Sertraline and the Risk of Serious Adverse Events

NCT07387120 | Completed

• 2 other identifiers: 2025 0906 615 000_3ICES # 2025 0906 615 000_3
• Study Type: observational
• Target: 6,893
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this population-based cohort study is to assess the safety of initiating a new outpatient prescription of 50 mg/day of Sertraline, a higher dose, compared to 25 mg/day, a lower dose, in adults aged 65+ with low kidney function. The primary question is whether initiating a new outpatient prescription of a higher dose of Sertraline (50mg/day) compared to a lower dose (25 mg/day) in older adults with low kidney function (an eGFR \<45 mL/min per 1.73 m2, but not receiving dialysis or having a history of kidney transplantation) is associated with a higher 30-day risk. The outcome measured will be a composite of all-cause hospitalization, all-cause emergency department visit, or all-cause mortality.

Conditions

Chronic Kidney Disease (CKD); Elderly; Outpatient

Keywords

Chronic Kidney Disease; High-throughput computing; Drug Adverse Events; Selective Serotonin Reuptake Inhibitors; Sertraline; Elderly; Geriatrics; Drug Safety

Outcome Measures

Primary Outcomes (1)

• A composite outcome of all-cause hospitalization, all-cause emergency department visit, or all-cause mortality.

  All-cause hospitalization, all-cause emergency department visits, and all-cause mortality will be combined into a composite measure. Only the first hospitalization or first emergency department visit occurring after the cohort entry date will be considered.

  Older adults exposed to high-dose (50mg/day) vs low-dose (25 mg/day) Sertraline between Jan 1, 2008, and Jan 1,2025 will enter the cohort and will be followed until study outcome (first event), death, or 30 days from the cohort entry date

Secondary Outcomes (3)

• All-cause hospitalization

  Exposed cohort to Sertraline (high dose (50mg/d) versus low dose (25 mg/d)) between January 1, 2008, and January 1, 2025 will enter the cohort and will be followed until study outcome (first event), death, or 30 days from the cohort entry date

• All-cause emergency department visit

  Exposed cohort to Sertraline (high dose (50mg/d) versus low dose (25 mg/d)) between January 1, 2008, and January 1, 2025 will enter the cohort and will be followed until study outcome (first event), death, or 30 days from the cohort entry date

• All-cause mortality

  Exposed cohort to Sertraline (high dose (50mg/d) versus low dose (25 mg/d)) between January 1, 2008, and January 1, 2025 will enter the cohort and will be followed until study outcome (first event), death, or 30 days from the cohort entry date

Other Outcomes (3)

• 30-day hospital encounter with composite outcome of Atrial Fibrillation/flutter or ventricular arrhythmia or other arrhythmia

  Exposed cohort to Sertraline (high dose (50mg/d) versus low dose (25 mg/d)) between January 1, 2008, and January 1, 2025 will enter the cohort and will be followed until study outcome (first event), death, or 30 days from the cohort entry date.

• 30-day composite outcome of a hospital encounter with delirium, encephalopathy, or hospital encounter with receipt of an urgent computed tomography scan of the head

  Exposed cohort to Sertraline (high dose (50mg/d) versus low dose (25 mg/d)) between January 1, 2008, and January 1, 2025 will enter the cohort and will be followed until study outcome (first event), death, or 30 days from the cohort entry date

• 30-day composite outcome of a hospital encounter with fracture, falls, hypotension, or syncope

  Exposed cohort to Sertraline (high dose (50mg/d) versus low dose (25 mg/d)) between January 1, 2008, and January 1, 2025 will enter the cohort and will be followed until study outcome (first event), death, or 30 days from the cohort entry date

Study Arms (2)

Low dose of Sertraline (25 mg/day)

Residents of Ontario (and possibly Alberta), aged 66 years or older with low kidney function (an eGFR \<45 mL/min per 1.73 m2 but not receiving dialysis or having a history of kidney transplantation) who have filled a new oral prescription for Sertraline (low-dose 25 mg/day) at an outpatient pharmacy under the Ontario Drug Benefit (ODB) program from January 01, 2008, to January 1, 2025, with a day supply of ≥7 days. The date when the prescription was filled will serve as the patient's entry or index date for the cohort, and each patient will enter the cohort only once.

Drug: Sertraline 25 mg

High dose of Sertraline (50 mg/day)

Residents of Ontario (and possibly Alberta), aged 66 years or older with low kidney function (an eGFR \<45 mL/min per 1.73 m2 but not receiving dialysis or having a history of kidney transplantation) who have filled a new oral prescription for Sertraline (high-dose: 50 mg/day) at an outpatient pharmacy under the Ontario Drug Benefit (ODB) program from January 01, 2008, to January 1, 2025, with a day supply of ≥7 days. The date when the prescription was filled will serve as the patient's entry or index date for the cohort, and each patient will enter the cohort only once.

Drug: Sertraline 50 mg

Interventions

Sertraline 50 mg DRUG

The primary exposure of interest will be oral Sertraline at a dose of 50 mg/day.

High dose of Sertraline (50 mg/day)

Sertraline 25 mg DRUG

The primary exposure of interest will be oral Sertraline at a dose of 25 mg/day.

Low dose of Sertraline (25 mg/day)

Eligibility Criteria

• Age: 66 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Adults aged 66 years or older with low kidney function (eGFR \<45 mL/min per 1.73 m2 but not receiving dialysis or having a history of kidney transplantation) who have filled a new outpatient prescription for Sertraline with a dose of 25 or 50 mg/day and a day supply of ≥7 days between 2008 and 2024 in Ontario. The study accrual period for Alberta (if needed) will be determined based on data availability.

You may qualify if:

• Older adult aged 66 years or greater with low kidney function (an eGFR \<45 mL/min per 1.73 m2 ) who have filled a new oral prescription for Sertraline at an outpatient pharmacy under the Ontario Drug Benefit (ODB) program with a dose of 25 or 50 mg/day and a day supply of ≥7 days from January 1, 2008, to January 1, 2025 for Ontario (if needed, dates in Alberta to be finalized based on data availability). The investigators will exclude individuals undergoing dialysis or those who have received a kidney transplant. The age criterion is set to guarantee that individuals in this population had at least one year of prior universal outpatient prescription drug coverage. The date when the prescription was filled will serve as the patient's entry or index date for the cohort, with each patient entering the cohort only once.

You may not qualify if:

• Individuals with missing administrative database number, missing or invalid age (\<0 or \>105 years), missing or invalid sex, death on or before the index date, non-Ontario resident (for Ontario data).
• Individuals less than 66 years of age on the index date.
• Those with evidence of any study drug prescription 180 days before the index date (to restrict to new users only).
• Individuals with other Selective Serotonin Reuptake Inhibitors (Citalopram, Escitalopram, Fluoxetine, Fluvoxamine, Paroxetine) prescription in the previous 180 days before the index date or on the index date.
• Individuals with more than one study drug prescription on the index date, as this complicates the ability to ascertain the prescribed dose accurately.
• Individuals with end-stage renal disease, chronic dialysis, or a kidney transplant prior to the index date.
• Evidence with hospital discharge or emergency department visit in the two days prior to or on the index date to ensure a new outpatient prescription.
• Individuals with no serum creatinine lab value in the 0-365 days prior to the index date.
• Individuals with unstable baseline kidney function:
• If the most recent serum creatinine test prior to the index date was an inpatient test \[ER or hospitalization\] (refer to this as test date 1), and there is not at least one 'outpatient' serum creatinine in the year before test date 1, OR
• If the most recent prior serum creatinine test prior to the index date was an inpatient test \[ER or hospitalization\] (refer to this as test date 1), and while there is at least 'outpatient' serum creatinine test in the year before (test date 1), the most recent outpatient test prior to (test date 1) differs by an eGFR 10 mL/min/1.73 m2 or more from the value on (test date 1).
• In Ontario, it has been shown that an outpatient serum creatinine measurement in the province, conducted on a single occasion, usually represents a stable value.
• Individuals receiving palliative care in the year prior to the index date, as in this setting dosing is less relevant; rather, the focus is comfort care. The investigators will restrict to the first prescription in individuals with more than one eligible prescription. Date of this prescription will be the index date (the date from which the outcomes start being assessed).

Sponsors & Collaborators

• London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's: lead

Study Sites (1)

London Health Sciences Centre Research Institute

London, Ontario, Canada

Location

Related Publications (1)

• Abdullah SS, Rostamzadeh N, Muanda FT, McArthur E, Weir MA, Sontrop JM, Kim RB, Kamran S, Garg AX. High-Throughput Computing to Automate Population-Based Studies to Detect the 30-Day Risk of Adverse Outcomes After New Outpatient Medication Use in Older Adults with Chronic Kidney Disease: A Clinical Research Protocol. Can J Kidney Health Dis. 2024 Jan 6;11:20543581231221891. doi: 10.1177/20543581231221891. eCollection 2024.

  PMID: 38186562 BACKGROUND

MeSH Terms

Conditions

Renal Insufficiency, Chronic; Drug-Related Side Effects and Adverse Reactions

Interventions

Sertraline

Condition Hierarchy (Ancestors)

Renal Insufficiency; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Chemically-Induced Disorders

Intervention Hierarchy (Ancestors)

1-Naphthylamine; Amines; Organic Chemicals; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Polycyclic Compounds

Study Officials

• Amit Garg

  London Health Sciences Centre Research Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: RETROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 28, 2026
• First Posted: February 4, 2026
• Study Start: January 1, 2008
• Primary Completion: January 1, 2025
• Study Completion: January 1, 2026
• Last Updated: February 4, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)