Venlafaxine Under the Microscope: Two Decades of FAERS Data

Venlafaxine (Effexor; Viatris) is a serotonin-norepinephrine reuptake inhibitor (SNRI) approved for major depressive disorder (MDD). MDD is a common condition, as 4% of the population experiences depression, although only one-third will seek treatment. Despite this, pharmacies dispensed more than 13.2 million venlafaxine prescriptions in 2023.¹

A recent study utilized the FDA Adverse Event Reporting System (FAERS) to collect data on adverse events from real-world use.¹ Since its approval in 1993, no further research has investigated a dose-response relationship for efficacy and tolerability.² The researchers aimed to expand knowledge about venlafaxine beyond the original randomized controlled trials.

The results confirmed most known adverse events, including the boxed warning for suicidal ideation. Other known adverse events seen in the FAERS data include anticholinergic effects, sexual dysfunction, hypertension, serotonin syndrome, and withdrawal syndrome.¹

The researchers also highlighted previously unknown adverse events. Events that appeared in the postmarketing data include “drug ineffective” (non-response), renal dysplasia, agitated depression, and parotid gland enlargement. All the newly noted adverse events were rare except for non-response. This study did not prove causation, but the authors urge others to further research the rare adverse effects.¹

The distribution of adverse events was bimodal, peaking at less than 30 days and again after 360 days. Randomized control trials would not have caught the second peak, as most only follow up for a few months. Over half of the late-onset adverse events were associated with hospitalization. Pediatric patients were most likely to report tachycardia and somnolence. Older adults (> 64 years) reported more emotional disorders, anger, and status epilepticus than other populations.¹

Long-term postmarketing data from FAERS can confirm known adverse events and reveal rare events not recognized in randomized control trials. Providers must consider risks and benefits unique to each patient’s population, such as the possible correlation between venlafaxine use and renal dysplasia. However, findings from observational studies are only as good as the data they use, and FAERS data is limited because not everyone reports their adverse events and some reports may contain incomplete information.¹

Investigations of real-world data are crucial to strengthening safety data. Although the authors were unable to draw conclusions on dose-response due to inconsistent reporting, they were able to pick out correlations with previously unrecognized adverse events and sub-population patterns.¹

REFERENCE

1. Chokkakula S, Yang H, Al-Masri AA, Zhang Y, Naveen B, Yang B. The post-marketing safety of venlafaxine: a real-world two-decade pharmacovigilance study using the FAERS database. Front Pharmacol. 2026;17:1-15. doi:10.3389/fphar.2026.1737113

2. Hillhouse TM, Porter JH. A brief history of the development of antidepressant drugs: from monoamines to glutamate. Exp Clin Psychopharmacol. 2015;23(1):1-21. doi:10.1037/a0038550