Serotonin Norepinephrine Reuptake Inhibitors and the Risk of Serious Adverse Events

Inclusion Criteria: * The cohort will include all older adults (≥66 years) with an eGFR \<45 mL/min per 1.73 m2 (not receiving dialysis or having a history of kidney transplantation) who received a new outpatient prescription for oral venlafaxine or duloxetine between January 1, 2008, and December 1, 2025. The age criterion is set to guarantee that individuals in this population have had at least one year of prior 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. Exclusion Criteria: * 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), or non-Alberta residents (for Alberta 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 more than one study drug prescription on the index date, as this complicates the ability to ascertain the prescribed dose accurately. * Evidence of clinically non-meaningful venlafaxine or duloxetine doses (doses that are either too low or too high). The recommended dose range for venlafaxine is 37.5 to 150 mg per day, and for duloxetine is 30 to 120 mg per day. * Individuals with end-stage renal disease, chronic dialysis, or a…