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PRADA Trial

PRADA (Prescribing the Right Antidepressant for Depression in Adults) is a randomised controlled trial recruiting participants with depression globally, exploring whether including genetic information when choosing antidepressant treatment helps people stay on their medication for longer and feel better, compared with an approach that does not use genetic data.

Aim

PRADA (Prescribing the Right Antidepressant for Depression in Adults) is a randomised controlled trial recruiting participants with depression globally, which aims to find out whether including genetic information when choosing antidepressant treatment helps people stay on their medication for longer and feel better, compared with an approach that does not use genetic data.  

The study uses a web-based clinical decision-support app to elicit patient preferences and integrated them into the shared decision-making process.  

 

Why is this important? 

This research comes after the PETRUSHKA trial (published in JAMA, March 2026), which showed that personalising anti-depressant treatment using clinical and demographic predictors, led to fewer patients stopping their medication. However, our new study PRADA goes one step further and will help us assess whether including genetic information will increase the rate of patients staying on their “personalised” medication.  

Understanding this could help improve how antidepressants are prescribed in the future and benefit the many people who are treated with these medications. 

 

Methods 

This is an international trial taking place in the UK, Pakistan, and Ethiopia, aiming to recruit just over 2,100 adults with depression who are willing to start an antidepressant treatment.  

The trial will use two different clinical decision-support tools to tailor antidepressant treatment and participants will be randomised to one of two groups in the trial: 

  • The PETRUSHKA tool arm, in which the decision support system uses clinical and demographic information, along with participant preferences about adverse events 

  • The PRADA tool arm, in which the decision support system also includes genetic information, on top of the clinical and demographic data and patient’s preferences 

The two tools look identical, so neither participants, nor clinicians will know which approach is being used, meaning the trial is fully “double-blind”. 

Participants will complete questionnaires about mood, quality of life, and their personal preferences, which include side-effects they wish to avoid and symptoms they wish to improve. They will then work with their doctor to use the web-based decision-support tool to select a recommended antidepressant as part of a shared decision-making process. They will have regular visits with their doctor (either online or in person) to review progress and side effects. The follow up will last 52 weeks, with the main outcome measured at 8 weeks. 

After 8 weeks, if they agree, participants will also undergo a second randomisation (with a factorial design) to receive genetic advice via a booklet and a genetic counsellor about depression.  

The PRADA study moves beyond a standard-of-care approach to selecting antidepressants, with all participants recruited in the trial receiving a personalised treatment recommendation. Primarily, PRADA is testing whether the inclusion of the genetic information improves this personalisation, and in turn, whether it improves treatment decisions and outcomes.  

Adults with depression who want to take antidepressant treatment will be recruited from healthcare settings in participating countries. Participants will take prescribed medication, attend clinical visits, complete questionnaires, and provide blood samples. Some UK participants may also choose to use a smartphone app to collect additional data, and to provide a stool sample for additional studies. 

 

How could this potentially benefit patients? 

PRADA aims to improve how antidepressant treatments are chosen for people with depression. At present, many patients need to try several medications before finding one that is effective and well tolerated. This trial-and-error process can take time and may lead to side effects, frustration, and early stopping (discontinuation) of treatment. 

We have already shown that we can improve on this standard-of-care approach by using the PETRUSHKA tool. PRADA aims to further improve upon PETRUSHKA by incorporating genetic information to further refine recommendations. 

If successful, this may help patients start more suitable treatments earlier, take effective medication for longer, reduce unnecessary changes of antidepressants, and improve response to treatment and quality of life. 

As PRADA is being conducted across the UK, Pakistan, and Ethiopia, the findings could also help inform treatment approaches internationally, including in low- and middle-income countries. 

The results from this study will contribute to clinical guidelines and decision-support tools used in routine mental health services, helping make personalised prescribing approaches more widely available and equitable.  

 

Next steps 

Recruitment of participants is expected to start in the UK towards Autumn 2026, with recruitment in Ethiopia, and Pakistan beginning in early 2027. The study team will collect clinical, questionnaire, and biological data from participants over the course of the trial. 

Once the study is completed, the findings will be shared through scientific publications, conferences, and engagement with patients, clinicians, and healthcare organisations. 

If the approach is shown to be effective, PRADA could support the future development of more personalised prescribing strategies and help inform clinical practice and mental health policy internationally.