Commentary on ‘Selective serotonin reuptake inhibitors (SSRIs) for autism spectrum disorders (ASD)’

The Cochrane review clearly provides important guidance for current clinical practice. There is a reasonable amount of support for the use of SSRIs to treat repetitive behaviors (and perhaps other core symptoms) in adults with ASD. Since review of existing studies does not support the efficacy of SSRIs in children and adolescents with ASDs, any use of these drugs within this younger age range should be done cautiously. We recognize that few psychotropic medications are specifically approved for use in children with ASD, and providers may choose to treat such patients in an off-label manner based on mechanistic hypotheses about possible beneficial drug effects or the presence of symptoms similar to those of other disorders for which SSRIs are approved. If clinicians offer to prescribe SSRIs to children with ASD, it is important that they inform parents about the lack of evidence of their efficacy in RCTs, discuss the potential risks (including behavioral side effects), and discuss alternative pharmacological and non-pharmacological treatments. When treating individuals in an off-label manner, it is particularly important to define clear target symptoms and assess whether such symptoms have improved with addition of the drug, keeping in mind the possibility of placebo effects and adverse drug reactions. If a drug does not seem to produce significant benefit or if side effects outweigh any beneficial effects, it is important to discontinue the ineffective drug rather than continuing that drug while adding on new medications. Given the evidence of adverse behavioral side effects from SSRIs in young patients with ASD, caution should be used with initial dosing and side effects must be closely monitored. The use of low initial doses and slow upward titration may help to reduce side effects. As a general rule, one of us has previously suggested starting with a half tablet of the smallest available tablet size and increasing by a half tablet per week to reach a moderate target dose (1). For example, in the case of sertraline, the recommended starting dose for treatment of obsessive-compulsive disorder in children age 6-12 years is 25mg (smallest tablet size), so starting at half that dose (12.5 mg) would be reasonable when treating a child in this age range who may be at some increased risk of behavioral side effects due to an ASD diagnosis. The dose could then be increased by 12.5mg per week (if well tolerated) to an initial target dose of 25-50 mg and held at 25-50mg for 4-6 weeks before any further increase is considered. Liquid formulations can allow for even smaller starting doses in children at the lower end of this age range or in those who have shown sensitivity to side effects of other medications. For adolescents and adults with ASD, it may also be advisable to start a bit below the FDA-recommended starting dose for the drug and to use a relatively slow upward titration. If side effects occur during upward titration, these may decrease with a dose reduction. If disinhibition is severe and present even at low doses, or if the medication does not result in symptom improvement, the SSRI should be tapered off and discontinued. Finally, we agree with the Cochrane review's call for additional study of SSRIs in ASD, including examination of possible sub-group variables, larger trials, examination of other target symptoms in children with ASD (e.g., anxiety, depression) and RCTs with three yet unstudied SSRIs.