Lithium toxicity profile: a systematic review and meta-analysis

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• 作者：Rebecca F McKnight ; BMBCh^a ; Marc Adida ; PhD^b ; Katie Budge ; MSc^a ; Sarah Stockton ; BA^a ; Guy M Goodwin ; FMedSci^a ; Prof John R Geddes ; MD^a ; ^{john.geddes@psych.ox.ac.uk}
• 刊名：The Lancet
• 出版年：2012
• 期刊代码：182_01406736
• 类别：med
• 出版时间：25 February-2 March, 2012
• 卷：379
• 期：9817
• 页码：721-728
• 文件大小：374 K

摘要

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Summary

Background

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.

Methods

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.

Findings

We screened 5988 abstracts for eligibility and included 385 studies in the analysis. On average, glomerular filtration rate was reduced by 鈭?路22 mL/min (95%CI 鈭?4路65 to 2路20, p=0路148) and urinary concentrating ability by 15%of normal maximum (weighted mean difference 鈭?58路43 mOsm/kg, 95%CI 鈭?29路78 to 鈭?7路07, p<0路0001). Lithium might increase risk of renal failure, but the absolute risk was small (18 of 3369 [0路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路78, 95%CI 2路00-16路67; p=0路001), and thyroid stimulating hormone was increased on average by 4路00 iU/mL (95%CI 3路90-4路10, p<0路0001). Lithium treatment was associated with increased blood calcium (+0路09 mmol/L, 95%CI 0路02-0路17, p=0路009), and parathyroid hormone (+7路32 pg/mL, 3路42-11路23, p<0路0001). Patients receiving lithium gained more weight than did those receiving placebo (OR 1路89, 1路27-2路82, p=0路002), but not those receiving olanzapine (0路32, 0路21-0路49, p<0路0001). We recorded no significant increased risk of congenital malformations, alopecia, or skin disorders.

Interpretation

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.

Funding

National Institute for Health Research Programme Grant for Applied Research.