Dr Andrea-Reinecke with patient in office

Improving CBT and Developing a Blood Pressure Drug to Treat Anxiety

Principal investigator: Dr Andrea Reinecke

Location: UK

Funding Period: 2015-2021

The project

Andrea and her team have already had major impact on the treatment of panic disorder (a form of anxiety) by developing a single-session Cognitive Behavioural Therapy (CBT) treatment that relieved symptoms for a third of patients. A course of CBT typically takes months.

This project was designed to explore the effects of the blood pressure medication losartan on cognitive and emotional processes relevant to anxiety and depression.

The process

There are two parts to this project, both of which build on previous clinical and lab research.

The first involves refining the single-session CBT treatments, to understand more about why CBT can reduce anxiety and to ensure the rapid treatment is as effective as possible.

And the second is the first major study of whether a blood pressure drug could also be used safely and successfully to treat anxiety.

The studies used both experimental paradigms in healthy volunteers and clinical interventions in patients, with rigorous publication and dissemination of results. The project faced challenges in budget management due to two maternity leaves, COVID-19 lockdown disruptions, and increased costs associated with clinical trials of investigational medicinal products (CTIMPs).

The outcome

Key Findings:

- Trait anxiety influences aversive reversal learning;
- A single dose of losartan reduces stress responses to traumatic stimuli and improves contextual processing, suggesting a reduced risk for PTSD development;
- Losartan improves learning from rewards, rapid recognition of positive facial expressions, and parahippocampal processing of visual stimuli, all consistent with potential antidepressant and anti-anxiety effects;
- The clinical trial is analysing whether losartan combined with cognitive-behaviour therapy improves outcomes for panic disorder patients

Papers:

The project has resulted in publications in top-tier journals (including Nature Communications, Biological Psychiatry, and Neuropsychopharmacology), with at least five more expected. The award has generated approximately £465,000 in follow-up grant income and secured an open-ended contract for the PI with their department.

Reinecke A, Thilo KV, Croft A, Harmer CJ. Early effects of exposure-based cognitive behaviour therapy on the neural correlates of anxiety. Transl Psychiatry. 2018 Oct
Pulcu E, Shkreli L, Holst CG, Woud ML, Craske MG, Browning M, Reinecke A. The Effects of the Angiotensin II Receptor Antagonist Losartan on Appetitive Versus Aversive Learning: A Randomized Controlled Trial. Biol Psychiatry. 2019
Shkreli L, Woud ML, Ramsbottom R, Rupietta AE, Waldhauser GT, Kumsta R, Reinecke A. Angiotensin involvement in trauma processing-exploring candidate neurocognitive mechanisms of preventing post-traumatic stress symptoms. Neuropsychopharmacology. 2020
Finnegan SL, Browning M, Duff E, et al Brain activity measured by functional brain imaging predicts breathlessness improvement during pulmonary rehabilitation Thorax 2023

The impact

The findings have significant implications for improving treatments for anxiety disorders and personalising treatment.

The research highlights the role of angiotensin-II receptors in antidepressant action, informing future grant applications and research directions;

Andrea has been awarded a four-year Oxford Science of the Mind fellowship to extend this research into adolescence, a critical period for the onset of anxiety disorders;

The team is preparing further submissions to major funding schemes (MRC Experimental Medicine and NIHR EME);

The project has contributed to scientific knowledge, clinical practice, and future research funding, despite operational challenges.

However the impact of this project can be best summarised by a quote from one of the study participants:

“I Just wanted to send you an email to say that life is still absolutely fantastic for me after the study. My husband and I have just come back off of holiday, we ventured to Mauritius which is a 12 hour flight and I sailed through it!! Every time I achieve something like this it always makes me think of you and the amazing change you have made to my life. Sometimes when I get a bit tired I have a couple of times began to feel a tiny bit panicky if I am doing something, but this is literally less than a handful of times and I have been able to control it.  

Seriously, I can’t thank you and your team enough.“ 

Dr Andrea Reinecke

Dr Andrea Reinecke is a Senior Research Fellow and Research Clinical Psychologist at the University of Oxford. She specialises in identifying the cognitive and neural mechanisms involved in emotional disorders.