Assessment of the association between use of doxycycline and suicide: a self-controlled case series and an active comparator study

Study type
Protocol
Date of Approval
Study reference ID
24_004221
Lay Summary

Doxycycline is an antibiotic widely used for treating bacterial infections including respiratory and sexually transmittable diseases, acne and rosacea (a redness on the face that may also present small bumps with pus inside). There have been reports on a potential association between use of doxycycline and suicide. Assessing this potential association is crucial for understanding the full safety profile of doxycycline and ensuring patient safety. This can be done by evaluating the risk of suicide or self-harm events in patients using doxycycline compared to other drugs that can be used (called active comparators).

Hence, this study aims to 1) evaluate if there is a causal association (i.e., a cause-and-effect relationship) between the use of doxycycline and suicide-related events; and 2) to evaluate if the association between doxycycline use and completed suicide and suicide-related events vary by the recorded indication of use (e.g., acne, chlamydia, etc.), when compared to active comparators.

Public health benefits from the study: it is crucial to assess whether there is a connection between doxycycline and suicide in order to guarantee the safety of doxycycline users.

Technical Summary

Doxycycline, a tetracycline antibiotic, is widely used for treating bacterial infections. There have been reports on a potential association between use of doxycycline and suicide.

This study aims to 1) evaluate if there is a causal association between the use of doxycycline and suicide-related events; and 2) evaluate if the association between doxycycline use and completed suicide and suicide-related events vary by indication of use, compared to active comparators.

>Study design: Cohort studyand Self-controlled case series (SCCS)

>Population:
-New-user cohort study: patients with a first prescription of doxycycline or active comparator.
-SCCS study: patients with a prescription of doxycycline and a record of the outcome within the study period (01/01/2010-actuality).
Patients will be excluded if the start date in the database or occurrence of the outcome falls within 365 days prior to the index date as this does not guarantee sufficient database history to track information on covariates.

>Exposure: new users of doxycycline

>Outcomes:
-Completed suicide (included in cohort study only).
-Composite outcome of completed suicide (included in cohort study only), suicide ideation, suicide attempting and self-harm.
-Composite outcome of depression or anxiety.

>Covariates:
- Age
-Calendar year
-Seasonality
-Patient specific characteristics in terms of indications of interest, conditions, etc.

>Analyses:
1) Incidence rates of the suicide-related events, depression or anxiety in people using doxycycline
2) Incidence rate ratios in a SCCS study between doxycycline and the study outcomes.
3) Propensity-score matching of patients prescribed doxycycline to active comparators in new-user cohort within different indication of use. Then cox-proportional hazards regression will estimate hazards ratios to assess the association of doxycycline with study outcomes.

Public health benefits: it is crucial to assess whether there is a connection between doxycycline and suicide in order to guarantee the safety of doxycycline users.

Health Outcomes to be Measured

Outcomes of interest are:
- Completed suicide (included in cohort study only).
- Composite outcome of completed suicide (included in cohort study only), suicide ideation, suicide attempting and self-harm.
- Composite outcome of depression or anxiety.

Collaborators

Daniel Prieto-Alhambra - Chief Investigator - University of Oxford
Marta Pineda Moncusi - Corresponding Applicant - University of Oxford
Annika Jodicke - Collaborator - University of Oxford
Antonella Delmestri - Collaborator - University of Oxford
Hezekiah Omulo - Collaborator - University of Oxford
Mandickel Kamtengeni - Collaborator - University of Oxford
Martí Català Sabaté - Collaborator - University of Oxford
Wai Yi Man - Collaborator - University of Oxford