Hyponatremia from SSRIs: What You Need to Know About Low Sodium and Confusion Risk

When you start an SSRI for depression, you expect better mood, more energy, maybe a good night’s sleep. But you might not expect to feel confused, dizzy, or nauseous - especially if you’re over 65. These aren’t just "normal aging" symptoms. They could be signs of something far more dangerous: hyponatremia - dangerously low sodium in your blood - triggered by the very medication meant to help you feel better.

What Exactly Is Hyponatremia?

Hyponatremia means your blood sodium level has dropped below 135 mmol/L. Sodium isn’t just table salt. It’s a key electrolyte that helps your nerves, muscles, and brain work right. When sodium gets too diluted, your cells swell - especially brain cells. That’s when things get serious: confusion, seizures, coma, even death. Severe cases have seen sodium levels crash to 105-125 mmol/L. This isn’t rare. A 2024 meta-analysis found that nearly 1 in 25 people taking SSRIs develop this condition. For those over 65? It’s closer to 1 in 6.

Why Do SSRIs Cause This?

It’s not the depression itself. It’s how SSRIs interact with your body’s water balance. These drugs boost serotonin - that’s how they lift mood. But serotonin also signals your brain to release antidiuretic hormone (ADH). Too much ADH means your kidneys hold onto water instead of flushing it out. The result? More water in your blood, diluted sodium. This is called SIADH - Syndrome of Inappropriate Antidiuretic Hormone Secretion.

Not all SSRIs are the same. Citalopram and sertraline carry the highest risk. Fluoxetine and paroxetine follow close behind. Why? Because they bind tightly to the serotonin transporter (SERT). The stronger the binding, the more ADH gets released. It’s not just the drug - it’s how your body reacts to it.

Who’s Most at Risk?

This isn’t a random side effect. Certain people are far more vulnerable:

• Age 65+: Your kidneys don’t handle fluid the same way. Risk jumps to 13.9-18.6%.
• Women: Over 65% of reported cases are in women, likely due to body size and hormone differences.
• Low body weight (under 60 kg): Less total fluid means less buffer against dilution.
• Renal impairment: If your eGFR is below 60, your kidneys can’t clear excess water.
• On diuretics: Thiazide diuretics (like hydrochlorothiazide) increase risk by over 4 times.
• Rapid dose increases: Going from 10mg to 40mg of sertraline in a week? Big red flag.

Many people don’t realize they’re in the danger zone until it’s too late. That’s why doctors need to ask: Are you on a diuretic? Are you thin? Are you over 65? If yes, this isn’t just a routine prescription.

When Do Symptoms Show Up?

This isn’t a day-one side effect. Most cases show up between two and four weeks after starting the SSRI - or after a dose increase. That’s why so many cases get missed. A 78-year-old starts citalopram for sadness after losing her husband. Two weeks later, she’s forgetting names, stumbling, vomiting. Her family thinks it’s dementia. The doctor thinks it’s stress. But it’s hyponatremia. A simple blood test would’ve caught it.

Symptoms start mild: headache, nausea, fatigue. Then come the red flags: confusion, disorientation, trouble walking, seizures. In elderly patients, these are often mistaken for Alzheimer’s or just getting older. But they’re not. They’re a medical emergency.

What Does the Science Say About Other Antidepressants?

SSRIs aren’t the only option. And some are much safer:

Hyponatremia Risk Comparison Across Antidepressants

Medication	Risk Compared to SSRIs	Notes
Citalopram	2.37x higher	Highest risk among SSRIs
Sertraline	2.15x higher	Commonly prescribed, high risk
Fluoxetine	1.98x higher	Long half-life, risk lingers
Mirtazapine	0.47x (much lower)	Best alternative for elderly patients
Bupropion	0.85x (low)	Doesn’t affect serotonin - safer choice
Venlafaxine (SNRI)	1.72x higher	Still higher risk than mirtazapine
Amitriptyline (TCA)	1.94x higher	Older drug, higher side effect burden

Here’s the bottom line: If you’re over 65, or have kidney issues, or take a diuretic - mirtazapine is the safest antidepressant choice. It doesn’t trigger ADH release. It doesn’t cause hyponatremia at anything close to the same rate. The numbers don’t lie: for every 1,000 patients, SSRIs cause 18.6 cases of hyponatremia. Mirtazapine? Only 6.5. That’s a 65% lower risk.

What Should You Do Before Starting an SSRI?

You wouldn’t start a new heart medication without checking your blood pressure. Don’t start an SSRI without checking your sodium.

• Get a baseline blood test within 7 days before starting the SSRI.
• Repeat the test at 2 weeks - that’s when levels start dropping.
• For high-risk patients (over 65, on diuretics, kidney problems), test monthly for the first 3 months.

Many primary care doctors don’t know this. A 2023 survey found that 63% didn’t know the typical onset window (2-4 weeks). If your doctor doesn’t mention testing, ask. Say: "I’ve heard SSRIs can cause low sodium. Can we check my levels before and after I start?"

What Happens If You Develop Hyponatremia?

If sodium is between 125-134 mmol/L and you’re not having seizures:

• Stop the SSRI immediately.
• Restrict fluids to 800-1000 mL per day (no more than 3-4 cups).
• Recheck sodium in 24-48 hours. Most people recover fully in 3-4 days.

If sodium drops below 125 mmol/L - this is life-threatening. You need the hospital. Treatment involves slow, controlled IV saline to raise sodium no more than 6-8 mmol/L in the first 24 hours. Too fast, and you risk permanent brain damage called osmotic demyelination syndrome.

Recovery isn’t instant. One Reddit user shared that their 82-year-old mother spent 5 days in the hospital after citalopram dropped her sodium to 122. She was confused for weeks after. Her memory didn’t fully bounce back.

Why Is This Still Underdiagnosed?

Because symptoms look like other things. Confusion? Must be dementia. Nausea? Just a stomach bug. Fatigue? Old age. In 2023, only 28.7% of patients were told about this risk before starting SSRIs. That’s not informed consent - that’s negligence.

And it’s expensive. In the U.S. alone, SSRI-induced hyponatremia costs $1.27 billion a year - mostly from ER visits and hospital stays. The FDA now requires SSRI labels to warn about this. But warnings don’t fix ignorance.

What’s Changing in 2025?

The tide is turning. Between 2018 and 2023, SSRI use in patients over 65 dropped 22%. Mirtazapine prescriptions for that group rose 35%. The American Geriatrics Society now lists SSRIs as "potentially inappropriate" for older adults. The European Medicines Agency is reviewing SSRI safety - results expected by fall 2025.

By 2027, mirtazapine could be prescribed to over 40% of elderly patients needing antidepressants. That’s not a trend - it’s a correction.

Final Thoughts: Balance Risk and Benefit

SSRIs work. They save lives. But they’re not risk-free. In young, healthy adults, the chance of hyponatremia is low - maybe 1 in 50. The benefit of lifting depression often outweighs that risk. But for older adults, especially those on other meds or with kidney issues? The math flips.

If you’re over 65, and your doctor suggests an SSRI, ask: "Is there a safer alternative?" Say "mirtazapine" or "bupropion." Don’t wait for confusion to set in. Don’t assume it’s just aging. Sodium levels can drop quietly - and dangerously - before you feel anything.

Ask for the blood test. Know the signs. Push for the right drug. Your brain deserves more than a guess.

What to Do Next

If you’re taking an SSRI and you’re over 65, on a diuretic, or have kidney disease:

• Ask for your last sodium level.
• Ask if you need another test in the next two weeks.
• Ask if mirtazapine or bupropion might be a safer option.
• If you’ve been feeling off - confused, tired, nauseous - don’t brush it off. Get tested.

This isn’t about avoiding antidepressants. It’s about choosing the right one - safely. Your mental health matters. So does your sodium. Don’t let one save you while the other puts you at risk.