Dataset Information

Loxapine add-on for adolescents and adults with autism spectrum disorders and irritability.

ABSTRACT: OBJECTIVES:Our clinical experience with low dose loxapine (5-15?mg/day) suggests promising efficacy and safety for irritability in autism spectrum disorders (ASD). We studied low dose loxapine prospectively in adolescents and adults with ASD and irritability. Additionally, we measured loxapine and metabolite concentrations, and brain-derived neurotrophic factor (BDNF) as a biomarker of neuromodulation. METHODS:We performed a 12 week open trial of add-on loxapine in subjects, ages 13-65 years, diagnosed with ASD, and Aberrant Behavior Checklist-Irritability (ABC-I) subscale scores >14. Loxapine was dosed flexibly up to 15?mg daily, starting with 5?mg on alternate days. From weeks 1 to 6, other psychoactive medications were tapered if possible; from weeks 6 to 12, all medication doses were held stable. The primary outcome was the Clinical Global Impressions-Improvement subscale (CGI-I), ratings of Much Improved or Very Much Improved. Secondary outcomes were the ABC-I, Repetitive Behavior Scale-Revised, and Schalock Quality of Life scale. Serum BDNF and loxapine and metabolite concentrations were assayed. BDNF rs6265 was genotyped. RESULTS:Sixteen subjects were enrolled; 12 completed all visits. Median age was 18 years (range 13-39). Median final loxapine dose was 7.5?mg/day (2.5-15). All 14 subjects (100%) with data at week 12 were rated as Much Improved on CGI-I at 12 weeks. Mean change on ABC-I at 12 weeks was -31%, p=0.01. Mean body mass index (BMI)-Z decreased between weeks 6 and 12, p=0.03. Side effects were minimal, and prolactin elevation occurred in only one subject. BDNF concentrations measured in 11 subjects increased significantly (p=0.04). Subjects with AG genotype for BDNF rs6265 required a lower dose of loxapine at study end, but had similar behavioral and BDNF concentration changes as the GG genotype. CONCLUSIONS:Low dose loxapine shows promise as a repurposed drug for irritability in ASD. Loxapine effects on BDNF warrant further study.

SUBMITTER: Hellings JA

PROVIDER: S-EPMC4442591 | biostudies-literature | 2015 Mar

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Loxapine add-on for adolescents and adults with autism spectrum disorders and irritability.

Hellings Jessica A JA Reed Gregory G Cain Sharon E SE Zhou Xinghua X Barth Francis X FX Aman Michael G MG Palaguachi Gladys I GI Mikhnev Dmytro D Teng Rujia R Andridge Rebecca R Logan Marilyn M Butler Merlin G MG Han Joan C JC

Journal of child and adolescent psychopharmacology 20150301 2

<h4>Objectives</h4>Our clinical experience with low dose loxapine (5-15 mg/day) suggests promising efficacy and safety for irritability in autism spectrum disorders (ASD). We studied low dose loxapine prospectively in adolescents and adults with ASD and irritability. Additionally, we measured loxapine and metabolite concentrations, and brain-derived neurotrophic factor (BDNF) as a biomarker of neuromodulation.<h4>Methods</h4>We performed a 12 week open trial of add-on loxapine in subjects, ages ...[more]

PMID: 25782098

Similar Datasets

Project description:Despite the clinically significant impact of executive dysfunction on the outcomes of adolescents and young adults with autism spectrum disorders (ASD), we lack a clear understanding of its prevalence, profile, and development. To address this gap, we administered the NIH Toolbox Cognition Battery to a cross-sectional Intelligence Quotient (IQ) case-matched cohort with ASD (n = 66) and typical development (TD; n = 66) ages 12-22. We used a general linear model framework to examine group differences in task performance and their associations with age. Latent profile analysis (LPA) was used to identify subgroups of individuals with similar cognitive profiles. Compared to IQ case-matched controls, ASD demonstrated poorer performance on inhibitory control (P < 0.001), cognitive flexibility (P < 0.001), episodic memory (P < 0.02), and processing speed (P < 0.001) (components of Fluid Cognition), but not on vocabulary or word reading (components of Crystallized Cognition). There was a significant positive association between age and Crystallized and Fluid Cognition in both groups. For Fluid (but not Crystallized) Cognition, ASD performed more poorly than TD at all ages. A four-group LPA model based on subtest scores best fit the data. Eighty percent of ASD belonged to two groups that exhibited relatively stronger Crystallized versus Fluid Cognition. Attention deficits were not associated with Toolbox subtest scores, but were lowest in the group with the lowest proportion of autistic participants. Adaptive functioning was poorer in the groups with the greatest proportion of autistic participants. Autistic persons are especially impaired on Fluid Cognition, and this more flexible form of thinking remains poorer in the ASD group through adolescence. LAY SUMMARY: A set of brief tests of cognitive functioning called the NIH Toolbox Cognition Battery was administered to adolescents and young adults with autism spectrum disorders (ASD; n = 66) and typical development (TD; n = 66) ages 12-22 years. Compared to TD, ASD showed poorer performance in inhibiting responses, acting flexibly, memorizing events, and processing information quickly (Fluid Cognition). Groups did not differ on vocabulary or word reading (Crystallized Cognition). Crystallized and Fluid Cognition increased with age in both groups, but the ASD group showed lower Fluid, but not Crystallized, Cognition than TD at all ages. A categorization analysis including all participants showed that most participants with ASD fell into one of two categories: a group characterized by poor performance across all tasks, or a group characterized by relatively stronger Crystallized compared to Fluid Cognition. Adaptive functioning was poorer for participants in these groups, which consisted of mostly individuals with ASD, while ADHD symptoms were lowest in the group with the greatest proportion of TD participants.

Dataset Information

Loxapine add-on for adolescents and adults with autism spectrum disorders and irritability.

Publications

Loxapine add-on for adolescents and adults with autism spectrum disorders and irritability.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets