What does this research mean for the field?

In cancer patients treated with immune checkpoint inhibitors, the use of SSRIs or SNRIs is associated with worse overall survival compared to no antidepressant exposure, though this may reflect confounding by depression and comorbidity burden. Novelty: ClaimNovelty.INCREMENTAL. Consensus alignment: ConsensusAlignment.NEUTRAL.

What question did this study set out to answer?

This research evaluates the effect of antidepressant use on overall survival in cancer patients receiving immune checkpoint inhibitors.

May 30, 2026

Antidepressant use and overall survival in ICI treated pan-cancer patients: A real-world analysis.

Key Points

This research evaluates the effect of antidepressant use on overall survival in cancer patients receiving immune checkpoint inhibitors.
Retrospective analysis using TriNetX Research Network to identify ICI treated adults with solid tumors.
Patients were grouped by antidepressant exposure and depression diagnosis using propensity score matching.
Overall survival was analyzed using Kaplan-Meier and Cox models, with comparisons made against sertraline as the reference.
SSRI/SNRI use was associated with increased mortality in ICI treated patients (42.4% vs 33.5%) and worse survival (p < 0.0001).
Bupropion showed improved overall survival compared to sertraline (39.5% vs 47.2%, p = 0.0019).
Bupropion was linked to higher mortality compared to no antidepressant use (38.6% vs 33.3%, p = 0.0002).

Abstract

e23395 Background: Antidepressants are frequently prescribed to cancer patients, yet their impact on outcomes during immune checkpoint inhibitor (ICI) therapy is unclear. We evaluated the association between SSRIs, SNRIs, and bupropion use and overall survival (OS) in ICI treated patients. Methods: This retrospective real world study used the TriNetX Research Network to identify ICI treated adults with solid tumors, grouped by antidepressant exposure and depression diagnosis, with propensity score matching and overall survival analyzed using Kaplan-Meier (KM) and Cox models, including agent-specific comparisons using sertraline (Ser) as the reference. Results: In the patients treated with ICI, SSRI/SNRI use was associated with inferior OS compared with no SSRI/SNRI exposure, with higher mortality (42.4 vs 33.5%), and worse KM survival (p < 0.0001). In patients with a diagnosis of depression, using Ser as reference, fluoxetine, escitalopram, citalopram, paroxetine, venlafaxine, and duloxetine showed no significant differences in OS. In contrast, bupropion demonstrated improved OS compared with Ser, with lower mortality (39.5 vs 47.2%) and reduced risk of death (p = 0.0019). However, when compared with no antidepressant exposure, bupropion was associated with higher mortality (38.6 vs 33.3%), and inferior KM survival (p = 0.0002). Conclusions: In ICI treated patients, SSRI/SNRI use was associated with inferior OS compared with no antidepressant exposure, potentially reflecting confounding by depression and comorbidity burden; in agent specific analyses, other SSRIs/SNRIs did not differ from Ser, while bupropion showed improved OS versus Ser, but remained inferior to no antidepressant use, underscoring the need for prospective validation. OS by antidepressant use in ICI treated pancancer population. Groups N per group Mean Follow up (days) Deaths (%) Risk Ratio(95% CI) KM Median survival (days) p for KM Hazard Ratio (95% CI) No AntidepressantvsAntidepressant 27032 741vs766 34vs42 0.79(0.774-0.809) 2045vs1156 0.0001 0.80(0.78-0.824) ServsFluoxetine 954 761vs684 44vs45 0.96(0.781-1.122) 953vs958 0.29 0.93(0.812-1.063) ServsEscitalopram 1946 757vs781 44vs44 0.99(0.921-1.062) 1020vs1156 0.82 1.01(0.92-1.112) ServsCitalopram 971 738vs788 45vs48 0.92(0.843-1.021) 957vs903 0.53 0.96(0.841-1.093) ServsEscitalopram 1946 757vs781 44vs44 0.99(0.921-1.062) 1020vs1156 0.82 1.01(0.92-1.112) ServsParoxetine 496 708vs758 48vs49 0.98(0.86-1.111) 809vs903 0.79 1.03(0.857-1.228) ServsVenlafaxine 804 746vs795 43vs47 0.93(0.833-1.032) 957vs868 0.51 0.95(0.823-1.101) ServsDuloxetine 1735 790vs758 47vs45 1.04(0.966-1.117) 963vs976 0.76 1.02(0.92-1.121) BupropionvsSer 982 756vs759</jats:

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