Abstract
Using a dataset involving 415 individuals with irritability, aggression, agitation and self-injury (IAAS) behaviors from the fragile X syndrome (FXS) FORWARD database, we describe the psychopharmacologic management of IAAS and features of the population of persons with FXS treated with drug therapy for IAAS. Among those with FXS exhibiting IAAS, individuals with FXS receiving drug treatment of IAAS were older, more predominantly male, have more significant intellectual disability, more like to have comorbid autism, hyperarousal, and social impairments. The most commonly utilized medications for IAAS in FXS are antipsychotic medications, specifically aripiprazole and risperidone (37% and 27%, respectively). The majority of subjects (63%) experienced no side effects noted from the use of their psychopharmacologic medications.
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Aman, M. G., Singh, N. N., Stewart, A. W., & Field, C. J. (1985). The aberrant behavior checklist: A behavior rating scale for the assessment of treatment effects. American Journal of Mental Deficiency, 5, 485–491.
Bailey, D. B., Jr., Hatton, D. D., Skinner, M., & Mesibov, G. (2001a). Autistic behavior, FMR1 protein, and developmental trajectories in young males with fragile X syndrome. Journal of Autism and Developmental Disorders, 31(2), 165–174.
Bailey, D. B., Jr., Hatton, D. D., Tassone, F., Skinner, M., & Taylor, A. K. (2001b). Variability in FMRP and early development in males with fragile X syndrome. American Journal of Mental Retardation, 106(1), 16–27. https://doi.org/10.1352/0895-8017(2001)106%3c0016:VIFAED%3e2.0.CO;2.
Bailey, D. B., Jr., Mesibov, G. B., Hatton, D. D., Clark, R. D., Roberts, J. E., & Mayhew, L. (1998). Autistic behavior in young boys with fragile X syndrome. Journal of Autism and Developmental Disorders, 28(6), 499–508.
Bailey, D. B., Jr., Raspa, M., Bishop, E., Mitra, D., Martin, S., Wheeler, A., et al. (2012a). Health and economic consequences of fragile X syndrome for caregivers. Journal of Developmental and Behavioral Pediatrics, 33(9), 705–712. https://doi.org/10.1097/DBP.0b013e318272dcbc.
Bailey, D. B., Jr., Raspa, M., Bishop, E., Olmsted, M., Mallya, U. G., & Berry-Kravis, E. (2012b). Medication utilization for targeted symptoms in children and adults with fragile X syndrome: US survey. Journal of Developmental and Behavioral Pediatrics, 33(1), 62–69. https://doi.org/10.1097/DBP.0b013e318236c0e1.
Bailey, D. B., Jr., Raspa, M., Olmsted, M., & Holiday, D. B. (2008). Co-occurring conditions associated with FMR1 gene variations: Findings from a national parent survey. American Journal of Medical Genetics Part A, 146A(16), 2060–2069. https://doi.org/10.1002/ajmg.a.32439.
Berry-Kravis, E., & Potanos, K. (2004). Psychopharmacology in fragile X syndrome—Present and future. Mental Retardation and Developmental Disabilities Research Reviews, 10(1), 42–48. https://doi.org/10.1002/mrdd.20007.
Berry-Kravis, E., Sumis, A., Hervey, C., & Mathur, S. (2012). Clinic-based retrospective analysis of psychopharmacology for behavior in fragile X syndrome. International Journal of Pediatrics, 2012, 843016. https://doi.org/10.1155/2012/843016.
Budimirovic, D. B., & Kaufmann, W. E. (2011). What can we learn about autism from studying fragile X syndrome? Developmental Neuroscience, 33(5), 379–394. https://doi.org/10.1159/000330213.
Chevreul, K., Berg Brigham, K., Brunn, M., des Portes, V., & Network, B.-R. R. (2015). Fragile X syndrome: Economic burden and health-related quality of life of patients and caregivers in France. Journal of Intellectual Disability Research, 59(12), 1108–1120. https://doi.org/10.1111/jir.12215.
Chevreul, K., Gandre, C., Brigham, K. B., Lopez-Bastida, J., Linertova, R., Oliva-Moreno, J., et al. (2016). Social/economic costs and health-related quality of life in patients with fragile X syndrome in Europe. The European Journal of Health Economics, 17(Suppl 1), 43–52. https://doi.org/10.1007/s10198-016-0784-3.
Constantino, J. N., Davis, S. A., Todd, R. D., Schindler, M. K., Gross, M. M., Brophy, S. L., et al. (2003). Validation of a brief quantitative measure of autistic traits: Comparison of the social responsiveness scale with the autism diagnostic interview-revised. Journal of Autism and Developmental Disorders, 33(4), 427–433.
Cordeiro, L., Ballinger, E., Hagerman, R., & Hessl, D. (2011a). Clinical assessment of DSM-IV anxiety disorders in fragile X syndrome: Prevalence and characterization. Journal of Neurodevelopmental Disorders, 3(1), 57–67. https://doi.org/10.1007/s11689-010-9067-y.
Cordeiro, L., Ballinger, E., Hagerman, R., & Hessl, D. (2011b). Clinical assessment of DSM-IV anxiety disorders in fragile X syndrome: Prevalence and characterization. Journal of Neurodevelopmental Disorders, 3(1), 57–67. https://doi.org/10.1007/s11689-010-9067-y.
Erickson, C. A., Davenport, M. H., Schaefer, T. L., Wink, L. K., Pedapati, E. V., Sweeney, J. A., et al. (2017). Fragile X targeted pharmacotherapy: Lessons learned and future directions. Journal of Neurodevelopmental Disorders, 9, 7. https://doi.org/10.1186/s11689-017-9186-9.
Erickson, C. A., Stigler, K. A., Posey, D. J., & McDougle, C. J. (2005). Risperidone in pervasive developmental disorders. Expert Review of Neurotherapeutics, 5(6), 713–719. https://doi.org/10.1586/14737175.5.6.713.
Erickson, C. A., Stigler, K. A., Posey, D. J., & McDougle, C. J. (2010). Aripiprazole in autism spectrum disorders and fragile X syndrome. Neurotherapeutics, 7(3), 258–263. https://doi.org/10.1016/j.nurt.2010.04.001.
Erickson, C. A., Stigler, K. A., Wink, L. K., Mullett, J. E., Kohn, A., Posey, D. J., et al. (2011). A prospective open-label study of aripiprazole in fragile X syndrome. Psychopharmacology (Berl), 216(1), 85–90. https://doi.org/10.1007/s00213-011-2194-7.
Guy, W. (1976). ECDEU assessment manual for psychopharmacology. Publication no. 76-338. Washington, DC: U.S. DHEW, NIMH.
Haessler, F., Gaese, F., Huss, M., Kretschmar, C., Brinkman, M., Peters, H., et al. (2016). Characterization, treatment patterns, and patient-related outcomes of patients with Fragile X syndrome in Germany: Final results of the observational EXPLAIN-FXS study. BMC Psychiatry, 16(1), 318. https://doi.org/10.1186/s12888-016-1020-5.
Hagerman, R. J., & Hagerman, P. J. (2008). Testing for fragile X gene mutations throughout the life span. JAMA, 300(20), 2419–2421. https://doi.org/10.1001/jama.2008.684.
Hagerman, R. J., & Polussa, J. (2015). Treatment of the psychiatric problems associated with fragile X syndrome. Current Opinion in Psychiatry, 28(2), 107–112. https://doi.org/10.1097/YCO.0000000000000131.
Hatton, D. D., Bailey, D. B., Jr., Hargett-Beck, M. Q., Skinner, M., & Clark, R. D. (1999). Behavioral style of young boys with fragile X syndrome. Developmental Medicine and Child Neurology, 41(9), 625–632.
Hatton, D. D., Wheeler, A. C., Skinner, M. L., Bailey, D. B., Sullivan, K. M., Roberts, J. E., et al. (2003). Adaptive behavior in children with fragile X syndrome. American Journal of Mental Retardation, 108(6), 373–390. https://doi.org/10.1352/0895-8017(2003)108%3c373:ABICWF%3e2.0.CO;2.
Hernandez, R. N., Feinberg, R. L., Vaurio, R., Passanante, N. M., Thompson, R. E., & Kaufmann, W. E. (2009). Autism spectrum disorder in fragile X syndrome: A longitudinal evaluation. American Journal of Medical Genetics Part A, 149A(6), 1125–1137. https://doi.org/10.1002/ajmg.a.32848.
Kaufmann, W. E., Abrams, M. T., Chen, W., & Reiss, A. L. (1999). Genotype, molecular phenotype, and cognitive phenotype: Correlations in fragile X syndrome. American Journal of Medical Genetics, 83(4), 286–295.
Kaufmann, W. E., Kidd, S. A., Andrews, H. F., Budimirovic, D. B., Esler, A., Haas-Givler, B., et al. (2017). Autism spectrum disorder in fragile X syndrome: Cooccurring conditions and current treatment. Pediatrics, 139(Suppl 3), S194–S206. https://doi.org/10.1542/peds.2016-1159F.
Lewis, P., Abbeduto, L., Murphy, M., Richmond, E., Giles, N., Bruno, L., et al. (2006). Cognitive, language and social-cognitive skills of individuals with fragile X syndrome with and without autism. Journal of Intellectual Disability Research, 50(Pt 7), 532–545. https://doi.org/10.1111/j.1365-2788.2006.00803.x.
Loesch, D. Z., Huggins, R. M., & Hagerman, R. J. (2004). Phenotypic variation and FMRP levels in fragile X. Mental Retardation and Developmental Disabilities, 10(1), 31–41. https://doi.org/10.1002/mrdd.20006.
McClellan, L., Pedapati, E., Wink, L., & Erickson, C. (2016). Evidence-based pharmacotherapy for autism spectrum disorders. Current Treatment Options in Psychiatry, 3(2), 161–181. https://doi.org/10.1007/s40501-016-0077-6.
McDougle, C. J., Stigler, K. A., Erickson, C. A., & Posey, D. J. (2008). Atypical antipsychotics in children and adolescents with autistic and other pervasive developmental disorders. Journal of Clinical Psychiatry, 69(Suppl 4), 15–20.
Posey, D. J., Stigler, K. A., Erickson, C. A., & McDougle, C. J. (2008). Antipsychotics in the treatment of autism. Journal of Clinical Investigation, 118(1), 6–14. https://doi.org/10.1172/JCI32483.
Sansone, S. M., Widaman, K. F., Hall, S. S., Reiss, A. L., Lightbody, A., Kaufmann, W. E., et al. (2012). Psychometric study of the aberrant behavior checklist in fragile X syndrome and implications for targeted treatment. Journal of Autism and Developmental Disorders, 42(7), 1377–1392. https://doi.org/10.1007/s10803-011-1370-2.
Sherman, S. L., Kidd, S. A., Riley, C., Berry-Kravis, E., Andrews, H. F., Miller, R. M., et al. (2017). FORWARD: A registry and longitudinal clinical database to study fragile X syndrome. Pediatrics, 139(Suppl 3), S183–S193. https://doi.org/10.1542/peds.2016-1159E.
Symons, F. J., Byiers, B. J., Raspa, M., Bishop, E., & Bailey, D. B. (2010). Self-injurious behavior and fragile X syndrome: Findings from the national fragile X survey. American Journal on Intellectual and Developmental Disabilities, 115(6), 473–481. https://doi.org/10.1352/1944-7558-115.6.473.
Symons, F. J., Clark, R. D., Hatton, D. D., Skinner, M., & Bailey, D. B., Jr. (2003). Self-injurious behavior in young boys with fragile X syndrome. American Journal of Medical Genetics Part A, 118A(2), 115–121. https://doi.org/10.1002/ajmg.a.10078.
Tsiouris, J. A., & Brown, W. T. (2004). Neuropsychiatric symptoms of fragile X syndrome: Pathophysiology and pharmacotherapy. CNS Drugs, 18(11), 687–703.
Wheeler, A. C., Raspa, M., Bishop, E., & Bailey, D. B., Jr. (2016). Aggression in fragile X syndrome. Journal of Intellectual Disability Research, 60(2), 113–125. https://doi.org/10.1111/jir.12238.
Williams, K., Brignell, A., Randall, M., Silove, N., & Hazell, P. (2013). Selective serotonin reuptake inhibitors (SSRIs) for autism spectrum disorders (ASD). Cochrane Database Systematic Review, 8, CD004677. https://doi.org/10.1002/14651858.cd004677.pub3.
Witwer, A. N., & Lecavalier, L. (2007). Autism screening tools: An evaluation of the Social Communication Questionnaire and the Developmental Behaviour Checklist-Autism Screening Algorithm. Journal of Intellectual Developmental Disability, 32(3), 179–187. https://doi.org/10.1080/13668250701604776.
Funding
The FORWARD project is supported by the Cooperative Agreement Numbers 5U01DD000231, 5U19DD000753, and 1U01DD001189 funded by the Centers for Disease Control and Prevention. The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention. No authors have a conflict financially or otherwise related to the content of this manuscript. The FORWARD database project was local IRB approved at all participating sites. The data reviewed in preparation of this manuscript was deidentified data.
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EME was the primary writer of the manuscript. KCD, EVP, LKW, RCS, and WEK participated in manuscript preparation and edited the manuscript. HA, TWC, and CC conducted the data analysis, participated in manuscript development and edited the manuscript. NT, EMB-K, and CAE participated in manuscript preparation, edited the document, and conceptualized the experiments in the manuscript.
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Eckert, E.M., Dominick, K.C., Pedapati, E.V. et al. Pharmacologic Interventions for Irritability, Aggression, Agitation and Self-Injurious Behavior in Fragile X Syndrome: An Initial Cross-Sectional Analysis. J Autism Dev Disord 49, 4595–4602 (2019). https://doi.org/10.1007/s10803-019-04173-z
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DOI: https://doi.org/10.1007/s10803-019-04173-z