Lithium: Blood Tests, Interactions and Toxicity Warning Signs

The effective and harmful concentrations can be uncomfortably close

Lithium is an established treatment for bipolar disorder and is also used in selected cases of recurrent depression. It can be very effective, but the body clears it almost entirely through the kidneys. Dehydration, illness, a change in kidney function or an interacting medicine can therefore raise the concentration even when the prescribed dose has not changed.

A lithium result is not interpreted in isolation. The prescriber also needs to know the dose, the formulation, when the last dose was taken, when the blood sample was collected, recent illness, changes in fluid or salt intake, other medicines and the symptoms being treated. A number without that context can be misleading.

Blood monitoring is not a sign that lithium is inherently unsafe. It is the safety system that makes a narrow therapeutic range manageable. Missing repeated tests removes an important early warning for kidney, thyroid, calcium and lithium-level changes.

The lithium level is only one part of monitoring

Before starting, standard guidance includes weight or BMI, a full blood count, kidney function, urea and electrolytes, calcium, thyroid function, pregnancy status where relevant, and an ECG when cardiac risk is present. The exact panel is individualised.

After lithium is started or the dose is changed, the level is commonly checked at about one week and repeated until stable. NICE recommends every three months during the first year. Once stable, many people have lithium levels every three to six months and kidney, thyroid, calcium and weight checks at least every six months. Older adults, pregnancy, interacting medicines, higher levels, poor symptom control, changes in sodium or fluid intake, and kidney or thyroid risk call for more frequent review.

Timing matters. A sample taken much earlier than 12 hours may look falsely high, while a much later sample may look lower. Tell the laboratory and prescriber the exact time of the last dose and the blood draw. Do not shift the dose merely to manufacture a reassuring result.

The commonest problem is a new medicine that changes kidney handling

Every clinician, dentist and pharmacist involved in your care should know that you take lithium. Check before starting any new prescription, over-the-counter medicine, supplement or restrictive diet.

• NSAID painkillers: ibuprofen, diclofenac, naproxen and related medicines can raise lithium unpredictably. Some are available without prescription. NICE specifically warns against over-the-counter NSAIDs while taking lithium.
• Blood-pressure medicines: ACE inhibitors such as ramipril and lisinopril, and angiotensin receptor blockers such as losartan and telmisartan, can raise lithium and may also affect kidney function.
• Diuretics or water tablets: thiazides such as hydrochlorothiazide and indapamide are particularly important. Loop diuretics can also interact, especially around initiation or during illness.
• Other medicines that alter sodium or the nervous system: some combinations may increase hyponatraemia or neurotoxicity risk even when the lithium number is not strikingly high.
• Brand or formulation changes: lithium preparations can differ in bioavailability. A change of brand or from tablet to liquid should be treated like a clinically relevant change and monitored.

An interaction does not always mean the two medicines can never be used together. It means the prescriber may need an alternative, a dose adjustment, or extra lithium and kidney checks. The unsafe version is an unrecognised interaction with no monitoring.

The dose can stay the same while the concentration moves

Vomiting, diarrhoea, fever, heavy sweating, poor intake and dehydration can all raise lithium. This is especially relevant in hot weather, during gastroenteritis, after prolonged exercise, while fasting, or when an illness makes it difficult to drink normally.

Keep fluid and salt intake reasonably consistent. Do not deliberately overdrink, suddenly restrict salt, or start a low-sodium diet without discussing lithium. Large changes in either direction can disturb the balance.

NICE advises seeking medical attention for diarrhoea, vomiting or acute illness and maintaining fluid intake during sweating, fever, immobility or chest infection. If illness is significant, same-day advice is safer than waiting for the next routine appointment.

Symptoms matter even if the last blood result looked normal

Toxicity becomes more likely around serum concentrations of 1.5 mmol/L and above, but the number is not an absolute boundary. Significant symptoms can occur with a lower or apparently therapeutic result, particularly in older adults, illness, kidney impairment or interacting medication.

A fine hand tremor, thirst, increased urination, mild nausea or metallic taste can occur as non-emergency adverse effects. A new coarse tremor, worsening gastrointestinal symptoms, drowsiness or poor coordination is different and should not be watched at home in the hope that it passes.

A small amount of preparation prevents guesswork

• Your lithium brand, formulation, dose and the times you actually take it.
• The exact time of the last dose and the blood sample.
• A complete list of prescriptions, over-the-counter painkillers, supplements and recent short courses of medicine.
• Any recent vomiting, diarrhoea, fever, fasting, heavy sweating or major change in diet or fluid intake.
• Changes in thirst, urination, tremor, balance, concentration, bowel symptoms, weight or mood.
• Pregnancy plans, a positive pregnancy test, or breastfeeding plans, because monitoring and risk decisions change.

Do not stop lithium abruptly because a routine result is late or because a side effect is worrying. Rapid discontinuation can increase relapse risk. Contact the prescriber for a specific plan, except when toxicity is suspected, which requires urgent action as described above.