Hyponatremia from SSRIs: Low Sodium and Confusion Risk in Older Adults

When you start an SSRI for depression, you expect to feel better - not worse. But for some people, especially older adults, a quiet but dangerous side effect can sneak in: hyponatremia. That’s when your blood sodium drops too low, and your body starts holding onto water like a sponge. The result? Confusion, dizziness, nausea, and in severe cases, seizures or coma. It’s not rare. It’s not theoretical. It’s happening right now in homes and clinics across the UK and beyond.

What Exactly Is Hyponatremia?

Hyponatremia means your blood sodium level falls below 135 mmol/L. Normal sodium? Between 135 and 145. When it dips below that, your brain cells swell with extra water. Your brain doesn’t have room to expand, so it starts to malfunction. That’s why people get confused, forget names, stumble, or seem "just off" - like they’re aging faster than they should. In extreme cases, sodium can crash to 118 mmol/L or lower. That’s life-threatening.

This isn’t just a side effect. It’s a direct chemical reaction. SSRIs - drugs like citalopram, sertraline, fluoxetine, and paroxetine - boost serotonin in the brain. That’s how they help with mood. But serotonin doesn’t just affect your emotions. It also talks to your pituitary gland and tells it to release more antidiuretic hormone (ADH). ADH makes your kidneys hold onto water. More water in your blood? Sodium gets diluted. That’s SIADH - Syndrome of Inappropriate Antidiuretic Hormone Secretion. It’s the root cause.

Who’s at Highest Risk?

Not everyone on SSRIs gets this. But some people are far more vulnerable.

• Age 65 and older: Risk jumps to nearly 1 in 6. Their kidneys don’t clear water as well, and their bodies are less able to balance fluids.
• Women: Over 65% of documented cases are in women, possibly due to body composition and hormone differences.
• Low body weight: People under 60 kg are more sensitive to drug effects.
• Already on diuretics: Thiazide diuretics (like hydrochlorothiazide) make the risk 4 times worse. Many older adults take them for high blood pressure - and then get an SSRI on top.
• Pre-existing kidney issues: If your eGFR is below 60, your kidneys are already struggling. Adding an SSRI can push them over the edge.

One case from a Reddit post in March 2024 tells the story: an 82-year-old woman started citalopram for depression. Two weeks later, she was so confused she couldn’t recognize her own daughter. Her sodium was 122 mmol/L. She ended up in the hospital. The doctor didn’t connect the dots until the blood test came back. That’s not unusual. In fact, studies show it takes an average of 7 days for hyponatremia to be correctly diagnosed in older patients - because symptoms look like dementia or just "getting old."

When Does It Happen?

Timing matters. This isn’t something that shows up on day one. It usually appears between two and four weeks after starting the SSRI - or after a dose increase. That’s why many doctors miss it. They check in at week one, see no issues, and assume everything’s fine. But the real danger window is weeks two to six.

That’s why the American Psychiatric Association now says: baseline sodium test before starting an SSRI, and another at two weeks. For anyone over 65, or on other risk factors, monthly checks for the first three months are recommended. Simple blood test. Zero cost. Could save a life.

Which SSRIs Are Riskiest?

Not all SSRIs are equal. Some are far more likely to trigger hyponatremia.

According to a 2024 meta-analysis of over 30 studies:

• Citalopram: Highest risk - 2.37 times more likely than non-SSRIs
• Sertraline: 2.15 times higher risk
• Fluoxetine: 1.98 times higher risk
• Paroxetine: 1.82 times higher risk

Why? It comes down to how tightly these drugs bind to the serotonin transporter (SERT). The tighter the grip, the more serotonin is released in the brain - and the more ADH gets triggered. Citalopram has the strongest binding. That’s why it’s the most dangerous.

And here’s the kicker: the FDA now requires all SSRI labels to clearly warn about hyponatremia risk. But most patients never see it. A 2023 survey found only 28.7% of people starting SSRIs were told about this side effect. That’s not informed consent. That’s negligence.

What Are the Safer Alternatives?

You don’t have to give up on treatment. There are antidepressants with much lower risk.

Mirtazapine is the standout. It’s not an SSRI. It works differently - blocking certain serotonin receptors instead of boosting them. And it doesn’t trigger ADH release. Studies show its hyponatremia risk is less than half that of SSRIs. In fact, it’s the safest option for older adults. The American Geriatrics Society’s 2023 Beers Criteria explicitly recommends mirtazapine over SSRIs for seniors.

Here’s the real number: for every 1,000 older adults treated with SSRIs, about 18.6 will develop hyponatremia. With mirtazapine? Only 6.5. That’s a number needed to harm (NNH) of 82. Meaning, if you switch 82 elderly patients from an SSRI to mirtazapine, you prevent one case of dangerous low sodium.

Bupropion (Wellbutrin) is another good alternative. It doesn’t affect serotonin much - it works on dopamine and norepinephrine. Its risk is nearly the same as non-SSRI antidepressants. SNRIs like venlafaxine and duloxetine carry moderate risk - higher than mirtazapine, but lower than citalopram.

What Happens If It’s Not Caught?

Mild hyponatremia (125-134 mmol/L) might just cause headaches, nausea, or fatigue. People write it off as the flu. But if it drops below 125, things get dangerous fast.

Severe cases require hospitalization. Treatment? Intravenous 3% saline - but carefully. Too fast, and you risk osmotic demyelination syndrome - a condition that destroys brain cells and can leave someone permanently disabled. Recovery takes days. Sodium levels usually take 72 to 96 hours to normalize after stopping the SSRI.

And it’s not just the sodium. Some patients develop serotonin syndrome at the same time - a rare but deadly mix of high serotonin causing muscle rigidity, fever, and confusion. One 78-year-old woman in a 2022 case report was admitted to the ICU after starting sertraline. Her sodium was 118. She had fever and tremors. She spent five days in intensive care.

What Should You Do?

If you or a loved one is on an SSRI - especially if over 65 - here’s what you need to do:

1. Ask for a baseline sodium test before starting the medication.
2. Request a repeat test at two weeks - no excuses.
3. Watch for early signs: headaches, nausea, feeling "foggy," unexplained tiredness, loss of balance.
4. Don’t assume it’s aging. Confusion in an older person is not normal. It’s a red flag.
5. Ask about alternatives. Is mirtazapine an option? Is bupropion right for you?
6. If you’re on a diuretic, tell your psychiatrist. This combo is a ticking time bomb.

Doctors aren’t always up to speed. A 2023 survey found that 63.4% of primary care physicians didn’t know hyponatremia typically shows up at 2-4 weeks. That’s why you need to be your own advocate.

The Bigger Picture

SSRIs are still the most prescribed antidepressants in the world. In the US alone, over 214 million were filled in 2023. But things are changing. Between 2018 and 2023, SSRI prescriptions for people over 65 dropped by 22.3%. Meanwhile, mirtazapine prescriptions for that group rose by 34.7%. That’s not coincidence. It’s evidence.

The cost of ignoring this? $1.27 billion a year in the US - mostly for hospital stays and ER visits. That’s not just money. It’s lost time, lost independence, lost dignity.

By 2027, mirtazapine is expected to be prescribed to over 40% of older adults starting antidepressants. That’s the future. And it’s a better one.

You don’t have to choose between depression and danger. There’s a safer path. You just need to ask for it.