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

Abstract

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.

Neural Functions of Hypothalamic Oxytocin and its Regulation

“…Relative to placebo, OT does not significantly increase the likelihood of adverse events. Chronic IAO appears safe and well-tolerated in generally healthy older men ( Rung et al, 2021 ). These facts highlight the anti-aging effects and therapeutic potential of OT in aging-associated diseases.…”

Evaluating the neuropeptide–social cognition link in ageing: the mediating role of basic cognitive skills

“…This approach is in line with other human research [22,128] and was based on evidence of strong correlations ( r = 0.80) between peripheral and central OT in humans and non-human primates (using enzyme-linked immunoassays; [131]; see also [22,146] for meta-analyses). Measurement of central neuropeptide levels after OT administration in their relation to endogenous levels and associated effects on social cognition constitutes a promising future research avenue [5,79]. This work will also benefit from investigating neuropeptide receptors or gene expression of OT/AVP, associated with social behaviour and cognitive states [41,110,147,148].…”

“…There are currently no effective pharmacological treatments to address age-related social-cognitive decline. Intranasal OT constitutes a promising candidate based on its effects on enhancing emotion identification in young adults [37,38] and has recently been discussed as a potential therapeutic agent for social-cognitive deficits in older adults [23,79,123]. In particular, exogenous OT has been found specifically beneficial for individuals low in social-cognitive abilities [124,125].…”

“…General cognition was assessed via the Telephone Interview of Cognitive Status (TICS; [77]; cut-off, less than 30). Exclusion criteria included heavy drug or alcohol use, blood pressure greater than 180/100 mmHg, as well as urine osmolality greater than 1200 l with blood sodium levels less than 134 mEq l −1 , history of inappropriate antidiuretic hormone secretion, and/or use of antidiuretic medication as OT and AVP are involved in water retention ( [78]; see [79] for details regarding inclusion/exclusion).…”

“…The study protocol was approved by the Institutional Review Board of the University of Florida. After written informed consent, participants took part in the larger clinical trial, which included one screening visit, followed by three pre-intervention visits, a four-week intranasal spray (OT or placebo) administration, and three post-intervention visits (intervention data not considered here; see [79] for details and procedural diagram, and [80] for an additional publication from the larger project). Participants were reimbursed for study participation.…”