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Off-Label Antidepressant Use in Pediatric Patients with Autism

By: Jacqueline Meaney, PharmD Candidate c/o 2015, University at Buffalo: School of Pharmacy and Pharmaceutical Sciences

Psychotropic medications are typically used in conjunction with cognitive behavioral therapy to treat behavioral problems that affect children with autism spectrum disorder (ASD). Symptoms of ASD typically include a need for routines (change intolerance), difficulty with verbal and nonverbal communication, difficulty with social interactions and relationships, and ritualistic or repetitive behaviors which are commonly seen in people with Obsessive-Compulsive Disorder (OCD).1 Currently, risperidone is the only FDA-approved medication to treat the symptoms of ASD in pediatric patients.  However, off-label prescribing of antidepressants, particularly, selective serotonin receptor inhibitors (SSRIs) are used in managing symptoms of ASD.

Autism is similar to other mental health conditions in that abnormalities in serotonin function are present in patients with autism spectrum disorder. As a result, physicians often prescribe selective serotonin reuptake inhibitors (SSRIs) off-label to treat symptoms of ASD.2 Fluoxetine has shown mixed results when used to treat obsessive-compulsive behaviors associated with autism. Some studies have demonstrated a significant effect while other studies failed to show clinically significant differences between treatment and placebo groups.3-5 Citalopram, another SSRI, has not shown significant improvement when used to treat core and non-core symptoms of autism spectrum disorder. In fact, treatment with citalopram in children with autism resulted in an increased rate of adverse events compared to children taking placebo, and as a result, citalopram is not recommended for the symptomatic treatment of ASD.6

Sertraline, which is in the same class of medications as fluoxetine and citalopram, has not been well-studied in autistic children with repetitive behaviors, but it has been shown to be effective in reducing repetitive behaviors in adults with autism.7 Sertraline is currently FDA-approved for the treatment of obsessive-compulsive disorder (OCD) in children ages 6 and older. For the treatment of OCD, children over 6 years of age should be started on 25 mg of sertraline daily, and titrated upwards if necessary to a maximum oral dose of 200 mg daily.8,9 Since sertraline is not FDA-approved for the treatment of autism in children, this dosing information cannot be directly applied to autistic pediatric patients. While it is also not approved for the treatment of obsessive-compulsive symptoms of children with autism, it has often been used for the treatment of repetitive behaviors associated with this condition. The efficacy of sertraline for the treatment of change intolerance in autistic children was shown by a small open study assessing the effects of a 25-50 mg daily dose of sertraline in a group of 9 children aged 6-12 who presented with anxiety or agitation as a result of changes in their daily schedules. Sertraline was shown to be safe and effective at this dose over a period of 6 months for the treatment of change intolerance in these children.8 However, additional research is needed to determine the efficacy and safety of sertraline in children with ASD.  A 2013 meta-analysis showed that there were no randomized controlled trials (RCTs) evaluating sertraline for use in autism spectrum disorder. However, there is currently one ongoing phase 3 RCT that is evaluating the use of fluvoxamine and sertraline in children with autism. These children will be started on 12.5 mg of sertraline for 8 weeks and then will be titrated upwards to a higher dose for another 8 weeks if no therapeutic response is seen at the initial dose. Overall, the use of sertraline in children with ASD is based on case reports and the clinical observation of physicians and the results of small, open, observational studies.6

In 2004, the FDA released a boxed warning for all antidepressant medications to warn the public that antidepressants may cause an increased risk of suicidal tendencies in children and adolescents. Patients should be closely monitored for signs of unusual changes in behavior, severe mood swings, or worsening depression during treatment.9 Therefore, it is important to use caution when prescribing these medications in patients younger than 25 years of age. The lowest effective dose should be prescribed and any side effects should be reported immediately.

Overall, further research is needed in order to prove that sertraline is safe and effective for use in pediatric patients with autism spectrum disorder. Although SSRIs have been shown to be effective in small open studies in treating symptoms of ASD, weaknesses in many of them suggest that further research is needed. Sertraline may be prescribed off-label to treat symptoms of autism by an experienced pediatrician or child psychiatrist who feels that the benefits of this medication outweigh the risks for the child being treated. Titration to doses greater than 50mg per day is not advised, as there are no reliable studies documenting safety and efficacy of sertraline for the treatment of autism at greater doses. Children taking sertraline for the symptomatic treatment of ASD should be closely monitored for adverse reactions, and the medication should be discontinued if there is no perceived efficacy or if adverse events arise.



  1. Makkonen I, Riikonen R, Kokki H, et al. Serotonin and dopamine transporter binding in children with autism determined by SPECT. Dev Med Child Neurol. 2008; 50(8): 593-7.
  2. Kolevzon A, Mathewson KA, Hollander E. Selective serotonin reuptake inhibitors in autism: a review of efficacy and tolerability. J Clin Psychiatry.2006; 67(3): 407-14.
  3. Soorya L, Kiarashi J, Hollander E. Psychopharmacologic interventions for repetitive behaviors in autism spectrum disorders. Child Adolesc Psychiatr Clin N Am. 2008; 17(4): 753-71, viii.
  4. Hollander E, Soorya L, Chaplin W, et al. A double-blind placebo-controlled trial of fluoxetine for repetitive behaviors and global severity in adult autism spectrum disorders. American Journal of Psychiatry 2012; 169(3): 292–9.
  5. DeLong GR, Ritch CR, Burch S. Fluoxetine response in children with autistic spectrum disorders: correlates with familial major affective disorder and intellectual achievement. Dev Med Child Neurol 2002; 44(3): 652-9.
  6. Brignell WK, Randall M, Silove N, et al. Selective serotonin reuptake inhibitors (SSRIs) for autism spectrum disorders (ASD). Cochrane database of systematic reviews. 1469-93.
  7. Moore ML, Eichner SF, Jones JR. Treating functional impairment of autism with selective serotonin-reuptake inhibitors. Ann Pharmacother.2004; 38(9): 1515-9. Epub 2004 Aug 3.
  8. Steingard RJ, Zimnitzky B, DeMaso DR, et al. Sertraline treatment of transition-associated anxiety and agitation in children with autistic disorder. J Child Adolesc Psychopharmacol.1997; 7(1): 9-15.
  9. Zoloft (sertraline) package insert. New York, NY: Pfizer; 2014 Aug.

[pubmed_related keyword1=”children” keyword2=”autism” keyword3=”disorder”]

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