Antihypertensive therapy in patients on chronic lithium treatment for bipolar disorders

Bipolar disorders are chronic conditions treated with lithium, which exerts deleterious effects on the kidney, among which nephrogenic diabetes insipidus, tubular acidosis and ultimately chronic kidney disease. Conversely, drugs that alter renal function can modify its serum levels and lead to the potentially fatal lithium intoxication. A search in the main library databases from 1975 to 2015 to identify interactions between antihypertensive drugs and lithium using the Population Intervention Comparison Outcome strategy provided only 30 reports of lithium intoxication. A regression analysis showed that the severity of lithium intoxication was significantly predicted by female, age, and use of certain classes of antihypertensive agents. A model including certain albeit not all diuretics and/or inhibitors of the renin–angiotensin system, but not age, serum lithium or creatinine levels at baseline and/or on admission to the hospital, predicted lithium toxicity. The true incidence of lithium intoxication is unknown but probably low, albeit underestimated. Nonetheless, in patients treated with lithium, monitoring of the serum lithium levels and clinical conditions is mandatory after the introduction of antihypertensive drugs, as diuretics and renin–aldosterone system inhibitors.