Lithium Interactions: How NSAIDs, Diuretics, and Dehydration Raise Toxicity Risk

When you're taking lithium for bipolar disorder, even small changes in your body can push your lithium levels into dangerous territory. You might not realize it, but common medications like ibuprofen or hydrochlorothiazide - and even something as simple as not drinking enough water - can turn your treatment into a health emergency. Lithium has a very narrow window where it works safely: between 0.6 and 1.2 mmol/L. Go just a little above that, and you risk serious, sometimes fatal, toxicity.

Why Lithium Is So Sensitive

Lithium doesn’t break down in your body. About 95% of it leaves through your kidneys, unchanged. That means anything that affects how your kidneys work - whether it’s a drug, a change in salt intake, or dehydration - directly changes how much lithium stays in your blood. Your kidneys filter lithium like they do sodium and water. If your body holds onto more sodium and water, lithium builds up. If you lose fluids or salt, lithium gets concentrated. That’s why even mild dehydration can spike lithium levels by 15-25%.

NSAIDs: The Silent Risk

Non-steroidal anti-inflammatory drugs (NSAIDs) like ibuprofen, naproxen, and indomethacin are among the most common culprits. People take them for headaches, arthritis, or muscle pain - often without thinking twice. But here’s the problem: NSAIDs block prostaglandins in the kidneys. These chemicals help keep blood flow steady to the filtering units. When they’re blocked, your kidneys slow down lithium clearance by 25-50%, depending on the drug.

Indomethacin is the worst offender, raising lithium levels by 30-60%. Ibuprofen isn’t far behind, increasing levels by 25-40%. Even celecoxib, often thought to be safer, still bumps lithium up by 15-30%. The rise usually happens within the first week of starting the NSAID. Elderly patients or those with existing kidney issues are at highest risk. One fatal case in New Zealand involved a 72-year-old woman who took an NSAID while already on lithium and an ACE inhibitor. Her lithium levels weren’t checked regularly - and she died from toxicity.

Diuretics: A Dangerous Duo

Diuretics are another major red flag. They’re often prescribed for high blood pressure or swelling, but they mess with lithium in unpredictable ways.

Thiazide diuretics - like hydrochlorothiazide - are the most dangerous. They cause lithium levels to jump by 25-50% within 7-10 days. Why? They make your kidneys reabsorb more sodium, and lithium rides along. Even though they’re commonly used, they’re rarely recommended for people on lithium. Loop diuretics like furosemide (frusemide) are less risky, but still dangerous - they can raise lithium by 10-25%. And potassium-sparing diuretics like spironolactone? Their effects are mixed and poorly studied, so they’re not safe to assume.

There’s a twist: some diuretics actually lower lithium. Osmotic diuretics like mannitol and carbonic anhydrase inhibitors like acetazolamide increase urine output and reduce lithium reabsorption, dropping levels by 15-30%. That’s a different kind of risk - suddenly your mood stabilizer stops working.

Herbal and ‘Natural’ Diuretics Are Not Safe

Many people turn to herbal teas, weight-loss supplements, or “natural” diuretics thinking they’re harmless. But that’s a myth. Plants like dandelion, green tea extract, and hibiscus have diuretic effects. They don’t show up on standard drug screens, so doctors might not know you’re taking them. Still, they can cause dehydration or alter sodium balance - and that’s enough to push lithium into toxic range. There are documented cases of lithium toxicity from these products, especially when combined with heat, exercise, or illness.

Dehydration: The Hidden Trigger

You don’t need to be hospitalized to be at risk. Even mild dehydration - losing just 2-3% of your body weight in water - can spike lithium levels. This happens during:

• Hot weather or physical activity
• Long flights
• Diarrhea or vomiting
• Fever
• Not drinking enough fluids

In Perth, where summer temperatures regularly hit 35°C, this isn’t theoretical. People on lithium who go for long walks, skip water at the beach, or get sick with the flu are at real risk. Lithium levels rise proportionally to how much fluid you lose. That’s why doctors always say: drink plenty of water. But it’s not just about water - your sodium intake matters too. Eating less salt increases lithium levels. Eating more salt lowers them. A change of just 20-30 mmol of sodium per day can shift lithium levels by 10-20%.

What Happens When Lithium Gets Too High?

Early signs of lithium toxicity are easy to miss:

• Diarrhea (68% of early cases)
• Lightheadedness (52%)
• Drowsiness (47%)
• Nausea
• Tremors

If it gets worse, you might get blurred vision, ringing in the ears, muscle weakness, or confusion. At severe levels, seizures, kidney damage, coma, or death can happen. And here’s the scary part: some kidney damage from lithium toxicity is permanent, especially in older adults.

What Should You Do?

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

1. Avoid NSAIDs if you can. Use paracetamol (acetaminophen) instead for pain or fever. If you must take an NSAID, use the lowest dose for the shortest time possible.
2. Never start a diuretic without talking to your doctor. Thiazides are usually off-limits. If you’re on one already, your lithium levels need urgent checking.
3. Drink water daily - even when you’re not thirsty. Aim for 1.5-2 liters a day, more if you’re active or in hot weather.
4. Keep your salt intake steady. Don’t suddenly go on a low-salt diet or eat way more salty food. Consistency matters more than quantity.
5. Get blood tests regularly. After starting any new medication, check lithium levels weekly for the first month. If you’re over 65 or have kidney problems, you may need checks every 2-4 weeks.
6. Watch for warning signs. If you feel dizzy, nauseous, shaky, or unusually tired - get your lithium level checked immediately.

When to Call Your Doctor

Call your prescriber right away if:

• You’ve started a new medication (even over-the-counter)
• You’ve had vomiting, diarrhea, or fever for more than 24 hours
• You’re sweating a lot from exercise or heat
• You’ve cut back on fluids or salt
• You notice new tremors, confusion, or trouble walking

Final Reality Check

Lithium is one of the most effective mood stabilizers we have. But it’s not a drug you can treat casually. It’s more like insulin - a precise tool that needs careful handling. Many people on lithium don’t realize how easily things can go wrong. Even a weekend of drinking less water or taking Advil for a headache can trigger a crisis.

The good news? With awareness, monitoring, and simple lifestyle adjustments, you can stay safe. Don’t wait for symptoms. Talk to your doctor before taking anything new. Keep a list of all your medications - including herbs and supplements - and review it every time you see a prescriber. Lithium doesn’t have to be a danger. But it will be, if you ignore the risks.