One-Year Retention Effects of Multiple-Dose Oxytocin Treatment on Repetitive and Restricted Behaviors, Social Responsiveness and Attachment: A Randomized, Placebo-Controlled Trial
Autism spectrum disorders (ASDs) are characterized by difficulties in social communication and repetitive and restricted behaviors. To date, no pharmacological treatment exists targeting the core symptoms of ASD, yet the past years, the pharmacological use of the neuropeptide oxytocin (OT), has gained increasing interest from the research community to explore its potential for elevating the core social deficits in ASD.
With our double-blind randomized placebo-controlled trial with thirty-nine young adult men with ASD (21 OT/18 Placebo (PL)) we previously showed that a four-week intranasal OT treatment (24 IU/day) improved repetitive behaviors, feelings of attachment and social responsiveness until one month post-treatment (poster presented at IMFAR 2017 ID#23322).
We conducted secondary analyses of this randomized trial to explore whether treatment-related behavioral improvements observed one month post-treatment were maintained at 12-month follow-up.
We included thirty-one participants that completed the four-week treatment (OT or PL) and a follow-up session 12 months post-treatment (17 OT/14 PL). Behavioral outcome measures that showed improvements one month post-treatment were assessed again at 12-month follow-up, including assessments of treatment-related changes in repetitive behavior (Repetitive Behavior Scale–Revised(RBS-R)); feelings of attachment (State Adult Attachment Scale(SAAM)); and social functioning (self-report and informant-based Social Responsiveness Scale(SRS)). For each treatment group, the maintenance of behavioral improvements (from baseline) was assessed and difference-in-difference analyses were performed to assess whether the observed improvements were significantly larger in the OT, compared to the PL group.
At 12-month follow-up, improvements in self-reported repetitive behaviors were shown to be maintained in the OT group (t(16)=-1.78,p=0.05), not in the PL group (t(12)=0.31,p=0.76)(Fig.1a). The effect was most pronounced for the subscale assessing ‘compulsive behavior’ (t(16)=-3.27,p=0.005). Also in terms of state attachment, participants who received OT still reported to feel less avoidant towards others until 12 months post-treatment (t(16)=-1.91,p=0.04), whereas no significant improvement was observed in the PL group (t(13)=0.18,p=0.86)(Fig.1b). Albeit significant in the OT group, direct comparison of these effects to the PL group showed that the observed improvements were only tentatively more pronounced in the OT, compared to the PL group (RBS: t(28)=-1.58, p=0.06, Cohen’s d=0.58; SAAM: t(29)=-1.59, p=0.06, Cohen’s d=0.83) (Fig.1) (note that for the compulsive behavior scale, the effect was specific to the OT treatment (t(28)=-2.26, p=0.02, Cohen’s d=0.83)).
In terms of social responsiveness, participants of the OT group still showed a tentative improvement in social responsiveness at 12-month follow-up (OT: informant-report: t(11)=-1.50,p=0.08; self-report: t(15)=-1.47, p=0.08)) (PL: informant-based: t(10)=0.59,p=0.30; self-report: t(13)=0.33,p=0.17). However, none of these tentative improvements were specific to the OT treatment (informant-based: t(21)=-0.44,p=0.33; self-report: t(28)=-0.33, p=0.37)(Fig.1c-d).
Based on a subsample of participants that underwent a 4-week OT treatment and completed a 12-month follow-up session, we show that the observed behavioral improvements in repetitive behavior and attachment avoidance tended to persist until 12 months post-treatment. The observed beneficial effect of OT on social functioning was no longer significant at 12-month follow-up. Our findings provide first indications that continual OT treatment (four weeks) can induce long-lasting behavioral changes in individuals with ASD that last until 12 months after the actual treatment.