Depression in older individuals is common. Previous studies indicate that damage to the smallest vessels in the brain may lead to depression. However, it is unknown whether medications that can improve the function of these small vessels also protect against depression. The aim of this study is to evaluate in all adults whether commonly used antihypertensive drugs that also improve the function of small vessels, so-called Renin Angiotensin System (RAS) inhibitors, are protective against depression. We will evaluate whether these RAS inhibitors are more protective against depression as compared to diuretics. Diuretics are drugs also commonly used to treat hypertension. We will evaluate the effect of RAS inhibitors on treated depression and non-fatal and fatal self-harm. This study will indicate whether RAS inhibitors may be used in clinical practice to prevent depression in older individuals.
It has been suggested that cerebral microvascular dysfunction is an important contributor to depression in older individuals. Renin angiotensin system (RAS) inhibitors can improve cerebral microvascular function via multiple mechanisms. However, it is unknown whether these medications can protect against depression. We will therefore conduct a pharmacoepidemiologic study using a propensity score-matched cohort design to study whether RAS inhibitors protect against depression.
In the Clinical Research Practice Datalink, we will determine all adults with hypertension, but without a prior diagnosis of depression, from 2004 onwards. We will compare initiators of RAS inhibitors versus thiazide(-like) diuretic initiators. Thiazides will be used as a control group, because they are not associated with mood disorders. Thiazides are, however, considered a second?line treatment for hypertension. We will therefore require patients in both groups to have previously used ?1 other class of an antihypertensive drug. The primary outcome is a composite end point of treated depression and nonfatal and fatal self-harm. We will apply Cox regression with propensity score matching to control for confounding.
Treated depression
Hypertension
Suicidal attempts
Renin angiotensin system inhibitors
Completed suicide
Use of other antihypertensive drugs
Patrick Souverein - Chief Investigator - Utrecht University
Patrick Souverein - Corresponding Applicant - Utrecht University
Coen Stehouwer - Collaborator - Maastricht University
Johanna Driessen - Collaborator - Utrecht University
Patrick Souverein - Collaborator - Utrecht University
Thomas van Sloten - Collaborator - Maastricht University Medical Centre
HES Admitted Patient Care;ONS Death Registration Data