Loxapine Add-on for Adolescents and Adults with Autism Spectrum Disorders and Irritability
| Autor: | Jessica A. Hellings, Dmytro Mikhnev, Marilyn Logan, Gladys I. Palaguachi, Xinghua Zhou, Sharon Cain, Merlin G. Butler, Rebecca Andridge, Gregory A. Reed, Rujia Teng, Michael G. Aman, Francis X. Barth, Joan C. Han |
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| Rok vydání: | 2015 |
| Předmět: |
Adult
Male medicine.medical_specialty Pediatrics Adolescent Autism Spectrum Disorder Loxapine Irritability behavioral disciplines and activities Young Adult Pharmacotherapy mental disorders medicine Humans Pharmacology (medical) Prospective Studies Young adult Psychiatry Prospective cohort study Psychiatric Status Rating Scales Brain-Derived Neurotrophic Factor Original Articles medicine.disease Irritable Mood Clinical trial Psychiatry and Mental health Treatment Outcome Autism spectrum disorder Pediatrics Perinatology and Child Health Autism Drug Therapy Combination Female medicine.symptom Psychology Antipsychotic Agents medicine.drug |
| Zdroj: | Journal of Child and Adolescent Psychopharmacology. 25:150-159 |
| ISSN: | 1557-8992 1044-5463 |
| DOI: | 10.1089/cap.2014.0003 |
| Popis: | 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.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 scores14. 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.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.Low dose loxapine shows promise as a repurposed drug for irritability in ASD. Loxapine effects on BDNF warrant further study. |
| Databáze: | OpenAIRE |
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