Discussion
ASD
SECONDARY
The current pediatric trial demonstrated no significant treatment-specific effects of a 4-week OT administration period on social responsiveness (SRS-2), nor on the secondary outcomes. Both the OT and the placebo groups displayed similar improvements, both immediately after the multiple-dose nasal spray administration and at the 4-week follow-up session. Notably, participants who were allocated to receive the placebo nasal spray during the first double-blind phase of the trial and continued to receive the active nasal spray during the second (single-blind) phase, displayed a significant improvement in social responsiveness, over and above the placebo-induced improvement noted in the first phase. Finally, albeit exploratory, moderator analyses preliminarily showed that children who received the OT nasal spray in combination with concomitant psychosocial training (three or more sessions per month) displayed a greater improvement in social responsiveness compared to children receiving the OT nasal spray alone or to children receiving the psychosocial training alone.Results of earlier multiple-dose OT trials in children with ASD have been equivocal: some with beneficial outcomes [Further, in phase II of the trial it was observed that children who continued from placebo (in phase I) to the actual OT nasal spray (in phase II) showed a significant further improvement in social responsiveness over and above the substantial placebo-induced improvement noted in phase I. Trial designs in which a phase of blinded placebo intervention is administered before actual nasal spray allocation have been put forward as an effective method to control for placebo effects and to improve detection of ‘real’ therapeutic responses [Children who received the actual OT nasal spray in the first phase and continued to a second phase of active nasal spray administration did not show a further improvement immediately after the second nasal spray administration period, although further changes did become apparent at the follow-up session, 4 weeks after cessation of the second nasal spray administration period. It is noted indeed, that at the last follow-up session of the trial, the majority of children of both the OT-first group and the placebo-first group displayed (reliable) beneficial effects in social responsiveness, indicating that both an 8-week (with a 4-week break in the middle) or a continual 4-week OT administration period were similarly able to induce a significant beneficial outcome in the social domain. This observation adds to the field’s uncertainty regarding to-be-administered dosing schemas and durations. In multiple-dose OT trials with individuals with ASD, daily dosing ranged from 8 to 80 IU and durations from 4 continual days to 24 weeks, but strong empirical support for favoring one dosing scheme over another is currently lacking. Some earlier single-dose trials suggested dose–response curves to exhibit U-shaped forms [