In one sentence
A 2012 Cochrane review found that tricyclic antidepressants have limited and conflicting evidence for treating autism-related symptoms in children, and they can cause significant side effects such as drowsiness.
What the researchers did
Some clinicians have tried tricyclic antidepressants (TCAs) for autistic children when irritability, hyperactivity, or obsessive-compulsive type behaviors are hard to manage. These medications affect how the brain uses serotonin and noradrenaline.
Researchers searched medical databases through May 2011 for randomised controlled trials comparing any oral TCA with placebo in children and adolescents with autism spectrum disorder. Two reviewers independently selected studies and assessed their quality.
Only three small trials met the criteria: two tested clomipramine and one tested tianeptine. Each study included between 12 and 32 participants.
What they found
In the tianeptine study, parents and teachers reported short-term reductions in irritability, hyperactivity, poor eye contact, and inappropriate speech. Clinician ratings, however, did not confirm those improvements. Children taking tianeptine also showed more drowsiness and lower activity levels.
The two clomipramine studies produced contradictory results. One suggested improvement in autistic symptoms, irritability, and obsessive-compulsive type behaviors; the other did not. Results for hyperactivity also conflicted between the two trials. Neither clomipramine study found clear changes in inappropriate speech.
Side effects were reported with clomipramine, and one study had high dropout rates in the medication group. Because the trials used different drugs and outcome measures, the reviewers could not combine results into a single analysis.
What this means for families and therapists
If a clinician suggests a TCA for an autistic child, it is reasonable to ask about the limited evidence base and the risk of side effects such as sedation or reduced energy.
These medications are not established first-line treatments for core autism features. Behavioral, communication, and educational supports remain the mainstay of care.
For therapists working with a child on a TCA, note any changes in sleep, alertness, or behavior and share observations with the prescribing doctor.
Limitations and what we don't know yet
Only three small, short-term trials were included, totaling roughly 72 children. That is too few to draw firm conclusions.
The studies tested different medications and relied partly on parent or teacher reports that did not always match clinician ratings. Long-term safety and effectiveness remain unknown. This review is from 2012, so newer research may exist but was not included here.
This is a simplified summary of Tricyclic antidepressants for autism spectrum disorders (ASD) in children and adolescents by Hurwitz R, Blackmore R, Hazell P, Williams K, Woolfenden S, Cochrane Database of Systematic Reviews (2012).
Source license: CC-BY-NC-4.0.
This is not medical advice. Please consult a qualified healthcare professional before making treatment decisions.