ABSTRACT. Objective. To investigate the efficacy and safety of risperidone for the treatment of disruptive behavioral symptoms in children with autism and other pervasive developmental disorders (PDD).Methods. In this 8-week, randomized, double-blind, placebo-controlled trial, risperidone/placebo solution (0.01-0.06 mg/kg/day) was administered to 79 children who were aged 5 to 12 years and had PDD. Behavioral symptoms were assessed using the Aberrant Behavior Checklist (ABC), Nisonger Child Behavior Rating Form, and Clinical Global Impression-Change. Safety assessments included vital signs, electrocardiogram, extrapyramidal symptoms, adverse events, and laboratory tests.Results. Subjects who were taking risperidone (mean dosage: 0.04 mg/kg/day; 1.17 mg/day) experienced a significantly greater mean decrease on the irritability subscale of the ABC (primary endpoint) compared with those who were taking placebo. By study endpoint, risperidone-treated subjects exhibited a 64% improvement over baseline in the irritability score almost double that of placebo-treated subjects (31%). Risperidone-treated subjects also exhibited significantly greater decreases on the other 4 subscales of the ABC; on the conduct problem, insecure/anxious, hyperactive, and overly sensitive subscales of the Nisonger Child Behavior Rating Form (parent version); and on the Visual Analog Scale of the most troublesome symptom. More risperidone-treated subjects (87%) showed global improvement in their condition compared with the placebo group (40%). Somnolence, the most frequently reported adverse event, was noted in 72.5% versus 7.7% of subjects (risperidone vs placebo) and seemed manageable with dose/dose-schedule modification. Risperidone-treated subjects experienced statistically significantly greater increases in weight (2.7 vs 1.0 kg), pulse rate, and systolic blood pressure. Extrapyramidal symptoms scores were comparable between groups.Conclusions. Risperidone was well tolerated and efficacious in treating behavioral symptoms associated with PDD in children. Pediatrics 2004;114:e634-e641. URL: www.pediatrics.org/cgi/doi/10.1542/peds.2003-0264-F; autistic disorder, pervasive developmental disorders, risperidone.ABBREVIATIONS. PDD, pervasive developmental disorders; EPS, extrapyramidal symptom; CARS, Childhood Autism Rating Scale; ESRS, Extrapyramidal Symptom Rating Scale; ABC, Aberrant Behavior Checklist; N-CBRF, Nisonger Child Behavior Rating Form; VAS, Visual Analog Scale; CGI-C, Clinical Global Impression-Change; ITT, intention-to-treat; RUPP, Research Units on Pediatric Psychopharmacology. T he pervasive developmental disorders (PDD) are a group of neuropsychiatric disorders that include autistic disorder, Asperger's disorder, childhood disintegrative disorder, Rett's disorder, and PDD not otherwise specified. 1 These disorders are characterized by atypical development in social, communicative, and behavior areas. Onset typically occurs within the first years of life. Prevalence rates as high as 63 per 10 000 children have recently been ...

Subgroup analysis of children (5-12 years) with autism enrolled in an 8-week, double-blind, placebo-controlled trial of risperidone for pervasive developmental disorders. The primary efficacy measure was the Aberrant Behavior Checklist-Irritability (ABC-I) subscale. Data were available for 55 children given risperidone (n=27) or placebo (n=28); mean baseline ABC-I ( +/- SD) was 20.6 (8.1) and 21.6 (10.2). Risperidone [mean dose ( +/- SD): 1.37 mg/day (0.7)] resulted in significantly greater reduction from baseline to endpoint in ABC-I versus placebo [mean change ( +/- SD): -13.4 (1.5) vs. -7.2 (1.4), P<0.05; ES=-0.7]. The most common adverse effect with risperidone was somnolence (74% vs. 7% with placebo). Risperidone treatment was well tolerated and significantly improved behavioral problems associated with autism.

Approximately one-third of persons with depression do not respond to antidepressant monotherapy. Studies suggest that atypical antipsychotic augmentation may benefit these patients. We investigated the longer-term efficacy of risperidone augmentation of serotonin-selective reuptake inhibitor treatment for resistant depression. In 57 in-and outpatient centers in three countries, we conducted a three-phase study with 4-6 weeks of open-label citalopram monotherapy, 4-6 weeks of open-label risperidone augmentation, and a 24-week double-blind, placebo-controlled discontinuation phase. A total of 489 patients with major depressive disorder and 1-3 documented treatment failures entered the citalopram monotherapy phase (20-60 mg/day). Patients with o50% reduction in HAM-D-17 scores entered the risperidone augmentation phase (0.25-2.0 mg/day). Patients with HAM-D-17p7 or CGISp2 were randomized to risperidone or placebo augmentation. The primary outcome was time to relapse during the double-blind phase. During citalopram monotherapy, 434 patients had o50% HAM-D-17 reduction; 299 (68.9%) were fully nonresponsive (o25% reduction) and 135 were partially nonresponsive (25-49% reduction). Of the 386 nonresponders who entered the augmentation phase, 243 remitted and 241 entered the double-blind phase. Median time to relapse was 102 days with risperidone augmentation and 85 days with placebo (NS); relapse rates were 53.3 and 54.6%, respectively. In a post hoc analysis of patients fully nonresponsive to citalopram monotherapy, median time to relapse was 97 days with risperidone augmentation and 56 with placebo (p ¼ 0.05); relapse rates were 56.1 and 64.1%, respectively (pp0.05). Open-label risperidone augmentation substantially enhanced response in treatment-resistant patients, but the longer-term benefits of augmentation were not demonstrated in this study.

Background: 5-Methoxy- N,N-dimethyltryptamine (5-MeO-DMT) is a naturally occurring, short-acting psychedelic tryptamine, produced by a variety of plant and animal species. Plants containing 5-MeO-DMT have been used throughout history for ritual and spiritual purposes. The aim of this article is to review the available literature about 5-MeO-DMT and inform subsequent clinical development. Methods: We searched PubMed database for articles about 5-MeO-DMT. Search results were cross-checked against earlier reviews and reference lists were hand searched. Findings were synthesised using a narrative synthesis approach. This review covers the pharmacology, chemistry and metabolism of 5-MeO-DMT, as well epidemiological studies, and reported adverse and beneficial effects. Results: 5-MeO-DMT is serotonergic agonist, with highest affinity for 5-HT1A receptors. It was studied in a variety of animal models, but clinical studies with humans are lacking. Epidemiological studies indicate that, like other psychedelics, 5-MeO-DMT induces profound alterations in consciousness (including mystical experiences), with potential beneficial long-term effects on mental health and well-being. Conclusion: 5-MeO-DMT is a potentially useful addition to the psychedelic pharmacopoeia because of its short duration of action, relative lack of visual effects and putatively higher rates of ego-dissolution and mystical experiences. We conclude that further clinical exploration is warranted, using similar precautions as with other classic psychedelics.

In this retrospective analysis, there was no evidence of statistically or clinically significant growth failure or delay in pubertal onset or progression in children treated for up to 1 year with risperidone.