This systematic review and meta-analysis of RCTs and observational studies was conducted to evaluate the evidence on the toxicity profile of lithium. Outcome measures were renal, thyroid, and parathyroid function; weight change; skin disorders; hair disorders; and teratogenicity.

A total of 385 studies were included in the analysis and the following findings were reported:

• On average, glomerular filtration rate was reduced by −6.22 mL/min (95% CI −14.65 to 2.20, p=0.148) and urinary concentrating ability by 15% of normal maximum (weighted mean difference −158.43 mOsm/kg, p<0.0001).

• Lithium might increase risk of renal failure, but the absolute risk was small (18 of 3369 [0.5%] patients received renal replacement therapy).

• The prevalence of clinical hypothyroidism was increased in patients on lithium compared with those given placebo (odds ratio [OR] 5.78, 95% CI 2.00 to 16.67; p=0.001), and thyroid stimulating hormone was increased on average by 4.00 iU/mL (95% CI 3.90 to 4.10, p<0.0001).

• Lithium was associated with increased blood calcium (+0.09 mmol/L, 95% CI 0.02 to 0.17, p=0.009), and parathyroid hormone (+7•32 pg/mL, 3.42 to 11.23, p<0.0001).

• Patients on lithium gained more weight than those on placebo (OR 1.89, 1.27 to 2.82, p=0•002), but weight gain was lower with lithium than with olanzapine (0.32; 0.21 to 0.49, p<0.0001).

• There was no significant increased risk of congenital malformations, alopecia, or skin disorders.

The researchers conclude that lithium is associated with increased risk of reduced urinary concentrating ability, hypothyroidism, hyperparathyroidism, and weight gain, but there is little evidence for a clinically significant reduction in renal function in most patients, and the risk of end-stage renal failure is low. In addition, whilst the risk of congenital malformations is uncertain, the balance of risks should be considered before lithium is withdrawn during pregnancy. They advise that because of the consistent finding of a high prevalence of hyperparathyroidism, calcium concentrations should be checked before and during treatment.

An accompanying Comment notes that “this study provides timely clarification of the toxicity associated with lithium therapy and, on balance, re affirms its role as a treatment of choice for bipolar disorder.”