Buspirone for the Treatment of Generalized Anxiety Disorder in Williams Syndrome: A Case Series

  • Robyn P. Thom
  • Christopher J. Keary
  • Jessica L. Waxler
  • Barbara R. Pober
  • Christopher J. McDougleEmail author
Brief Report


Co-morbid anxiety disorders, including generalized anxiety disorder (GAD), are highly prevalent among individuals with Williams syndrome (WS). However, reports of the pharmacologic treatment of only a limited number of previous anxiety disorders in WS have appeared in the literature. Here, we review the case histories of three adolescents/young adults with WS and the treatment course of co-morbid GAD with buspirone. Treatment with buspirone was well-tolerated and resulted in sustained response in all three cases. Common medical disorders in WS are highlighted with regards to safe and appropriate pharmacologic treatment of GAD. Buspirone’s generally benign side effect profile is a major benefit of its use for treating GAD in individuals with WS.


Williams syndrome Anxiety Buspirone 



This work was funded by the Nancy Lurie Marks Family Foundation.

Author Contributions

RPT, CJK and CJM drafted the manuscript. CJM performed the ratings of the Pediatric Anxiety Rating Scale with the mother of each subject. RPT, CJK, JLW, BRP and CJM reviewed the final version of the manuscript and gave approval for its submission.

Compliance with Ethical Standards

Conflict of interest

Drs. Thom, Pober and McDougle and Ms. Waxler declare that they have no conflicts of interest. Dr. Keary has been a compensated consultant, served on a scientific advisory board and received research support from Ovid Therapeutics.

Informed Consent

Informed consent was obtained from the legal guardian of all individual participants included in the study.

Research Involving Human Participants and/or Animals

The study was granted exemption from requiring ethics approval by the Partners Human Research Committee Institutional Review Board because the number of subjects included in the study is less than four.


  1. Alexander, A., Gallagher, A., Pober, B., Waxler, J., & McDougle, C. (2019). Post-traumatic stress disorder following cardiac surgery: A case report of a nine-year-old female with Williams syndrome. Journal of Intellectual & Developmental Disability,44(2), 244–247.CrossRefGoogle Scholar
  2. Beach, S. R., Celano, C. M., Sugrue, A. M., Adams, C., Ackerman, M. J., Noseworthy, P. A., et al. (2018). QT prolongation, Torsades de Pointes, and psychotropic medications: A 5-year update. Psychosomatics,59(2), 105–122. Scholar
  3. Bergman, J., Roof, R. A., Furman, C. A., Conroy, J. L., Mello, N. K., Sibley, D. R., et al. (2013). Modification of cocaine self-administration by buspirone (buspar®): Potential involvement of D3 and D4 dopamine receptors. International Journal of Neuropsychopharmacology,16(2), 445–458. Scholar
  4. Buitelaar, J. K., van der Gaag, R. J., & van der Hoeven, J. (1998). Buspirone in the management of anxiety and irritability in children with pervasive developmental disorders: Results of an open-label study. The Journal of Clinical Psychiatry,59(2), 56–59.CrossRefGoogle Scholar
  5. Ceranoglu, T. A., Wozniak, J., Fried, R., Galdo, M., Hoskova, B., Fong, M. D., et al. (2018). A retrospective chart review of buspirone for the treatment of anxiety in psychiatrically referred youth with high-functioning autism spectrum disorder. Journal of Child and Adolescent Psychopharmacology. Scholar
  6. Chugani, D. C., Chugani, H. T., Wiznitzer, M., Parikh, S., Evans, P. A., Hansen, R. L., et al. (2016). Efficacy of low-dose buspirone for restricted and repetitive behavior in young children with autism spectrum disorder: A randomized trial. The Journal of Pediatrics,170(45–53), e1–e4. Scholar
  7. Collins, R. T. (2018). Cardiovascular disease in Williams syndrome. Current Opinion in Pediatrics,30(5), 609–615. Scholar
  8. Collins, R. T., Aziz, P. F., Gleason, M. M., Kaplan, P. B., & Shah, M. J. (2010). Abnormalities of cardiac repolarization in Williams syndrome. The American Journal of Cardiology,106(7), 1029–1033. Scholar
  9. Dykens, E. M. (2003). Anxiety, fears, and phobias in persons with Williams Syndrome. Developmental Neuropsychology,23(1–2), 291–316. Scholar
  10. Edwards, D. J., Chugani, D. C., Chugani, H. T., Chehab, J., Malian, M., & Aranda, J. V. (2006). Pharmacokinetics of buspirone in autistic children. The Journal of Clinical Pharmacology,46(5), 508–514. Scholar
  11. Ewart, A. K., Morris, C. A., Atkinson, D., Jin, W., Sternes, K., Spallone, P., et al. (1993). Hemizygosity at the elastin locus in a developmental disorder, Williams syndrome. Nature Genetics,5(1), 11–16. Scholar
  12. Feighner, J. P., Merideth, C. H., & Hendrickson, G. A. (1982). A double-blind comparison of buspirone and diazepam in outpatients with generalized anxiety disorder. The Journal of Clinical Psychiatry,43(12 Pt 2), 103–108.PubMedGoogle Scholar
  13. Guaiana, G., Barbui, C., & Cipriani, A. (2010). Hydroxyzine for generalised anxiety disorder. Cochrane Database of Systematic Reviews,12, CD006815. Scholar
  14. Kim, Y.-M., Cho, J. H., Kang, E., Kim, G.-H., Seo, E.-J., Lee, B. H., et al. (2016). Endocrine dysfunctions in children with Williams-Beuren syndrome. Annals of Pediatric Endocrinology & Metabolism,21(1), 15–20. Scholar
  15. Leyfer, O. T., Woodruff-Borden, J., Klein-Tasman, B. P., Fricke, J. S., & Mervis, C. B. (2006). Prevalence of psychiatric disorders in 4 to 16-year-olds with Williams syndrome. American Journal of Medical Genetics Part B, Neuropsychiatric Genetics: The Official Publication of the International Society of Psychiatric Genetics,141B(6), 615–622. Scholar
  16. Martens, M. A., Seyfer, D. L., Andridge, R. R., Foster, J. E. A., Chowdhury, M., McClure, K. E., et al. (2012). Parent report of antidepressant, anxiolytic, and antipsychotic medication use in individuals with Williams syndrome: Effectiveness and adverse effects. Research in Developmental Disabilities,33(6), 2106–2121. Scholar
  17. Martens, M. A., Wilson, S. J., & Reutens, D. C. (2008). Research Review: Williams syndrome: a critical review of the cognitive, behavioral, and neuroanatomical phenotype. Journal of Child Psychology and Psychiatry,49(6), 576–608. Scholar
  18. Mervis, C. B., Robinson, B. F., Bertrand, J., Morris, C. A., Klein-Tasman, B. P., & Armstrong, S. C. (2000). The Williams syndrome cognitive profile. Brain and Cognition,44(3), 604–628. Scholar
  19. Morris, C. A. (1993). Williams Syndrome. GeneReviews ®. Retrieved January 23, 2019, from
  20. Pariente, A., de Gage, S. B., Moore, N., & Bégaud, B. (2016). The benzodiazepine-dementia disorders link: Current state of knowledge. CNS Drugs,30(1), 1–7. Scholar
  21. Pecknold, J. C., Matas, M., Howarth, B. G., Ross, C., Swinson, R., Vezeau, C., et al. (1989). Evaluation of buspirone as an antianxiety agent: Buspirone and diazepam versus placebo. Canadian Journal of Psychiatry. Revue canadienne de psychiatrie,34(8), 766–771.CrossRefGoogle Scholar
  22. Pober, B. R. (2010). Williams-Beuren syndrome. The New England Journal of Medicine,362(3), 239–252. Scholar
  23. Realmuto, G. M., August, G. J., & Garfinkel, B. D. (1989). Clinical effect of buspirone in autistic children. Journal of Clinical Psychopharmacology,9(2), 122–125.CrossRefGoogle Scholar
  24. Royston, R., Howlin, P., Waite, J., & Oliver, C. (2017). Anxiety disorders in Williams syndrome contrasted with intellectual disability and the general population: A systematic review and meta-analysis. Journal of Autism and Developmental Disorders,47(12), 3765–3777. Scholar
  25. Schatzberg, A., & DeBattista, C. (2015). Manual of clinical psychopharmacology (8th ed.). Arlington, VA: American Psychiatric Publishing Inc.CrossRefGoogle Scholar
  26. Solmi, M., Murru, A., Pacchiarotti, I., Undurraga, J., Veronese, N., Fornaro, M., et al. (2017). Safety, tolerability, and risks associated with first- and second-generation antipsychotics: A state-of-the-art clinical review. Therapeutics and Clinical Risk Management,13, 757–777. Scholar
  27. Sramek, J. J., Frackiewicz, E. J., & Cutler, N. R. (1997). Efficacy and safety of two dosing regimens of buspirone in the treatment of outpatients with persistent anxiety. Clinical Therapeutics,19(3), 498–506.CrossRefGoogle Scholar
  28. Strømme, P., Bjømstad, P. G., & Ramstad, K. (2002). Prevalence estimation of Williams syndrome. Journal of Child Neurology,17(4), 269–271. Scholar
  29. The Pediatric Anxiety Rating Scale (PARS): Development and psychometric properties. (2002). Journal of the American Academy of Child and Adolescent Psychiatry, 41(9), 1061–1069. Retrieved August 19, 2019, from
  30. Urgeles, D., Alonso, V., & Ramos-Moreno, T. (2013). Neuropsychiatric and behavioral profiles of 2 adults with Williams syndrome: Response to antidepressant intake. Primary Care Companion to the Journal of Clinical Psychiatry. Scholar
  31. Wenzel-Seifert, K., Wittmann, M., & Haen, E. (2011). QTc prolongation by psychotropic drugs and the risk of Torsade de Pointes. Deutsches Arzteblatt International,108(41), 687–693. Scholar
  32. Woodruff-Borden, J., Kistler, D. J., Henderson, D. R., Crawford, N. A., & Mervis, C. B. (2010). Longitudinal course of anxiety in children and adolescents with Williams syndrome. American Journal of Medical Genetics Part C: Seminars in Medical Genetics,154C(2), 277–290. Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Massachusetts General HospitalBostonUSA
  2. 2.Lurie Center for AutismLexingtonUSA
  3. 3.Department of PsychiatryHarvard Medical SchoolBostonUSA
  4. 4.Department of PediatricsHarvard Medical SchoolBostonUSA

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