Table 4.

Clinical pharmacological neuropeptide administration studies.

Article title	First author & publication year	Sample characteristics	Study design	Manipulation & outcome measures	Relevant findings
“Oxytocin may be useful to increase trust in others and decrease disruptive behaviours in patients with Prader-Willi syndrome: a randomised placebo-controlled trial in 24 patients”	Tauber et al. (2011)	Human adult study Age range: 18–44 y Median age: 28.5 y PWS: n = 24 Females: 16 Males: 8	Double-blind, randomized, placebo-controlled	Manipulation: single intranasal dose of 24 IU OXT or placebo Outcomes: -Study specific behavioral measures -Sally-Anne Test -Reading the Mind in the Eyes Test	-Significant improvements were found in the two days following single intranasal dose of OXT on 3 items in the caregiver reported behavior grid: increase in trust, decrease in sadness tendencies, and a decrease in disruptive behaviors compared to placebo group -No improvement was found on validated social skills measures -Intranasal OXT was well tolerated without any adverse events
“A double-blind randomized controlled trial of oxytocin nasal spray in Prader Willi syndrome”	Einfeld et al. (2014)	Human adolescent and adult study Age range: 12–30 y Mean age: 17.8 y PWS: n = 30 Females: 10 Males: 20	Double-blind, randomized, placebo-controlled, cross-over	Manipulation: twice daily intranasal OXT or placebo (a washout period of 2 weeks before cross over to the alternative treatment) administration in the following doses for 8 weeks: -The first 11 PWS participants: 24 IU OXT (16 years and over) and 18 IU OXT (13–15 years) -Remaining 18 PWS participants: 40 IU OXT (16 years and over) and 32 IU OXT (13–15 years) Outcomes: -3 items on the Developmental Behavior Checklist (hyperphagia/pica, temper outbursts and weight)	-No significant improvement was found for any outcome measures or treatment groups -Significant increase in temper outbursts was found in the OXT group compared to the placebo group -The increase in temper outbursts was more significant in the high dose of OXT group than the overall group, but was not significant in the lower dose of OXT group -No side effects were reported
“Dyssynchrony and perinatal psychopathology impact of child disease on parents-child interactions, the paradigm of Prader Willi syndrom”	Viaux-Savelon et al. (2016) (Note: same study/population as Tauber et al., 2017 below)	Human infant study Age range: 0.8–5.7 m Mean age: 3.9 m PWS: n = 18 Females: 8 Males: 10	Unblinded dose escalation with 3 steps over 7 days	Manipulation: intranasal dose of 4 IU OXT every other day, daily, or twice daily for one week Outcomes: -Alarm Distress Baby Scale -Coding Interactive Behavior Scale	-Significant improvements on 4 out of the 8 Alarm Distress Baby Scale items: increase in eye contact, facial expression, general level of activity, and relationships were found after intranasal OXT treatment compared to baseline - Significant improvements on 4 out of 7 Coding Interactive Behavior Scale composites: increase in parental sensitivity, dyadic reciprocity, child social engagement and child state were found after intranasal OXT treatment compared to baseline -No adverse events were reported
“Promising effects of oxytocin on social and food-related behavior in young children with Prader-Willi syndrome: a randomized, double-blind, controlled crossover trial”	Kuppens et al. (2016)	Human child study Age range: 6–14 y Mean age: 9.3 y PWS: n = 25 Females: 11 Males: 14	Double-blind, randomized, placebo-controlled, cross-over	Manipulation: twice daily intranasal dose of 24–48 IU OXT or placebo for 4 weeks followed by no washout period to cross over to the alternative treatment for further 4 weeks Outcomes: -Food intake -Hyperphagia Questionnaire -Oxytocin Study Questionnaire (focused on changes in emotions, social, and eating behavior, as well as possible side effects)	-When all participants were included in the analysis, no significant effect of OXT was found on any outcome measures -When participants were divided into groups based on age (older vs. younger than 11 years), the younger participants showed significant improvements in social behavior, food-related behavior, anger, sadness, and conflicts during OXT treatment compared to placebo -Lower serum oxytocin levels after OXT treatment were associated with positive effects on social behavior in the younger children. This effect was not found in the older children. (Note: blood samples were not extracted). -No side effects or adverse events were reported
“Oxytocin treatment in children with Prader-Willi syndrome: A double-blind, placebo-controlled, crossover study”	Miller et al. (2017)	Human child study Age range: 5–11 y Mean age: 8.2 y PWS: n = 24 Females: 15 Males: 9	Double-blind, randomized, placebo-controlled, cross-over	Manipulation: daily intranasal dose of 16 IU OXT or placebo for 5 days followed by a minimum of 4-week washout period to cross over to the alternative treatment for further 5 days Outcomes: -Aberrant Behavior Checklist -Social Responsiveness Scale -Repetitive Behavior Scale-Revised -Hyperphagia Questionnaire -Clinical Global Impression Scale	- No significant improvements in any of the measures but trend towards significance was reported in all of the measures following intranasal OXT treatment -Intranasal OXT treatment was shown to be safe and well tolerated with a few adverse events (i.e., nasal irritation and irritability)
“The use of oxytocin to improve feeding and social skills in infants with Prader–Willi syndrome”	Tauber et al. (2017) (Note: same study/population as Viaux-Savelon et al., 2016 above)	Human infant study Age range: 0.8–5.7 m Mean age: 3.9 m PWS: n = 18 Females: 8 Males: 10	Unblinded dose escalation with 3 steps over 7 days	Manipulation: intranasal dose of 4 IU OXT every other day, daily, or twice daily for one week Outcomes: -Neonatal Oral-Motor Assessment -Clinical Global Impression -Alarm Distress Baby Scale - Coding Interactive Behavior Scale	-Significant improvements in sucking, swallowing, Clinical Global Impression scores, social withdrawal behavior and mother-infant interactions were reported following intranasal OXT treatment compared to baseline - Intranasal OXT was well tolerated without any adverse events
“Intranasal carbetocin reduces hyperphagia in individuals with Prader-Willi syndrome”	Dykens et al. (2018)	Human adolescent study Age range: 10–18 y Mean age: 13.7 y PWS: n = 37 Females: 23 Males: 14	Double-blind, randomized, placebo-controlled parallel trial between Subjects	Manipulation: thrice daily intranasal dose of 9.6 mg carbetocin or placebo for two weeks Outcomes: -Hyperphagia in PWS Questionnaire-Responsiveness -Children’s Yale-Brown Obsessive- Compulsive Scale -Clinical Global Impression-Improvement Scale -Reiss Profile food domain	-Significant improvements in hyperphagic symptoms, food-related behaviors and emotions, compulsivity, and overall functioning were found following intranasal carbetocin treatment compared to placebo -Intranasal carbetocin was well tolerated
“Oxytocin in young children with Prader-Willi syndrome: Results of a randomized, double-blind, placebo-controlled, crossover trial investigating 3 months of oxytocin”	Damen et al. (2021)	Human child study Age range: 3–11 y Mean age: 7.5 y PWS: n = 26 Females: 13 Males: 13	Double-blind, randomized, placebo-controlled, cross-over	Manipulation: twice daily intranasal dose of 16–40 IU OXT or placebo for 3 months followed by a 1-month washout period to cross over to the alternative treatment for further 3 months Outcomes: -Oxytocin Study Questionnaire (focused on changes in emotions, social, and eating behavior, as well as possible side effects) -Hyperphagia Questionnaire -Repetitive Behavior Scale-Revised -Social Responsiveness Scale	-No significant improvement in hyperphagia or social behavior was found following OXT treatment in the total group -Oxytocin Study Questionnaire scores improved significantly only in boys but not in girls following OXT treatment compared to placebo -Significant improvements in hyperphagia and social behavior were found in children with PWS who had paternal deletion on chromosome 15 -Intranasal OXT was well tolerated without significant side effects
“Intranasal oxytocin versus placebo for hyperphagia and repetitive behaviors in children with Prader-Willi Syndrome: A randomized controlled pilot trial”	Hollander et al. (2021)	Human child and adolescent study Age range: 5–18 y Mean age: 8.87 y PWS: n = 23 Females: n = 5 Males: n = 18	Double-blind, randomized, placebo-controlled parallel trial	Manipulation: daily intranasal dose of 16 IU OXT or placebo for 8 weeks Outcomes: -Hyperphagia Questionnaire -Repetitive Behavior Scale-Revised -World Health Organization Quality of Life Scale-BREF -Caregiver Strain Questionnaire	-No significant improvement in hyperphagia or repetitive behaviors was found following OXT treatment but there were significant reductions in these domains in the placebo group -Intranasal OXT was well tolerated with only one adverse event (i.e., nocturia)

IU, international units; OXT, oxytocin; PWS, Prader-Willi syndrome