28 mars 2017

Antagonistes de la dopamine pour la résistance au traitement dans les troubles du spectre de l'autisme: examiner et se concentrer sur les stimulateurs du BDNF, la loxapine et l'amitriptyline

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. 

Expert Opin Pharmacother. 2017 Mar 24. doi: 10.1080/14656566.2017.1308483.

Dopamine antagonists for treatment resistance in autism spectrum disorders: review and focus on BDNF stimulators loxapine and amitriptyline

Author information

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.

PMID: 28335658 

DOI: 10.1080/14656566.2017.1308483

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