Lithium and diuretics (water tablets): why levels can rise

Lithium is used mainly to treat and prevent mood episodes in bipolar disorder, and the NHS also describes it as a treatment for mania. It works well for many people, but NICE Clinical Knowledge Summaries describe it as having a narrow therapeutic index, meaning the gap between a helpful level and a harmful level is small.

Diuretics make you pee more, as the NHS puts it, and so change the fluid and salt balance of the body. NICE CKS links low sodium and dehydration with raised lithium levels, which is why medicines that alter that balance can leave more lithium in the blood than expected. The BNF summarises this for individual medicines by stating that bendroflumethiazide, hydrochlorothiazide, indapamide and furosemide increase the concentration of lithium.

Nothing about this means the two medicines can never be used together. Some people with bipolar disorder also have high blood pressure, heart failure or fluid retention and need a diuretic. It means that the combination should be a deliberate decision, with extra monitoring.

Not all water tablets behave the same way. NICE CKS separates them into groups. Thiazide diuretics can cause a rapid increase in serum lithium levels, and CKS gives a range for the size of the increase that is wide. Loop diuretics also cause lithium retention, but are less likely to result in lithium toxicity.

The BNF lists the following entries for lithium and tells prescribers what to do about each.

• Bendroflumethiazide, hydrochlorothiazide and indapamide: the BNF says the manufacturer advises avoiding the combination or adjusting the dose and monitoring the concentration.

• Furosemide: the BNF entry says it increases the concentration of lithium and the manufacturer advises monitoring and adjusting the dose.

• Spironolactone: the BNF says it potentially increases the concentration of lithium and rates the interaction as moderate.

The NHS lists the signs of lithium toxicity: stomach ache, feeling sick and diarrhoea, blurred vision, feeling very thirsty, needing to pee more than normal and lack of control over pee or poo, feeling lightheaded or drowsy, confusion and blackouts, shaking, muscle weakness, muscle twitches, jerks or spasms affecting the face, tongue, eyes or neck, and difficulty speaking.

CKS adds that toxicity can occur at serum concentrations of about 1.5 mmol/L and above, but may occur despite an apparently normal level, and that mild symptoms can appear below full toxicity but still need rapid assessment.

The NHS is clear about what to do: call 999 or go to A&E now, stop taking lithium straight away, do not drive yourself, and bring all your medicines. A diuretic can turn a stable level into a high one over days, so new symptoms after a medicine change deserve attention even if you felt well beforehand.

People on lithium are given a treatment pack, usually a purple folder or book with a record booklet and an alert card, according to the NHS. Show the record booklet every time you see a doctor, go to hospital or collect a prescription. It lists your dose and blood levels, which helps whoever is prescribing the diuretic.

CKS says lithium levels are normally measured one week after starting, one week after every dose change and weekly until stable, then usually every 3 months, 10 to 14 hours after the dose. When a diuretic is added, an extra level soon afterwards is a reasonable thing to ask about. The NHS explains that this is why lithium is usually taken at night: the blood test should be 12 hours after the dose.

CKS also lists urea and electrolytes and eGFR among the routine tests, about every 6 months, and says lithium levels may be measured more often if urea or creatinine rise or eGFR declines. If these tests change, ask whether more frequent lithium levels are needed.

Keep the dose of both medicines exactly as prescribed, and do not add or remove either without advice. Tell any new prescriber, dentist or pharmacist that you take lithium, as the NHS side-effects page instructs.

The NHS also gives advice that helps keep lithium levels steady: attend the blood tests arranged, do not suddenly cut the salt in your diet, drink plenty of fluids especially in hot weather or when exercising, and avoid drinking too much alcohol because it causes the body to lose water.

If you become ill with severe diarrhoea, vomiting, a high temperature or sweating, or you are not eating and drinking much, the NHS says to call 111 now, because illness can affect lithium levels.

Lithium treatment can involve both specialist and primary care teams, and a diuretic may be prescribed by yet another clinic, so information can easily fail to reach everyone. A shared record, your lithium booklet and an up-to-date medicines list are the practical solution, whether you are seen on the NHS or privately.

If you are offered a diuretic and take lithium, ask the prescriber whether an alternative blood-pressure or fluid medicine would be suitable, and who will arrange the extra lithium level.