ANGIOTENSIN AGENTS AND REDUCTION OF THE PRESCRIPTION OF ANTIDEPRESSANT DRUGS: A RETROSPECTIVE COHORT STUDY USING REAL-WORLD DATA

Study Overview
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Brief Summary
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A retrospective cohort study will be performed by analyzing data obtained from the Catalan Southern Metropolitan data warehouse system, which collects data from both hospitalized and primary care patients from the Bellvitge University Hospital's area of influence. The investigators will begin by gathering information only on patients treated with antihypertensive drugs, which then will be stratified in two groups: 1) Angiotensin Agents group; 2) Other Antihypertensive Agents (Non-Angiotensin Agents) group. Afterwards, a separated analysis will be performed to assess the effects of ARBs and ACEIs separately on the prescription of antidepressant drugs.

Detailed Description
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Hypertension is a multifactorial disease and an important risk factor for cardiovascular and cerebrovascular diseases. Also, major depression is commonly found on these patients. Together, they represent a substantial burden for patients and their families, with an increased morbimortality and reduced life-quality. It also has a major social impact by increasing healthcare assistance demand and by affecting patients' daily-life productivity, therefore generating direct and indirect health-associated costs. The Renin-Angiotensin System is one of the known pathways that modulate systemic and central nervous system inflammation. Basic research studies have shown ARBs-related allosteric changes on receptors implicated on the pathophysiology of schizophrenia and depression, and also a pharmacological reversal of depression-like behavior in rats after the administration of losartan. Human research studies have also presented evidence that points towards an antidepressant effect of some antihypertensive drugs. A retrospective cohort study will be performed by analyzing data obtained from the Catalan Southern Metropolitan data warehouse system, which collects data from both hospitalized and primary care patients from the Bellvitge University Hospital's area of influence. The investigators will begin by gathering information only on patients treated with antihypertensive drugs, which then will be stratified in two groups: 1) Angiotensin Agents group; 2) Other Antihypertensive Agents (Non-Angiotensin Agents) group. Afterwards, a separated analysis will be performed to assess the effects of ARBs and ACEIs separately on the prescription of antidepressant drugs. Our primary objective is to estimate the prevalence, incidence, and clearance (incidence of antidepressant drugs withdrawal) of antidepressant drugs prescription in hypertensive patients under treatment with angiotensin agents (ARBs and/or ACEIs). Our secondary objectives are as follows: I. For ARBs: To estimate the prevalence of antidepressant drugs prescription in hypertensive patients under treatment with ARBs. To estimate the clearance of antidepressant drugs prescription in patients concomitantly treated with ARBs and antidepressant drugs. To estimate the incidence of antidepressant drugs initiation in patients with hypertension treated with ARBs. II. For ACEIs: To estimate the prevalence of antidepressant drugs prescription in hypertensive patients under treatment with ACEIs. To estimate the clearance (incidence of antidepressant drugs withdrawal) of antidepressant drugs prescription in patients concomitantly treated with ACEIs and antidepressant drugs. To estimate the incidence of antidepressant drugs initiation in patients with hypertension treated with ACEIs. III. For other antihypertensive drugs (i.e., non-angiotensin agents: CCBs, β-blockers, and diuretics): To estimate the prevalence of antidepressant drugs prescription in hypertensive patients under treatment with other antihypertensive drugs (non-angiotensin agents). To estimate the clearance (incidence of antidepressant drugs withdrawal) of antidepressant drugs prescription in patients concomitantly treated with other antihypertensive drugs and antidepressant drugs. To estimate the incidence of antidepressant drugs initiation in patients with hypertension treated with other antihypertensive drugs. IV. To perform an exploratory comparative analysis among the different antihypertensive drugs sub-cohorts. The protocol (Final Version: February 18th, 2021) was approved by the local Institutional Review Board (Ethic-and-Clinical-Investigation- Committee, code HUB-FC-2020-01, date April 20th, 2021). The study findings will be submitted to peer-reviewed journals and presented at relevant national and international scientific meetings.

Official Title
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ANGIOTENSIN AGENTS AND REDUCTION OF THE PRESCRIPTION OF ANTIDEPRESSANT DRUGS: A RETROSPECTIVE COHORT STUDY USING REAL-WORLD DATA

Conditions
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ACE Inhibitors, ARB, Hypertension, Depression

Intervention / Treatment
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* Drug: With an Antidepressant Drug
* Drug: Without an Antidepressant Drug


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients that had an antihypertensive drug prescribed between January 1st, 2015 and December 31st, 2017, whose ATC codes can be obtained from the 'DATA WAREHOUSE' database Age ≥ 18 years old Both genders Patients with information available on the 'DATA WAREHOUSE' database Patients with a clinical visit or prescription done afterwards the date when the information for the study was last collected (this way we ensure that the patient included on the study remained alive after the end of the observation period) Exclusion Criteria: Lack of information about the beginning of treatment with an antihypertensive and/or with an antidepressant drug.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| ARBs only<br>Hypertensive patients under pharmacological treatment with ARBs | Drug: With an Antidepressant Drug<br>* Current users of an antidepressant drug.<br>Drug: Without an Antidepressant Drug<br>* Non-current users of an antidepressant drug.<br>|
| ACEIs only<br>Hypertensive patients under pharmacological treatment with ACEIs | Drug: With an Antidepressant Drug<br>* Current users of an antidepressant drug.<br>Drug: Without an Antidepressant Drug<br>* Non-current users of an antidepressant drug.<br>|
| ARBs + ACEIs<br>Hypertensive patients under pharmacological treatment with ARBs and ACEIs | Drug: With an Antidepressant Drug<br>* Current users of an antidepressant drug.<br>Drug: Without an Antidepressant Drug<br>* Non-current users of an antidepressant drug.<br>|
| Other Antihypertensive Drugs<br>Hypertensive patients under pharmacological treatment with non-angiotensin agents (diuretics, calcium channel blockers and/or β-blockers alone or combined among them) | Drug: With an Antidepressant Drug<br>* Current users of an antidepressant drug.<br>Drug: Without an Antidepressant Drug<br>* Non-current users of an antidepressant drug.<br>|
| Angiotensin Agents and Other Antihypertensive Drugs<br>Hypertensive patients under combined pharmacological treatment with Angiotensin Agents (ACEIs and/or ARBs) and Other Antihypertensives (non-angiotensin agents) | Drug: With an Antidepressant Drug<br>* Current users of an antidepressant drug.<br>Drug: Without an Antidepressant Drug<br>* Non-current users of an antidepressant drug.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Patients treated with antihypertensive drugs | Number of patients under treatment with antihypertensive drugs | 3 years | 
| Patients treated with an antidepressant drug | Number of patients under treatment with antidepressant drug | 3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Patients diagnosed with Hypertension | Number of patients diagnosed with Hypertension | 3 years | 
| Patients diagnosed with Depression | Number of patients diagnosed with Depression | 3 years | 
| Patients treated with ARBs | Number of patients treated with ARBs | 3 years | 
| Patients treated with ACEIs | Number of patients treated with ACEIs | 3 years | 
| Patients treated with other antihypertensive drugs | Number of patients treated with other antihypertensive drugs (i.e., non-ARBs and non-ACEIs). | 3 years | 
| Patients treated with Amitriptyline | Number of patients treated with Amitriptyline, since this is an antidepressant drug commonly used to treat neuropathic pain in our usual practice. | 3 years | 
| Patients treated with Duloxetine | Number of patients treated with Duloxetine, since this is an antidepressant drug commonly used to treat neuropathic pain in our usual practice. | 3 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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ACEI, ARB, ACE, RAS, Angiotension, Depression, Hypertension