure we are administering fluoxetine to patients with a diagnosis of depression.
• Presence of any past or present conditions that would make treatment with fluoxetine unsafe. This includes allergy to fluoxetine, liver or kidney disease, unstable heart disease, and/or pregnancy (or being sexually active without using acceptable methods to prevent pregnancy).
• Use of selective serotonin reuptake inhibitors (SSRIs), serotonin norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants (TCAs), monoamine oxidase inhibitors (MAOIs), bupropion, mirtazapine, antipsychotics, lithium, valproic acid, or carbamazepine. Subjects will need to be off these classes of medications for at least 5 elimination half-lives prior to beginning the trial.
• Use of other psychotropic medications which are ineffective, poorly tolerated, or sub-optimal in terms of dose. A board-certified psychiatrist will assess any other psychotropic medications being used and determine whether they are effective, tolerated, and optimal in terms of dose. If medications are ineffective, poorly tolerated, or sub-optimal in terms of dose, the study psychiatrist will work with the subject and his/her treatment team to either taper or optimize the dose of psychotropic medications prior to study enrollment. Concurrent use of a psychotropic medication (other than SSRIs, SNRIs, TCAs, MAOIs, bupropion, mirtazapine, antipsychotics, lithium, valproic acid, or carbamazepine) will be allowed if the dose has been stable for 30 days and if they meet the criteria of effectiveness, tolerability, and dose.
• Previous adequate trial of fluoxetine. An adequate trial will be defined as a total daily dose of ≥30 mg for at least 4 weeks. In addition, subjects who developed significant adverse effects during a trial of fluoxetine at any dose or duration will be excluded.
• Severe or profound intellectual disability based on clinical assessment and review of standardized assessment of cognitive skills. Participants determined to have severe or profound intellectual disability will be excluded.
• Use of medications that pose a clinically significant risk of a drug-drug interaction with fluoxetine.

Sponsors & Collaborators

• Massachusetts General Hospital: lead

Study Sites (1)

Lurie Center for Autism

Lexington, Massachusetts, 02421, United States

Location

MeSH Terms

Conditions

Down Syndrome; Depression

Interventions

Fluoxetine

Condition Hierarchy (Ancestors)

Intellectual Disability; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Abnormalities, Multiple; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Chromosome Disorders; Genetic Diseases, Inborn; Behavioral Symptoms; Behavior

Intervention Hierarchy (Ancestors)

Propylamines; Amines; Organic Chemicals

Results Point of Contact

• Title: Dr. Robyn Thom
• Organization: Massachusetts General Hospital Lurie Center for Autism

rthom@mgh.harvard.edu

7818601700

Study Officials

• Robyn P. Thom, MD

  Lurie Center for Autism

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Instructor of Psychiatry

Study Record Dates

• First Submitted: July 11, 2022
• First Posted: July 14, 2022
• Study Start: December 5, 2022
• Primary Completion: February 26, 2024
• Study Completion: February 26, 2024
• Last Updated: March 30, 2025
• Results First Posted: March 30, 2025

Record last verified: 2025-03

Locations

US (1)