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Modulation of the Locus Coeruleus-Noradrenergic System with Milnacipran Vs Placebo in Autism Spectrum Disorder
Objectives: To determine whether MLN improves attention dysfunction, irritability, repetitive behaviors and social cognition in patients with autism.
Methods: A 12 week randomized, double-blind, placebo-controlled trial of MLN up to 200mg/ was performed in subjects aged 18 – 50 with a DSM-IV TR ASD diagnosis, confirmed by ADI-R and ADOS. Comorbid medical, neurological and psychiatric illnesses with the exception of ADHD and OCD were excluded. Conners Adults ADHD Rating Scale-Observer Version (CAARS-O), Aberrant Behavior Checklist (ABC), and Clinical Global Impressions Improvement Scale (CGI-I) were measured.
Results: Interim analyses revealed clinically meaningful improvement on milnacipran versus placebo in CGI-I, CAARS-O Inattention/Memory Hyperactivity/Restlessness, Problems with self-concept, DSM-IV Inattentive Symptoms, ADHD Symptoms Total and ADHD Index. Improvements on milnacipran versus placebo were also observed on the ABC Irritability, Stereotypy, and Hyperactivity subscales. No significant differences between treatment groups were found on the CAARS Impulsivity/Emotional Lability and DSM-IV Hyperactive-Impulsive Symptoms subscales or the ABC-Social Withdrawal or Inappropriate Speech subscales.
Conclusions: Treatment with MLN versus placebo produced clinically meaningful improvements in several domains of the core symptoms of ASD. We posit that this was accomplished via activation of the LC-NA system by MLN mimicking the effects of fever, however more research is needed.
See more of: Specific Interventions - Pharmacologic