Lithium Toxicity: How Diuretics and NSAIDs Raise Risk and What to Do

Most people don’t realize that a common mood stabilizer like lithium can turn dangerous with just a simple over-the-counter painkiller or a water pill. Lithium has been used for over 50 years to treat bipolar disorder, and for many, it’s the only thing that keeps their moods stable. But its narrow window between helping and harming means even small changes in your body can push lithium into toxic territory. The biggest culprits? Diuretics and NSAIDs. These aren’t rare or exotic drugs-they’re among the most commonly prescribed and self-administered medications in the world. And when they mix with lithium, the results can be deadly.

Why Lithium Is So Fragile

Lithium doesn’t get broken down by your liver. It doesn’t bind to proteins. It doesn’t hide in fat tissue. It travels through your bloodstream and gets filtered out by your kidneys-exactly like sodium. That’s why anything that changes how your kidneys handle sodium also changes how much lithium stays in your body. The therapeutic range? Just 0.6 to 1.2 mmol/L. Go above 1.5 mmol/L, and you’re in mild toxicity territory. At 2.0 mmol/L, symptoms get serious: tremors, confusion, vomiting. Above 2.5 mmol/L, you’re at risk of seizures, coma, or death.

Most people on lithium have their levels checked every 3 to 6 months. But if you start a new medication, especially a diuretic or NSAID, that schedule isn’t enough. Levels can spike within days. A 2018 study found that lithium toxicity often shows up within the first week of starting these drugs. That’s why monitoring needs to jump to every 4 to 5 days after beginning a new interaction.

Diuretics: The Silent Lithium Triggers

Diuretics make you pee more. That sounds harmless-until you’re on lithium. When your kidneys excrete more sodium, they also reabsorb more lithium. It’s a direct, mechanical link. Thiazide diuretics like hydrochlorothiazide and bendroflumethiazide are the worst offenders. They can push lithium levels up by 25% to 40%, and in some cases, even fourfold. That’s not a small bump. That’s crossing from safe to toxic in under a week.

Loop diuretics like furosemide are less risky, but still dangerous. They raise lithium levels by 10% to 25%, especially if you already have reduced kidney function (eGFR under 60). The key difference? Thiazides act where lithium reabsorption is highest. Loop diuretics act higher up in the kidney, so the effect is weaker-but not safe.

Here’s the reality: many patients are prescribed thiazides for high blood pressure without their psychiatrist knowing. A 72-year-old woman in New Zealand died after starting hydrochlorothiazide while on lithium. Her levels went from 0.8 to 1.9 mmol/L in seven days. She had kidney issues, but no one checked her lithium levels after the new prescription. That case isn’t rare. It’s a textbook example of preventable harm.

NSAIDs: The Over-the-Counter Killer

NSAIDs are everywhere. Ibuprofen. Naproxen. Aspirin. People take them for headaches, arthritis, menstrual cramps. They’re sold in grocery stores and pharmacies without a prescription. But they’re one of the top causes of lithium toxicity.

NSAIDs block prostaglandins in the kidneys. That reduces blood flow to the filtering units, lowering the glomerular filtration rate by 10% to 20%. Less filtration means less lithium gets flushed out. The result? Lithium builds up.

Not all NSAIDs are equal. Indomethacin is the strongest-raising levels by 20% to 40%. Piroxicam and naproxen follow closely. Ibuprofen? It’s common, but still risky: 15% to 30% increase. Celecoxib? It’s the safest NSAID option for lithium users, with only a 5% to 10% rise. That’s why guidelines now recommend celecoxib if you absolutely need an NSAID.

Here’s the hidden danger: people don’t tell their doctors they’re taking Advil or Aleve. They think it’s harmless. But a 2023 case report described a patient who took 600 mg of ibuprofen three times a day for back pain. Lithium levels jumped to 2.8 mmol/L. He needed dialysis. Even after his blood levels dropped, he stayed at risk because lithium lingers inside cells. The blood test can lie. Symptoms matter more.

Other Drugs That Can Worsen the Risk

It’s not just diuretics and NSAIDs. ACE inhibitors like lisinopril and ARBs like valsartan also reduce kidney filtration and raise lithium levels by 10% to 25%. Calcium channel blockers like verapamil don’t change lithium levels much, but they make neurological side effects like tremors and ringing in the ears much worse.

Even some antidepressants-especially SSRIs like fluoxetine-can interfere with lithium clearance. And don’t assume herbal supplements are safe. St. John’s wort, ginkgo biloba, and others have no safety data with lithium. The NHS warns: “There’s not enough information to say they’re safe.”

What You Should Do

If you’re on lithium, here’s what you need to do right now:

1. Never start a new medication without telling your psychiatrist. That includes OTC painkillers, diuretics, blood pressure pills, or supplements.
2. Ask for a lithium level check 4 to 5 days after starting any new drug. Don’t wait for your next routine check-up.
3. If you’re on a diuretic, ask if furosemide can replace a thiazide. It’s not perfect, but it’s safer.
4. If you need pain relief, choose celecoxib over ibuprofen or naproxen. And use the lowest dose for the shortest time possible.
5. Watch for symptoms. Tremors, nausea, confusion, dizziness, muscle weakness, or frequent urination could mean lithium is building up. Don’t wait for a blood test-call your doctor.

Some patients are told to reduce their lithium dose by 20% when starting a thiazide, or 15% with NSAIDs. But that’s not a fix. It’s a band-aid. The real solution is avoiding the interaction altogether.

The Bigger Picture

Lithium isn’t going away. It’s still the most effective mood stabilizer for preventing suicide in bipolar disorder-studies show a 44% reduction compared to placebo. But it’s a powerful tool that demands respect. The market for lithium monitoring is growing because more people are being prescribed it, and more are getting hurt by drug interactions.

New tools are emerging. In 2023, the FDA approved a home-monitoring device called LithoLink™ that lets patients test their levels with a finger-prick and send results directly to their doctor. It’s still new, but it’s a step forward. Researchers are also testing nano-encapsulated lithium that releases slower and is less affected by kidney changes. Early results show 40% less fluctuation when taken with ibuprofen.

But technology won’t fix the problem if patients and doctors don’t talk. Electronic health records now flag lithium interactions, but only 45% of psychiatrists consistently follow up after a new drug is added. That’s not enough. Every patient on lithium deserves a full medication review every time a new prescription is written.

Final Warning

Lithium toxicity doesn’t always come with warning signs. Sometimes, it just shows up as fatigue, a headache, or a slight tremor-symptoms people dismiss as stress or aging. But if you’re on lithium and you take NSAIDs or diuretics, those symptoms could be your body screaming for help. Don’t wait. Check your levels. Talk to your doctor. And never assume a common drug is safe just because it’s sold over the counter.

What to Do Next

If you’re on lithium, take 10 minutes today to review your medication list. Write down every prescription, OTC drug, and supplement you take. Then call your psychiatrist or pharmacist. Ask: “Could any of these raise my lithium levels?” Don’t rely on memory. Bring the list. If you’re not sure about a drug, assume it’s risky until proven otherwise.

Keep a log of your lithium levels and the dates they were checked. Note any new medications or changes in how you feel. This isn’t just paperwork-it’s your safety net. Lithium saves lives. But only if you treat it with the respect it demands.