Mirtazapine is a treatment for depression in adults. Some studies have found a link between mirtazapine and increased risk of death compared to other antidepressants. However, other factors may make this link seem stronger than it is. For example, doctors may prescribe mirtazapine to terminally ill patients as it can increase appetite and promote sleep.
The aim of this study is to better understand the relationship between mirtazapine and risk of death. We will look at the risk of specific causes of death, including heart disease and cancer. We will also look at whether there is a link between mirtazapine and attempted suicide.
We will use data from the Clinical Practice Research Datalink (CPRD) for this study. The dataset will include anonymised electronic medical records from general practices and hospitals, as well as anonymised death records. We will compare a group of patients taking mirtazapine with groups of patients taking other antidepressants. The groups will be made up of adult patients with depression. We will compare the risk of death or attempted suicide between the groups. Risk factors such as age, sex, and other health conditions will be taken into account in the analyses.
The study will provide further information about whether there is a link between mirtazapine and risk of death or attempted suicide. This will include whether there is a link with particular causes of death. This will be important information for doctors and patients when considering suitable antidepressant treatment.
Previous studies have found an association between the antidepressant mirtazapine and increased risk of mortality. Further research is needed to confirm this association and to examine specific causes of death. The proposed study will compare mirtazapine to other antidepressants and investigate cause-specific mortality, controlling for relevant confounding.
We will perform a cohort study using the active-comparator new user design, selecting patients prescribed antidepressants between 1st January 2005 and 30th November 2018. Linked CPRD primary care data, Office for National Statistics (ONS) mortality data, and Hospital Episode Statistics (HES) admitted patient care data will be used.
The study population will comprise adult patients diagnosed with depression whose first antidepressant was a selective serotonin reuptake inhibitor (SSRI) and who were subsequently prescribed mirtazapine, venlafaxine, amitriptyline, or a different SSRI. Follow-up will start from the date of starting the new antidepressant.
There will be five exposure groups: those who switched to mirtazapine, those who started mirtazapine while continuing the original SSRI, and those who switched to venlafaxine, amitriptyline, or a different SSRI.
The outcomes will be all-cause and cause-specific mortality, and suicide/near-fatal deliberate self-harm. Cause-specific mortality will include cardiovascular disease, cancer, and the most common causes of death found within the study population. Date and cause of death will be taken from the ONS mortality dataset while near-fatal deliberate self-harm will be defined using a combination of primary care and HES data.
We will account for confounding factors including demographic characteristics, lifestyle factors, drug exposures, and comorbidities. These will be used to estimate propensity scores for each of the comparator drugs compared with mirtazapine.
Baseline characteristics and the most frequent causes of death will be summarised. Survival analysis using Cox and Fine-Gray (competing risk) regression will be performed, accounting for propensity scores.
All-cause mortality; cause-specific mortality (including cardiovascular disease and cancer); suicide or near-fatal deliberate self-harm
Carol Coupland - Chief Investigator - University of Nottingham
Ruth Jack - Corresponding Applicant - University of Nottingham
Chris Hollis - Collaborator - University of Nottingham
Julia Hippisley-Cox - Collaborator - University of Oxford
Richard Morriss - Collaborator - University of Nottingham
Roger Knaggs - Collaborator - University of Nottingham
Ruth Jack - Collaborator - University of Nottingham
HES Admitted Patient Care;ONS Death Registration Data;Patient Level Townsend Score