Selective Serotonin Reuptake Inhibitors (SSRI) Use in Children with Autism and Other Neurodevelopmental Disabilities

Autism spectrum disorder (ASD) and other neurodevelopmental disorders are frequently complicated by behavior and mood disorders. While selective serotonin reuptake inhibitor (SSRI) medications do not treat the core symptoms of ASD, those with ASD and comorbid anxiety may benefit from a trial of an SSRI. [King: 2009] Data suggests that use of an SSRI in this population may significantly reduce anxiety and related aggressive behavior. [Kolevzon: 2006]
SSRI medication use may lead to an “activation syndrome” with hyperactivity, disinhibition, and agitation. This potential adverse effect is less likely if the medication is started at a lower dose than would be considered in the typically developing population with a slow upward adjustment (holding at each dose increment for at least 4 weeks to ensure dose tolerability and assess response). Other potential adverse effects associated with SSRI use include but are not limited to headaches, gastrointestinal disturbance, sedation, aggressiveness, and sleep difficulty.
It has been noted in one clinical trial that with some SSRIs, new onset suicidal ideation or action exceeded the rate occurring in patients given placebo. While this occurred in 3-4% of the patients given SSRIs, it raised enough concern for the FDA to issue a “black box” warning regarding SSRI use. While these results have not been replicated, families should be made aware of this warning and instructed to monitor for negative behavioral or emotional changes in children prescribed SSRIs. It should be further noted that in the studies that raised this concern, subjects included adults and adolescents being treated for depression, a population distinct from children with autism and other neurodevelopmental disabilities.
Guidelines for the initiation and adjustment of SSRI medication in children with ASD and other neurodevelopmental disabilities:
  • Suggestions for initial SSRI trial:
    • Sertraline (available in 25, 50, 100 mg tabs, 20 mg/ml liquid)
      • Child: start at 6 mg daily for 4 weeks, then 12.5 mg, and then increase by 12.5 mg every 4 weeks (maximum dose: 100 mg)
      • Teenager: 12.5 mg for 4 weeks, then 25 mg, then increase by 25 mg increments every 4 weeks. (maximum dose: 200 mg)
    • Fluoxetine (available in 10, 20 mg tabs, 20 mg/5ml liquid) may have more anticholinergic side effects and cause more activation than sertraline or citalopram
      • Child: 2 mg once daily for 4 weeks, then 4 mg, and then increase by 4 mg every 4 weeks (maximum dose: 40 mg)
      • Teenager: 5 mg once daily for 4 weeks, then 10 mg, then increase by 5 mg every 4 weeks (maximum dose: 40 mg)
    • Citalopram (available in 10, 20, 40 mg tabs, 10 mg/5ml liquid)
      • Child: 2 mg once daily for 4 weeks, then increase by 2 mg increments every 4 weeks (maximum dose: 20 mg)
      • Teenager 5 mg once daily for 4 weeks, then increase by 5 mg increments every 4 weeks (maximum dose: 40 mg)
    • Escitalopram - paroxetine-anticholinergic side effects and/or activation limits the tolerance of these medications
Monitor closely for favorable and adverse effects with frequent in-office or phone follow-up. Positive effects are generally not observed until 4-6 weeks. Keep this in mind before titrating upward or discontinuing. Mild adverse effects may be transient and improve over time while taking the medication.
As with typically developing children, target behaviors in the home and school should be identified at the onset of treatment and monitored for treatment effectiveness. Establish a plan with the family for follow-up. Use objective rating scales such the Nisonger Child Behavior Rating Form (NCBRF) (NCBRF) to get an objective measure of problem behaviors. The NCBRF is a standardized scale for assessing child and adolescent behavior. Scales are available for typically developing children as well as for those with disabilities. They may be downloaded free of charge.
If an SSRI is discontinued abruptly, withdrawal effects may occur. These include flu-like symptoms, dizziness, headaches, memory problems, irritability and emotional lability. The following suggested tapering schedules will help reduce withdrawal syndromes:
  • Fluoxetine: Reduce by 5 mg every 2 weeks until dose is 5 mg/day, then decrease by 2.5 mg every 2 weeks.
  • Sertraline: Reduce by 25 mg every two weeks until dose is 25 mg/day, then decrease by 12.5 mg every 2 weeks.
  • Citalopram: Reduce by 5 mg every 2 weeks until dose is 5 mg/day, then decrease by 2.5 mg every 2 weeks.
Overdose or misuse of these medications may be life-threatening. Keep this and other medications out of reach from the patient and other children in the household.


Information & Support

For Professionals

Nisonger Child Behavior Rating Form (NCBRF)
A standardized tool used in assessing child and adolescent behaviors.

Authors & Reviewers

Initial publication: August 2009; last update/revision: November 2016
Current Authors and Reviewers:
Authors: Deborah Bilder, MD
Catherine Jolma, MD
Reviewer: Mary Steinmann, MD

Page Bibliography

King BH, Hollander E, Sikich L, McCracken JT, Scahill L, Bregman JD, Donnelly CL, Anagnostou E, Dukes K, Sullivan L, Hirtz D, Wagner A, Ritz L.
Lack of efficacy of citalopram in children with autism spectrum disorders and high levels of repetitive behavior: citalopram ineffective in children with autism.
Arch Gen Psychiatry. 2009;66(6):583-90. PubMed abstract

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. PubMed abstract