Predictable interaction between lithium and ACE inhibitors or diuretics?

Lithium is a commonly used drug in the treatment of unipolar and bipolar affective disorders. Angiotensin converting enzyme (ACE) inhibitors and diuretics are two frequently used classes of drugs in the treatment of hypertension and heart failure. In patients, suffering from cardiovascular and neuropsychiatric diseases, a combination therapy of lithium with both classes of cardiovascular drugs may therefore be necessary. However, an increased risk of lithium intoxication has been described for co-medication with ACE inhibitors and thiazide diuretics, yet.

Analysis of three cases of lithium intoxication from our hospital due to a potential interaction between ACE inhibitors and lithium did not show a unique picture. Patients were treated safely with both drugs for more than ten years. Intoxication developed in the context of co-medication with hydrochlorothiazide and dehydration, suggesting prerenal failure to account for lithium intoxication, rather than ACE inhibitors alone. Several mechanisms have been suggested to be involved in these interactions, which are discussed in the context of the cases.

Combining lithium therapy with ACE inhibitors makes a sufficient hydration mandatory and serum lithium concentrations need to be controlled on a tight regular basis. Co-treatment with hydrochlorothiazide should be avoided.