Dopamine antagonists for treatment resistance in autism spectrum disorders: review and focus on BDNF stimulators loxapine and amitriptyline.
Drug development and repurposing are urgently needed for individuals with autism spectrum disorders (ASD) and psychiatric comorbidity, which often presents as aggression and self-injury. Areas covered: We review dopamine antagonists, including classical and atypical, as well as unconventional antipsychotics in ASD. The older antipsychotic loxapine is discussed in terms of preliminary albeit limited evidence in ASD. Emerging promise of amitriptyline in ASD is discussed, together with promising BDNF effects of loxapine and amitriptyline. Expert opinion: In ASD, pharmacotherapy and specifically dopamine antagonist drugs are often prescribed for challenging behaviors including aggression. The novel antipsychotics risperidone and aripiprazole have received most study in ASD and are FDA-approved for irritability in children with ASD over age 5 years; individuals with ASD are prone to weight gain, Type II diabetes and associated side effects. Low dose loxapine has properties of classical and 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, 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 stimulate BDNF; further studies are warranted.
a Kansas City Regional Center of Missouri Department of Mental Health , University of Missouri-Kansas City , Kansas City , MO , USA.
Jessica A
JA
Hellings
b Department of Psychiatry , The Ohio State University Nisonger Center , Columbus , OH , USA.
L Eugene
LE
Arnold
c 454R Le Bonheur Children's Foundation Research Center , University of Tennessee , Memphis , TN , USA.
Joan C
JC
Han
D000293:Adolescent; D000328:Adult; D000639:Amitriptyline / Q000494:pharmacology / Q000627:therapeutic use*; D014150:Antipsychotic Agents / Q000627:therapeutic use; D000068180:Aripiprazole / Q000627:therapeutic use; D000067877:Autism Spectrum Disorder / Q000188:drug therapy*; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D002648:Child; D018492:Dopamine Antagonists / Q000627:therapeutic use; D006801:Humans; D007508:Irritable Mood / Q000187:drug effects; D008152:Loxapine / Q000627:therapeutic use*; D018967:Risperidone / Q000627:therapeutic use
D014150:Antipsychotic Agents; D019208:Brain-Derived Neurotrophic Factor; D018492:Dopamine Antagonists; D000639:Amitriptyline; D000068180:Aripiprazole; D018967:Risperidone; D008152:Loxapine
BDNF; Dopamine antagonists; aggression; amitriptyline; antipsychotics; autism; loxapine