Lithium and thiazide diuretics: a high-risk combination explained

Thiazide and thiazide-like diuretics are a long-established group of medicines used to lower blood pressure and to reduce fluid build-up. The NHS describes bendroflumethiazide as a diuretic used to treat high blood pressure and build-up of fluid. The BNF lists indapamide and hydrochlorothiazide alongside it as increasing lithium concentration.

Several teams can be involved in prescribing for one person, such as a GP, a hospital clinic and a mental health team. That is one reason the combination with lithium is a recurring safety topic: each prescriber needs to know about the other medicine.

NICE CKS states that thiazide diuretics can cause a rapid increase in serum lithium, over 7 to 10 days, by reducing the clearance of lithium, and that the increase varies between 25% and 400%. Those numbers show both the speed and the unpredictability: for one person the change may be modest, for another it may push the level into the toxic range.

The BNF classes the interactions of lithium with bendroflumethiazide, hydrochlorothiazide and indapamide as severe, with the advice to avoid the combination or adjust the dose and monitor the concentration. The same BNF page lists furosemide as increasing lithium concentration but with manufacturer advice to monitor and adjust, reflecting CKS comment that loop diuretics are less likely to result in toxicity.

Sometimes a person stable on lithium develops high blood pressure or swelling, and a thiazide is the obvious option. Sometimes a person on a thiazide for years is started on lithium. In both directions the principle is the same. CKS lists receiving diuretic treatment among the situations in which lithium should be prescribed with caution because of the risk of toxicity.

When the combination is judged worthwhile, the BNF entries point to the safeguards: adjusting the dose and monitoring the lithium concentration. If the combination is not essential, a different class of blood pressure medicine may be chosen instead, although some other classes, such as ACE inhibitors, also interact with lithium, as the NHS lithium page shows.

CKS lists signs of lithium toxicity including increasing diarrhoea, vomiting, loss of appetite, muscle weakness, lethargy, dizziness, unsteadiness, lack of coordination, tinnitus, blurred vision, coarse tremor and drowsiness. The NHS patient version adds thirst, needing to pee more, confusion, blackouts, and muscle twitches or spasms of the face, tongue, eyes or neck.

Early signs can be subtle: a tremor that worsens, new unsteadiness or stomach upset can be easy to blame on something else. Anyone who started or changed a thiazide in the past couple of weeks should treat these as possible signs of high lithium until proved otherwise. Per the NHS, call 999 or go to A&E for toxicity symptoms and stop lithium, and do not drive yourself.

Make sure the prescriber who started the thiazide knew about the lithium, and the lithium prescriber knows about the thiazide. Ask when the next lithium level is due and whether an earlier one is sensible. Keep your lithium record booklet with you; the NHS says to show it every time you see a doctor, go to hospital or collect a prescription.

Stay hydrated, keep salt intake steady, and be cautious with alcohol, as the NHS side-effects page advises. If you become unwell with vomiting, diarrhoea or fever, the NHS says to call 111.

Do not stop either medicine on your own. The NHS warns that stopping lithium suddenly may cause the symptoms of your condition to come back quickly, and stopping a blood pressure medicine abruptly has its own risks.

People who need both medicines can often do well with careful monitoring, and many do. CKS lists weight or BMI, urea and electrolytes, eGFR, calcium and thyroid function tests about every 6 months, alongside lithium levels. A change of thiazide brand, dose or timing is a good prompt to ask for an extra level.

Private and NHS clinicians use the same references, so the advice does not change by route; the practical difference is whether records are shared. Carrying your own list makes a difference.