Cochrane Review: Selective serotonin reuptake inhibitors (SSRIs) for autism spectrum disorders (ASD)
Article first published online: 5 JUL 2011
Copyright © 2010 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Evidence-Based Child Health: A Cochrane Review Journal
Volume 6, Issue 4, pages 1044–1078, July 2011
How to Cite
Williams, K., Wheeler, D. M., Silove, N. and Hazell, P. (2011), Cochrane Review: Selective serotonin reuptake inhibitors (SSRIs) for autism spectrum disorders (ASD). Evid.-Based Child Health, 6: 1044–1078. doi: 10.1002/ebch.804
- Issue published online: 5 JUL 2011
- Article first published online: 5 JUL 2011
- Age Factors;
- Autistic Disorder [*drug therapy; psychology];
- Citalopram [therapeutic use];
- Fenfluramine [therapeutic use];
- Fluoxetine [therapeutic use];
- Fluvoxamine [therapeutic use];
- Obsessive-Compulsive Disorder [*drug therapy];
- Randomized Controlled Trials as Topic;
- Serotonin Uptake Inhibitors [*therapeutic use];
Autism spectrum disorders (ASD) are characterised by abnormalities in social interaction and communication skills, as well as stereotypic behaviours and restricted activities and interests. Selective serotonin reuptake inhibitors (SSRIs) are prescribed for the treatment of co-morbidity associated with ASD such as depression, anxiety and obsessive-compulsive behaviours.
To determine if treatment with an SSRI:
1. improves the core features of autism (social interaction, communication and behavioural problems);
2. improves other non-core aspects of behaviour or function such as self-injurious behaviour;
3. improves the quality of life of children and their carers;
4. has short and long term effects on outcome;
5. causes harms.
We searched the Cochrane Central Register of Controlled Trials (The Cochrane Library 2009, Issue 4), MEDLINE ( December 2009), EMBASE (December 2009), CINAHL (December 2009), PsycINFO (December 2009) and ERIC (December 2009), without language restrictions.
Randomised controlled trials (RCTs) of any dose of oral SSRI compared with placebo, in participants with autism spectrum disorders. Trials must have included at least one standardised outcome measure.
Data collection and analysis
Two authors independently selected and appraised studies for inclusion and risk of bias. All data were continuous. Meta-analysis, where possible, used a random-effects model.
Seven RCTs with a total of 271 participants were included. Four SSRIs were evaluated: fluoxetine (two studies), fluvoxamine (two studies), fenfluramine (two studies) and citalopram (one study). Five studies included only children and two studies included only adults. Varying inclusion criteria were used with regard to diagnostic criteria and intelligence of participants. Seventeen different outcome measures were reported. Although more than one study reported data for Clinical Global Impression (CGI) and obsessive-compulsive behaviour (OCB), different tool types or components of these outcomes were used in each study. As such, data were unsuitable for meta-analysis. One large, high quality study in children showed no evidence of positive effect of citalopram. Two small studies in adults showed positive outcomes for CGI and OCB; one study showed improvements in aggression, and another in anxiety.
There is no evidence of effect of SSRIs in children and emerging evidence of harm. There is limited evidence of the effectiveness of SSRIs in adults from small studies in which risk of bias is unclear.
Plain Language Summary
Selective serotonin reuptake inhibitors for the treatment of autism spectrum disorders
Autism spectrum disorders (ASD) are characterised by problems with social interaction and communication, as well as repetitive behaviours and limited activities and interests. Selective serotonin reuptake inhibitors (SSRIs) are a class of antidepressants which are sometimes given to help anxiety or obsessive compulsive behaviours. We found seven trials which evaluated four SSRIs: fluoxetine, fluvoxamine, fenfluramine and citalopram. Five studies included only children and two studies included only adults. One trial enrolled 149 children, but all other trials were small. We found no trials which evaluated sertraline, paroxetine or escitalopram. There is no evidence to support the use of SSRIs to treat autism in children. There is limited evidence, which is not yet sufficiently robust, to suggest effectiveness of SSRIs in adults with autism. Treatment with an SSRI may cause side effects. Decisions about the use of SSRIs for established clinical indications that may co-occur with autism, such as obsessive compulsive disorder and depression in adults or children, and anxiety in adults, should be made on a case by case basis.