Connection Between Antidepressants and Cancer Treatment Outcomes

Activities that once seemed enjoyable often become burdensome. Simple tasks, like waking up, chatting with friends, or just completing everyday chores, can feel increasingly daunting for individuals grappling with depression. Thankfully, there are treatment options that can help restore a sense of normalcy.

Similarly, those undergoing cancer treatment may find themselves battling feelings of depression or anxiety. Often, they end up taking mental health medications alongside their cancer therapies. Recently, researchers have begun to explore an unexpected link between these treatments.

A recent analysis revealed that patients on commonly prescribed antidepressants showed a reduction in mortality over a two-year period following the initiation of immunotherapy, a treatment designed to empower the immune system against cancer.

Oncologist Cho-Hao Lee from Tri-Service General Hospital and National Defense Medical University in Taiwan shared insights with ScienceAlert, explaining, “In simple terms, SSRIs might provide an additional boost to immunity alongside what checkpoint inhibitors already offer.”

SSRIs, or selective serotonin reuptake inhibitors, play a role in increasing serotonin levels, a crucial neurotransmitter. This category includes medications like fluoxetine, sertraline, and escitalopram.

To examine the potential effects of antidepressants on cancer outcomes, the research team analyzed the medical histories of adults dealing with depression or anxiety with solid tumors, while excluding blood-related cancers.

All participants were beginning treatment with immune checkpoint inhibitors. These drugs work by blocking signals that might inhibit immune cells from attacking cancer cells.

Under the guidance of physician Po-Huang Chen, the team identified suitable patients via the TriNetX electronic health network, focusing on those who started immunotherapy between 2015 and 2025.

In the study, researchers matched 1,567 SSRI users with 1,567 individuals taking benzodiazepines, which are typically prescribed for conditions like anxiety and insomnia. The matching process accounted for 49 different characteristics, including demographics, tumor types, other health issues, medications taken, and lab results.

The focus was to compare two similarly situated groups rather than contrasting those on antidepressants with those who took none at all.

Over the two-year period, the findings indicated that 368 patients in the SSRI group passed away, compared to 539 in the benzodiazepine group, translating to mortality rates of 23.5 percent and 34.4 percent respectively.

In a deeper analysis of timing for the deaths, SSRI usage was linked to a roughly 37 percent lower hazard of death, which is a relative measure—not to be confused with indicating longer lifespans.

All five SSRIs assessed were individually linked to reduced mortality rates. When compared to patients on neither medication type, those using SSRIs experienced about a 25 percent reduction in the hazard of death.

One possible explanation for these findings could be the role of serotonin beyond the central nervous system. T cells, critical for fighting tumors, also respond to serotonin.

A 2025 study published in Cell identified the serotonin transporter, the target of SSRIs, as a suppressor of these immune cells in mice. Blocking this transporter appeared to enhance antitumor immunity.

Moreover, combining an SSRI with anti-PD-1 immunotherapy showed improved tumor management in lab settings. This new research seeks to determine if similar outcomes can be observed in human patients.

The researchers also examined 8,272 tumor samples from The Cancer Genome Atlas. Across 13 of 20 different cancer types, higher levels of the gene responsible for the serotonin transporter correlated with lower T-cell inflammation scores.

However, it’s worth noting that these samples were from patients different from those whose survival records were analyzed in this study.

The findings lend support to the proposed mechanism but do not confirm that antidepressants directly affect tumor conditions. It remains unclear if doses of antidepressants might influence serotonin levels or T-cell activity within tumors.

Medical records also highlighted differences in thyroid health. Thyroid issues were noted in 31.6 percent of SSRI users, contrasted with 26.7 percent among those using benzodiazepines. Other health conditions showed no significant differences.

Questions about the implications of thyroid dysfunction also arose since diagnosis codes couldn’t clarify if these issues were immune-related, suggesting more investigations are needed.

A notable limitation of the study was the absence of data regarding patients’ daily functioning, which is significant for predicting cancer survival rates.

It’s important to acknowledge that benzodiazepines may also be prescribed for anxiety or insomnia when a patient’s cancer worsens. Consequently, those using them might have been more severely ill despite appearing comparable in recorded characteristics.

On the other hand, SSRI prescriptions could indicate broader psychological and health care, not necessarily a direct anticancer influence. Lee admits that such differences might contribute to the observed association.

Lee emphasizes, “Only through a randomized trial can we clarify how much of this is truly causal versus confounding.”

As patients were not randomly assigned to either medication in this observational study, findings couldn’t definitively say that SSRIs prolong life.

Going forward, future trials should examine survival rates, cancer progression, and potential side effects, while tumor samples collected before and after treatment could disclose immune activity changes.

It’s also essential to determine which specific drugs, their dosages, and treatment durations might yield the best outcomes. Including patients without depression or anxiety could help differentiate the effects of psychological treatments from any potential anticancer impacts.

For patients currently navigating these challenges, Lee’s advice is straightforward: “This is not a reason to start an SSRI to enhance immunotherapy or to discontinue benzodiazepines on your own.”

The research has been published in PLOS Medicine.