Chronic oxytocin administration as a tool for investigation and treatment: A cross-disciplinary systematic review

Horta, Marilyn; Kaylor, Kathryn; Feifel, David; Ebner, Natalie C.

doi:10.1016/j.neubiorev.2019.10.012

Cited by 47 publications

(35 citation statements)

References 186 publications

(449 reference statements)

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“…Second, it is unclear whether chronic administration of oxytocin will emerge as a long-term treatment for patients [ 146 ], or if short-term adjunctive treatment with oxytocin might be more appropriate. Given the manifold effects of oxytocin on social cognitive functions, it seems conceivable that oxytocin is capable to augment therapeutic interventions in various ways.…”

Section: Future Directions For Clinical Research Using Intranasal Oxymentioning

confidence: 99%

Advances in the field of intranasal oxytocin research: lessons learned and future directions for clinical research

et al. 2020

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Reports on the modulatory role of the neuropeptide oxytocin on social cognition and behavior have steadily increased over the last two decades, stimulating considerable interest in its psychiatric application. Basic and clinical research in humans primarily employs intranasal application protocols. This approach assumes that intranasal administration increases oxytocin levels in the central nervous system via a direct nose-to-brain route, which in turn acts upon centrally-located oxytocin receptors to exert its behavioral effects. However, debates have emerged on whether intranasally administered oxytocin enters the brain via the nose-to-brain route and whether this route leads to functionally relevant increases in central oxytocin levels. In this review we outline recent advances from human and animal research that provide converging evidence for functionally relevant effects of the intranasal oxytocin administration route, suggesting that direct nose-to-brain delivery underlies the behavioral effects of oxytocin on social cognition and behavior. Moreover, advances in previously debated methodological issues, such as pre-registration, reproducibility, statistical power, interpretation of non-significant results, dosage, and sex differences are discussed and integrated with suggestions for the next steps in translating intranasal oxytocin into psychiatric applications.

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Section: Future Directions For Clinical Research Using Intranasal Oxymentioning

confidence: 99%

Advances in the field of intranasal oxytocin research: lessons learned and future directions for clinical research

et al. 2020

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“…Second, there has been intense debate about the optimal scheme of administration when treatment with intranasal oxytocin involves repeated applications (Horta, Kaylor, Feifel & Ebner, 2020). Given the high propensity of the OT receptor to desensitization (Robinson, Schumann, Zhang & Young, 2003), long-term exposure to high concentrations of OT might down-regulate the OT signalling machinery and thus attenuate the effect of OT on brain function.…”

Section: Discussionmentioning

confidence: 99%

Heterogeneity in response to repeated intranasal oxytocin in schizophrenia and autism spectrum disorders: A meta‐analysis of variance

Martins

Paduraru

Paloyelis

2021

British J Pharmacology

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Intranasal oxytocin (OT) has been suggested as a putative adjunctive treatment for patients with schizophrenia and autism spectrum disorders (ASD). Here, we examine available evidence from trials investigating the effects of repeated administrations of intranasal OT on the core symptoms of patients with schizophrenia and ASD, focusing on its therapeutic efficacy and heterogeneity of response (meta-analysis of variance). The repeated administration of intranasal OT does not improve most of the core symptoms of schizophrenia and ASD, beyond a small tentative effect on schizophrenia general symptoms. However, we found significant moderator effects for dose in schizophrenia total psychopathology and positive symptoms, and percentage of included men and duration of treatment in schizophrenia general symptoms. We found evidence of heterogeneity (increased variance) in the response of schizophrenia negative symptoms to intranasal OT compared to placebo, which supports the idea that subgroups of responsive and non-responsive patients might coexist. For other core symptoms of schizophrenia, or any of the core symptom dimensions in ASD, the response to repeated treatment with intranasal OT did not show evidence of heterogeneity.

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“…This research has several strengths in providing important information on the safety and tolerability of intranasal OT. First, safety and tolerability of intranasal OT were assessed over a longer period of administration and at a higher dose than in most previous studies (i.e., 4 weeks, 48 IUs daily), which is necessary for determining safe, therapeutically relevant applications of OT (Horta et al 2020a ). This study is also the largest examination ( N = 95) of safety and tolerability of repeated intranasal OT administration among older adults to date.…”

Section: Discussionmentioning

confidence: 99%

Safety and tolerability of chronic intranasal oxytocin in older men: results from a randomized controlled trial

et al. 2021

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Rationale Most studies evaluating the safety and tolerability of intranasal oxytocin (OT) have not reported consistent adverse events (AEs), but they have largely focused on young men and single-dose administration. Thus, it is unclear whether these findings translate to older individuals and with longer administration periods. Objective Extending previous work, this study investigated the safety and tolerability of chronic intranasal OT in generally healthy older men. Methods Data were from a randomized, placebo (P)-controlled, double-blind clinical trial evaluating the effects of 4 weeks of self-administered intranasal OT (24 IU twice daily) in older adults with no major physical or cognitive impairments. Heart rate, blood pressure, urine osmolality, and serum metabolic biomarkers were obtained before and at the end of the intervention. AEs were collected during the first 3 weeks and 1 week after cessation of treatment. Results Of 103 participants recruited, 95 were randomized and received the intervention (OT = 49, P = 46). OT had no significant impact on cardiovascular, urine, or serum measures. The AEs reported for both treatments were generally mild and few in number, though one participant assigned to OT and two assigned to P dropped out due to AEs. Relative to P, OT did not significantly increase the likelihood of reporting AEs, nor the number or severity of AEs reported. Conclusion Chronic intranasal OT appears safe and well-tolerated in generally healthy older men. These findings provide support for continued human research on potential benefits of chronic OT in older adult populations. Supplementary Information The online version contains supplementary material available at 10.1007/s00213-021-05862-3.

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Chronic oxytocin administration as a tool for investigation and treatment: A cross-disciplinary systematic review

Cited by 47 publications

References 186 publications

Advances in the field of intranasal oxytocin research: lessons learned and future directions for clinical research

Advances in the field of intranasal oxytocin research: lessons learned and future directions for clinical research

Heterogeneity in response to repeated intranasal oxytocin in schizophrenia and autism spectrum disorders: A meta‐analysis of variance

Safety and tolerability of chronic intranasal oxytocin in older men: results from a randomized controlled trial

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