High-Dose Propranolol for Severe and Chronic Aggression in Autism Spectrum Disorder: A Pilot, Double-Blind, Placebo-Controlled, Randomized Crossover Study.

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.

The Safety and Effectiveness of High-Dose Propranolol as a Treatment for Challenging Behaviors in Individuals With Autism Spectrum Disorders.

PURPOSE/BACKGROUND: Individuals with autism spectrum disorders present with social communication deficits and a rigid adherence to sameness. Along with these symptoms, many individuals also present with severe challenging behaviors that place themselves as well as their families and communities at risk for injury. For these individuals, new and effective treatments are acutely needed. Propranolol has been used worldwide for over 50 years. Its primary indication is for hypertension, but there is evidence that, at higher doses, propranolol inhibits rage and anger through its effects on the central nervous system. This effect has been demonstrated in a variety of neuropsychiatric disorders. METHODS/PROCEDURES: Here, we present 46 retrospective analyses of clinical cases that were followed by a psychiatrist. Propranolol was prescribed as an add-on to the patients' existing medications. The doses ranged from 120 to 960 mg per day (mean = 462 mg). FINDINGS/RESULTS: Thirty-nine (85%) of 46 patients were found to be much improved or very much improved on the physician-rated Clinical Global Impression Improvement scale. There were few side effects noted, with only 2 subjects unable to tolerate the propranolol. IMPLICATIONS/CONCLUSIONS: It appears that high-dose propranolol can be given safely with minimal adverse cardiovascular problems, provided that close clinical monitoring is maintained. A more rigorous clinical trial is needed to elucidate and verify its clinical utility, clinical practice parameters, and the effects of propranolol as a monotherapy versus as an add-on to the patient's existing medication regimen.

The Discrimination of Printed Words by Prereading Children.

In addition to the discrimination of individual printed letters, beginning readers must learn to perceive individual letters within complex, whole-word stimuli. The present study shows that the discrimination of letters presented individually does not automatically entail the discrimination of 3-letter printed words that differ only in the first letter (e.g., sat, mat). Thirty-two children ranging in age from 3½ to 5½ years participated in two studies. All showed highly accurate discrimination of individual letters in identity matching-to-sample procedures before being exposed to the word-matching task. On the word-matching task, 21 of the 32 children showed accuracy of less than 85%, and 11 of these showed accuracy of 65% or less. Word-discrimination accuracy did not improve in retests of a subset of children after periods ranging from 3 weeks to 3 months. In Study 2, six children who initially showed relatively low word-matching accuracy were taught using fading procedures. Moreover, generalization to untaught words was shown. These results extend basic laboratory studies that have shown difficulties discriminating multi-element stimuli despite the discrimination of the individual component elements.

Controlled evaluation of the effects of hyperbaric oxygen therapy on the behavior of 16 children with autism spectrum disorders.

Hyperbaric oxygen therapy (HBOT) has been used to treat individuals with autism. However, few studies of its effectiveness have been completed. The current study examined the effects of 40 HBOT sessions at 24% oxygen at 1.3 ATA on 11 topographies of directly observed behavior. Five replications of multiple baselines were completed across a total of 16 participants with autism spectrum disorders. No consistent effects were observed across any group or within any individual participant, demonstrating that HBOT was not an effective treatment for the participants in this study. This study represents the first relatively large-scale controlled study evaluating the effects of HBOT at the level of the individual participant, on a wide array of behaviors.

Relevance of donepezil in enhancing learning and memory in special populations: a review of the literature.

This review discusses the laboratory and clinical research supporting the rationale for the efficacy of donepezil (Aricept USA) in enhancing cognition in autism, Alzheimer disease, Down syndrome, traumatic brain injury, Attention Deficit Hyperactivity Disorder (ADHD), and schizophrenia. While preliminary animal models have shown effective, human studies exclusive of Alzheimer disease are sparse. Although attention and memory are unlikely a sole operation of the cholinergic system, evidence indicates a promising direction for further examination of this hypothesis in autism. Studies that examine changes in operationally defined behaviors and reliable and valid measure of changes in attention and memory are needed.

The effects of blocking mouthing of leisure items on their effectiveness as reinforcers.

Leisure items are commonly used as reinforcers in behavior-analytic applications. However, a defining feature of autism is the occurrence of stereotypy, and individuals with autism often engage leisure items in a stereotyped manner. The opportunity for stereotyped interaction may be the only aspect of a contingent stimulus that makes it a reinforcer for appropriate behavior. Therefore, this study investigated the effects of blocking stereotyped reinforcer interaction on reinforcer efficacy for 2 children with autism. Results showed that blocking stereotypic reinforcer interaction did not influence reinforcer efficacy.

Rate-decreasing effects of the atypical neuroleptic risperidone attenuated by conditions of reinforcement in a woman with mental retardation.

Effects of two doses of risperidone on the performance of a matching task under tangible reinforcement and nonreinforcement conditions were measured in a woman with mental retardation. In both conditions, time to complete the task increased and response rates decreased under two doses of risperidone. Accuracy was generally unchanged. These changes were much smaller in the tangible reinforcement condition; thus, reinforcement seemed to protect performance from the rate-decreasing effects of risperidone.