Prescribing the Right Agent for Depression in Adults (PRADA): a Double-blind, Randomised Controlled Trial Using a Web-based Multi-modal Clinical Decision Support System and Genetic Information to Personalise Antidepressant Treatment in Diverse Clinical Settings Across the Globe

NCT07796295 | Not Yet Recruiting DMC

• 2 other identifiers: 365942303135/Z/23/Z
• Study Type: interventional
• Target: 2,142
• Locations: 3 countries
• Sites: 3

Brief Summary

Depression is a common mental health problem affecting almost 300 million people worldwide. Antidepressants are recommended as one of the first line treatments for people with moderate-to-severe symptoms of depression. In our recent trial, PETRUSHKA, on the acute treatment of depression, we demonstrated that the PETRUSHKA Tool, an evidence-based shared decision support system to personalise antidepressant treatment, in comparison with usual care reduced by almost 40% the number of participants stopping their antidepressant early, also improving their depression and anxiety symptoms. To identify the best treatment for each individual, the PETRUSHKA Tool used clinical and demographic predictors. Pilot data show that genetic information can aid stratification of people experiencing depression and better target their treatment. Genetic data can be collected using low-cost DNA-sequencing technology in diverse clinical settings and low-resource environments. Hence, we hypothesised that individual-level pharmacogenomic information can further personalise antidepressant treatment. In this project called PRADA ("Prescribing the Right Agent for Depression in Adults"), we will develop and test in a global trial across Ethiopia, Pakistan and the UK, an evidence-based multimodal web-tool to help participants and clinicians choose the best pharmacological treatment for depression jointly, based on participant preferences and their individual clinical, demographic, cultural, and also genetic profile (PRADA Tool). We will compare the new tool with the PETRUSHKA Tool in a blind fashion, measuring adherence to antidepressant treatment, clinical response and quality of life over a 12-month follow-up.

Conditions

Major Depressive Disorder (MDD)

Keywords

Depression; Mental health

Outcome Measures

Primary Outcomes (1)

• All-cause treatment discontinuation

  To determine whether using the PRADA Tool to "personalise" antidepressant treatment, results in an increased proportion of participants continuing the allocated treatment, compared to the PETRUSHKA Tool.

  Baseline to week 8

Study Arms (2)

PRADA Tool

EXPERIMENTAL

A web-based clinical decision-support system for participants and clinicians to enable personalised antidepressant treatment decision-making, using clinical and demographic predictors, pharmacogenomic information and individual preferences about adverse events. At week 8, participants who consent to the optional Polygenic Score (PGS) sub-study will be randomised to receive either the Polygenic Score (PGS) material alone, or Polygenic Score (PGS) material with psychiatric genetic counselling (1:1, factorial)

Other: PRADA Tool

PETRUSHKA Tool

ACTIVE COMPARATOR

A web-based clinical decision-support system to enable personalised antidepressant treatment decision-making, using clinical and demographic predictors, and individual preferences about adverse events, but not pharmacogenomic information. At week 8, participants who consent to the optional Polygenic Score (PGS) sub-study will be randomised to receive either the Polygenic Score (PGS) material alone, or Polygenic Score (PGS) material with psychiatric genetic counselling (1:1, factorial)

Other: PETRUSHKA Tool

Interventions

PRADA Tool OTHER

The PRADA Tool will incorporate a personalised evidence-based prediction model based on participants' demographic and clinical characteristics, their individual preferences on adverse events and specific symptom clusters, and information about their pharmacogenetic profile. The tool will be delivered at the baseline visit. Once particpants have provided their preferences on adverse events and symptom clusters, the participant and clinician will then choose one antidepressant from a personalised list of ranked antidepressants.

PRADA Tool

PETRUSHKA Tool OTHER

The PETRUSHKA Tool use participants' demographic and clinical characteristics together with individual preferences on adverse events to personalise antidepressant treatment. To preserve the blinding, the PETRUSHKA Tool used in the PRADA Trial has been modified to collect pharmacogenetic data and preferences on symptom clusters, but this information will not be used at all to inform decisions in the PETRUSHKA Tool. The tool will be delivered at the baseline visit. Once particpant has provided their preferences on adverse events and symptom clusters, the participant and clinician will then choose one antidepressant from a personalised list of ranked antidepressants.

PETRUSHKA Tool

Eligibility Criteria

• Age: 18 Years - 74 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Aged 18-74 years inclusive;
• Willing and able to give informed consent for participation in the trial;
• Clinical primary diagnosis of major depressive episode, for which an antidepressant is clinically indicated;
• PHQ-9 score of at least 10;
• Willing and able to start antidepressant treatment as monotherapy;
• Able to understand and answer self-administered questionnaires in their local language.

You may not qualify if:

• Taken an antidepressant in the preceding 4 weeks at a therapeutic dose;
• Current or historical diagnosis (lifetime) of ADHD, bipolar disorder, dementia, mania/hypomania, psychosis/schizophrenia
• Current or historical diagnosis (within 10 years) of any eating disorders, PTSD, OCD or alcohol/substance use disorder
• Treatment Resistant Depression (i.e., having tried 2 or more antidepressants for the same depressive episode at adequate dose and time);
• Known diagnosis of arrhythmias (including Q-T prolongation, heart block), recent myocardial infarction (within 5 years), difficult-to-treat epilepsy, acute porphyrias;
• Requires urgent mental care or admission (including suicidal intent/plans);
• Concurrently enrolled in another investigational medicinal product (IMP) trial that, in the opinion of the investigator, is likely to interfere with the PRADA trial or an interventional trial about depression;
• Pregnant, planning pregnancy or lactating (self-reported);
• Unable to give blood sample for genetic analysis.

Sponsors & Collaborators

• University of Oxford: lead
• King's College London: collaborator
• Centre for Addiction and Mental Health: collaborator
• Addis Ababa University: collaborator
• University of Bristol: collaborator
• University of Bern: collaborator
• University of Manchester: collaborator
• Pakistan Institute of Living and Learning: collaborator
• MQ Mental Health Researh: collaborator

Study Sites (3)

Amanuel Mental Specialized Hospital

Addis Ababa, Ethiopia

Location

Pakistan Institute of Living and Learning (PILL)

Karachi, Pakistan

Location

NIHR Clinical Research Facility Oxford Health

Oxford, Oxfordshire, OX3 7JX, United Kingdom

Location

MeSH Terms

Conditions

Depressive Disorder, Major; Depression; Psychological Well-Being

Condition Hierarchy (Ancestors)

Depressive Disorder; Mood Disorders; Mental Disorders; Behavioral Symptoms; Behavior; Personal Satisfaction

Central Study Contacts

Andrea Cipriani

CONTACT

+441865613172; andrea.cipriani@psych.ox.ac.uk

PRADA Trial

CONTACT

+441865613172; prada.trial@psych.ox.ac.uk

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Double-blind, randomised controlled trial (including an optional factorial randomisation at Week 8 (unblinded))

Study Record Dates

• First Submitted: August 27, 2026
• First Posted: September 1, 2026
• Study Start: October 1, 2026
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): October 1, 2028
• Last Updated: September 1, 2026

Record last verified: 2026-08

Data Sharing

• IPD Sharing: Will not share

Locations

ET (1); PA (1); GB (1)