Trazodone For Longevity & Aging: What Research Shows Today

October 13, 2025/Adrian Blackwell

Trazodone has been prescribed for decades as an antidepressant, and it’s often used off-label to help people with sleep problems.

Yet even after all these years, researchers are still uncovering how it really works. Its effects reach beyond mood and sleep, raising new questions about what else this medicine might influence.

Could trazodone affect not just how you feel day to day, but even how long you live? In this article, you’ll find what current science suggests, along with the unanswered questions that still remain.

🔑 Key takeaways

➤ Trazodone works in multiple ways. It boosts serotonin activity, blocks certain serotonin receptors, and affects histamine and adrenergic pathways, which explains both its antidepressant effects and its sedative properties.

➤ Its main approved use is depression, but in practice, it’s widely prescribed off-label for insomnia, anxiety, PTSD-related nightmares, and dementia-related agitation.

➤ Improved mood and sleep with trazodone can indirectly support healthier aging, since better rest, activity, and engagement with self-care often follow effective treatment.

➤ There is growing research interest in brain protection, with animal studies showing reduced cell death, better memory, and even longer survival, though human results remain inconsistent.

➤ Sleep continuity is one of its strongest benefits, and better sleep is closely linked with improved cognition, heart health, and long-term survival.

➤ Trazodone is not without risks, especially in older adults, who are more prone to falls, low sodium, blood pressure drops, and fainting.

How does trazodone work in the body?

Trazodone is an antidepressant that belongs to a group of medicines called serotonin antagonist and reuptake inhibitors (SARIs). It mainly increases serotonin by slowing down how quickly it’s reabsorbed, and it also blocks certain serotonin receptors like 5-HT2A and 5-HT2C.

On top of that, it affects histamine and alpha-1 adrenergic receptors, which explains why it often makes people feel drowsy. Scientists don’t fully understand everything about how trazodone works, which is why it’s used for a variety of conditions.

Recent studies also suggest it may reduce inflammation in brain cells called astrocytes, which could improve brain support functions that are often disrupted in depression.

What is trazodone used for?

Trazodone is officially approved to treat major depressive disorder and has been available since the early 1970s.

Research shows trazodone works about as well as other antidepressant classes like SSRIs, SNRIs, and TCAs when treating major depression. But unlike many SSRIs and SNRIs, trazodone causes fewer problems with insomnia, anxiety, or sexual side effects.

Off-label uses of trazodone

Doctors often prescribe it in low doses to help with insomnia. A review found that there is enough evidence to support the effectiveness and general safety of low-dose trazodone as a treatment for insomnia, though it is still considered an off-label use.

Beyond sleep, trazodone is sometimes prescribed off-label for conditions such as:

  • Anxiety
  • Alzheimer’s disease
  • Substance misuse
  • Bulimia nervosa
  • Fibromyalgia

In 2018, the American Academy of Sleep Medicine recommended trazodone as a treatment option for PTSD-related nightmares.

An 8-week PTSD treatment program showed that doses between 50 and 200 mg reduced nightmares and improved sleep in patients with PTSD. That said, it’s not the first choice, because in some people with panic symptoms, trazodone has made things worse.

Trazodone has also been studied in obstructive sleep apnea (OSA). Research shows it can reduce the number of apnea (pauses in breathing) and hypopnea (shallow breathing) episodes without worsening oxygen levels.

Potential benefits of trazodone for longevity

Beyond its role as an antidepressant, trazodone has drawn interest for possible links to longevity.

  1. Mood and day-to-day function

Depression can take a heavy toll on daily life. It often disrupts sleep, appetite, and the ability to keep up with regular routines like exercise or medical visits.

When treatment works and mood lifts, people usually start moving more, eating better, and staying engaged in self-care. These changes can support healthier aging in the long run.

In one case report, a 77-year-old widow had become tearful, withdrawn, and less able to care for herself. She also struggled with anxiety, sleep, and alcohol. She was diagnosed with moderate depression and anxiety, with evidence of cognitive decline from brain scans.

After 20 days of taking trazodone, her sleep and anxiety improved. After two months, she had much less anxiety and anguish, though some memory and attention problems persisted due to her underlying brain changes.

Another case describes a 66-year-old man with Parkinson’s disease who experienced worsening depression, anxiety, slowed movements, and poor sleep. His depression had previously responded to SSRIs and SNRIs, but this time neither worked.

Doctors decided to start trazodone in a once-a-day extended-release form, beginning at 150 mg and later increasing to 300 mg. Within weeks, his anxiety and depression improved, and after a month, his sleep quality was much better, with fewer nighttime restlessness episodes. His wife also reported he was less preoccupied with health and financial worries.

  1. Sleep continuity

Getting good sleep is one of the best things you can do for your health and longevity. Research shows that people with insomnia who also experience short sleep durations are two to four times more likely to develop heart disease and have a shorter lifespan.

That’s why in 2022 the American Heart Association (AHA) updated its checklist for heart health, turning “Life’s Simple 7” into “Life’s Essential 8” by adding sleep to the list.

When your sleep improves, your energy, mood, and focus often improve the next day too. Over time, steady sleep can also support brain health and metabolism.

In a 4-week study, patients taking trazodone had better sleep efficiency, more deep sleep, and fewer nighttime interruptions. The better their sleep quality, the better their memory and focus.

Another research looked at 25 older adults who had either Alzheimer’s disease, mild cognitive impairment, or normal cognition at the start. They were followed for about four years, with repeated cognitive testing.

Researchers found that people not taking trazodone declined 2.6 times faster on the Mini-Mental State Examination (MMSE), a common memory and thinking test. The benefit was strongest in people who reported improved sleep while on trazodone.

  1. Possible brain protection

A major series of experiments looked at existing drugs to see if any could help restore the brain’s ability to make proteins, which is a process that often stops in degenerating neurons. Out of all the drugs tested, trazodone was one of the few that showed promise and moved into animal studies.

In mice with prion disease, a fatal brain disorder caused by misfolded proteins, trazodone was shown to:

  • Improved memory
  • Prevented brain cell death
  • Reduced neurological symptoms
  • Helped the animals live longer

In mice with frontotemporal dementia, it also protected brain cells, rescued memory, and reduced brain shrinkage.

Trazodone even lowered levels of harmful tau protein, which disrupts cell communication, damages neurons, and contributes to memory loss and cognitive decline.

In a small human study, involving 26 patients with frontotemporal dementia, trazodone led to a significant reduction in behavioral symptoms, measured by the Neuropsychiatry Inventory (NPI) score. Ten patients (about 40%) improved by more than 50% on the NPI scale.

The biggest improvements were in irritability, agitation, depressive symptoms, and eating disorders. The drug was generally well tolerated, with no major side effects reported.

However, a recent meta-analysis found that trazodone can help some patients but carries a higher risk of side effects.

A systematic review also had mixed results. Some studies showed no effect on cognition, while others suggested trazodone helped by improving thinking or slowing decline. There were also studies that found trazodone actually worsened cognitive function.

So far, the benefits have only been seen in animal models. We don’t yet know whether trazodone can protect human brains in the same way or at the doses used in everyday medical practice.

Things to watch out for with trazodone

Even though trazodone has benefits, it also carries risks, especially in older adults.

Falls, fractures, and mortality

A large study looking at older adults who took trazodone for insomnia found that they were more likely to experience falls and even had a higher risk of death compared to similar people who weren’t treated for sleep issues.

Trazodone also does not appear to be a safer choice than antipsychotics when it comes to preventing falls or fractures in older adults with dementia.

In addition, trazodone may cause sudden drops in blood pressure when standing up, which makes falls more likely.

A 2025 study in older adults with high blood pressure showed that trazodone was linked to bigger drops in blood pressure upon standing. Fainting or falls occurred in 58% of trazodone users compared with only 21% of non-users.

Low sodium levels

Like many antidepressants, trazodone can sometimes cause hyponatremia (low sodium in the blood), especially in older adults and shortly after starting or increasing the dose.

Low sodium can trigger confusion, seizures, or more falls. A simple blood test in the first few weeks of treatment can help catch this problem early.

🎉 Fun fact!

A 2024 meta-analysis found that trazodone had the lowest risk of causing low sodium compared to SNRIs (like venlafaxine, duloxetine), SSRIs (like sertraline, fluoxetine), and older antidepressants (like TCAs, mirtazapine).

Heart rhythm concerns

Trazodone can affect a heart channel that helps regulate its rhythm. This may lengthen the heart’s recovery time between beats (QT interval prolongation) and, in rare cases, trigger irregular heart rhythms (arrhythmias).

Most people never notice an issue, but those with a history of long QT syndrome, recent heart attack, or those taking other QT-prolonging drugs should be cautious.

Rare but serious effects

A few rare but serious reactions can occur, including:

  • Priapism (a painful, prolonged erection) that requires urgent medical care
  • Serotonin syndrome, especially when combined with other drugs that raise serotonin levels
  • Risk of bleeding, especially when combined with other drugs that thin the blood or prevent clotting, like aspirin, NSAIDs (such as ibuprofen or naproxen), blood thinners (warfarin, apixaban, rivaroxaban), or antiplatelet drugs (like clopidogrel)
  • Angle-closure glaucoma
  • Activation of mania or hypomania, especially in people with bipolar disorder
  • Severe allergic reactions

These are all listed in trazodone’s official safety labeling.

Practical guidance if you are considering trazodone

These practical tips can help you weigh the pros and cons.

Who might be a reasonable candidate:

  • An adult with depression who has not responded to or tolerated first-line antidepressants and who would benefit from a sedating bedtime option.
  • A person with dementia who has distressing agitation or sleep disruption where non-drug steps have not worked and where antipsychotics are being considered. Some teams will try low-dose trazodone to limit antipsychotic exposure.
  • A person with insomnia who has already tried light therapy, regular sleep and wake hours, and cognitive behavioral therapy for insomnia. Short-term use at very low doses is common in practice, but formal guidelines often suggest non-drug care first.

Who should be cautious:

  • Adults with a history of falls or fainting.
  • Adults with orthostatic hypotension or neuropathy.
  • Adults on multiple drugs that lower blood pressure.
  • Adults on other serotonergic drugs that raise the chance of serotonin syndrome.
  • Adults with known long QT or who take other QT-prolonging agents.
  • Adults with hyponatremia in the past after taking an antidepressant.
  • Adults who drink heavily in the evening or who use other sedatives.

More importantly, trazodone treatment should always be personalized with a healthcare professional.

Decisions about dosing, safety checks such as blood tests or an ECG, and ongoing follow-ups depend on factors like your age, overall health, and other medications. For this reason, it’s best to work closely with your doctor or pharmacist.

Final thoughts

Trazodone helps by improving serotonin balance, calming the brain, and promoting sleep. It is officially used for depression but is often prescribed off-label for insomnia, anxiety, PTSD-related nightmares, and dementia-related agitation. Research shows it can improve sleep quality, daily function, and mood, with some evidence suggesting possible brain-protective effects.

For the right patient, trazodone can be useful, but it is not risk-free. Treatment should always be guided by a doctor, with proper monitoring to balance its benefits and safety.

FAQs on trazodone for longevity

Is trazodone addictive?

Trazodone is not considered addictive in the way that substances like benzodiazepines or opioids are. It does not produce a euphoric effect or cravings, which lowers its potential for abuse. However, stopping it suddenly after long-term use may cause withdrawal-like symptoms such as anxiety or sleep problems, so we recommend tapering under medical guidance.

Can trazodone help migraine?

Its effect on migraines is less studied, though improved sleep from trazodone may indirectly reduce headache frequency. A study back in 1993 suggested that trazodone may be a safe and useful option for preventing migraines in young people. But more research is needed to confirm this.

Can I take trazodone with other antidepressants?

Trazodone can sometimes be combined with other antidepressants, especially in treatment-resistant depression, but it requires careful medical supervision. Combining it with SSRIs, SNRIs, or MAOIs increases the risk of serotonin syndrome.

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Author Bio: Dr. Adrian Blackwell is the founder and CEO of PonteVita Rx, a telehealth practice dedicated to making medication access simpler, more affordable, and less stressful. Licensed to practice medicine in all 50 states and DC, Dr. Blackwell is board certified in obesity medicine and emergency medicine. He combines clinical expertise with personal experience navigating the healthcare system as a patient and parent to children with chronic illnesses. His mission: ensure everyone has access to their necessary medications without unnecessary barriers.

Medical Disclaimer: All the information here, on these videos, YouTube, social media, or in any other format, is for informational purposes only and is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Always consult your personal physician or other qualified health provider with any questions you may have regarding a medical condition. Never replace professional medical advice given to you personally or delay in seeking it because of something you have read or heard on this website. This information is not meant to diagnose, treat, or cure any medical condition. No patient-physician relationship is formed. If you’re my patient, please text me before you make any changes to your medication. If you believe you are having a medical emergency please call 911.

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