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. 2019 Aug;21(5):394-409.
doi: 10.1111/bdi.12805. Epub 2019 Jun 20.

What is the optimal serum level for lithium in the maintenance treatment of bipolar disorder? A systematic review and recommendations from the ISBD/IGSLI Task Force on treatment with lithium

Willem A Nolen  1 , Rasmus W Licht  2   3 , Allan H Young  4 , Gin S Malhi  5   6   7 , Mauricio Tohen  8 , Eduard Vieta  9 , Ralph W Kupka  10   11 , Carlos Zarate  12 , René E Nielsen  2   3 , Ross J Baldessarini  13   14 , Emanuel Severus  15 ; ISBD/IGSLI Task Force on the treatment with lithium
Affiliations

What is the optimal serum level for lithium in the maintenance treatment of bipolar disorder? A systematic review and recommendations from the ISBD/IGSLI Task Force on treatment with lithium

Willem A Nolen et al. Bipolar Disord. 2019 Aug.

Abstract

Aims: To systematically review the existing trials on optimal serum levels for lithium for maintenance treatment of bipolar disorder and to develop clinical recommendations.

Methods: Systematic literature search. Discussion of major characteristics, limitations, methodological quality, and results of selected trials. Delphi survey consisting of clinical questions and corresponding statements. For statements endorsed by at least 80% of the members, consensus was considered as having been achieved.

Results: With strict inclusion criteria no studies could be selected, making it difficult to formulate evidence-based recommendations. After loosening the inclusion criteria 7 trials were selected addressing our aims at least to some extent. Four of these studies suggest better efficacy being associated with lithium serum levels in a range above a lower threshold around 0.45/0.60 and up to 0.80/1.00 mmol/L. These findings support the outcome of the Delphi survey.

Conclusions: For adults with bipolar disorder there was consensus that the standard lithium serum level should be 0.60-0.80 mmol/L with the option to reduce it to 0.40-0.60 mmol/L in case of good response but poor tolerance or to increase it to 0.80-1.00 mmol/L in case of insufficient response and good tolerance. For children and adolescents there was no consensus, but the majority of the members endorsed the same recommendation. For the elderly there was also no consensus, but the majority of the members endorsed a more conservative approach: usually 0.40-0.60 mmol/L, with the option to go to maximally 0.70 or 0.80 mmol/L at ages 65-79 years, and to maximally 0.70 mmol/L over age 80 years.

Keywords: Lithium; bipolar disorder; maintenance treatment; serum level.

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Conflict of interest statement

The following authors reported a potential conflict of interest: Dr Licht has received research grant from Glaxo Smith Kline, honoraria for lecturing from Pfizer, Glaxo Smith Kline, Eli Lilly, Astra‐Zeneca, Bristol‐Myers Squibb, Janssen Cilag, Lundbeck, Otsuka, Servier, and honoraria from advisory board activity from Glaxo Smith Kline, Eli Lilly, Astra‐Zeneca, Bristol‐Myers Squibb, Janssen Cilag, and Sunovion. Dr Nielsen has received research grants from H. Lundbeck and Otsuka Pharmaceuticals for clinical trials, received speaking fees from Bristol‐Myers Squibb, Astra Zeneca, Janssen & Cilag, Lundbeck, Servier, Otsuka Pharmaceuticals, and Eli Lilly and has acted as advisor to Astra Zeneca, Eli Lilly, Lundbeck, Otsuka Pharmaceuticals, Takeda, and Medivir. Dr Severus received speaker honoraria from Servier, Roche and Aristo in the past 3 years. Dr Vieta has received grants and served as consultant, advisor or CME speaker for the following entities: AB‐Biotics, Abbott, Allergan, Angelini, AstraZeneca, Bristol‐Myers Squibb, Dainippon Sumitomo Pharma, Farmindustria, Ferrer, Forest Research Institute, Gedeon Richter, Glaxo‐Smith‐Kline, Janssen, Lundbeck, Otsuka, Pfizer, Roche, SAGE, Sanofi‐Aventis, Servier, Shire, Sunovion, Takeda, the Brain and Behaviour Foundation, the Spanish Ministry of Science and Innovation (CIBERSAM), EU Horizon 2020, and the Stanley Medical Research Institute. Dr Zarate is a full‐time U.S government employee and is an inventor on several patent and patent applications related to ketamine and ketamine metabolites that have all been assigned to the US Government. He will share a percentage of any royalties that may be received by the Government in accordance to NIH policy.

Figures

Figure 1
Figure 1
Prisma flow diagram of the selection of papers [Colour figure can be viewed at wileyonlinelibrary.com]
Figure 2
Figure 2
Recommendation for optimal lithium serum levels in the maintenance treatment of bipolar disorder: endorsed in consensus by the Task Force members for adults (18‐65 y) and by the majority of the members for children (wileyonlinelibrary.com]
Figure 3
Figure 3
Recommendation for optimal lithium serum levels in the maintenance treatment of bipolar disorder in elderly patients, endorsed by the majority of the Task Force members for elderly patients (65 y and older) [Colour figure can be viewed at wileyonlinelibrary.com]
See this image and copyright information in PMC

Comment in

  • Lithium levels and treatment efficacy.
    Andrade C. Andrade C. Bipolar Disord. 2020 Feb;22(1):89-90. doi: 10.1111/bdi.12836. Epub 2019 Oct 2. Bipolar Disord. 2020. PMID: 31520561 No abstract available.

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