Trial Outcomes & Findings for Fluoxetine Treatment of Depression in Down Syndrome (NCT NCT05458479)

Last Updated: 2025-03-30

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

4 participants

Primary outcome timeframe

Week 16

Results posted on

2025-03-30

Participant Flow

Participant milestones

Participant milestones
Measure	Fluoxetine 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. Fluoxetine: 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.
Overall Study STARTED	4
Overall Study Still Enrolled at Week 4	3
Overall Study COMPLETED	3
Overall Study NOT COMPLETED	1

Reasons for withdrawal

Reasons for withdrawal
Measure	Fluoxetine 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. Fluoxetine: 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.
Overall Study Lost to Follow-up	1

Baseline Characteristics

Fluoxetine Treatment of Depression in Down Syndrome

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Fluoxetine n=4 Participants 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. Fluoxetine: 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.
Age, Continuous	25.9 years n=93 Participants
Sex: Female, Male Female	1 Participants n=93 Participants
Sex: Female, Male Male	3 Participants n=93 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=93 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	4 Participants n=93 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=93 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=93 Participants
Race (NIH/OMB) Asian	0 Participants n=93 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=93 Participants
Race (NIH/OMB) Black or African American	1 Participants n=93 Participants
Race (NIH/OMB) White	3 Participants n=93 Participants
Race (NIH/OMB) More than one race	0 Participants n=93 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=93 Participants
Region of Enrollment United States	4 participants n=93 Participants

PRIMARY outcome

Timeframe: Week 16

Population: All four enrolled participants were included. The participant lost to follow-up prior to completing week 16 assessments was considered not to have responded to fluoxetine treatment.

Outcome measures

Outcome measures
Measure	Fluoxetine n=4 Participants 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. Fluoxetine: 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.
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)	0.75 Proportion of participants Interval 0.3 to 0.95

SECONDARY outcome

Timeframe: Baseline, Week 16

Population: Three participants contributed both baseline and week 16 total MADRS scores to the analysis. The fourth enrolled participant was missing MADRS total score at baseline and was lost to follow-up prior to the 16 week assessment.

The MADRS is one of the most frequently used outcome measures in antidepressant efficacy trials and was developed to assess change in depressive symptoms after treatment with antidepressants. It is clinician-rated and consists of 10 items, each rated on a 0-6 scale and summed to determine the total score (minimum score: 0, maximum score: 60). A total score of 7-19 is indicative of mild depression, 20-34 of moderate depression, and 35-60 of severe depression. The MADRS will be conducted at screening, baseline, and each follow-up visit.

Outcome measures

Outcome measures
Measure	Fluoxetine n=3 Participants 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. Fluoxetine: 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.
Mean 16-Week Change in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score	-23.7 units on a scale Standard Error 2.0

SECONDARY outcome

Timeframe: Baseline, Week 16

Population: Three participants contributed both baseline and week 16 total HAM-D scores to the analysis. The fourth enrolled participant contributed a baseline total score but was lost to follow-up prior to week 16 assessments. Mean change was estimated using repeated measures linear regression accommodating all observed baseline and week 16 total scores.

The HAM-D is a clinician-rated scale with scores based on clinical interview and family report. It addresses both somatic and psychological symptoms of depression. Items are rated on either a 5-point scale (0 to 4) or 3-point scale (0 to 2), where higher scores represent increasing severity of depression. The scores of the 17 items are summed to obtain a total score (minimum score: 0, maximum score: 52).

Outcome measures

Outcome measures
Measure	Fluoxetine n=4 Participants 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. Fluoxetine: 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.
Mean 16-Week Change in Hamilton Depression Rating Scale (HAM-D) Total Score	-11.3 units on a scale Standard Error 1.9

SECONDARY outcome

Timeframe: Baseline, Week 16

Population: Two participants contributed both baseline and Week 16 total GDS-LD scores to the analysis. Of the two participants who did not contribute scores, one was unable to provide ratings at baseline and week 16 due to cognitive ability, and one was unwilling to answer most questions at baseline and was lost to follow-up prior to Week 16 assessments.

The GDS-LD was developed to describe and quantify depressive symptoms in adults with mild-to-moderate learning disabilities. The GDS-LD consists of 19 items scored from 0 to 2. The 19 item scores are summed to obtain the GDS-LD total score (minimum score: 0, maximum score: 38). Higher scores are indicative of more severe depression.

Outcome measures

Outcome measures
Measure	Fluoxetine n=2 Participants 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. Fluoxetine: 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.
Mean 16-Week Change in Glasgow Depression Scale for People With a Learning Disability (GDS-LD) Total Score	-8.5 units on a scale Standard Error 0.5

SECONDARY outcome

Timeframe: Baseline, Week 16

Population: Three participants contributed both baseline and week 16 total GDS-CS scores to the analysis. The fourth enrolled participant was excluded from GDS-CS analysis due to incomplete ratings at baseline and loss to follow-up prior to the 16 week assessment.

The GDS-CS was developed to describe and quantify depressive symptoms in adults with mild-to-moderate learning disabilities. The GDS-CS consists of 16 items scored from 0 to 2. The 16 item scores are summed to obtain the GDS-CS total score (minimum score: 0, maximum score: 32). Higher scores are indicative of more severe depression.

Outcome measures

Outcome measures
Measure	Fluoxetine n=3 Participants 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. Fluoxetine: 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.
Mean 16-Week Change in Glasgow Depression Scale for People With a Learning Disability Carer Supplement (GDS-CS) Total Score	-9.3 units on a scale Standard Error 0.6

Adverse Events

Fluoxetine

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Fluoxetine n=4 participants at risk 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. Fluoxetine: 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.
Nervous system disorders Headache	25.0% 1/4 • The earlier of loss to follow-up or 16 weeks
Infections and infestations Ear infection	25.0% 1/4 • The earlier of loss to follow-up or 16 weeks
General disorders Dry mouth	25.0% 1/4 • The earlier of loss to follow-up or 16 weeks
Infections and infestations Nasal congestion or cold	25.0% 1/4 • The earlier of loss to follow-up or 16 weeks
Infections and infestations Sinus condition	25.0% 1/4 • The earlier of loss to follow-up or 16 weeks
Respiratory, thoracic and mediastinal disorders Cough	25.0% 1/4 • The earlier of loss to follow-up or 16 weeks
Gastrointestinal disorders Diarrhea	25.0% 1/4 • The earlier of loss to follow-up or 16 weeks
Gastrointestinal disorders Stomach or abdominal discomfort	25.0% 1/4 • The earlier of loss to follow-up or 16 weeks
Gastrointestinal disorders Vomiting	25.0% 1/4 • The earlier of loss to follow-up or 16 weeks
Skin and subcutaneous tissue disorders Localized rash	25.0% 1/4 • The earlier of loss to follow-up or 16 weeks
Psychiatric disorders Interrupted sleep	25.0% 1/4 • The earlier of loss to follow-up or 16 weeks
General disorders Foot injury	25.0% 1/4 • The earlier of loss to follow-up or 16 weeks

Additional Information

Dr. Robyn Thom

Massachusetts General Hospital Lurie Center for Autism

Phone: 7818601700

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place