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Early Intervention With Fluoxetine in Autism

This study has been completed.
National Institute of Mental Health (NIMH)
Information provided by (Responsible Party):
Linmarie Sikich, MD, University of North Carolina, Chapel Hill Identifier:
First received: September 6, 2005
Last updated: February 7, 2014
Last verified: February 2014
This study is a pilot study to evaluate the feasibility and safety of conducting a year long, double-blind, placebo-controlled trial of fluoxetine in pre-school children to enhance developmental processes in core areas impacted by autism.

Condition Intervention Phase
Autistic Disorder Drug: Fluoxetine Drug: Placebo Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Randomized, Placebo-controlled Trial of Fluoxetine in Preschool Children

Resource links provided by NLM:

Further study details as provided by Linmarie Sikich, MD, University of North Carolina, Chapel Hill:

Primary Outcome Measures:
  • Rate of Recruitment [ Time Frame: 19 months ]
    In order for a larger trial with similar design to be feasible a number of factors needed to be examined. The first was whether families would enroll very young children with ASD into a year long blinded medication study. To determine this we examined the average number of months to randomize 1 participant per site. We calculated this (as total # months required for recruitment* 2sites ) /[ # participants randomized ] and compared it to the typical # of months required to recruit an older child with ASD for a double-blind 12 week placebo controlled medication study, which is typically about 1.2 months at each of the sites involved in the study.

Secondary Outcome Measures:
  • Rate of Attrition [ Time Frame: Measured at Month 12 ]
    The percentage of participants who discontinued treatment prior to completion of the 12 month study

  • Change From Baseline to 12 Months in Total Score on Caregiver Strain Questionnaire [ Time Frame: 12 months ]
    This is a caregiver completed measure that assesses the extent to which the caregiver feels care of the participant influences the caregiver's and other family members' emotional states and/or activities. There are a total of 22 items rated from 1 - not at all to 5 - very much (with one item reverse scored). Total score is the sum of all the items (with one item reverse scored). There are three subscales objective strain -12 items, internalized subjective strain 6 items, externalized subjective 4 items. The total score can range from a minimum of 0 - no strain at all, to 110 all items rated as very much.

  • Change From Baseline to Month 12 in Aberrant Behavior Checklist Irritability Subscale Score (ABC-I) [ Time Frame: 12 months ]
    The Aberrant Behavior Checklist (ABC) is a caregiver completed rating scale that assesses problem behaviors frequently seen in individuals with developmental disabilities. There are a total of 58 items on 5 subscales that are rated from 0 - not at all a problem to 3 - problem is severe in degree. The ABC-I consists of 15 items that reflect mood swings, self-injury and aggression. The subscale score is the sum of the score on each of the 15 items. The minimum score on the ABC-I is 0 and the maximum score is 45. Higher scores reflect more severe behavioral problems. A score > or = to 18 is generally considered clinically significant.

Enrollment: 18
Study Start Date: July 2005
Study Completion Date: February 2008
Primary Completion Date: February 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: Placebo
Placebo, liquid solution flexible dose 0.5 to 5ml every morning (AM)
Drug: Placebo
Between 0.5ml per day and 5ml per day of liquid placebo will be given in the morning using a flexible dosing strategy, following a 36-week dose titration schedule.
Experimental: fluoxetine
Fluoxetine, 20mg/5ml solution, flexible dose 0.5 to 5ml every AM
Drug: Fluoxetine
Between 2 mg per day and 20 mg per day of liquid fluoxetine will be given in the morning using a flexible dosing strategy, following a 36-week dose titration schedule.
Other Name: Prozac

Detailed Description:

Autism, a brain disorder that affects a small percentage of Americans, often results in a lifetime of impaired thinking, feeling, and social functioning. The disorder generally becomes apparent in children by the age of 3. Autism typically affects a person's ability to communicate, form relationships with others, and respond appropriately to the external world. Some people with autism can function at a relatively high level, with speech and intelligence intact. Others have serious cognitive impairments and language delays, and some never speak. This study will assess the safety and effectiveness of treating autistic children with fluoxetine to enhance developmental processes in core areas impacted by autism.

Each participant was randomly assigned to treatment with double-blinded placebo or fluoxetine for 12 months. After initial screening and randomization, participants were assessed every two weeks for approximately the first 3 months, or until the dose of medication is stabilized. After this initial period, they were assessed on a monthly basis. Dosing was flexible as determined by the adverse and beneficial responses to treatment although there was a suggested titration schedule.


Ages Eligible for Study:   30 Months to 58 Months   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Diagnosis of autism

Exclusion Criteria:

  • Diagnosis of Asperger Syndrome, Rett Syndrome, Childhood Disintegrative Disorder, or Pervasive Development Disorder-Not Otherwise Specified
  • Informed that treatment with a selective serotonin reuptake inhibitor (SSRI) is medically inadvisable
  • Need for ongoing psychotropic medication (except for diphenhydramine, clonidine, or melatonin for sleep)
  • Recent use of stimulants within 5 days prior to enrollment
  • Ongoing need for or recent use of most psychotropic medications within 14 days of enrollment
  • Recent initiation of specialized educational, behavioral, or diet intervention for autism in the month prior to enrollment
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its identifier: NCT00183339

United States, New York
Mount Sinai School of Medicine
New York, New York, United States, 10029
United States, North Carolina
University of North Carolina, Chapel Hill
Chapel Hill, North Carolina, United States, 25714
Sponsors and Collaborators
University of North Carolina, Chapel Hill
National Institute of Mental Health (NIMH)
Study Chair: Linmarie Sikich, MD University of North Carolina, Chapel Hill
  More Information

Responsible Party: Linmarie Sikich, MD, Associate Professor, University of North Carolina, Chapel Hill Identifier: NCT00183339     History of Changes
Other Study ID Numbers: U54MH066418 ( U.S. NIH Grant/Contract )
Study First Received: September 6, 2005
Results First Received: September 10, 2013
Last Updated: February 7, 2014

Keywords provided by Linmarie Sikich, MD, University of North Carolina, Chapel Hill:

Additional relevant MeSH terms:
Autistic Disorder
Child Development Disorders, Pervasive
Neurodevelopmental Disorders
Mental Disorders
Serotonin Uptake Inhibitors
Neurotransmitter Uptake Inhibitors
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents
Serotonin Agents
Physiological Effects of Drugs
Antidepressive Agents, Second-Generation
Antidepressive Agents
Psychotropic Drugs
Cytochrome P-450 CYP2D6 Inhibitors
Cytochrome P-450 Enzyme Inhibitors
Enzyme Inhibitors processed this record on September 21, 2017