A phase II randomised controlled trial of intranasal oxytocin in anorexia nervosa.

BACKGROUND: Anorexia nervosa (AN) is an eating disorder (ED) with high mortality rates and limited response to existing treatments, prompting the need to identify effective agents and adjuncts. There is evidence for an emerging role for the neuropeptide oxytocin (OT) in the pathophysiology of AN, with studies showing a perturbed oxytocinergic system in patients with AN. Preliminary evidence has demonstrated that intranasal OT (IN-OT) can produce anxiolytic effects in AN, as well as reducing concern about eating, and dysfunctional attentional biases related to the disorder. IN-OT is a non-invasive treatment option for AN that requires investigation as an adjunct to nutritional rehabilitation. METHODS: This multi-site study (Trial Registration:ACTRN1261000897460) sought to replicate and extend a previous randomised placebo-controlled pilot trial of repeated dose IN-OT in patients with AN hospitalised for nutritional rehabilitation. Patients with AN (N=61) received daily IN-OT (18 IU twice per day) or placebo for four weeks, whilst undergoing inpatient hospital treatment. Outcome measures included ED psychopathology (primary) as measured by the Eating Disorder Examination (EDE) and Body Mass Index (BMI; secondary). Participants were assessed pre- and post-treatment, and at six months following the intervention. The effects of the first and last doses of IN-OT on responses (anxiety ratings and salivary cortisol) to a high-energy snack were also examined. RESULTS: Sixty-one female inpatients (Mage=24.36,SD=7.87) with an average BMI of 16.24 (range: 11.43-18.55), were recruited into the study. No significant differences were found between placebo and OT groups at any of the time points on the outcomes of interest, but significant improvements in almost all psychological parameters in both groups were evident over time. IN-OT did not significantly reduce anxiety nor salivary cortisol in response to a high-calorie snack. CONCLUSION: This is the largest randomised placebo-controlled trial of repeated dose intranasal OT in people with AN, during refeeding. The therapeutically promising findings of the pilot study were not replicated. Limitations and reasons for the non-replication included relatively large variance, baseline psychopathology scores being higher in this patient group, potential ceiling effects in BMI and ED psychopathology as well as differing comorbidities.

Intolerance of uncertainty and eating disorder behaviour: Piloting a consumption task in a non-clinical sample.

BACKGROUND AND OBJECTIVES: Intolerance of uncertainty (IU) is a transdiagnostic process contributing to the maintenance of anxiety disorders, and is a potential target for treatment. Recent literature has investigated IU as a cognitive process underpinning pathological fear and anxiety in Anorexia Nervosa (AN). The current study was designed to examine trait and state IU, and their relationship to restrictive eating disorder symptoms, anxiety, worry, cognitive rigidity and eating behaviour. METHODS: A sample of undergraduate women (N = 85) completed measures of eating disorder symptoms, IU, cognitive rigidity and worry. Participants were randomised to complete an eating task under one of two conditions: the "certain" condition received a high-calorie meal and nutritional information, while the "uncertain" condition received the meal alone. During the meal, state IU and state anxiety were examined at three time-points (baseline, pre-eating, post-eating). RESULTS: Trait IU was correlated with cognitive rigidity, worry, global eating disorder symptoms, and, in particular, dietary restraint. No differences emerged between conditions with respect to eating-related anxiety, or amount of food eaten. Controlling for condition and eating disorder symptoms, state IU predicted pre-eating anxiety. Beyond the contribution of condition, BMI and eating disorder symptoms, state IU predicted consumption, specifically greater dietary restriction. LIMITATIONS: The study employed a non-clinical sample. CONCLUSIONS: IU may be implicated in a rigid cognitive style, the anxiety response to energy-dense food, and restrictive eating behaviour. Should these findings be replicated in a clinical sample, then IU might emerge as an adjunctive treatment target for AN.

Intranasal oxytocin in the treatment of anorexia nervosa: Randomized controlled trial during re-feeding.

BACKGROUND: Nutritional rehabilitation in anorexia nervosa (AN) is impeded by fear of food, eating and change leading to treatment resistance. Oxytocin (OT) exerts prosocial effects and modulates trust, fear, anxiety and neuroplasticity. The current placebo-controlled RCT examined the effects of intranasal oxytocin (IN-OT) in AN. The aim was to ascertain whether repeated doses of IN-OT enhance treatment outcomes in AN. METHODS: AN patients self-administered 36 IU IN-OT or placebo daily for 4-6 weeks during hospital treatment. The outcome measures were change in the Eating Disorders Examination (EDE) scale, weight gain, cognitive rigidity, social anxiety, obsessive and autistic symptoms. The effects of the first and last doses of IN-OT were assessed relative to placebo before and after a high-energy afternoon snack, to determine potential dampening of cortisol and anxiety levels by OT. RESULTS: Weight gain was similar in both groups. The EDE eating concern subscale score was significantly lower after IN-OT treatment as was cognitive rigidity. There were no significant differences in social anxiety or any of the other outcomes at follow-up. After four weeks IN-OT, salivary cortisol levels were significantly lowered in anticipation of an afternoon snack compared to placebo. Morning plasma OT levels did not change after chronic IN-OT or with weight restoration. CONCLUSION: IN-OT might enhance nutritional rehabilitation in AN by reducing eating concern and cognitive rigidity. Lower salivary cortisol levels in response to IN-OT suggest diminished neuroendocrine stress responsiveness to food and eating. Such effects require replication with inclusion of more sensitive subjective measures.

Intolerance of Uncertainty in eating disorders: An update on the field.

Pathological fear and anxiety regarding food, eating, weight and body shape are at the core of eating disorder (ED) psychopathology. To manage anxiety, patients develop complicated repertoires of ritualistic and repetitive behaviours, which can lead to total functional impairment. Yet the cognitive processes underlying anxiety, fear, and anxiety-driven behaviours in EDs remain poorly understood. Intolerance of Uncertainty (IU) is defined as a tendency to react negatively on an emotional, cognitive, and behavioural level to uncertain situations and events. There is substantial evidence that IU is a transdiagnostic process that contributes to the maintenance of anxiety disorders; however, IU may also be relevant to the understanding and treatment of EDs. The current review summarises the growing literature examining IU in relation to ED symptoms, including restriction, bingeing, purging, ritualised behaviours, reassurance-seeking and body checking. Extending from the obsessive-compulsive disorder (OCD) and anxiety disorder literature, we propose that IU provides a novel theoretical and clinical framework from which to understand the anxiety, fixation with rules and rituals, and the cognitively rigid profile that is characteristic of ED presentations. We conclude with suggestions for future research, and discuss IU as a potential treatment target for core features of EDs and comorbid symptoms.