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

When you start an SSRI for depression, you expect to feel better - not confused, dizzy, or suddenly unable to think clearly. But for some people, especially older adults, the very medication meant to lift their mood can trigger a dangerous drop in sodium levels. This isn’t rare. It’s not a myth. It’s a well-documented, preventable risk tied directly to how SSRIs interact with your body’s water balance.

What Exactly Is Hyponatremia?

Hyponatremia means your blood sodium is too low - 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 drops too far, water floods into your cells, including brain cells. That’s when things get serious: confusion, headaches, nausea, seizures, and in extreme cases, coma or death.

Studies show that SSRIs - drugs like citalopram, sertraline, fluoxetine, and paroxetine - are among the most common causes of drug-induced hyponatremia. In people over 65, the risk jumps to nearly 1 in 6. That’s not a small number. It’s a major safety issue.

Why Do SSRIs Lower Sodium?

It comes down to serotonin. SSRIs boost serotonin in your brain to improve mood. But serotonin also acts on your hypothalamus - the part of your brain that controls antidiuretic hormone (ADH). Too much serotonin = too much ADH. That tells your kidneys to hold onto water instead of flushing it out.

Result? Your body keeps water, but sodium stays the same. So your blood gets diluted. Sodium levels sink. This is called SIADH - syndrome of inappropriate antidiuretic hormone secretion. It’s not a side effect you can just ‘tough out.’ It’s a physiological chain reaction that starts within days of starting or increasing an SSRI dose.

Who’s at Highest Risk?

Not everyone on SSRIs gets hyponatremia. But certain people are far more vulnerable:

• Age 65+: Risk triples. The older you are, the less your kidneys can adjust to fluid shifts.
• Women: Over 65% of reported cases are in women, likely due to lower body weight and hormonal differences.
• Low body weight (under 60 kg): Less total body water means even small fluid changes have bigger effects.
• Renal impairment: If your eGFR is below 60, your kidneys can’t clear excess water efficiently.
• On diuretics: Especially thiazides. Taking a water pill with an SSRI increases hyponatremia risk by over four times.
• Starting or increasing dose: The biggest spike in risk happens in the first two to four weeks.

One case from a Reddit caregiver in March 2024 described her 82-year-old mother becoming severely confused two weeks after starting citalopram. Sodium dropped to 122 mmol/L. She was hospitalized. The medication was stopped. It took days to recover. This isn’t unusual.

Which SSRIs Are Most Dangerous?

Not all SSRIs carry the same risk. Data from the 2024 European Psychiatry meta-analysis shows clear differences:

SSRI Hyponatremia Risk Compared to Other Antidepressants

Medication	Risk vs. Non-SSRI	Notes
Citalopram	2.37x higher	Highest risk among SSRIs
Sertraline	2.15x higher	Commonly prescribed, high incidence
Fluoxetine	1.98x higher	Long half-life - risk persists
Paroxetine	1.82x higher	Strong anticholinergic effects add complexity
Mirtazapine	0.47x (lower)	Safest alternative for elderly
Bupropion	0.85x (lower)	Non-serotonergic - minimal hyponatremia risk
Venlafaxine (SNRI)	1.72x higher	Still higher than mirtazapine

For every 1,000 people treated with SSRIs, about 19 develop hyponatremia. With mirtazapine? Only 7. That’s a number needed to harm (NNH) of 82 - meaning you’d have to treat 82 people with an SSRI instead of mirtazapine to cause one extra case of low sodium.

What Do Symptoms Look Like?

Early signs are often mistaken for aging, dementia, or just ‘getting older.’ That’s the problem.

• Mild: Headache, nausea, fatigue, loss of appetite
• Moderate: Confusion, trouble concentrating, dizziness, muscle weakness
• Severe: Seizures, slurred speech, loss of coordination, coma

One study found patients waited an average of 7.2 days before their hyponatremia was correctly diagnosed. In elderly patients, doctors often assume confusion is Alzheimer’s or just depression worsening - not a drug reaction. That delay can be deadly.

What Should Doctors Do?

The American Psychiatric Association and the American Geriatrics Society now say: test sodium before starting SSRIs.

• Baseline test: Do a blood test for sodium within 7 days before starting an SSRI.
• Repeat at 2 weeks: That’s when levels usually drop.
• High-risk patients: Check monthly for the first 3 months.

And here’s the kicker: 63% of primary care doctors didn’t even know the typical onset window is 2-4 weeks. If your doctor didn’t mention testing, ask. It’s simple. It’s cheap. It’s life-saving.

What If Sodium Is Already Low?

If sodium is between 125-134 mmol/L:

• Stop the SSRI immediately
• Restrict fluids to 800-1000 mL per day
• Recheck sodium every 12-24 hours
• Most cases improve within 72 hours

If sodium is below 125 mmol/L - it’s an emergency. Hospitalization is required. Treatment involves slow IV infusion of 3% hypertonic saline. But here’s the catch: correcting sodium too fast can cause osmotic demyelination syndrome - a devastating brain injury. Doctors must move slowly: no more than 6-8 mmol/L increase in the first 24 hours.

What Are the Safer Alternatives?

If you’re over 65, or have kidney issues, or take diuretics - consider switching away from SSRIs.

• Mirtazapine: Lowest risk. Doesn’t affect serotonin in the same way. Often used for sleep and appetite too.
• Bupropion: Works on dopamine and norepinephrine, not serotonin. Minimal hyponatremia risk.
• Nortriptyline (a TCA): Lower risk than amitriptyline. Still needs monitoring, but better than SSRIs in high-risk groups.

Between 2018 and 2023, SSRI use in people over 65 dropped 22%. Mirtazapine prescriptions for that group rose 35%. That’s not a coincidence. Doctors are learning.

Why Isn’t This Common Knowledge?

Only 28.7% of patients surveyed in 2023 said they were warned about hyponatremia before starting an SSRI. That’s unacceptable. The FDA updated SSRI labels in 2022 to include this risk. But warnings on a pill bottle don’t reach most patients. It falls to the prescriber.

And here’s the reality: SSRIs are still the most prescribed antidepressants in the U.S. - over 214 million prescriptions in 2023. That means millions are still being started without sodium checks. The annual cost of hospitalizations for this preventable issue? Over $890 million in the U.S. alone.

What Should You Do?

If you or a loved one is on an SSRI:

• Ask your doctor: “Have my sodium levels been checked?”
• Watch for new confusion, nausea, or headaches - especially in the first month.
• If symptoms appear, don’t wait. Get a blood test. Sodium levels can drop fast.
• If you’re over 65 and starting antidepressants, ask if mirtazapine or bupropion are options.

Depression is serious. But so is hyponatremia. You don’t have to choose between them. With the right screening and smarter choices, you can treat depression safely - without risking brain damage from low sodium.

Hyponatremia from SSRIs isn’t a glitch. It’s a predictable, preventable outcome. The science is clear. The tools exist. What’s missing is routine action. If you’re prescribing, testing, or taking these drugs - don’t wait for confusion to become a crisis. Ask the question. Get the test. Choose the safer option. Your brain will thank you.