Abstract
This study was a 10-week double-blind, placebo-controlled pilot trial of mirtazapine for anxiety in youth with autism spectrum disorder (ASD). Participants were ages 5 to 17 years with ASD and clinically significant anxiety (Pediatric Anxiety Rating Scale [PARS] score ≥10). Thirty participants were randomized to mirtazapine (7.5–45 mg/day) or placebo in a 2:1 ratio. The co-primary outcome measures were the PARS and the Clinical Global Impressions-Improvement subscale (CGI-I). Mirtazapine resulted in a statistically significant within group decrease in anxiety on the PARS (ES 1.76, p < 0.001). The improvement in PARS score for mirtazapine versus placebo was clinically meaningful but not statistically significant (ES = 0.63, p = 0.64). Forty-seven percent of participants assigned to mirtazapine (95% CI 22%: 74%) and 20% assigned to placebo (95% CI 2%: 60%) were rated “much improved” (CGI-I = 2) or “very much improved” (CGI-I = 1) for anxiety, p = 0.46. No statistically significant differences in mean 10-week changes between mirtazapine and placebo occurred on any outcome measure. There were no statistically significant differences in adverse effect frequency between mirtazapine and placebo. The results are consistent with mirtazapine’s safety and tolerability and meet three of four pre-specified indicators of efficacy (statistically significant change in total PARS score for mirtazapine, numerically greater reduction in total PARS score for mirtazapine than placebo, numerically higher number of responders to mirtazapine than placebo, but not greater than 50% of participants receiving mirtazapine rated as responders). Implementation of a larger randomized controlled trial of mirtazapine for the treatment of anxiety in this population is supported.
Clinical trial registration information: Mirtazapine Treatment of Anxiety in Children and Adolescents with Pervasive Developmental Disorders; https://clinicaltrials.gov; NCT01302964.
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This work was funded by Autism Speaks.
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Christopher J. McDougle. Substantial contributions to the conception or design of the work; or the acquisition, analysis or interpretation of data for the work. Drafting the work or revising it critically for important intellectual content. Final approval of the version to be published. Agreement to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. Robyn P. Thom. Substantial contributions to the conception or design of the work; or the acquisition, analysis or interpretation of data for the work. Drafting the work or revising it critically for important intellectual content. Final approval of the version to be published. Caitlin T. Ravichandran. Substantial contributions to the conception or design of the work; or the acquisition, analysis, or interpretation of data for the work. Drafting the work or revising it critically for important intellectual content. Final approval of the version to be published. Michelle L. Palumbo. Substantial contributions to the conception or design of the work; or the acquisition, analysis, or interpretation of data for the work. Final approval of the version to be published. Laura C. Politte. Substantial contributions to the conception or design of the work; or the acquisition, analysis, or interpretation of data for the work. Final approval of the version to be published. Jennifer E. Mullett. Substantial contributions to the conception or design of the work; or the acquisition, analysis, or interpretation of data for the work. Final approval of the version to be published. Christopher J. Keary. Substantial contributions to the conception or design of the work; or the acquisition, analysis, or interpretation of data for the work. Final approval of the version to be published. Craig A. Erickson. Substantial contributions to the conception or design of the work; or the acquisition, analysis, or interpretation of data for the work. Final approval of the version to be published. Kimberly A. Stigler. Substantial contributions to the conception or design of the work; or the acquisition, analysis, or interpretation of data for the work. Final approval of the version to be published. Lauren Mathieu-Frasier. Substantial contributions to the conception or design of the work; or the acquisition, analysis, or interpretation of data for the work. Final approval of the version to be published. David J. Posey. Substantial contributions to the conception or design of the work; or the acquisition, analysis, or interpretation of data for the work. Drafting of the work or revising it critically for important intellectual content. Final approval of the version to be published. Agreement to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.
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Dr. McDougle is a consultant to Precidiag, Receptor Life Sciences, and Sage Therapeutics, and receives royalties from Oxford University Press and Springer Publishing. Dr. Thom receives research support from Precidiag. Dr. Palumbo receives research support from Otsuka Pharmaceuticals. Dr. Keary serves on the advisory board and receives research support from Ovid Therapeutics. Dr. Erickson is a consultant to Autifony, Stalicla, Scitoto Bioscience, Impel, and Confluence Pharmaceuticals. He is an inventor on patents describing methods of treatment in neurodevelopmental disorders held by the Cincinnati Children’s Hospital Research Foundation. Drs. Ravichandran and Politte, Ms. Mullett, Dr. Stigler, Ms. Mathieu-Frasier, and Dr. Posey have no disclosures or conflicts of interest to report.
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McDougle, C.J., Thom, R.P., Ravichandran, C.T. et al. A randomized double-blind, placebo-controlled pilot trial of mirtazapine for anxiety in children and adolescents with autism spectrum disorder. Neuropsychopharmacol. 47, 1263–1270 (2022). https://doi.org/10.1038/s41386-022-01295-4
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DOI: https://doi.org/10.1038/s41386-022-01295-4
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