Liam Davenport

September 06, 2017

PARIS ― Administering a commonly available hormone via a nasal spray could help prevent the development of posttraumatic stress disorder (PTSD) and reduce symptoms in those who already have the condition, results of several clinical studies suggest.

Intranasal oxytocin significantly reduced the likelihood of the development of PTSD among patients in an emergency department (ED) who had a high degree of baseline trauma symptoms, said Miranda Olff, PhD, Department of Psychiatry, Academic Medical Center, University of Amsterdam, the Netherlands.

The findings were presented here at the 30th European College of Neuropsychopharmacology (ECNP) Congress.

Promising Candidate?

The hormone also improved neural emotion regulation processing and reduced neural fear processing in a group of police officers who had already developed PTSD. However, the studies also suggested that, if not given in sufficient doses, the hormone could increase fear after a trauma.

Oxytocin "may seem a promising candidate, in addition to the currently available PTSD treatments, to enhance emotion regulation, to dampen fear, but also to enhance social support and motivation for psychotherapy," said Dr Olff.

"Of course, we need a lot more research before we can do anything in the clinical setting," she added.

Although a number of psychotherapies are used as first-line treatments for patients with PTSD, one third respond poorly, said Dr Olff.

Previous imaging research has shown that PTSD is associated with hyperactivity in the amygdala, hypoactivity in the ventromedial prefrontal cortex (vmPFC), and reduced connectivity between these two brain regions. Also, in patients with PTSD, control over the fear response by the PFC is reduced, leading to excessive fear.

There has been interest in the use of oxytocin administered via nasal spray in the treatment of PTSD because its release is associated with positive social interactions and a reduction in stress.

Moreover, the hormone has been shown to reduce amygdala hyperactivity and to increase amygdala-PFC connectivity, reward processing, and social functioning.

To examine whether early administration of intranasal oxytocin could prevent the development of PTSD following a trauma and whether oxytocin could reduce the symptoms of PTSD once it has developed, the investigators conducted a series of studies.

In the first, they screened patients 8 days after being brought to the ED following a trauma, performed fMRI on day 12, and randomly assigned the study participants to receive either a single dose of intranasal oxytocin (n = 23) or placebo (n = 18).

Contrary to expectation, the investigators found that oxytocin was associated with increased amygdala reactivity, reduced amygdala-PFC communication, increased amygdala-insula communication, reduced sleepiness, and an increase in flashbacks to the trauma.

High CAPS Baseline Score, Higher Effect

In another study that was published last year, patients who had undergone a trauma were randomly assigned to receive intranasal oxytocin 40 IU twice daily (n = 53) or placebo (n = 54) for 8 days within 12 days of admission to the ED.

The participants completed the Clinician-Administered PTSD Scale (CAPS) at baseline (10 days postadmission) and at 1.5, 3, and 6 months posttrauma.

There were no overall significant differences in CAPS total scores between the oxytocin and placebo groups either at 1.5 months or across the follow-up period, with both groups showing similarly significant reductions in scores.

However, the researchers observed that among patients with high CAPS total scores at baseline (defined as a score of ≥45), those given oxytocin had significantly lower CAPS scores at all time points during follow-up compared with those given placebo (P = .017).

Moreover, for patients with high CAPS baseline scores who were given oxytocin, there were had significant reductions in CAPS scores (P = .006), whereas the reduction in score in the placebo group was nonsignificant (P = .367).

No treatment differences were seen in trauma patients with low baseline CAPS scores.

A third study, also published previously, involved 80 police officers; 40 (including 21 men) had been diagnosed with PTSD and 40 (including 20 men) had been exposed to trauma but had not developed PTSD. A control group was matched to the patients with PTSD with respect to age, sex, years of service, and educational level.

In a crossover design, the police officers, during fMRI, were administered either intranasal oxytocin or placebo before performing a task to assess amygdala reactivity toward emotional faces. The task was then repeated an average of 11.5 days later after administration of the other intervention.

Results showed that in the PTSD-only group, oxytocin was associated with reductions in amygdala reactivity to emotional faces and reductions in anxiety and nervousness.

There were also differential effects of oxytocin in PTSD patients by sex.

Men demonstrated increased connectivity between the right ventromedial nucleus in the amygdala and the vmPFC. In contrast, women showed decreased connectivity between the basolateral nucleus in the amygdala and the dorsal anterior cingulate cortex.

"Promising Effects"

Discussing the potential role for oxytocin for PTSD, Dr Olff said that it could be used to boost the effect of psychotherapies, "maybe giving it right before each session."

Although it is not the "miracle drug" that some would claim it to be, "there are some indications of some promising effects," she said.

In terms of future research, Dr Olff noted that the results indicating that oxytocin is most effective in preventing PTSD in those with high baseline symptoms need to be investigated carefully. "What would be the optimal dosing regimen? We don't really know yet," she added.

"I think oxytocin might be promising as a prevention for a high-risk group and for medication-enhanced psychotherapy. We also need to look at single vs multiple dosing, because there might be something going on there too, as well as at interindividual contextual differences."

Dr Olff told Medscape Medical News that she and her colleagues are planning to conduct a clinical trial with oxytocin.

They had initially attempted the study in a refugee population but found that the group was too traumatized for this kind of approach. "We had to stop that study, and now we're applying to do it in a less severely traumatized population," said Dr Olff.


Session co-chair Inga D. Neumann, PhD, Department of Behavioral and Molecular Neurobiology, University of Regensburg, Germany, told Medscape Medical News that if intranasal oxytocin is to be useful for something, "then it is for sure in trauma patients.

"But I strongly believe it is strongly dependent on the context," she said. "I think it is more efficient in social trauma than in nonsocial trauma, for example. That is also based on animal research, where we know oxytocin may have even opposite effects in the nonsocial context, and that needs to be considered."

Dr Neumann emphasized that, aside from the questions raised in the presentation, "there are many, many issues which are still open, [and] there is so much homework to do," such as reconciling the observation that increases in plasma oxytocin levels are seen only after the effects are observed in the brain.

She also believes that clinicians should be very careful about suggesting that it should be used in patients, especially over the long term, "because we have molecular data showing that long-term treatment with oxytocin alters oxytocin receptor signaling in the brain.

"So there's a lot of things to do still before we can really use it as a safe treatment option, for example, in PTSD patients, or especially in children," said Dr Neumann.

The research was funded by the Netherlands Research Organization for Health Research and Development and by the AMC Research Council. The investigators and Dr Neumann have disclosed no relevant financial relationships.

30th European College of Neuropsychopharmacology (ECNP) Congress. Abstract S.03.02, presented September 2, 2017.

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