Asthma is one of the most common respiratory disorders in the UK. Leukotriene receptor antagonists (LTRAs) and inhaled corticosteroids (ICS) are two classes of medicines used to prevent the symptoms of asthma. Although they are widely used, there have been concerns about the mental health side effects of LTRAs and ICS.
Suicide attempt is one of the most serious side effects, however, the association between the use of each medication and suicide attempt remains unclear. This study, therefore, aims to explore whether the use of LTRAs or ICS is related to suicide attempt. This study will allow us to better understand the mental health side effects of LTRAs and ICS, and further help to inform the risk-benefit of the medicines and develop strategies to reduce the risk. If we find that the use of LTRAs or ICS increases the risk of suicide attempt, our study will further alert the healthcare professionals. If we find that the use of the medications is not related to the increased risk of suicide attempt, our study will provide reassurance regarding the safety of LTRAs and ICS to some extent.
Leukotriene receptor antagonists (LTRAs) are prescribed primarily as an adjunct therapy to inhaled corticosteroids (ICS) in patients with asthma in the UK. Although there have been concerns about the psychiatric side effects of LTRAs and ICS, the association between the use of each medication and suicide attempt, one of the most severe outcomes, remains unclear. This study, therefore, aims to evaluate the association between LTRA and ICS use and suicide attempt, using data from CPRD. The Hospital Episode Statistics (HES) data will be used for identifying hospital records of suicide attempt. The Office of National Statistics (ONS) data will be used to identify any suicidal death.
We will conduct a self-controlled case series study including individuals aged 10 years and over, who had received at least one prescription of ICS, one prescription of LTRA, and with at least one outcome event (suicide attempt) between 1 January 2005 to 31 December 2022. Individuals will serve as their own control, and thus time-invariant confounders will be controlled. The observation period will be divided into the following categories: 90 days before the first use of each drug exposure (LTRA and ICS), use of LTRA alone, use of ICS alone, combination use of LTRA and ICS, and non-treatment period. The incidence of suicide attempt during LTRA alone, ICS alone, or combination use period will be compared with the non-treatment period. The incidence of suicide attempt during the combination period will be compared with the incidence during the ICS alone period to investigate whether the additional use of LTRA will increase the risk of suicide attempt. The adjusted incidence rate ratio (IRRs) will be calculated using conditional Poisson regression.
This study will allow us to better understand the psychiatric side effects of LTRAs and ICS, and further help to guide prescribing in patients.
The main effect estimates will be the incidence rate ratios (IRRs), which are estimated by comparing the rate of events (i.e., first suicide attempt) between the periods of:
1. LTRAs alone vs non-treatment
2. ICS alone vs non-treatment
3. Combination of LTRAs and ICS vs non-treatment
4. Combination of LTRAs and ICS vs ICS alone
Wallis Lau - Chief Investigator - University College London ( UCL )
Boqing Chen - Corresponding Applicant - University College London ( UCL )
Kenneth Man - Collaborator - University College London ( UCL )
Yogini Jani - Collaborator - University College London ( UCL )
HES Accident and Emergency;HES Admitted Patient Care;HES Outpatient;ONS Death Registration Data;Patient Level Index of Multiple Deprivation;Practice Level Index of Multiple Deprivation