Lithium toxicity profile: a systematic review and meta-analysis.


This meta-analysis found that lithium is associated with risk of reduced urinary concentrating ability, hypothyroidism, hyperparathyroidism, and weight gain. There is low risk of significantly reduced renal function. Risk of congenital malformations, alopecia, or skin disorders did not reach statistical significance, and is thus uncertain.


  • Meta-analysis of 385 studies involving patients with mood disorders taking lithium. Only 22 of these were randomized controlled trials. Most studies were case-control, uncontrolled cohort, cross-sectional, or case reports.
  • Primary outcomes: renal, thyroid, parathyroid function; weight change, skin disorders, hair disorders, teratogenicity.
  • A major limitation of this study was the lack of high-quality data from long-term randomized or controlled cohort studies. Most studies involved lithium at normal therapeutic doses, and not at toxic levels. Additionally, many included studies published incomplete data (doses, reasons for drop out), and most excluded patients with a history of lithium toxicity.


  • GFR was reduced by an average of 6.22 mL/min, but this did not reach significance (P=0.148).
  • Urinary concentrating ability was reduced on average by 15% of normal maximum (P<0.0001).
  • Risk of renal failure may be increased but absolute risk was low, as 0.5% of patients received renal replacement therapy.
  • Clinical hypothyroidism was significantly increased compared to placebo (odds ratio: 5.78, P=0.001). TSH was increased by 4.00 iU/mL (P<0.0001).
  • Blood calcium was increased by an average of 0.09 mmol/L (P=0.009). Parathyroid hormone was increased by an average of 7.32 pg/mL (P<0.0001)
  • Weight gain of more than 7% was more frequent when taking lithium than placebo (odds ratio 1.89, P=0.002). Weight gain was even higher with olanzapine than with lithium.
  • Studies of teratogenicity associated with lithium did not yield statistically significant results, potentially due to the low number of events. In one case-control study that compared 10,698 infants born with any congenital abnormality to 21,546 healthy controls, only 6 of the cases were exposed to lithium, compared with 5 controls exposed to lithium.


McKnight RF, Adida M, Budge K, Stockton S, Goodwin GM, Geddes JR. Lithium toxicity profile: a systematic review and meta-analysis. Lancet. 2012;379:721–8.

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