Fluvoxamine and Sertraline in Childhood Autism - Does SSRI Therapy Improve Behaviour and/or Mood?

A Double-Blind Placebo-Controlled Randomized Clinical Trial of Fluvoxamine and Sertraline in Childhood Autism - Does SSRI Therapy Improve Behaviour and/or Mood?

The purpose of this study is to determine if fluvoxamine or sertraline reduce the fequency or severity of aggressive behaviour, obsessive symptoms, or anxiety in young children with autism. The within-patient variability in this patient population using standard neuropsychological instruments will also be determined and a predictor model for SSRI responsitivity based on baseline neuropsychological testing will be developed.

Study Overview

• Status: Completed
• Conditions: Autism
• Intervention / Treatment: Drug: Placebo; Drug: fluvoxamine; Drug: sertraline

Detailed Description

Autism is a neuropsychiatric disorder diagnosed in early childhood. Approximately 10 Canadian children per 10 000 live births suffer from the disorder, which is three to four times more common in males than in females. It is characterized by social and and communicative deficits and restricted, repetitive interests and behaviours. Most autistic children are delayed in the acquisition of both verbal and non-verbal communication skills and many never develop useful language. Three-quarters of autistic children have mild to severe mental retardation and a quarter develop seizures during later childhood or adolescence. Its etiology is heterogenous and there is no cure. Although behaviour therapy is an important tool in management, pharmacotherapy remains a necessity for many children. Current therapy is limited to antipsychotic drugs that can carry an unacceptable risk of chronic neurotoxicity (tardive dyskinesia) or tricyclic antidepressants that have undesireble cardiovascular effects. This study proposes to evaluate the potential benefit of selective seratonin reuptake inhibitors (SSRIs) in autism.

All autistic children whose symptoms are not currently well controlled will be offered entry into the trial. Each child will randomized to eight weeks of fluvooxamine, sertraline, or placebo. If they do not improve on their initial dose, they may have a dose increase and continue in the study for a further eight weeks. Due to the significant amount of within- and between- patient variability, multiple baseline evaluations will be completed prior to the initiation of drug therapy. Parents may choose to continue therapy that was effective for their child; if their child was randomized to placebo, parents may choose to try an SSRI for a period of 8 weeks to assess effectiveness.

• Study Type: Interventional
• Enrollment (Actual): 108
• Phase: Phase 3

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada
      • The Hospital for Sick Children

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 3 years to 10 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• diagnosis of autism based on Autism Dignostic Interview -Revised and/or Autism Diagnostic Observation Schedule, depending on which is appropriate for the child's chronological age
• ages 3-10 inclusive
• free of psychoactive medication for at least 3 months prior to entry into the trial

Exclusion Criteria:

• known contra-indications to SSRIs (i.e. hepatic dysfunction)
• Lactose intolerance
• concurrent psychotropic medications (SSRIs can interact with lithium, tricyclic antidepressants, monoamine oxidase inhibitors, and benzodiazepines)
• taking warfarin (SSRIs can increase levels)
• Inability of parents to give informed consent, travel to the clinic visits, administer study medication, or arrange for completion of rating scales by self/school staff

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 2	Drug: fluvoxamine; Children will be started on 12.5 mg. If there is no therapeutic effectivenss observed after eight weeks, then the child may have their dose increased. In this case, the child will be followed for an additional eight weeks.
Placebo Comparator: 1	Drug: Placebo; Patients in this study arm will receive capsules that appear identical to those of the two study drugs but will contain no active ingredient.
Experimental: 3	Drug: sertraline; Children will be started on 12.5 mg. If there is no therapeutic effectivenss observed after eight weeks, then the child may have their dose increased. In this case, the child will be followed for an additional eight weeks.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
The severity of the autistic child's behaviour or condition (assessed by parents)	At baseline and weekly thereafter until the study is completed

Secondary Outcome Measures

Outcome Measure	Time Frame
Weight and vital signs	Weeks 1, 7 and 11
Blood count and liver function studies	Weeks 1 and 11

Collaborators and Investigators

• Sponsor: The Hospital for Sick Children
• Investigators: Principal Investigator: Sunita Vohra, MD, Stollery Children's Hospital

Study record dates

Study Major Dates

• Study Start: June 1, 1999
• Primary Completion (Actual): September 1, 2006
• Study Completion (Actual): January 1, 2007

Study Registration Dates

• First Submitted: April 4, 2008
• First Submitted That Met QC Criteria: April 4, 2008
• First Posted (Estimate): April 9, 2008

Study Record Updates

• Last Update Posted (Estimate): April 9, 2008
• Last Update Submitted That Met QC Criteria: April 4, 2008
• Last Verified: April 1, 2008

More Information

Terms related to this study

• Keywords: autism; sertraline; fluvoxamine; selective seratonin reuptake inhibitors; paediatrics
• Additional Relevant MeSH Terms: Mental Disorders; Neurodevelopmental Disorders; Child Development Disorders, Pervasive; Autism Spectrum Disorder; Autistic Disorder; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Enzyme Inhibitors; Tranquilizing Agents; Psychotropic Drugs; Serotonin Uptake Inhibitors; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Serotonin Agents; Antidepressive Agents; Anti-Anxiety Agents; Cytochrome P-450 Enzyme Inhibitors; Antidepressive Agents, Second-Generation; Cytochrome P-450 CYP1A2 Inhibitors; Cytochrome P-450 CYP2C19 Inhibitors; Sertraline; Fluvoxamine
• Other Study ID Numbers: 0019990290