Insufficient evidence to recommend tricyclic antidepressants as a treatment for autism spectrum disorders


Young people with autism spectrum disorders (ASD) are usually given some kind of behavioural or educational intervention to help improve their overall functioning. However, in some cases, those individuals who have high levels of repetitive, obsessive-compulsive type behaviours and mood disorders are treated with drug interventions, although there is little high quality evidence to support these treatments in this group (Posey et al).

It has been suggested that TCAs might help manage symptoms in people with ASD:

Pharmacological interventions that target the serotonin system may provide assistance with problematic symptoms such as repetitive behaviours similar to those seen in obsessive-compulsive disorders, stereotyped mannerisms and difficulty with change, or with comorbidities such as affective lability, depression and anxiety (Volkmar et al).

It sounds like the time is right for a systematic summary of the randomised trials in this field, so I’m delighted to see a new Cochrane review that is focusing on whether TCAs:

  • Improve the core features of autism, including restricted social interaction, restricted communication, and stereotypical and repetitive behaviours
  • Improve non-core features such as challenging behaviours
  • Improve comorbid states, such as depression and anxiety
  • Cause adverse effects

The reviewers carried out the usual hardcore Cochrane search looking for randomised controlled trials of any dose, duration and frequency of oral TCAs compared with placebo, in children and adolescents with a diagnosis of ASD, where at least one standardised outcome measure had been used.

They only found 3 trials that met their inclusion criteria: two looking at the antidepressant clomipramine and the other looking at tianeptine. All of the studies were small (between 12 -32 participants). There was heterogeneity across the studies, so the reviewers were unable to conduct a meta-analysis.

Here’s what they found:

  • In the tianeptine study:
    • Parents and teachers reported that it reduced irritability, hyperactivity, inadequate eye contact and inappropriate speech
    • But clinician ratings found no significant impact on these symptoms
    • There were also significant side effects (increased drowsiness and reduced activity levels)
  • The two clomipramine studies produced contradictory evidence:
    • There was improvement in autistic symptoms, irritability and obsessive-compulsive disorder type symptoms, but conflicting evidence in relation to hyperactivity across the two studies, and no significant changes found with inappropriate speech
    • Side effects were again reported, although side effect ratings were not significantly different to placebo
    • There were significant dropout rates in the clomipramine arm of one study

The reviewers concluded:

Clinicians considering the use of tricyclic antidepressants (TCAs) need to be aware of the limited and conflicting evidence of effect and the side effect profile when discussing this treatment option with people who have autism spectrum disorders (ASD) and their carers. Further research is required before TCAs can be recommended for treatment of individuals with ASD.


Hurwitz R, Blackmore R, Hazell P, Williams K, Woolfenden S. Tricyclic antidepressants for autism spectrum disorders (ASD) in children and adolescents. Cochrane Database of Systematic Reviews 2012, Issue 3. Art. No.: CD008372. DOI: 10.1002/14651858.CD008372.pub2.

Posey DJ, McDougle CJ. Pharmacotherapeutic management of autism. Expert Opinion of Pharmacotherapy 2001;2(4):587-685. [PubMed abstract]

Volkmar FR, Lord C, Bailey A, Schultz RT, Klin A. Autism and Pervasive Developmental Disorders. Journal of Child Psychology and Psychiatry 2004;45(1):135-70. [Abstract]

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Andre Tomlin

André Tomlin is an Information Scientist with 20 years experience working in evidence-based healthcare. He's worked in the NHS, for Oxford University and since 2002 as Managing Director of Minervation Ltd, a consultancy company who do clever digital stuff for charities, universities and the public sector. Most recently André has been the driving force behind the Mental Elf and the National Elf Service; an innovative digital platform that helps professionals keep up to date with simple, clear and engaging summaries of evidence-based research. André is a Trustee at the Centre for Mental Health and an Honorary Research Fellow at University College London Division of Psychiatry. He lives in Bristol, surrounded by dogs, elflings and lots of woodland!

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