Do Antidepressants Affect Lifespan? Sorting Fact from Fiction on Long-Term Use

October 6, 2025 •

4 min read

According to a 2025 analysis published in PLOS ONE, overall antidepressant use in individuals with depression showed no statistically significant association with all-cause mortality after controlling for confounding factors, though initial unadjusted rates appeared higher. However, the question "Do antidepressants affect lifespan?" remains complex, with conflicting studies and a critical need to differentiate between the effects of medication and the profound impact of the underlying illness itself.

Quick Summary

The debate over antidepressants and longevity involves conflicting research, with some studies suggesting an elevated mortality risk, while others, more robustly controlled, find no significant link. A key challenge is separating medication effects from the impact of underlying depression. The risks appear to differ across drug classes and patient populations, underscoring the importance of personalized treatment.

Key Points

Conflicting Evidence: Some studies link long-term antidepressant use to increased mortality, especially from cardiovascular events, while others with better controls find no significant association with overall mortality.
Underlying Depression is a Risk Factor: Untreated depression is a major health risk, contributing to a shorter lifespan through suicide, unhealthy habits, and higher rates of chronic physical illness.
Complex Research Limitations: Many studies struggle to separate the effects of the medication from the underlying depression severity and other health conditions, a problem known as "confounding by indication".
Cardiovascular Risks: Long-term antidepressant use, especially certain classes, is associated with specific cardiovascular risks, including potential sudden cardiac death, though this is heavily debated and may depend on the patient's existing health.
Individual Drug Class Profiles: The long-term safety profiles vary significantly between different types of antidepressants, with older TCAs generally having more cardiovascular side effects than newer SSRIs.
Risks vs. Benefits: The decision to use antidepressants involves weighing the potential risks of the medication against the known, significant health risks of untreated depression, a process best done with a healthcare provider.

Untreated Depression: A Significant Threat to Longevity

Before exploring the potential risks of medication, it is crucial to understand that untreated depression is a serious health condition with well-documented negative impacts on longevity. Beyond the immediate risk of suicide, which is significantly elevated in individuals with major depressive disorder, depression is associated with a higher incidence of various chronic diseases, including cardiovascular issues, diabetes, and certain cancers. It often leads to unhealthy lifestyle habits, such as poor diet, reduced physical activity, and sleep disturbances, which further contribute to health deterioration.

Treatment for depression, which may include antidepressants, can mitigate these risks and is associated with improved quality of life and potentially increased longevity. By alleviating symptoms, effective treatment can lead to healthier behaviors and better management of co-existing physical illnesses. This context is vital for interpreting the findings on antidepressant use and mortality, as it highlights the primary health burden that treatment aims to address.

The Conflicting Evidence on Antidepressants and Lifespan

Research investigating whether antidepressants affect lifespan has produced conflicting and complex results, mainly from observational studies. The difficulty lies in isolating the effects of the medication from the underlying depression and other health issues prevalent in the treated population. Some studies have suggested an increased risk of all-cause mortality and cardiovascular events among antidepressant users, with one meta-analysis citing a 33% higher all-cause mortality risk and a 14% higher risk of adverse cardiovascular events compared to non-users. A 2022 study also linked long-term use to elevated risks of coronary heart disease, cardiovascular mortality, and all-cause mortality, particularly with non-SSRI antidepressants.

However, other studies using more advanced statistical methods to control for confounding factors like the severity of depression and other health conditions have found no significant association between antidepressant use and all-cause mortality in individuals with depression. These analyses suggest that the observed higher mortality rates in some studies might be due to baseline differences in patient populations, where individuals on antidepressants may be sicker to begin with. This challenge, known as "confounding by indication," makes it difficult to definitively determine the direct impact of antidepressants on lifespan.

Cardiovascular and Other Long-Term Health Concerns

A 2025 study suggested a potential link between long-term use and increased risk of sudden cardiac death, particularly in individuals over 40. Other potential long-term side effects may include weight gain, metabolic changes, sexual dysfunction, and effects on bone health.

Comparison of Antidepressant Classes and Long-Term Risks

Different classes of antidepressants have varying long-term safety profiles. The table below provides a general overview of potential risks:


Antidepressant Class	Example Drugs	Cardiovascular Risk (Long-Term)	All-Cause Mortality Risk (Long-Term)	Other Notable Long-Term Risks
SSRIs	Citalopram, Sertraline	Generally low, but potential for QT prolongation at high doses. Some studies link to sudden cardiac death.	Conflicting; some studies show increased risk, while controlled analyses find no significant link.	Sexual dysfunction, weight gain, potential metabolic changes, bone health issues.
SNRIs	Venlafaxine, Duloxetine	Mild increases in heart rate and blood pressure possible.	Some studies suggest increased risk, especially long-term.	Higher risk of discontinuation syndrome.
Tricyclics (TCAs)	Amitriptyline, Nortriptyline	Higher risk of arrhythmias, orthostatic hypotension, and QTc prolongation.	Some studies find increased risk.	Anticholinergic side effects, weight gain, increased diabetes risk.
Other/Atypical	Mirtazapine, Bupropion	Generally lower cardiovascular risk than TCAs. Some studies link non-SSRIs to higher mortality risk.	Some studies link to increased risk (non-SSRIs).	Risks vary.

Conclusion: The Importance of Personalized Assessment

The question of whether antidepressants affect lifespan is complex, with research offering conflicting findings. While some studies suggest a potential link to reduced longevity, more robust analyses controlling for underlying depression severity and other health factors often find no significant association with overall mortality. Untreated depression itself is known to increase health risks and shorten life expectancy.

Ultimately, the decision regarding long-term antidepressant use should involve a personalized assessment of risks and benefits with a healthcare provider. For many, the advantages of effectively treating depression, such as reducing suicide risk and improving quality of life, may outweigh the potential long-term risks.

List of Factors Influencing Antidepressant Effects on Longevity

Underlying Depression Severity: A strong predictor of reduced lifespan, independent of medication.
Comorbidities: Pre-existing physical health conditions can interact with antidepressant effects.
Medication Class: Different types carry distinct risk profiles.
Duration of Use: Requires ongoing monitoring for long-term side effects.
Lifestyle Factors: Independently influenced by depression and affect overall health.
Confounding by Indication: Challenges separating medication effects from baseline patient health.
Response to Treatment: Successful treatment positively influences health and potentially lifespan.
Patient Vulnerability: Individual factors like age, genetics, and other risk factors modify the safety profile.

Frequently Asked Questions

Yes, extensive research shows that untreated depression can significantly shorten a person's lifespan. This is due to an increased risk of suicide, as well as higher rates of chronic physical illnesses like cardiovascular disease and diabetes, often worsened by the unhealthy behaviors associated with depression.

No, the findings are conflicting. While some observational studies have suggested an increased risk, more recent and robust studies that carefully control for confounding factors like depression severity and comorbidities have found no statistically significant link between overall antidepressant use and all-cause mortality.

'Confounding by indication' is a methodological challenge where sicker patients, who are at higher risk of adverse outcomes, are more likely to be prescribed a medication. In the context of antidepressants, this means that those taking the drugs may have more severe depression or more comorbidities, which are the true cause of increased mortality, not the medication itself.

Yes, different classes of antidepressants have varying long-term safety profiles. Older tricyclic antidepressants (TCAs) are known for higher cardiovascular risks than newer selective serotonin reuptake inhibitors (SSRIs), though long-term data for all classes is still evolving.

Long-term SSRI side effects can include sexual dysfunction (including persistent symptoms after discontinuation, or PSSD), weight gain, emotional blunting, metabolic changes potentially increasing diabetes risk, and effects on bone health.

Patients should approach this decision in a balanced way with their healthcare provider. The known risks of untreated depression, including shortened lifespan, must be weighed against the potential long-term side effects of medication. Open communication and regular monitoring are crucial to ensure the treatment plan remains appropriate.

Some recent research, particularly a 2025 study presented at a European heart conference, suggests a link between long-term antidepressant use and an increased risk of sudden cardiac death, especially in middle-aged individuals. However, this is an area of ongoing research, and the findings are observational, requiring further investigation to confirm causality.