Decision tool improved antidepressant persistence and symptoms
A web-based decision-support tool reduced antidepressant stopping and modestly improved depression and anxiety symptoms.
*Randomized clinical trial; Level 1b (OCEBM).
Citation
Cipriani A, Fernandes KBP, Mulsant BH, et al; for the PETRUSHKA Team. A Decision-Support System to Personalize Antidepressant Treatment in Major Depressive Disorder: A Randomized Clinical Trial. JAMA. 2026;335(14):1219-1231. doi:10.1001/jama.2026.1327
Background
Many people stop antidepressants early, often because the first choice is a poor fit. This trial tested whether a shared, web-based tool that considers patient characteristics and side-effect preferences improves treatment continuation and symptoms.
Patients
Adults aged 18-74 years with major depressive disorder at 47 sites (Brazil, Canada, UK). Key exclusions: treatment-resistant depression, pregnancy, heart rhythm problems, urgent mental health care or hospitalization.
Intervention
PETRUSHKA decision-support tool used to select an antidepressant.
Control
Usual clinician-selected antidepressant.
Outcome
Primary: stopping the prescribed antidepressant for any reason at 8 weeks. Secondary: stopping due to adverse events; depression (Patient Health Questionnaire-9; 0-27) and anxiety (Generalized Anxiety Disorder-7; 0-21) at 24 weeks.
Follow-up Period
24 weeks (primary outcome at 8 weeks).
Results
Primary analysis included 493 participants (median age 35 years; 58% female). Analyses followed assigned groups; some 24-week outcomes had substantial missing data.
| Outcome |
PETRUSHKA |
Usual care |
Adjusted effect (95% CI) |
NNT |
| Stopped antidepressant by 8 weeks (primary) |
17% (41/241) |
27% (69/252) |
Relative risk 0.62 (0.44 to 0.88) |
10 |
| Stopped due to adverse events by 8 weeks |
9% (22/241) |
16% (39/252) |
Relative risk 0.59 (0.36 to 0.97) |
15 |
| Depression symptoms at 24 weeks |
Mean 7.1 |
Mean 9.2 |
1.92 points lower (0.78 to 3.06 lower) |
— |
| Anxiety symptoms at 24 weeks |
Mean 4.6 |
Mean 5.8 |
1.39 points lower (0.52 to 2.26 lower) |
— |
Limitations
Patients and clinicians were not blinded, which could influence stopping decisions and self-rated symptoms. Many 24-week outcomes were missing, and improvements in symptom scores were statistically significant but modest.
Funding
UK National Institute for Health and Care Research; University of Oxford sponsor.
Clinical Application
Consider PETRUSHKA-style shared decision tools to reduce early antidepressant stopping, especially in primary care; interpret symptom gains cautiously due to missing data and open-label design.