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Cited by 164Bipolar Disorder and TreatmentSchizophrenia research and treatmentTreatment of Major Depression

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

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Nolen, Willem A., Licht, Rasmus W., Young, Allan H., Malhi, Gin S., Tohen, Mauricio, Vieta, Eduard, Kupka, Ralph W., Zarate, Carlos +4 more·2019·Bipolar Disorders
DOI 10.1111/bdi.12805PMC PMC6688930
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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.

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  • Before conducting the study, the authors chose a threshold that required ≥80% of experts to endorse a statement as Essential or Important, on the basis of ≥80% being a commonly employed threshold in mental health research and to be consistent with Delphi studies conducted by three independent ISBD Task Forces.

    “Before conducting the study, we chose a threshold that required ≥ 80% of experts to endorse a statement as Essential or Important, on the basis of ≥ 80% being a commonly employed threshold in mental health research [47, 48, 49], and to be consistent with Delphi studies conducted by three independent ISBD Task Forces [50, 51, 52].”

    From Essential Information About Chronobiology and Chronotherapy for the Optimal Care of People With Bipolar Disorders: An Expert Consensus (2026) · cites this paper as [52]

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Authors
Nolen, W. A., Licht, R. W., Young, A. H., Malhi, G. S., Tohen, M., Vieta, E., Kupka, R. W., Zarate, C., Nielsen, R. E., Baldessarini, R. J., Severus, E., & the ISBD/IGSLI Task Force on the treatment with lithium
Affiliations
  • University Medical Center Groningen (NL)
  • Aalborg University Hospital (DK)
  • King's College London (GB)
  • The University of Sydney (AU)
  • University of New Mexico Health Sciences Center (US)
  • Centro de Investigación Biomédica en Red de Salud Mental (ES)
  • Amsterdam Public Health (NL)
  • National Institute of Mental Health (US)
  • Harvard University (US)
  • University Hospital Carl Gustav Carus (DE)
Corresponding author
Nolen, Willem A.
ORCID
Venue
Bipolar Disorders
Publisher
Wiley
Published
2019-06-20
Volume
21
Issue
5
Pages
394-409
ISSN
  • 1398-5647 (ISSN-L)
  • 1399-5618
DOI
10.1111/bdi.12805
PMC
PMC6688930
OpenAlex
W2946375730
Cited by
164
References
47
Citations by year
2026: 26 · 2025: 11 · 2024: 25 · 2023: 26 · 2022: 22 · 2021: 20 · 2020: 27 · 2019: 6 · 2018: 1
FWCI
3.15
Type
journal article
Language
en
Open access
Licence
Locations
  • Bipolar Disorders (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Pure Amsterdam UMC (publishedVersion, cc-by)
  • Amsterdam UMC (VU Amsterdam) - Institutional Repository (publishedVersion, other-oa)
  • VBN Forskningsportal (Aalborg Universitet) (publishedVersion, cc-by)
  • University of Groningen research database (University of Groningen / Centre for Information Technology) (publishedVersion, cc-by)
  • Figshare (submittedVersion, cc-by)
  • Minerva Access (University of Melbourne) (submittedVersion, cc-by)
  • Research Portal (King's College London) (submittedVersion, cc-by)
  • University of Groningen research database (University of Groningen / Centre for Information Technology) (submittedVersion, cc-by)
  • Data Archiving and Networked Services (DANS) (submittedVersion, other-oa)
Funders
  • National Institute for Health Research
  • South London and Maudsley NHS Foundation Trust
  • King’s College London
Topics
  • Health Sciences › Medicine › Psychiatry and Mental health › Bipolar Disorder and Treatment
  • Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
  • Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
Keywords
lithium, serum lithium levels, bipolar disorder, maintenance therapy, therapeutic drug monitoring, lithium dose adjustment, treatment response, tolerability, children and adolescents, elderly patients, clinical guidelines
MeSH terms
Bipolar Disorder, Drug Tolerance, Humans, Surveys and Questionnaires, Practice Guidelines as Topic, Lithium Compounds, Advisory Committees, Consensus

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