Hyponatremia from SSRIs: How Low Sodium and Confusion Risk Affect Antidepressant Use

When you start an SSRI for depression, you expect better mood, more energy, maybe better sleep. You don’t expect to become confused, nauseous, or stumble like you’re drunk. Yet for some people-especially older adults-this is exactly what happens. It’s not dementia. It’s not aging. It’s hyponatremia-a dangerous drop in blood sodium caused by the very medication meant to help.

What Is Hyponatremia, Really?

Hyponatremia means your blood sodium level has fallen below 135 mmol/L. Sodium isn’t just table salt. It’s a key electrolyte that keeps your nerves, muscles, and brain working right. When sodium drops too low, water floods into your cells-including brain cells. That’s when confusion, dizziness, headaches, and seizures start. In severe cases, sodium can plunge to 118 mmol/L or lower, leading to coma or death.

This isn’t rare. A 2024 meta-analysis in European Psychiatry found that 1.9% to 4.4% of people taking SSRIs develop hyponatremia. But for those over 65? The risk jumps to nearly 1 in 6. That’s not a small side effect. It’s a major clinical hazard.

Why Do SSRIs Cause Low Sodium?

SSRIs boost serotonin in your brain to fight depression. But serotonin doesn’t just stay in the brain. It also triggers the release of antidiuretic hormone (ADH), which tells your kidneys to hold onto water. Normally, your body balances water and sodium. But too much ADH? Your kidneys keep water, dilute your blood, and sodium levels crash.

This is called SIADH-Syndrome of Inappropriate Antidiuretic Hormone Secretion. It’s not a mistake. It’s a direct pharmacological effect. The stronger the SSRI binds to the serotonin transporter (SERT), the higher the risk. That’s why citalopram and sertraline carry the highest risk, followed by fluoxetine and paroxetine.

It’s not just the drug. It’s who’s taking it. Women, people under 60 kg, those with kidney issues (eGFR below 60), and anyone on diuretics-especially thiazides-are at much higher risk. Combine SSRI with a water pill? Your hyponatremia risk shoots up 4.2 times.

When Does It Happen?

Most cases show up within two to four weeks of starting the SSRI-or after a dose increase. That’s why many doctors miss it. They assume confusion in an elderly patient is just dementia. Or they think nausea is just stomach flu. The symptoms are subtle at first: fatigue, headache, feeling off. Then it escalates: disorientation, falls, seizures.

A 78-year-old woman in a 2022 case report started sertraline at 50 mg daily. Ten days later, her sodium dropped to 118 mmol/L. She ended up in the ICU. Another case from Reddit: an 82-year-old woman on citalopram became so confused her family thought she had a stroke. Her sodium? 122 mmol/L. She needed hospitalization. Both cases were misdiagnosed for days.

On average, it takes 7.2 days from symptom onset to the correct diagnosis. That’s a lot of time for brain swelling to happen.

Who’s at Highest Risk?

It’s not random. Certain people are far more vulnerable:

• Age 65+: Risk is 3.7 times higher than younger adults
• Women: 65% of reported cases are female
• Low body weight: Under 60 kg increases susceptibility
• Chronic kidney disease: eGFR below 60 means less ability to excrete excess water
• On diuretics: Especially hydrochlorothiazide
• Multiple medications: Polypharmacy increases interaction risk

And here’s the kicker: only 28.7% of patients report being told about this risk before starting SSRIs. That’s not informed consent. That’s negligence.

How Do Doctors Miss It?

A 2023 survey in The Carlat Report found that 63.4% of primary care doctors didn’t know hyponatremia typically develops 2-4 weeks after starting an SSRI. Many assume symptoms are behavioral or neurological decline. In nursing homes, hyponatremia is often chalked up to “getting older.”

But the signs are there. If an elderly patient suddenly becomes confused, falls more often, or loses appetite, check their sodium. It’s a simple blood test. Yet, in 37.8% of mild cases, it goes undetected in primary care. That’s why so many end up in the ER-or worse.

What About Other Antidepressants?

Not all antidepressants are equal when it comes to sodium risk.

SSRIs as a class have 2.86 times higher risk than non-SSRIs. But some alternatives are much safer:

Hyponatremia Risk Comparison Among Antidepressants

Medication	Risk Relative to SSRIs	Notes
Citalopram	2.37x	Highest risk SSRI
Sertraline	2.15x	Commonly prescribed, high risk
Fluoxetine	1.98x	Long half-life, risk lingers
Paroxetine	1.82x	Also anticholinergic, adds confusion risk
Venlafaxine (SNRI)	1.72x	Moderate risk
Amitriptyline (TCA)	1.94x	Higher risk than nortriptyline
Bupropion	0.85x	Lower risk, no serotonin effect
Mirtazapine	0.47x	Lowest risk-recommended for elderly

For older adults, mirtazapine is now the preferred first-line option. It doesn’t affect serotonin the same way. No SIADH. No water retention. No sodium crash. Studies show that for every 1,000 elderly patients switched from SSRIs to mirtazapine, you prevent 12 cases of hyponatremia. That’s not just safer-it’s life-saving.

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. Get it repeated at 2 weeks after starting or increasing the dose.
3. Watch for early signs: Headache, nausea, fatigue, mild confusion.
4. Don’t assume it’s aging. Confusion in the elderly is not normal.
5. Ask about alternatives. Is mirtazapine or bupropion an option?
6. Report any changes to your doctor immediately-even if they seem minor.

The American Psychiatric Association and American Geriatrics Society now recommend sodium testing before and within two weeks of starting antidepressants in older adults. This isn’t optional. It’s standard care.

What Happens If It’s Diagnosed?

If sodium is below 135 mmol/L and symptoms are present:

• Mild (125-134 mmol/L): Stop the SSRI. Restrict fluids to 800-1,000 mL per day. Sodium usually normalizes in 3-4 days.
• Severe (<125 mmol/L): Hospitalization. IV hypertonic saline (3%) at controlled rates. Too fast? You risk osmotic demyelination-a permanent brain injury.

Recovery takes time. Even after sodium normalizes, brain fog and balance issues can linger for weeks. That’s why prevention matters more than treatment.

The Bigger Picture

SSRIs are still the most prescribed antidepressants in the U.S.-over 214 million prescriptions in 2023. But prescribing patterns are shifting. Between 2018 and 2023, SSRI use in patients over 65 dropped by 22.3%. Meanwhile, mirtazapine prescriptions for seniors rose by 34.7%.

The cost? $1.27 billion annually in the U.S. for hospitalizations and ER visits tied to SSRI-induced hyponatremia. That’s not just a medical issue. It’s a financial and human crisis.

The FDA now requires SSRI labels to include hyponatremia warnings. The European Medicines Agency is reviewing safety data. And by 2027, mirtazapine is projected to be the top antidepressant for patients over 65.

Final Thought

Antidepressants save lives. But they can also harm-especially when we ignore the science. Hyponatremia isn’t a rare side effect. It’s a predictable, preventable danger. For younger adults with no other health issues, the benefits often outweigh the risks. But for older adults? The math changes.

There’s no reason to risk confusion, falls, or brain damage when safer alternatives exist. Ask the questions. Demand the test. Push for the right medication. Your brain-and your life-deserve nothing less.