Aperçu: G.M.
Le
développement de médicaments est urgent pour les personnes avec un diagnostic de trouble du spectre de l'autisme (TSA) et des comorbidités psychiatriques,
qui se présentent souvent comme l'agression et l'automutilation.
L'ancien
antipsychotique loxapine est discuté en termes de preuves
préliminaires, bien que limitées pour l'efficacité et la sécurité, ainsi
que les possibles effets neurotrophiques dans le cerveau.
Les
antipsychotiques classiques sont encore
souvent utilisés dans la poly pharmacologie antipsychotique cependant les personnes avec TSA sont plus sensibles aux effets secondaires
neuromoteurs qui peuvent tard compromettre la mobilité aussi
bien que provoquer une dyskinésie tardive et un syndrome malin
neuroleptique.
Les
nouveaux antipsychotiques risperidone et aripiprazole sont approuvés par la FDA pour l'irritabilité chez les
enfants plus de 5 ans. Cependant,
les personnes avec un diagnostic de TSA sont plus sujettes au gain de poids, au diabète de type II et aux effets secondaires associés.
La
pratique courante de prescrire des ISRS qui inhibent le métabolisme de
nombreux médicaments psychoactifs avec des antipsychotiques aggrave les effets secondaires.
Une faible dose de loxapine possède des propriétés des antipsychotiques
classiques et nouveaux mais elle semble
surtout plus neutre en poids, et avec une utilisation prometteuse chez
les adolescents et les adultes avec TSA.
L'amitriptyline
semble efficace dans les TSA pour l'irritabilité, l'agressivité
impulsive, les problèmes gastro-intestinaux et l'insomnie, chez les
enfants, les adolescents et les adultes.
- 1
- a
University of Missouri-Kansas City , Kansas City Regional Center of
Missouri Department of Mental Health , Kansas City Missouri , USA.
- 2
- b The Ohio State University Nisonger Center , Columbus , Ohio , USA.
- 3
- c University of Tennessee , 454R Le Bonheur Children's Foundation Research Center , Memphis , Tennessee , USA.
Abstract
INTRODUCTION:
Drug development is urgently needed for individuals with autism
spectrum disorders (ASD) and psychiatric comorbidity, which often
presents as aggression and self-injury. At the same time, most
psychiatric medications are drugs that have been repurposed following
clinical observations of efficacy for a new treatment purpose. Areas
Covered: This review aims to provide an overview of dopamine
antagonists, including classical and atypical, as well as unconventional
antipsychotics in ASD, since they are a mainstay of treatment for such
problems. In the event of only partial treatment response practitioners
urgently need other prescribing options. The older antipsychotic
loxapine is discussed in terms of preliminary albeit limited evidence
for efficacy and safety, as well as possible neurotrophic effects in the
brain. Emerging promise of the unconventional weak dopamine
blocking/tricyclic antidepressant amitriptyline in ASD is discussed more
briefly. Promising BDNF effects of loxapine and amitriptyline are
included. The need for any antipsychotic tapering plan to be extremely
gradual, unless neuroleptic malignant syndrome is present, is also
emphasized. Expert Opinion: While behavioral treatments can improve core
symptoms in ASD, pharmacotherapy and specifically dopamine antagonists
are often prescribed for serious challenging behaviors including
aggression. The classical antipsychotics received some study and are
still often used in antipsychotic polypharmacy however individuals with
ASD are more susceptible to the neuromotor side effects which may
further impair already compromised mobility as well as cause tardive
dyskinesia and neuroleptic malignant syndrome. The novel antipsychotics
risperidone and aripiprazole have received most study in ASD and are
FDA-approved for irritability in children over age 5 years. However
individuals with ASD are more prone to weight gain, Type II diabetes and
associated side effects, for which most novel antipsychotics carry a
black box warning. The common practice of prescribing SSRIs that inhibit
metabolism of many psychoactive drugs together with antipsychotics
compounds the side effects. Low dose loxapine has properties of
classical as well as novel antipsychotics but importantly appears more
weight neutral, and with promising use in adolescents and adults with
ASD. Amitriptyline appears effective in ASD for irritability, impulsive
aggression, gastrointestinal problems, and insomnia, in children,
adolescents and adults however our adult data on amitriptyline in ASD is
still in preparation for publication. Both loxapine and amitriptyline
may have positive BDNF effects. Further studies are warranted of both
medications in ASD.
