This study is about a severe mental illness called Major Depressive Disorder characterized by persistent low mood, low self-esteem, loss of interest or pleasure in normally enjoyable activities, and, in severe cases, suicidal thoughts. This illness affects around 2% of the European population and is growing fast. The management of this disease is complex and involves several types of interventions including pharmacological treatments. Despite therapeutic advancements, between 10% and 30% of patients show limited or no response to available medications, highlighting the need for novel therapeutic approaches.
Clinical trials play a crucial role in evaluating treatments, but more understanding is needed about events occurring in real life after the trials end. This study aims to fulfil this gap by providing valuable insights into primary care treatment initiation, switching, and discontinuation among patients newly diagnosed with this disease.
The European Medicines Agency has commissioned the Data Analysis and Real-World Interrogation Network (DARWIN) European Union (EU) centre to understand how this disease is treated in clinical practice in Europe. We will contribute to this network via federated analyses to give answers for affected patients.
We will use data between 01/01/2013 and 31/12/2022 from Clinical Practice Research Datalink (CPRD) GOLD database to understand better affected patients in the UK, the prescription patterns used in clinical practice, and their effectiveness, together with risks and benefits.
This study has the potential to offer policy makers an informed baseline for the development of better guidelines focussed on improving everyday patient care and outcomes for this disease.
BACKGROUND: Primary care records provide a unique source of data for estimating drug utilisation in the community. The DARWIN EU© initiative created by the European Medicines Agency (EMA) intends to draw upon such data to inform regulatory decision-making, and has requested a drug utilisation study on antidepressants and psycholeptics to study rates of occurrence of treatment-related intercurrent events in patients with major depressive disorder (MDD).
RATIONALE: In clinical trials involving patients with MDD, participants who start treatment may experience intercurrent events (IEs) during follow-up (e.g. treatment discontinuation, switch to alternative therapies, or changes in background/concomitant therapies). However it is still unclear if the rate of occurrence of these IEs in real-life settings is comparable to what is observed in the clinical trials: the results of this study aim to provide valuable information regarding the generalisability of clinical trial findings to real-world scenarios.
STUDY DESIGN: Cohort study
POPULATION: All people in CPRD GOLD between 2013 and 2022 with at least 365 days of data availability before the day they become eligible for study inclusion.
CONDITION OF INTEREST: Major depressive disorder (MDD).
DRUGS OF INTEREST: antidepressants (NSRIs, SSRIs, or other anti-depressants) and psycholeptics (antipsychotics, anxiolytics, hypnotics, and sedatives)
VARIABLES: Exposure to antidepressants and psycholeptics in a cohort of patients with a MDD diagnosis will be based on diagnoses and prescription data in CPRD GOLD [medical and product codes mapped to the OMOP Common Data Model].
ANALYSES:
1) Patient level characterisation for people with newly diagnosed MDD and assessment of the use patterns of the respective drugs of interest.
2) Summary descriptive statistics (mean, median, quantiles 25% and 75%, minimum and maximum) considering duration of antidepressant use for the first exposure episode of the respective antidepressant class of interest
This study will examine the following primary outcomes of interest.
• Treatment Initiation
Initiation of treatments will be assessed within a window of 4, 6, 8, 12, and 24 weeks following diagnosis. In relation to the outcome, a predefined list of MDD treatments will be compiled to address Objectives 1 and 3. MDD treatments will include NSRIs, SSRIs, other antidepressants, and concomitant drugs of interest (Psycholeptics - N05A, N05B, and N05C) as listed in Table 7 of the attachment.
• Treatment Switching
Switching of treatments will be assessed within a window of 4, 6, 8, 12, and 24 weeks following treatment initiation. In relation to the outcome, a predefined list of MDD treatments will be compiled to address Objectives 1 and 3. MDD treatments will include NSRIs, SSRIs, other antidepressants, and concomitant drugs of interest (Psycholeptics - N05A, N05B, and N05C) as listed in Appendix1 of the attachment.
• Treatment Discontinuation
Discontinuation of treatments will be assessed within a window of 4, 6, 8, 12, and 24 weeks following treatment initiation. In relation to the outcome, a predefined list of MDD treatments will be compiled to address Objectives 1 and 3. MDD treatments will include NSRIs, SSRIs, other antidepressants, and concomitant drugs of interest (Psycholeptics - N05A, N05B, and N05C) as listed in Appendix1 of the attachment.
Antonella Delmestri - Chief Investigator - University of Oxford
Antonella Delmestri - Corresponding Applicant - University of Oxford
Daniel Prieto-Alhambra - Collaborator - University of Oxford
Hezekiah Omulo - Collaborator - University of Oxford
Martí Català Sabaté - Collaborator - University of Oxford
Wai Yi Man - Collaborator - University of Oxford