Science1 publisherNot yet confirmed elsewhere2 min readPublished
Immunotherapy patients on SSRIs died less often over two years, a matched records study finds
Researchers in Taiwan found 23.5 percent of SSRI users died within two years of starting immunotherapy, against 34.4 percent of matched benzodiazepine users. It is an observational analysis, and the team cannot show the drugs changed anything inside the tumors.
The Scientist · Science desk
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What happened
- The team matched 1,567 SSRI users to 1,567 benzodiazepine users across 49 baseline characteristics, from demographics and tumor type to other illnesses and lab results.
- A 2025 Cell study had tagged the serotonin transporter, the protein SSRIs block, as a brake on T cells in mice, and releasing it alongside anti-PD-1 therapy improved tumor control.
- In 8,272 tumor samples from The Cancer Genome Atlas, higher expression of the transporter gene tracked with lower T-cell inflammation across 13 of 20 cancer types.
- Thyroid dysfunction was recorded in 31.6 percent of SSRI users against 26.7 percent on benzodiazepines, while hepatitis, pneumonitis and colitis rates were similar.
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Why it matters
- constraint A matched records analysis can rank the association but cannot prove the SSRIs caused the fewer deaths; only a randomized trial would settle that.
- contradiction The survival records and the tumor-genomics data come from different patients, so the longer survival and the proposed brake-release have not been seen in the same people.
- capability SSRIs such as fluoxetine, sertraline and escitalopram are already taken by many cancer patients, so a confirmed effect would give oncologists a familiar drug class to pair with checkpoint immunotherapy.
Depression and anxiety track with worse cancer outcomes on their own. Comparing antidepressant users against people on no psychiatric drug would blend the effect of the pill with the effect of the condition it treats, so Po-Huang Chen's team used a benzodiazepine comparator instead [7]. The patients came from the TriNetX records network, all adults with depression or anxiety and solid tumors who began checkpoint immunotherapy between 2015 and 2025 [5][4].
In a secondary comparison against matched patients on no psychiatric medication, the association was smaller, about a 25 percent lower hazard of death, and all five SSRIs examined individually pointed the same way [10]. Over two years, 368 SSRI patients died against 539 on benzodiazepines, a gap of about 11 percentage points [8][19]. The modeled 37 percent lower hazard describes a lower rate of dying during follow-up, not patients living 37 percent longer [9].
Cancer-fighting T cells respond to serotonin, the messenger SSRIs act on [11]. "The simplest way to put it is that SSRIs may release a second brake on immunity that sits right next to the one checkpoint inhibitors release," oncologist Cho-Hao Lee of Tri-Service General Hospital and National Defense Medical University told ScienceAlert [2].
The records cannot show what happened inside the tumors [16]. Whether antidepressant doses change serotonin levels or T-cell behavior within a patient's cancer is unknown [16]. The analysis also lacked data on patients' ability to carry out everyday activities, one of the stronger predictors of cancer survival [18].
What to watch
- A randomized trial of SSRIs added to checkpoint inhibitors would be needed to show the drugs cause the survival difference.
- Whether the higher thyroid-dysfunction rate among SSRI users holds up and turns out to be immune-related.
- Whether the serotonin-transporter brake can be measured inside human tumors, not only in mouse models and genomic correlations.