Autism SSRIs

Based on existing findings, there are many important hypotheses in pediatric psychopharmacogenetics. Selective serotonin transporter inhibitors have been shown to have efficacy in double-blind studies in children and/ or adolescents in the treatment of autism, major depression, OCD, and anxiety disorders. Given the association of the serotonin transporter promoter variant with SSRI treatment response in adult depression (Smeraldi et ah, 1998), all of the SSRI-responsive phenotypes should be tested for promoter variant influence on response using family-based or population-based controlled association studies. The report of strong 5-HTTLPR allelic effects on SSRI-induced mania (Mundo et ah, 2000) is of special interest given frequent SSRI-induced activation in children. 

There has been an increasing interest in the use of serotonin reuptake inhibitors (SSRIs) in the treatment of autism (McDougle et al., 1996). Serotonin binds to several types of receptors including the 5-HT2, and 5-HTlc receptors, which are linked to inositol signaling. A double-blind crossover study was completed at a dose of 200 mg/kg per day, and the results demonstrated no significant improvement on inositol therapy (Levine et al., 1997). 

Although favorable reports for other SSRIs have been reported in open-label studies (reviewed by Posey et al., 2006), these are of doubtful value for the reasons discussed above. The fact that the largest, most comprehensive study to date failed to find a benefit of a SSRI for the specific indication for which these agents are most commonly prescribed in ASD casts doubt on the value of this class of medications in ASD. Indeed, aside from one study of fluvoxamine in adults (McDougle et al., 1996) and one of fluoxetine in children (Hollander et al., 2005) (discussed above), there is little to support the use of SSRIs in ASD. Moreover, even in the studies that have reported favorable results, improvement in core symptoms has been found to be variable and generally rather modest, providing little support for the hypothesis that abnormalities in serotonin systems play a central role in autism. 

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