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Sniffing around oxytocin: review and meta-analyses of trials in healthy and clinical groups with implications for pharmacotherapy
Open accessAbstract
The popularity of oxytocin (OT) has grown exponentially during the past decade, and so has the number of OT trials in healthy and clinical groups. We take stock of the evidence from these studies to explore potentials and limitations of pharmacotherapeutic applications. In healthy participants, intranasally administered OT leads to better emotion recognition and more trust in conspecifics, but the effects appear to be moderated by context (perceived threat of the 'out-group'), personality and childhood experiences. In individuals with untoward childhood experiences, positive behavioral or neurobiological effects seem lowered or absent. In 19 clinical trials, covering autism, social anxiety, postnatal depression, obsessive-compulsive problems, schizophrenia, borderline personality disorder and post-traumatic stress, the effects of OT administration were tested, with doses ranging from 15 IU to more than 7000 IU. The combined effect size was d=0.32 (N=304; 95% confidence interval (CI): 0.18-0.47; P<0.01). However, of all disorders, only studies on autism spectrum disorder showed a significant combined effect size (d=0.57; N=68; 95% CI: 0.15-0.99; P<0.01). We hypothesize that for some of the other disorders, etiological factors rooted in negative childhood experiences may also have a role in the diminished effectiveness of treatment with OT.
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“These studies yielded summarized effect sizes ranging from d=0.21 to d=0.48.”
From Statistical and Methodological Considerations for the Interpretation of Intranasal Oxytocin Studies (2016) · cites this paper as [11]
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“The meta-analyses mentioned in this paper all tested for evidence of publication bias in the IN-OT literature, with mixed results (9–11).”
From Statistical and Methodological Considerations for the Interpretation of Intranasal Oxytocin Studies (2016) · cites this paper as [11]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Finally, in the meta-analysis by Bakermans-Kranenburg and Van IJzendoorn (11) IN-OT seems to have the largest effect size in individuals with autism. Only four studies of autism were included in the analysis and should therefore be interpreted cautiously. However, the larger effect size for autism (d=0.57) compared to all clinical studies (d=0.32)”
From Statistical and Methodological Considerations for the Interpretation of Intranasal Oxytocin Studies (2016) · cites this paper as [11]
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“Bakermans-Kranenburg and Van IJzendoorn studied the effect of IN-OT in clinical trials (19 effect sizes, total N=304)(11).”
From Statistical and Methodological Considerations for the Interpretation of Intranasal Oxytocin Studies (2016) · cites this paper as [11]
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“To date three meta-analyses of the effects of IN-OT on human behavior have been published.”
From Statistical and Methodological Considerations for the Interpretation of Intranasal Oxytocin Studies (2016) · cites this paper as [11]
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“Only four studies of autism were included in the analysis and should therefore be interpreted cautiously.”
From Statistical and Methodological Considerations for the Interpretation of Intranasal Oxytocin Studies (2016) · cites this paper as [11]
In the citing paper
“Several clinical studies have also investigated the potential of intranasal oxytocin as a treatment for socio-cognitive, behavioral, and socio-affective symptoms of ASD. So far, these studies cannot provide a certain conclusion about oxytocin’s therapeutic potential43–47.”
From Randomized clinical trial shows no substantial modulation of empathy-related neural activation by intranasal oxytocin in autism (2021) · cites this paper as [46]
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“In typically developing individuals, OT has been linked to interpersonal bonding, parental care, and the ability to establish trust and form social attachments [2, 3].”
From Behavioral effects of multiple-dose oxytocin treatment in autism: a randomized, placebo-controlled trial with long-term follow-up (2020) · cites this paper as [2]
In the citing paper
“the genetic background of oxytocin system might influence efficacy of oxytocin administration.19, 20”
From Oxytocin efficacy is modulated by dosage and oxytocin receptor genotype in young adults with high-functioning autism: a 24-week randomized clinical trial (2016) · cites this paper as [19]
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“oxytocin is emerging as a pharmacological target for social dysfunction in clinical trials (29, 30).”
From Placebo treatment facilitates social trust and approach behavior (2018) · cites this paper as [30]
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“Twenty-four Prader–Willi syndrome patients (8 males) were tested with a single dose of 24 IU OT (n1⁄4 12) or placebo (n1⁄4 12).(99) Patients were observed in their daily routines and scored by trained staff on behavioral scales before and immediately after treatment and during two days following treatment.”
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“Moreover, recent research indicates that positive OT effects on behavior or neurobiology are lowered or absent in individuals with negative childhood experiences.(78,79,91)”
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The adaptive human parental brain: implications for children's social development
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Statistical and Methodological Considerations for the Interpretation of Intranasal Oxytocin Studies
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“Finally, in the meta-analysis by BakermansKranenburg and Van IJzendoorn (11) IN-OT seems to have the largest effect size in individuals with autism.”
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Does Oxytocin Increase Trust in Humans? A Critical Review of Research
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Metadata
- Authors
- Bakermans-Kranenburg, M. J., & van IJzendoorn, M. H.
- Venue
- Translational Psychiatry
- Published
- 2013-05-21
- Volume
- 3
- Issue
- 5
- Pages
- e258-e258
- ISSN
- 2158-3188 (ISSN-L)
- PMC
- PMC3669921
- OpenAlex
- W1966317054
- Cited by
- 383
- References
- 142
- Citations by year
- 2026: 7 · 2025: 13 · 2024: 12 · 2023: 18 · 2022: 11 · 2021: 24 · 2020: 22 · 2019: 29 · 2018: 41 · 2017: 55 · 2016: 43 · 2015: 59 · 2014: 40 · 2013: 9
- FWCI
- 6.67
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by-nc-nd
- www.springer.com/tdm (unspecified)
- Locations
- Translational Psychiatry (publishedVersion, cc-by-nc-nd)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Funders
- Nederlandse Organisatie voor Wetenschappelijk Onderzoek
- Topics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Neuroendocrine regulation and behavior
- Life Sciences › Neuroscience › Sensory Systems › Olfactory and Sensory Function Studies
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Keywords
- oxytocin, intranasal administration, pharmacotherapy, autism spectrum disorder, social anxiety, postpartum depression, obsessive-compulsive disorder, schizophrenia, borderline personality disorder, post-traumatic stress disorder, emotion recognition, trust, child abuse, personality moderators, treatment effect size
- MeSH terms
- Administration, Intranasal, Anxiety, Mental Disorders, Child, Child Development Disorders, Pervasive, Depression, Humans, Oxytocin, Personality Disorders, Phobic Disorders, Schizophrenia, Stress Disorders, Post-Traumatic, Anti-Anxiety Agents, Trust
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