Clinical trials in depression: Integrated collection across EU and US registries

Background
Depression affects millions worldwide with both pharmacological and psychological therapies offering limited treatment success. In collaboration with Medicines Discovery Catapult (MDC), we developed a comprehensive database of depression-related clinical trials, including information on the availability of additional biological samples, to identify trials suitable for pharmacogenetic studies.

Methods
We systematically extracted structured and unstructured data from ClinicalTrials.gov (using the Aggregated Analysis of ClinicalTrials.gov (AACT) database) and the EU Clinical Trials Register. Summary data from clinical trial records and publications were extracted on interventions, conditions, drugs, sample sizes, trial phase, status, dates, demographics, and sponsors. To identify trials likely to include blood samples or genetic information, we applied a semantic similarity approach using vector-based natural language processing. This method scored trial records based on textual indicators, prioritising those most likely to contain genetic information.

Results
We identified 8,853 unique clinical trials registered between 1987 and 2024, with the majority (86%) from the AACT database. In total, 3,659 (41%) trials involved a drug intervention, of which 1,160 were testing antidepressants. Selective serotonin reuptake inhibitors (SSRIs) were the most commonly tested drug class (n=899), with escitalopram the most frequently studied drug (n=322). Other interventions included behavioural interventions and digital devices. SSRI trials peaked around 2009, while NMDA receptor antagonist trials (e.g., ketamine) increased post-2015. Sponsors included universities, healthcare organisations, and pharmaceutical companies. Vector scores prioritised trials likely to have biological samples or genetic data, and initial validation confirmed the accuracy of these indicators. Participant demographic data and final sample size were incomplete for many trials.

Conclusion
This comprehensive resource summarises the landscape of clinical trials in depression performed since 1987, enabling researchers to identify clinical trials with genetic samples to expand pharmacogenetic studies.