A major issue in lithium dosing is consideration of possible drug–drug interactions. Angiotensin converting enzyme (ACE) inhibitors, loop diuretics [15], NSAIDs [82, 83], cyclo-oxygenase 2 (COX2) inhibitors [84], and diuretics (including thiazide diuretics) [85], all have been associated with an up to 50 % increase in serum lithium levels, although the percent increase is highly variable among individuals. Therefore, it is advisable, whenever initiating these medications or adjusting their dose, to check serum lithium levels 5–7 days after a dose change. Because of the potential for mood relapse with lithium dose reduction [139] and the unpredictability of the extent to which a drug interaction will affect lithium levels, it is often best to keep the lithium dose constant when starting a medication with a potential drug–drug interaction (e.g., NSAIDs) in a chronic lithium user, check the lithium level 5–7 days afterward, and if necessary titrate the lithium dose to whichever lithium level the patient was previously stabilized on.

Close monitoring of renal function and lithium levels is a key to preventing AKI and CKD. Ideally this should be every 3 months in geriatric patients [102]. Using once-daily dosing and avoiding prolonged-release formulations has also been found to be helpful [67]. Both twice-daily dosing and prolonged-release formulations have been associated with increased renal disease risk. It has been hypothesized that single-dose/short-acting formulations give longer periods per day where the kidney is relatively unexposed to lithium, during which the kidney recovers [59]. Geriatric lithium levels and renal function do not appear to be markedly affected by environmental temperature in temperate climates where mean daily temperatures are seldom >20 °C [140, 141], although environmental temperatures (e.g., 40 °C) have been associated with lithium toxicity in tropical and desert climates [142].