Hyponatremia from SSRIs: Low Sodium and Confusion Risk in Elderly Patients

When you start an SSRI for depression, you expect better mood, more energy, maybe a good night’s sleep. But for some people-especially those over 65-something far more dangerous can happen: hyponatremia. That’s when your blood sodium drops too low, and your brain starts to swell. The symptoms? Confusion, dizziness, nausea, headaches. In severe cases, seizures, coma, or even death. This isn’t rare. It’s one of the most common and serious side effects of SSRIs, yet most patients never hear about it before they start taking the drug.

How SSRIs Cause Low Sodium

SSRIs like sertraline, citalopram, fluoxetine, and paroxetine work by increasing serotonin in the brain. That’s how they help with depression. But serotonin doesn’t just affect mood. It also talks to your kidneys and brain through receptors that control how much water your body holds onto. When serotonin levels rise too much, your body releases too much antidiuretic hormone (ADH). This hormone tells your kidneys to hold onto water instead of flushing it out. The result? Your blood gets diluted. Sodium levels drop. You end up with hyponatremia-serum sodium below 135 mmol/L.

This isn’t a slow, quiet process. It usually happens within two to four weeks of starting the medication or increasing the dose. That’s why so many cases are missed. Doctors and patients assume confusion or fatigue in older adults is just part of aging. But it could be your sodium dropping dangerously low.

Who’s at Highest Risk?

Not everyone on SSRIs gets hyponatremia. But some groups are at much higher risk:

• People over 65 - Their kidneys don’t handle fluid as well, and their hormone systems are more sensitive. Incidence hits 13.9% to 18.6% in this group.
• Women - Over 65% of documented cases are in women, likely due to body composition and hormonal differences.
• People on diuretics - Especially thiazide diuretics like hydrochlorothiazide. Using them with an SSRI raises your risk by over four times.
• Those with low body weight - Under 60 kg? Your blood volume is smaller. Even a small water gain can tank your sodium.
• People with kidney problems - If your eGFR is below 60 mL/min, your body can’t clear excess water effectively.

A 78-year-old woman in a 2022 case report developed sodium levels of 118 mmol/L-life-threateningly low-just 10 days after starting sertraline. She ended up in the ICU. Another case from early 2024 involved an 82-year-old woman whose family noticed she was “acting like a different person.” Her sodium was 122 mmol/L. She had been on citalopram for two weeks. No one told them this could happen.

How to Spot It Early

The early signs of hyponatremia are easy to miss:

• Mild nausea or loss of appetite
• Headaches that won’t go away
• Feeling unusually tired or weak
• Confusion or trouble remembering things
• Balance problems or unexplained falls

These symptoms look exactly like dementia, depression worsening, or just getting older. That’s why it’s so often misdiagnosed. The average time from symptom start to correct diagnosis? Over seven days. By then, sodium levels may already be below 125 mmol/L-danger zone.

There’s no home test for sodium. But if you’re on an SSRI and start feeling off, especially within the first month, ask your doctor for a simple blood test. A serum sodium level is quick, cheap, and can save your life.

What Doctors Should Do

The American Psychiatric Association and the American Geriatrics Society now say: Test before you start. Baseline sodium should be checked within 7 days before beginning an SSRI. Then, test again at 2 weeks. For high-risk patients-those over 65, on diuretics, or with kidney issues-monthly checks for the first three months are recommended.

If sodium drops below 135 mmol/L and you’re on an SSRI, the first step is almost always stopping the drug. For mild cases (125-134 mmol/L), fluid restriction to 800-1000 mL per day and stopping the SSRI usually fixes it in 72 to 96 hours. Severe cases-below 125 mmol/L-need hospitalization. Intravenous hypertonic saline (3%) is given slowly, no more than 6-8 mmol/L increase in the first 24 hours. Too fast, and you risk permanent brain damage from osmotic demyelination.

Alternatives to SSRIs That Are Safer

Not all antidepressants carry the same risk. Here’s what the data shows:

Hyponatremia Risk Comparison Across Antidepressants

Medication	Risk Relative to SSRIs	Notes
Citalopram	2.37x higher	Highest risk among SSRIs
Sertraline	2.15x higher	Very commonly prescribed
Fluoxetine	1.98x higher	Long half-life, risk lasts longer
Paroxetine	1.82x higher	Also causes more dry mouth and constipation
Venlafaxine (SNRI)	1.72x higher	Still higher risk than non-SSRIs
Amitriptyline (TCA)	1.94x higher	Older drug, more side effects
Bupropion	0.85x (lower)	Doesn’t affect serotonin; safest SSRI alternative
Mirtazapine	0.47x (much lower)	Best choice for elderly patients

For older adults, mirtazapine is now the go-to alternative. It works differently-it doesn’t boost serotonin the same way. It’s not perfect (it can cause weight gain and drowsiness), but its hyponatremia risk is less than half that of SSRIs. In fact, for every 1,000 elderly patients switched from SSRIs to mirtazapine, about 12 cases of hyponatremia are prevented each year.

Why This Isn’t Common Knowledge

Only 28.7% of patients surveyed in 2023 said they were told about hyponatremia risk before starting an SSRI. And 63.4% of primary care doctors didn’t know the typical onset window was 2-4 weeks. That’s not because they’re careless. It’s because this risk has been buried in fine print for years. FDA labeling now requires hyponatremia warnings, but many prescribers still don’t read them.

Meanwhile, prescribing patterns are changing. Between 2018 and 2023, SSRI use in patients over 65 dropped 22.3%. Mirtazapine prescriptions for the same group jumped 34.7%. The cost of treating SSRI-induced hyponatremia in the U.S. alone? Over $1.27 billion a year-mostly from ER visits and hospital stays that could have been avoided.

What You Should Do

If you or a loved one is on an SSRI:

• Ask for a baseline sodium test before starting.
• Request a repeat test at 2 weeks.
• Watch for confusion, nausea, or unexplained fatigue-especially in older adults.
• If you’re over 65, ask if mirtazapine or bupropion might be a safer option.
• Don’t assume confusion is “just aging.” Low sodium is reversible. Dementia isn’t.

Depression is serious. But so is hyponatremia. You don’t have to choose between treating your mood and risking your brain. With the right testing and alternatives, you can do both safely.