دورية أكاديمية
High-Dose Propranolol for Severe and Chronic Aggression in Autism Spectrum Disorder: A Pilot, Double-Blind, Placebo-Controlled, Randomized Crossover Study.
| العنوان: | High-Dose Propranolol for Severe and Chronic Aggression in Autism Spectrum Disorder: A Pilot, Double-Blind, Placebo-Controlled, Randomized Crossover Study. |
|---|---|
| المؤلفون: | London EB; From the New York State Institute for Basic Research, Department of Psychology, Staten Island, NY., Zimmerman-Bier BL; Rutgers University Robert Wood Johnson Medical School and the Children's Health Institute, New Brunswick, NJ., Yoo JH; From the New York State Institute for Basic Research, Department of Psychology, Staten Island, NY., Gaffney JW; Rutgers University Robert Wood Johnson Medical School and the Children's Health Institute, New Brunswick, NJ. |
| المصدر: | Journal of clinical psychopharmacology [J Clin Psychopharmacol] 2024 Sep-Oct 01; Vol. 44 (5), pp. 462-467. Date of Electronic Publication: 2024 Aug 23. |
| نوع المنشور: | Journal Article; Randomized Controlled Trial |
| اللغة: | English |
| بيانات الدورية: | Publisher: Williams And Wilkins Country of Publication: United States NLM ID: 8109496 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1533-712X (Electronic) Linking ISSN: 02710749 NLM ISO Abbreviation: J Clin Psychopharmacol Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: Baltimore Md : Williams And Wilkins Original Publication: Baltimore, Md. : Williams & Wilkins, [c1981- |
| مواضيع طبية MeSH: | Autism Spectrum Disorder*/drug therapy , Cross-Over Studies* , Propranolol*/administration & dosage , Propranolol*/adverse effects , Aggression*/drug effects , Adrenergic beta-Antagonists*/administration & dosage , Adrenergic beta-Antagonists*/adverse effects , Adrenergic beta-Antagonists*/pharmacology, Humans ; Double-Blind Method ; Male ; Adolescent ; Child ; Pilot Projects ; Young Adult ; Female ; Treatment Outcome ; Adult |
| مستخلص: | Background: Despite the use of behavioral interventions and psychotropic medications, many individuals with autism spectrum disorder (ASD) who engage in severe aggression remain refractory to conventional treatment. Propranolol, a beta-blocker, has accumulated much anecdotal evidence as a promising option. However, well-designed studies are rare, and the apprehension about cardiovascular side effects from large doses continues to exist. Purpose: The aims of this study were (1) to demonstrate the feasibility of treating aggression with high-dose propranolol using telehealth study visits and (2) to document cardiac safety. Methods: This study utilized a randomized, double-blind, placebo-controlled, crossover design. Dosing was titrated up in a flexible but stepwise fashion until therapeutic response was obtained or up to 200 mg tid. Following washout, those who were assigned propranolol were crossed over to placebo and vice versa. Six participants between the ages 12-19 participated. The primary outcome measures were the final Clinical Global Impression Improvement Scale (CGI-I) and the Aberrant Behavior Checklist-Community Irritability (ABC-C/I) scores at 200 mg tid. Results: The CGI-I indicated a 50% reduction in symptoms in the propranolol phase, while the ABC-I indicated a 37% reduction in comparison to placebo. The effect sizes ( r ) for the CGI-I and the ABC-C/I were large, -0.74 and -0.64, respectively. The average blood pressure was 122/68 during the placebo phase and 109/72 during the propranolol phase. All Holter monitor exams were unremarkable. Conclusion: These results suggest that propranolol is an effective option in decreasing aggression in individuals with ASD. As this was a small study, a larger clinical trial is needed. (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.) |
| References: | Carroll D, Hallett V, McDougle CJ, et al. Examination of aggression and self-injury in children with autism spectrum disorders and serious behavioral problems. Child Adolesc Psychiatr Clin N Am . 2014;23:57–72. Kanne SM, Mazurek MO. Aggression in children and adolescents with ASD: prevalence and risk factors. J Autism Dev Disord . 2011;41:926–937. Laverty C, Oliver C, Moss J, et al. Mol Autism . 2020;11:8. Published 2020 Jan 20. Laverty C, Agar G, Sinclair-Burton L, et al. The 10-year trajectory of aggressive behaviours in autistic individuals. J Intellect Disabil Res . 2023;67:295–309. Myrbakk E, von Tetzchner S. Psychiatric disorders and behavior problems in people with intellectual disability. Res Dev Disabil . 2008;29:316–332. Lecavalier L, Leone S, Wiltz J. The impact of behaviour problems on caregiver stress in young people with autism spectrum disorders. J Intellect Disabil Res . 2006;50(Pt 3):172–183. Matson JL, Jang J. Treating aggression in persons with autism spectrum disorders: a review. Res Dev Disabil . 2014;35:3386–3391. Mandell DS, Morales KH, Marcus SC, et al. Psychotropic medication use among Medicaid-enrolled children with autism spectrum disorders. Pediatrics . 2008;121:e441–e448. Mandell DS. Psychiatric hospitalization among children with autism spectrum disorders. J Autism Dev Disord . 2008;38:1059–1065. Mandell DS, Cao J, Ittenbach R, et al. Medicaid expenditures for children with autistic spectrum disorders: 1994 to 1999. J Autism Dev Disord . 2006;36:475–485. Cidav Z, Lawer L, Marcus SC, et al. Age-related variation in health service use and associated expenditures among children with autism. J Autism Dev Disord . 2013;43:924–931. Fish R, Culshaw E. The last resort? Staff and client perspectives on physical intervention. J Intellect Disabil . 2005;9:93–107. Hawkins S, Allen D, Jenkins R. The use of physical interventions with people with intellectual disabilities and challenging behavior—the experiences of service users and staff members. J Appl Res Intellect Disabil . 2005;18:19–34. Van Schalkwyk GI, Lewis AS, Qayyum Z, et al. Reduction of aggressive episodes after repeated transdermal nicotine administration in a hospitalized adolescent with autism spectrum disorder. J Autism Dev Disord . 2015;45:3061–3066. Adler BA, Wink LK, Early M, et al. Drug-refractory aggression, self-injurious behavior, and severe tantrums in autism spectrum disorders: a chart review study. Autism . 2015;19:102–106. Orsolini L, Tomasetti C, Valchera A, et al. An update of safety of clinically used atypical antipsychotics. Expert Opin Drug Saf . 2016;15:1329–1347. Bobo WV, Cooper WO, Stein CM, et al. Antipsychotics and the risk of type 2 diabetes mellitus in children and youth. JAMA Psychiatry . 2013;70:1067–1075. Correll CU, Manu P, Olshanskiy V, et al. Cardiometabolic risk of second-generation antipsychotic medications during first-time use in children and adolescents [published correction appears in JAMA. 2009;302(21):2322]. JAMA . 2009;302:1765–1773. Ruedrich S, Erhardt L. Beta-adrenergic blockers in mental retardation and developmental disabilities. Ment Retard Dev Disabil Res Rev . 1999;5:290–298. Jenkins SC, Maruta T. Therapeutic use of propranolol for intermittent explosive disorder. Mayo Clin Proc . 1987;62:204–214. Silver JM, Yudofsky SC, Slater JA, et al. Propranolol treatment of chronically hospitalized aggressive patients. J Neuropsychiatry Clin Neurosci . 1999;11:328–335. Ward F, Tharian P, Roy M, et al. Efficacy of beta blockers in the management of problem behaviours in people with intellectual disabilities: a systematic review. Res Dev Disabil . 2013;34:4293–4303. Williams DT, Mehl R, Yudofsky S, et al. The effect of propranolol on uncontrolled rage outbursts in children and adolescents with organic brain dysfunction. J Am Acad Child Psychiatry . 1982;21:129–135. Ratey JJ, Mikkelsen E, Sorgi P, et al. Autism: the treatment of aggressive behaviors. J Clin Psychopharmacol . 1987;7:35–41. Fleminger S, Greenwood RJ, Oliver DL. Pharmacological management for agitation and aggression in people with acquired brain injury. Cochrane Database Syst Rev . 2006;4:CD003299. London EB, Yoo JH, Fethke ED, et al. The safety and effectiveness of high-dose propranolol as a treatment for challenging behaviors in individuals with autism Spectrum disorders. J Clin Psychopharmacol . 2020;40:122–129. Sagar-Ouriaghli I, Lievesley K, Santosh PJ. Propranolol for treating emotional, behavioural, autonomic dysregulation in children and adolescents with autism spectrum disorders. J Psychopharmacol . 2018;32:641–653. Bachmann CJ, Manthey T, Kamp-Becker I, et al. Psychopharmacological treatment in children and adolescents with autism spectrum disorders in Germany. Res Dev Disabil . 2013;34:2551–2563. Guy W. Clinical global impression scale. In: The ECDEU Assessment Manual for Psychopharmacology-Revised Volume DHEW Publ No ADM vol. 76. 1976:218–222. Aman MG, Burrow WH, Wolford PL. The aberrant behavior checklist-community: factor validity and effect of subject variables for adults in group homes. Am J Ment Retard . 1995;100:283–292. McDougle CJ, Scahill L, McCracken JT, et al. Research units on pediatric psychopharmacology (RUPP) autism network. Background and rationale for an initial controlled study of risperidone. Child Adolesc Psychiatr Clin N Am . 2000;9:201–224. Arnold LE, Vitiello B, McDougle C, et al. Parent-defined target symptoms respond to risperidone in RUPP autism study: customer approach to clinical trials. J Am Acad Child Adolesc Psychiatry . 2003;42:1443–1450. Hurlemann R, Walter H, Rehme AK, et al. Human amygdala reactivity is diminished by the β-noradrenergic antagonist propranolol. Psychol Med . 2010;40:1839–1848. Leal Santos S, Stackmann M, Muñoz Zamora A, et al. Propranolol decreases fear expression by modulating fear memory traces. Biol Psychiatry . 2021;89:1150–1161. Devilbiss DM, Waterhouse BD. Phasic and tonic patterns of locus coeruleus output differentially modulate sensory network function in the awake rat. J Neurophysiol . 2011;105:69–87. Haruvi-Lamdan N, Horesh D, Zohar S, et al. Autism spectrum disorder and post-traumatic stress disorder: an unexplored co-occurrence of conditions. Autism . 2020;24:884–898. Rumball F, Brook L, Happé F, et al. Heightened risk of posttraumatic stress disorder in adults with autism spectrum disorder: the role of cumulative trauma and memory deficits. Res Dev Disabil . 2021;110:103848. Wang DW, Mistry AM, Kahlig KM, et al. Propranolol blocks cardiac and neuronal voltage-gated sodium channels. Front Pharmacol . 2010;1:144. Dawson AK, Reele SB, Wood AJ, et al. Electrophysiological effects of high-dose propranolol in dogs: evidence in vivo for effects not mediated by the beta adrenoceptor. J Pharmacol Exp Ther . 1984;229:91–97. Scahill L, McDougle CJ, Aman MG, et al. Effects of risperidone and parent training on adaptive functioning in children with pervasive developmental disorders and serious behavioral problems. J Am Acad Child Adolesc Psychiatry . 2012;51:136–146. |
| المشرفين على المادة: | 9Y8NXQ24VQ (Propranolol) 0 (Adrenergic beta-Antagonists) |
| تواريخ الأحداث: | Date Created: 20240822 Date Completed: 20240909 Latest Revision: 20240909 |
| رمز التحديث: | 20240909 |
| DOI: | 10.1097/JCP.0000000000001895 |
| PMID: | 39174017 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 1533-712X |
|---|---|
| DOI: | 10.1097/JCP.0000000000001895 |