Lithium is a widely used and effective treatment for mood disorders. There has been
concern about its safety but no adequate synthesis of the evidence for adverse effects.
We aimed to undertake a clinically informative, systematic toxicity profile of lithium.
We undertook a systematic review and meta-analysis of randomised controlled trials
and observational studies. We searched electronic databases, specialist journals,
reference lists, textbooks, and conference abstracts. We used a hierarchy of evidence
which considered randomised controlled trials, cohort studies, case-control studies,
and case reports that included patients with mood disorders given lithium. Outcome
measures were renal, thyroid, and parathyroid function; weight change; skin disorders;
hair disorders; and teratogenicity.
We screened 5988 abstracts for eligibility and included 385 studies in the analysis.
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, 95% CI -229·78 to -87·07, 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 taking lithium compared with those given placebo (odds ratio
[OR] 5·78, 95% CI 2·00-16·67; p=0·001), and thyroid stimulating hormone was increased
on average by 4·00 iU/mL (95% CI 3·90-4·10, p<0·0001). Lithium treatment was associated
with increased blood calcium (+0·09 mmol/L, 95% CI 0·02-0·17, p=0·009), and parathyroid
hormone (+7·32 pg/mL, 3·42-11·23, p<0·0001). Patients receiving lithium gained more
weight than did those receiving placebo (OR 1·89, 1·27-2·82, p=0·002), but not those
receiving olanzapine (0·32, 0·21-0·49, p<0·0001). We recorded no significant increased
risk of congenital malformations, alopecia, or skin disorders.
Lithium is associated with increased risk of reduced urinary concentrating ability,
hypothyroidism, hyperparathyroidism, and weight gain. 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. The risk of congenital malformations is uncertain;
the balance of risks should be considered before lithium is withdrawn during pregnancy.
Because of the consistent finding of a high prevalence of hyperparathyroidism, calcium
concentrations should be checked before and during treatment.
National Institute for Health Research Programme Grant for Applied Research.
Copyright © 2012 Elsevier Ltd. All rights reserved.