Behavioral effects of multiple-dose oxytocin treatment in autism: a randomized, placebo-controlled trial with long-term follow-up
- PMID:31969977
- PMCID: PMC6964112
- DOI: 10.1186/s13229-020-0313-1
Behavioral effects of multiple-dose oxytocin treatment in autism: a randomized, placebo-controlled trial with long-term follow-up
Abstract
Background: Intranasal administration of the "prosocial" neuropeptide oxytocin is increasingly explored as a potential treatment for targeting the core characteristics of autism spectrum disorder (ASD). However, long-term follow-up studies, evaluating the possibility of long-lasting retention effects, are currently lacking.
Methods: Using a double-blind, randomized, placebo-controlled, parallel design, this pilot clinical trial explored the possibility of long-lasting behavioral effects of 4 weeks of intranasal oxytocin treatment (24 International Units once daily in the morning) in 40 adult men with ASD. To do so, self-report and informant-based questionnaires assessing core autism symptoms and characterizations of attachment were administered at baseline, immediately after 4 weeks of treatment (approximately 24 h after the last nasal spray administration), and at two follow-up sessions, 4 weeks and 1 year post-treatment.
Results: No treatment-specific effects were identified in the primary outcome assessing social symptoms (Social Responsiveness Scale, self- and informant-rated). In particular, with respect to self-reported social responsiveness, improvements were evident both in the oxytocin and in the placebo group, yielding no significant between-group difference (p = .37). Also informant-rated improvements in social responsiveness were not significantly larger in the oxytocin, compared to the placebo group (between-group difference:p = .19). Among the secondary outcome measures, treatment-specific improvements were identified in the Repetitive Behavior Scale and State Adult Attachment Measure, indicating reductions in self-reported repetitive behaviors (p = .04) and reduced feelings of avoidance toward others (p = .03) in the oxytocin group compared to the placebo group, up to 1 month and even 1 year post-treatment. Treatment-specific effects were also revealed in screenings of mood states (Profile of Mood States), indicating higher reports of "vigor" (feeling energetic, active, lively) in the oxytocin, compared to the placebo group (p = .03).
Conclusions: While no treatment-specific improvements were evident in terms of core social symptoms, the current observations of long-term beneficial effects on repetitive behaviors and feelings of avoidance are promising and suggestive of a therapeutic potential of oxytocin treatment for ASD. However, given the exploratory nature of this pilot study, future studies are warranted to evaluate the long-term effects of OT administration further.
Trial registration: The trial was registered with the European Clinical Trial Registry (Eudract 2014-000586-45) on January 22, 2014 (https://www.clinicaltrialsregister.eu/ctr-search/trial/2014-000586-45/BE).
Keywords: Attachment; Autism spectrum disorder; Oxytocin; Repetitive and restricted behavior; Social responsiveness.
© The Author(s). 2020.
Conflict of interest statement
Competing interestsThe authors declare that they have no competing interests.
Figures


Similar articles
- Effects of multiple-dose intranasal oxytocin administration on social responsiveness in children with autism: a randomized, placebo-controlled trial.Daniels N, Moerkerke M, Steyaert J, Bamps A, Debbaut E, Prinsen J, Tang T, Van der Donck S, Boets B, Alaerts K.Daniels N, et al.Mol Autism. 2023 Apr 20;14(1):16. doi: 10.1186/s13229-023-00546-5.Mol Autism. 2023.PMID:37081454Free PMC article.Clinical Trial.
- Changes in endogenous oxytocin levels after intranasal oxytocin treatment in adult men with autism: An exploratory study with long-term follow-up.Alaerts K, Steyaert J, Vanaudenaerde B, Wenderoth N, Bernaerts S.Alaerts K, et al.Eur Neuropsychopharmacol. 2021 Feb;43:147-152. doi: 10.1016/j.euroneuro.2020.11.014. Epub 2020 Dec 10.Eur Neuropsychopharmacol. 2021.PMID:33309460Clinical Trial.
- Oxytocin induces long-lasting adaptations within amygdala circuitry in autism: a treatment-mechanism study with randomized placebo-controlled design.Alaerts K, Bernaerts S, Prinsen J, Dillen C, Steyaert J, Wenderoth N.Alaerts K, et al.Neuropsychopharmacology. 2020 Jun;45(7):1141-1149. doi: 10.1038/s41386-020-0653-8. Epub 2020 Mar 11.Neuropsychopharmacology. 2020.PMID:32161366Free PMC article.Clinical Trial.
- [Therapeutic effects of oxytocin in autism: Current status of the research].Gauthier C, Doyen C, Amado I, Lôo H, Gaillard R.Gauthier C, et al.Encephale. 2016 Feb;42(1):24-31. doi: 10.1016/j.encep.2015.07.006. Epub 2016 Jan 18.Encephale. 2016.PMID:26797566Review.French.
- The neural effects of oxytocin administration in autism spectrum disorders studied by fMRI: A systematic review.Fathabadipour S, Mohammadi Z, Roshani F, Goharbakhsh N, Alizadeh H, Palizgar F, Cumming P, Michel TM, Vafaee MS.Fathabadipour S, et al.J Psychiatr Res. 2022 Oct;154:80-90. doi: 10.1016/j.jpsychires.2022.06.033. Epub 2022 Aug 4.J Psychiatr Res. 2022.PMID:35933858Review.
Cited by
- Pharmacogenetics May Prevent Psychotropic Adverse Events in Autism Spectrum Disorder: An Observational Pilot Study.de Miguel L, Ballester P, Egoavil C, Sánchez-Ocaña ML, García-Muñoz AM, Cerdá B, Zafrilla P, Ramos E, Peiró AM.de Miguel L, et al.Pharmaceuticals (Basel). 2023 Oct 20;16(10):1496. doi: 10.3390/ph16101496.Pharmaceuticals (Basel). 2023.PMID:37895967Free PMC article.
- Neuroenhancement: State of the Art and Future Perspectives.Marazziti D, Avella MT, Ivaldi T, Palermo S, Massa L, Vecchia AD, Basile L, Mucci F.Marazziti D, et al.Clin Neuropsychiatry. 2021 Jun;18(3):137-169. doi: 10.36131/cnfioritieditore20210303.Clin Neuropsychiatry. 2021.PMID:34909030Free PMC article.
- Repetitive Restricted Behaviors in Autism Spectrum Disorder: From Mechanism to Development of Therapeutics.Tian J, Gao X, Yang L.Tian J, et al.Front Neurosci. 2022 Mar 2;16:780407. doi: 10.3389/fnins.2022.780407. eCollection 2022.Front Neurosci. 2022.PMID:35310097Free PMC article.Review.
- Oxytocin enhances neural approach towards social and non-social stimuli of high personal relevance.Alaerts K, Taillieu A, Daniels N, Soriano JR, Prinsen J.Alaerts K, et al.Sci Rep. 2021 Dec 8;11(1):23589. doi: 10.1038/s41598-021-02914-8.Sci Rep. 2021.PMID:34880300Free PMC article.Clinical Trial.
- Oxytocin-based therapies for treatment of Prader-Willi and Schaaf-Yang syndromes: evidence, disappointments, and future research strategies.Althammer F, Muscatelli F, Grinevich V, Schaaf CP.Althammer F, et al.Transl Psychiatry. 2022 Aug 8;12(1):318. doi: 10.1038/s41398-022-02054-1.Transl Psychiatry. 2022.PMID:35941105Free PMC article.Review.
References
- American Psychiatric Association. Diagnostic and statistical manual of mental disorders (DSM-5®) [Internet]. 5th ed. Arlington, editor. American Psychiatric Association; 2013 [cited 2016 Feb 4]. 50–59. Available from:https://books.google.com/books?hl=nl&lr=&id=-JivBAAAQBAJ&pgis=1
- Bartz JA, Zaki J, Bolger N, Ochsner KN. Social effects of oxytocin in humans: context and person matter. Trends Cogn Sci [Internet]. 2011;15(7):301–309. - PubMed
Publication types
MeSH terms
Substances
Related information
LinkOut - more resources
Full Text Sources