Opinion Review
Copyright ©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Psychiatry. Jun 19, 2023; 13(6): 262-277
Published online Jun 19, 2023. doi: 10.5498/wjp.v13.i6.262
Pharmacotherapy in autism spectrum disorders, including promising older drugs warranting trials
Jessica Hellings
Jessica Hellings, Department of Psychiatry, University of Missouri-Kansas City, Lee's Summit, MO 64063, United States
Author contributions: Hellings J is responsible for all contributions to this manuscript.
Conflict-of-interest statement: The author has been an investigator for Janssen Pharmaceuticals, Abbott Laboratories, Forest Laboratories, Supernus, Young Living Essential Oils, NIMH and NICHD. NICHD previously funded a risperidone program project grant with the author as principal investigator of the drug study project. The author currently has internal funding from University of Missouri-Kansas City to study amitriptyline in ASD.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Jessica Hellings, MB.BCh., MMed, Professor, Department of Psychiatry, University of Missouri-Kansas City, 300 SE Second St, Lee's Summit, MO 64063, United States. jessica.hellings@uhkc.org
Received: December 28, 2022
Peer-review started: December 28, 2022
First decision: February 21, 2023
Revised: March 6, 2023
Accepted: April 18, 2023
Article in press: April 18, 2023
Published online: June 19, 2023
Processing time: 172 Days and 12.1 Hours
Abstract

Available pharmacotherapies for autism spectrum disorders (ASD) are reviewed based on clinical and research experience, highlighting some older drugs with emerging evidence. Several medications show efficacy in ASD, though controlled studies in ASD are largely lacking. Only risperidone and aripiprazole have Federal Drug Administration approval in the United States. Methylphenidate (MPH) studies showed lower efficacy and tolerability for attention deficit hyperactivity disorder (ADHD) than in the typically developing (TD) population; atomoxetine demonstrated lower efficacy but comparable tolerability to TD outcomes. Guanfacine improved hyperactivity in ASD comparably to TD. Dex-troamphetamine promises greater efficacy than MPH in ASD. ADHD medications reduce impulsive aggression in youth, and may also be key for this in adults. Controlled trials of the selective serotonin reuptake inhibitors citalopram and fluoxetine demonstrated poor tolerability and lack of efficacy for repetitive behaviors. Trials of antiseizure medications in ASD remain inconclusive, however clinical trials may be warranted in severely disabled individuals showing bizarre behaviors. No identified drugs treat ASD core symptoms; oxytocin lacked efficacy. Amitriptyline and loxapine however, show promise. Loxapine at 5-10 mg daily resembled an atypical antipsychotic in positron emission tomography studies, but may be weight-sparing. Amitriptyline at approximately 1 mg/ kg/day used cautiously, shows efficacy for sleep, anxiety, impulsivity and ADHD, repetitive behaviors, and enuresis. Both drugs have promising neurotrophic properties.

Keywords: Autism; Pharmacotherapy; Dextroamphetamine; Loxapine; Amitriptyline; Minimally verbal; Neurotrophic

Core Tip: Most prescribing in autism spectrum disorders (ASD) is off-label; only risperidone and aripiprazole are Federal Drug Administration-approved in ASD, for irritability. Atypical antipsychotics are associated with metabolic side effects. Loxapine at 5-10 mg/day resembled an atypical antipsychotic in positron emission tomography studies; preliminary studies and clinical experience in ASD suggest efficacy and a promising metabolic profile. Controlled attention deficit hyperactivity disorder (ADHD) medication trials in ASD youth include methylphenidate, atomoxetine and guanfacine. The author recommends dextroamphetamine as an important treatment option for ADHD in ASD. Amitriptyline often improves impulsive aggression, self-injury, sleep, anxiety and enuresis. This article recommends additional older drug trials in ASD: Detroamphetamine, amitriptyline, loxapine, and lamotrigine for likely seizures.