Oxytocin for Male Subjects with Autism Spectrum Disorder and Comorbid Intellectual Disabilities: A Randomized Pilot Study

Abstract

Approximately half of autism spectrum disorder (ASD) individuals suffer from comorbid intellectual disabilities (IDs). Oxytocin (OXT) receptors are highly expressed in temporal lobe structures and are likely to play a modulatory role in excitatory/inhibitory balance, at least based on animal model findings. Thus, it is feasible that in the highly representative group of Kanner-type ASD subjects, OXT could have a beneficial effect on social communication and social interaction. The aim of this pilot study is to investigate the feasibility and adverse events, such as epilepsy, of the long-term administration of intranasal OXT for adolescent and adult ASD subjects with ID because such patients frequently have seizures. We also addressed the question on how to scale the OXT effects to the core symptoms of social deficits because of the relative difficulty in obtaining objective measurements. Twenty-nine males (aged 15–40 years old) participated in a randomized, double-blind, and placebo-controlled crossover study (each for 8 weeks) with OXT (16 IU/day). Except for seizures experienced by one participant, other serious adverse events did not occur. The primary and secondary outcomes measured using the Childhood Autism Rating Scale and several standard scales, respectively, revealed no difference between the OXT and placebo groups. Instead, in an exploratory analysis, the social interactions observed in the play sessions or in daily life were significantly more frequent in the initial half period in the OXT-first arm of the crossover trial. There were also significant correlations between the plasma OXT concentration and subscale scores for irritability on the Aberrant Behavior Checklist. In conclusion, this pilot study demonstrates that long-term administration of intranasal OXT is tolerable in a representative cohort of ASD individuals with ID and suggests that future multicenter trials of OXT are warranted and should include measurements of reciprocal social interactions based on daily life under closer surveillance for epilepsy. Trial registration: UMIN000007250.

Systematic review and meta‐analysis of reported adverse events of long‐term intranasal oxytocin treatment for autism spectrum disorder

“…Only Yatawara et al and Munesue et al reported severe adverse events. In all, two of these occurred in the placebo group, and three in the oxytocin group.…”

“…Hence, it was decided that data from both phases of the crossover trials would be used regardless of the length of the washout periods. A detailed description of the included studies can be found in Table …”

“…The dose of oxytocin administered in each study varied from 16 to 48 IU per day. Four out of the six studies administered intranasal oxytocin with the brand name Syntocinon . Out of these four studies, two of them used a placebo that contained all the ingredients of Syntocinon except oxytocin, while Kosaka et al did not specify the formulation of the placebo used, and Anagnostou et al used normal saline as the placebo.…”

An immunohistochemical, enzymatic, and behavioral study of CD157/BST-1 as a neuroregulator

“…This observation suggests that OT can be used for the treatment of social avoidance in psychological disorders. Furthermore, whether we can extend the results obtained in the mouse to human behavioral recovery is of interest, especially since there have been reports regarding the effectiveness of OT for impaired social interaction in cases of autism spectrum disorder (ASD) [53–55]. …”

Intranasal oxytocin treatment for social deficits and biomarkers of response in children with autism

“…However, evidence from OXT treatment trials in ASD patients is more equivocal: Several studies have reported that OXT administration improves social abilities in individuals with ASD (19,20), but others have found no improvement in the trial's primary outcome measure (21)(22)(23)(24). Interestingly, many OXT administration studies have documented significant Significance Autism spectrum disorder (ASD) is characterized by social deficits.…”