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Department of Psychiatry, University of Oxford
It is the first time ever a mental health clinical prediction tool has been demonstrated as effective.
The PETRUSHKA tool, developed by the University of Oxford and funded by the National Institute for Health and Care Research (NIHR), supports clinicians and patients to choose the antidepressant that is better tailored to each individual. It uses AI to combine clinical and demographic information with patient preferences, particularly around side effects, to support treatment personalisation and shared decision-making in routine care.
The tool was tested in a large international randomised clinical trial across Brazil, Canada and the UK involving more than 500 adults with major depressive disorder (MDD) and launched in 2024. The findings, published in the Journal of American Medical Association (JAMA), show that people whose antidepressant was selected using PETRUSHKA were significantly more likely to continue their treatment and experienced better mental health outcomes compared with usual care up to six months.
Choosing the right antidepressant remains a major challenge in everyday practice, with many people stopping treatment early because of side effects or a lack of perceived benefit. PETRUSHKA was designed to address this by using evidence from clinical trials and real‑world data alongside what matters most to patients, helping to identify the most suitable options from the outset.
In the trial, participants using PETRUSHKA were around 40 per cent less likely to discontinue their antidepressant within the first eight weeks of treatment. Fewer people stopped treatment because of adverse effects, and by 24 weeks those in the PETRUSHKA group also reported greater improvements in depressive and anxiety symptoms.
The tool was co-produced with people with lived experience of depression, it takes 3 minutes to be administered and is designed to be easy to use in everyday clinical settings, including primary care. Clinicians and patients use PETRUSHKA together during a consultation, either in person or remotely, ensuring that treatment decisions reflect both clinical evidence and individual priorities.
NIHR Research Professor Andrea Cipriani, Professor of Psychiatry at the University of Oxford, honorary consultant psychiatrist at Oxford Health NHS Foundation Trust and lead investigator of the study, said:
Mental health is lagging behind other fields of medicine and for too long, antidepressant treatment has relied on trial and error. PETRUSHKA shows that by combining the best available evidence with patients’ own preferences, we can personalise antidepressant treatment from the outset and help more people in the NHS stay on the medication that is right for them.”
The potential impact of PETRUSHKA is transformational. By improving treatment continuation and outcomes, the tool could help reduce the personal, clinical and economic burden of depression, particularly in settings where specialist psychiatric support is limited. It may be especially valuable in primary care and other non-specialist services, where most people with depression are treated and clinicians are pressed for time.
Mike Lewis, Scientific Director for Innovation at the National Institute for Health and Care Research (NIHR), said: “This study shows the real power of combining digital technology and personalised treatment.
"By harnessing data and embracing cutting-edge digital tools, we can tailor care more precisely to each patient — improving outcomes for individuals. Forward-thinking research such as this shows the impact of using innovative technologies to ensure patients across the UK receive smarter, more effective care.”
While further research is needed to explore long-term outcomes and cost-effectiveness, the findings provide strong evidence that digital, patient-centred decision-support tools can play an important role in advancing precision psychiatry and improving mental health care at scale.
Henry Winchester, 45, a freelance writer from Bristol, was a participant of the study. He said: “I was quite sceptical of antidepressants, I’d never really got on with them and had had severe side effects.
“PETRUSHKA found one that was much milder than what I had taken before. It’s been life changing in a way, having one tailored, and finding the right one for me. It could change the way antidepressants are prescribed and make it a lot easier for patients and better for GPs.”
PETRUSHKA stands for Personalising antidEpressant Treatment foR Unipolar depreSsion combining individual cHoices, risKs and big datA. The study was conducted across 47 sites in the UK, Brazil and Canada.
The research was also supported by the NIHR Oxford Health Biomedical Research Centre and the NIHR Applied Research Collaboration Oxford and Thames Valley.