Nasal oxytocin for social deficits in childhood autism: A randomized controlled trial

Several recent trials meet some of these recommended conditions, especially by reporting clear primary outcomes.

“Several recent trials conform to some of these conditions, particularly in reporting clear primary outcomes.”

Recent trials found no effect of intranasal oxytocin in young people with autism spectrum disorders.

“or in youths with autism spectrum disorders (106,107).”

Clinical trials examining core symptoms of ASD have failed to consistently demonstrate efficacy of intranasal OT treatment.

“Clinical trials examining core symptoms of ASD have failed to consistently demonstrate efficacy of intranasal OT treatment (Anagnostou et al., 2012; Dadds et al., 2014; Guastella et al., 2015; Hollander et al., 2007)”

Two studies did not demonstrate any OXT specific improvements in social responsiveness or repetitive behavior in children with ASD.

“another 2 studies did not demonstrate any OXT specific improvements in social responsiveness or repetitive behavior in children with ASD [84, 85].”

Results of OXT studies in children have overall been more equivocal with mixed results.

“Results of OXT studies in children have overall been more equivocal with mixed results.”

Most randomized clinical trials have found some oxytocin effects on ASD symptoms and brain function, but not all trials have reported effects.

“While most randomized clinical trials have found some oxytocin effects on ASD symptoms33,50–52 and brain function50–52,80,81, not all trials have reported effects82.”

Most studies among patients with other psychiatric disorders utilizing repeated dosing of 1-3 daily doses are only 8 days or less.

“while some studies among patients with other psychiatric disorders (e.g., autism, alcohol use disorder) have utilized a repeated dosing strategy in the form of 1–3 daily doses, most of these studies are only 8 days or less (Dadds et al., 2014; Guastella et al., 2015; Pedersen et al., 2011).”

Dadds et al. found no oxytocin-specific improvements in repetitive behaviors or social responsiveness after 4-day intranasal oxytocin treatment in 38 boys with ASD.

“For example, Dadds et al. [11] assessed behavioral effects of a 4-day intranasal OT treatment in 38 boys with ASD (7 to 16 years old) during parent-child interaction training, but found no OT-specific improvements in repetitive behaviors or social responsiveness.”

Taken together, initial multiple-dose trials provided indications for a more consistent positive pattern of results for oxytocin trials with adults with ASD compared to trials with children with ASD.

“Taken together, findings of these initial multiple-dose trials provided indications for a more consistent (positive) pattern of results for OT trials with adults with ASD [8–10], compared to trials with children with ASD [11–14].”

Beneficial effects of OT treatment on repetitive behaviors were mostly demonstrated in studies that adopted assessments based on self-reports, whereas no beneficial effects were evident in studies adopting informant-based reports of repetitive behavior.

“In this view, it appears that beneficial effects of OT treatment on repetitive behaviors were mostly demonstrated in studies that adopted assessments based on self-reports (current study, [4, 8]), whereas no beneficial effects were evident in studies adopting informant-based reports of repetitive behavior [9–14].”

In the current study, participants administered the OT nasal spray once a day (in the morning) while the majority of prior multiple-dose OT studies administered two doses/day.

“Second, in the current study, participants administered the OT nasal spray once a day (in the morning) while the majority of prior multiple-dose OT studies administered two doses/day (one in the morning and one in the afternoon) ([8–10, 12–14], but see [11]).”

There is considerable debate regarding whether peripheral levels of oxytocin reflect central expression in humans, with mixed evidence reported to date.

“Lastly, there exists considerable debate regarding whether peripheral levels of oxytocin reflect central expression in humans, with mixed evidence reported to date.26,27”

A series of negative results, mixed meta-analytic results and doubts surrounding oxytocin research methods dampened initial enthusiasm.

“However, a series of negative results,24, 25, 26 mixed meta-analytic results27 and doubts surrounding oxytocin research methods28 somewhat dampened initial enthusiasm.”