From the New York State Institute for Basic Research, Department of Psychology, Staten Island, NY.
Rutgers University Robert Wood Johnson Medical School and the Children's Health Institute, New Brunswick, NJ.
J Clin Psychopharmacol. 2024;44(5):462-467. doi: 10.1097/JCP.0000000000001895. Epub 2024 Aug 23.
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.
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.
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.
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.
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.
尽管采用了行为干预和精神药物治疗，许多患有自闭症谱系障碍（ASD）的严重攻击行为患者仍然对常规治疗无反应。普萘洛尔，一种β受体阻滞剂，已经积累了很多轶事证据，被认为是一种很有前途的选择。然而，设计良好的研究很少，并且对大剂量的心血管副作用的担忧仍然存在。
本研究的目的是（1）展示使用远程医疗就诊治疗高剂量普萘洛尔治疗攻击性的可行性，以及（2）记录心脏安全性。
本研究采用随机、双盲、安慰剂对照、交叉设计。剂量以灵活但逐步的方式滴定，直到获得治疗反应或达到 200mg tid。洗脱后，接受普萘洛尔治疗的患者交叉到安慰剂组，反之亦然。共有 6 名 12-19 岁的参与者参与了研究。主要结局指标是最终的临床总体印象改善量表（CGI-I）和异常行为检查表-社区激惹性（ABC-C/I）在 200mg tid 时的评分。
CGI-I 表明在普萘洛尔阶段症状减轻了 50%，而 ABC-I 表明与安慰剂相比减轻了 37%。CGI-I 和 ABC-C/I 的效应大小（r）分别为-0.74 和-0.64，均较大。安慰剂阶段的平均血压为 122/68，普萘洛尔阶段的平均血压为 109/72。所有动态心电图检查均无异常。
这些结果表明，普萘洛尔是减少 ASD 患者攻击行为的有效选择。由于这是一项小型研究，需要进行更大规模的临床试验。
