Multi-Site Randomised Controlled Trial of Fluoxetine in Children and Adolescents with Autism (FAB): Rationale and Design

Background: Serotonin reuptake inhibitors (SSRIs) are commonly prescribed ‘off -label’ for children with autism despite caution regarding their use. To date, clinical trials examining the use of SSRIs in autism have been limited by small sample sizes and inconclusive results. The efficacy and safety of SSRIs for moderating repetitive stereotyped mannerisms in children with autism is yet to be examined. The aims of the FAB study are:

1. To determine the efficacy of low- dose fluoxetine compared to placebo, for reducing the frequency and severity of restricted, repetitive and stereotypic behaviours in children and adolescents with an Autism Spectrum Disorder (ASD). 
2. To assess the safety of using low- dose fluoxetine. 
3. To explore the relationship between the effectiveness of low- dose fluoxetine and the serotonin transporter genotype. 

Objectives: To describe the rationale and methodology of the FAB study and a summary of the patient profiles to date.

Methods: The FAB study is a multi-site randomized controlled trial. As at October 2013, fifty- eight participants (52 males) aged between 8- 17 years with a confirmed DSM-IV-TR diagnosis of ASD have been recruited. Recruitment is expected to continue until early 2014. Following pre- assessment, eligible participants were randomised to either placebo or active fluoxetine groups. Medication was titrated upwards over a four-week period. Reponses to medication were monitored on a weekly/fortnightly basis using the Clinical Global Impressions Scale (CGI). The primary outcome measure is the Children’s Yale-Brown Obsessive Compulsive Scale- Modified for Pervasive Developmental Disorders (CYBOCS-PDD) at 16 weeks. Secondary outcome measures include the Aberrant Behaviour Scale (ABC), Spence Children’s Anxiety Scale Parent version (SCAS-P) and the Repetitive Behaviours Scale (RBS-R) also at 16 weeks. Participants were also invited to undergo genetic testing for SLC6A4 allele variants via a cheek swab. The primary outcome (total score on the CYBOCS-PDD at 16 weeks) will be compared for the active and placebo groups using unadjusted linear regression. Secondary outcomes will also be compared using unadjusted linear regression with proportions compared using unadjusted logistic regression.

Results: N/A

Conclusions: The FAB study is the first clinical trial to specifically investigate the efficacy and safety of low dose fluoxetine for restricted, repetitive and stereotyped behaviours in children with ASD.

Funding: The study is funded by a National Health and Medical Research Council (NHMRC 607332) grant by the Australian Government. All study- related expenses including publication costs for manuscripts are to be covered by this grant.

Competing Interests: Philip Hazell and Michael Kohn have received payment from Eli Lilly (the manufacturer of fluoxetine) for participation in consultancies, advisory boards, speaker’s bureau, and the conduct of clinical trials.