A large-scale observational comparison of antidepressants and their effects

Selective Serotonin Reuptake Inhibitors (SSRIs) represent a diverse class of medications widely prescribed for depression and anxiety. Despite their common use, there is an absence of large-scale, real-world evidence capturing the heterogeneity in their effects on individuals. This study addresses this gap by utilizing naturalistic search data to explore the varied impact of six different SSRIs on user behavior.

The study sample included ∼508 thousand Bing users with searches for one of six SSRIs (citalopram, escitalopram, fluoxetine, fluvoxamine, paroxetine, sertraline) from April-December 2022, comprising 510 million queries. Cox proportional hazard models were employed to examine 30 topics (e.g., shopping, tourism, health) and 195 health symptoms (e.g., anxiety, weight gain, impotence), using each SSRI as a reference. We assessed the relative hazard ratios between drugs and, where feasible, ranked the SSRIs based on their observed effects. We used Cox proportional hazard models in order to account for both the likelihood of users searching for a particular topic or symptom and the associated time to that search. The temporal aspect aided in distinguishing between potential symptoms of the disorder, short-term medication side effects, and later appearing side effects.

Differences were found in search behaviors associated with each SSRI. E.g., fluvoxamine was associated with a significantly higher likelihood of searching weight gain compared to all other SSRIs (HRs 1.85-2.93). Searches following citalopram were associated with significantly higher rates of later impotence queries compared to all other SSRIs (HRs 5.11-7.76), except fluvoxamine. Fluvoxamine was associated with a significantly higher rate of health related searches than all other SSRIs (HRs 2.11-2.36).

Our study reveals new insights into the varying SSRI impacts, suggesting distinct symptom profiles. This novel use of large-scale, naturalistic search data contributes to pharmacovigilance efforts, enhancing our understanding of intra-class variation among SSRIs, potentially uncovering previously unidentified drug effects.