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

Why Lithium Can Turn Dangerous With Common Medications

Lithium has been treating bipolar disorder for over 50 years, and it still works better than most alternatives at preventing suicide. But here’s the catch: it’s a tightrope walk. The difference between a therapeutic dose and a toxic one is tiny. A serum level of 0.6-1.2 mmol/L keeps mood stable. Go above 1.5 mmol/L, and you risk tremors, confusion, nausea, and worse. At 2.5 mmol/L or higher, lithium toxicity can be fatal.

What makes this even more dangerous is that lithium doesn’t get broken down by the liver. It’s filtered out by the kidneys-and that’s where things go wrong. If your kidneys slow down how much lithium they clear, the drug builds up fast. And two of the most common medications people take-diuretics and NSAIDs-do exactly that.

How Diuretics Push Lithium Into Toxic Territory

Diuretics help reduce fluid buildup by making you pee more. But they also mess with how your kidneys handle sodium. And lithium? It rides along with sodium in the kidney tubules. Less sodium reabsorption? Lithium gets reabsorbed more, too.

Not all diuretics are the same. Thiazides like hydrochlorothiazide and bendroflumethiazide are the worst offenders. They can bump lithium levels up by 25-40%, sometimes even fourfold. A patient on a steady 600 mg daily dose of lithium might suddenly hit 1.8 mmol/L after starting a low-dose thiazide. That’s not just a lab number-it’s a red flag for dizziness, muscle weakness, and confusion.

Loop diuretics like furosemide are less risky, but still dangerous. They usually raise lithium by 10-25%, especially in older adults or those with reduced kidney function. If someone’s eGFR is below 60 mL/min/1.73m², even a small dose of furosemide can tip them over the edge.

Doctors often avoid thiazides entirely in people on lithium. If a patient needs a diuretic for high blood pressure or heart failure, furosemide is the safer pick-but only if lithium levels are checked every few days after starting it. Never assume it’s safe just because the dose is low.

NSAIDs: The Silent Lithium Boosters

NSAIDs-like ibuprofen, naproxen, and indomethacin-are everywhere. You can buy them over the counter. People take them for headaches, back pain, arthritis. But they’re also one of the most common causes of unexpected lithium toxicity.

How? NSAIDs block prostaglandins in the kidneys. Prostaglandins help keep blood flow steady to the filtering units. When they’re blocked, the glomerular filtration rate drops by 10-20%. Less filtration means less lithium gets flushed out. Levels creep up slowly, often unnoticed until symptoms appear.

Some NSAIDs are worse than others. Indomethacin is the biggest culprit, raising lithium levels by 20-40%. Piroxicam and naproxen aren’t far behind. Ibuprofen? It’s common, but still risky-typically increasing levels by 15-30%. Celecoxib is the exception. It has a much weaker effect, raising levels by only 5-10%. For patients who absolutely need an NSAID, celecoxib is the best option.

Here’s the scary part: patients don’t always tell their doctors they’re taking NSAIDs. A 68-year-old woman on lithium for bipolar disorder might grab a bottle of Advil for her knee pain. Three days later, she’s vomiting, shaky, and confused. Her lithium level? 1.9 mmol/L. She didn’t think it mattered. But it did.

What Happens When Lithium Levels Spike

Toxicity doesn’t always show up in blood tests right away. Symptoms often come first: nausea, diarrhea, tremors, slurred speech, muscle weakness, dizziness. Then come the neurological signs-confusion, seizures, loss of coordination. In severe cases, patients slip into coma or develop kidney failure.

One case from 2013 described a man who started taking 600 mg of ibuprofen three times a day. His lithium level jumped to 2.8 mmol/L. He needed hemodialysis-not because his blood level was high, but because lithium had soaked into his brain and nerve cells. Even after dialysis, his levels stayed dangerous for days because lithium leaves cells slowly.

That’s why doctors don’t just rely on numbers. If someone looks toxic, they treat them as toxic-even if the blood test shows 1.7 mmol/L. Clinical signs matter more than lab values.

How to Stay Safe: Monitoring and Management

If you’re on lithium and your doctor prescribes a diuretic or NSAID, here’s what needs to happen:

1. Check lithium levels before starting-baseline is key.
2. Test again within 4-5 days after starting the new drug.
3. Test weekly for the first month, then every 3-6 months if stable.
4. Reduce lithium dose by 15-25% if combining with thiazides or strong NSAIDs.
5. Monitor kidney function-eGFR, sodium, potassium. Low sodium makes lithium toxicity worse.
6. Never start an NSAID without telling your psychiatrist. Even a 5-day course of ibuprofen can be risky.

Some patients get a lithium level check every time they refill their NSAID prescription. That’s not overkill-it’s necessary.

Also, don’t forget about other drugs. ACE inhibitors like lisinopril and ARBs like valsartan can also raise lithium levels by 10-25%. Calcium channel blockers don’t change lithium levels much, but they can worsen tremors and ringing in the ears.

What to Do If You’re Already Taking These Drugs Together

If you’re on lithium and already taking a diuretic or NSAID, don’t stop suddenly. That can cause a relapse of bipolar symptoms. Instead:

• Call your doctor or pharmacist right away.
• Ask for a lithium level test within the next 48 hours.
• If you have symptoms like shaking, confusion, or vomiting, go to the ER.
• Ask if you can switch to celecoxib or furosemide instead.
• Keep a list of all your meds-including supplements and OTC drugs-and review it with your prescriber every 3 months.

Many people don’t realize that herbal supplements like St. John’s wort or ginkgo biloba can also interfere with lithium. The NHS warns there’s not enough data to say any herbal product is safe with lithium. Play it safe-disclose everything.

New Tools and Future Hope

There’s good news on the horizon. In 2023, the FDA approved LithoLink™, a home-testing device that lets patients check their lithium levels with a finger-prick test. Results sync to their doctor’s system automatically. This could finally fix the biggest problem: missed monitoring.

Researchers are also testing nano-encapsulated lithium citrate, which releases the drug more slowly and reduces how much it’s affected by kidney changes. Early trials show it’s 40% less likely to spike when taken with ibuprofen.

And now, genetic testing is being explored. Some people have a CYP2D6 gene variation that makes them clear lithium slower. If you’re a poor metabolizer, even small doses of NSAIDs could push you into danger. Future care may include genetic screening before starting lithium.

For now, though, the rules are simple: know your risks. Know your numbers. And never, ever take an NSAID or diuretic without talking to your care team first.