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

For people taking lithium to manage bipolar disorder, even a small change in their body’s chemistry can turn a safe medication into a dangerous one. Lithium has a razor-thin line between helping and harming - a therapeutic range of just 0.6 to 1.2 mmol/L. Go above 1.5 mmol/L, and symptoms like tremors, confusion, and nausea start showing up. Above 2.5 mmol/L, and you’re in a medical emergency. The problem isn’t the lithium itself. It’s what else you’re taking - especially common drugs like diuretics and NSAIDs.

Why Lithium Is So Sensitive

Lithium doesn’t get broken down by your liver. It doesn’t bind to proteins. It doesn’t linger in tissues. Instead, it rides through your bloodstream and gets filtered out by your kidneys - almost entirely. That’s why anything that changes how your kidneys work can throw off lithium levels. Your kidneys reabsorb lithium along with sodium. When sodium levels drop, your kidneys hang on tighter to lithium. That’s where diuretics and NSAIDs come in.

Diuretics: The Silent Lithium Triggers

Diuretics - often called water pills - are prescribed for high blood pressure, heart failure, or swelling. But not all diuretics affect lithium the same way.

Thiazide diuretics like hydrochlorothiazide and bendroflumethiazide are the worst offenders. They act on a part of the kidney where lithium gets reabsorbed. Even a low dose - 25 mg of hydrochlorothiazide daily - can raise lithium levels by 25% to 40%. In some cases, levels have spiked fourfold. This isn’t rare. Studies show 75% to 85% of patients on thiazides and lithium see dangerous increases. The rise often happens within 3 to 5 days. Many people don’t notice symptoms until it’s too late.

Loop diuretics like furosemide are less risky, but still dangerous. They increase lithium levels by 10% to 25%, especially in people with reduced kidney function (eGFR under 60). Furosemide is sometimes used on purpose in patients with lithium-induced nephrogenic diabetes insipidus - a condition where the kidneys can’t concentrate urine. But even then, levels must be checked every few days.

There’s no safe diuretic when you’re on lithium. But if you absolutely need one, furosemide is the lesser evil. Still, your doctor should lower your lithium dose by 20% to 25% and check your blood levels every 4 to 5 days for the first month.

NSAIDs: The Over-the-Counter Danger

NSAIDs - ibuprofen, naproxen, diclofenac - are taken by millions for headaches, arthritis, or back pain. What most people don’t realize is that these common painkillers can turn a stable lithium dose into a toxic one.

NSAIDs block prostaglandins in the kidneys. Prostaglandins help keep blood flow steady to the filtering units. When they’re blocked, the kidneys filter less blood. That means less lithium gets cleared. The result? Lithium builds up.

The risk varies by drug:

• Indomethacin: Increases lithium by 20% to 40% - the strongest interaction.
• Piroxicam: 20% to 30% increase.
• Naproxen: 15% to 25% increase.
• Ibuprofen: 15% to 20% increase - and it’s sold over the counter.
• Celecoxib: Only 5% to 10% increase - the safest NSAID option if you must use one.

Here’s the scary part: people take ibuprofen and naproxen without telling their doctor. They think it’s just an occasional pill for a headache. But even a few days of use can push lithium into toxic territory. A 2017 case in New Zealand documented a 72-year-old woman who died after starting an NSAID. Her lithium level jumped from 0.8 to 1.9 mmol/L in just seven days. She had no warning signs until it was too late.

Other Drugs That Can Raise Lithium Levels

It’s not just diuretics and NSAIDs. Other common medications can interfere too:

• ACE inhibitors (like lisinopril) - raise levels by 15% to 25%.
• ARBs (like valsartan) - increase levels by 10% to 20%.
• Calcium channel blockers (like verapamil) - don’t raise lithium levels much, but can worsen side effects like tremors and ringing in the ears.
• Some antidepressants - especially SSRIs like fluoxetine - can also increase lithium levels, though less predictably.

And don’t forget herbal supplements. There’s not enough data to say any are safe with lithium. Ginger, ginkgo, or St. John’s wort could interact in ways we don’t yet understand.

What Happens When Lithium Goes Toxic

Toxicity isn’t always obvious. Early signs include:

• Hand tremors that get worse
• Frequent urination or thirst
• Nausea, vomiting, or diarrhea
• Slurred speech or confusion
• Muscle weakness or twitching

As levels climb above 2.0 mmol/L, symptoms become neurological: seizures, loss of coordination, or even coma. Levels above 2.5 mmol/L are life-threatening. Standard treatment includes stopping lithium, giving fluids, and monitoring closely. But here’s the catch: even when blood levels drop, lithium stays trapped inside brain and nerve cells. That’s why severe cases often need hemodialysis - not just to clear the blood, but to pull lithium out of tissues. One case report showed a patient needed multiple dialysis sessions because lithium kept leaking back into the bloodstream from cells.

How to Stay Safe

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

1. Never start a new medication without checking with your doctor - even an OTC painkiller.
2. Get your lithium level checked before starting any new drug, and again 4 to 5 days after.
3. If you’re prescribed a diuretic or NSAID, your lithium dose should be lowered by 15% to 25% upfront.
4. Monitor your symptoms. If you feel off, get tested - don’t wait.
5. Use celecoxib instead of ibuprofen if you need an NSAID.
6. Ask for furosemide instead of hydrochlorothiazide if you need a diuretic.
7. Keep a list of all your meds - including supplements - and share it with every doctor you see.

Many patients don’t realize their doctor isn’t automatically checking their lithium levels every time they refill a prescription. You have to be your own advocate. Ask: “Have you checked my lithium level since I started this new pill?”

New Tools Are Coming

There’s hope on the horizon. In 2023, the FDA approved a home-monitoring device called LithoLink™ - a small device you use like a glucose meter. It tests your lithium level with a finger prick and sends results directly to your doctor. Early users report better adherence and fewer hospital visits.

Researchers are also testing a new form of lithium - nano-encapsulated citrate - that’s less dependent on kidney function. In trials, it showed 40% less fluctuation when taken with ibuprofen. This could change everything for people who need both lithium and pain relief.

Final Reality Check

Lithium is one of the most effective mood stabilizers we have. It cuts suicide risk by nearly half compared to placebo. But that power comes with responsibility. The interaction risks aren’t theoretical - they’re deadly. Every year, people end up in emergency rooms because they took Advil for a headache and didn’t realize it could poison them.

The solution isn’t to avoid lithium. It’s to treat it with the respect it demands. Know your numbers. Know your meds. Ask questions. And never assume a drug is “too common” to be dangerous.