Improvement in the applicability of clinical practice guidelines on the use of lithium in the treatment of bipolar disorder and treatment-resistant depression is necessary, according to the results of a study published in Bipolar Disorders.

Lithium is often used in the treatment of bipolar disorder and for the augmentation of therapy in patients with treatment-resistant depression. However, close monitoring of lithium therapy is essential to maintain lithium levels within a narrow therapeutic window. In addition, there is a high degree of both interindividual and intraindividual variability. High levels of lithium increase the risk for adverse effects and toxicity, including the development of renal impairment and hypothyroidism. Early identification of individuals at increased risk for either of these serious adverse effects requires regular measurement of biomarkers.

Mariette Nederlof, PhD candidate, of the Division of Pharmacoepidemiology and Clinical Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, The Netherlands, and colleagues evaluated clinical practice guidelines from acknowledged professional organizations from multiple continents. They rated the guidelines on the clarity of presentation and applicability of lithium monitoring instructions using the Appraisal of Guidelines Research and Evaluation (AGREE) II tool. They assessed the applicability of monitoring instructions using the Systematic Information for Monitoring (SIM) score.

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The authors included 9 clinical practice guidelines in the analysis — 2 published between 2005 and 2010, 5 published between 2010 and 2015, and 2 published after 2015. The clarity of presentation was good in most clinical practice guidelines, with 6 of 9 scoring >70% of the maximum score using the AGREE II scoring tool. Most of the recommendations were specific, with a mean percentage of 69% of the maximum score. The guidelines presented different options for the management of the condition or health issue, with a score of 67%.

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In contrast, scores for the applicability of the guidelines were lower. Only one guideline scored more than 70% of the maximum score — the National Collaborating Centre for Mental Health (NICE) guidelines, with a score of 88%. Information on the resource implications of monitoring in particular was lacking, with a score of 31%, and information about facilitators and barriers to lithium monitoring was insufficient (35%). Tools and advice on how to monitor lithium levels in clinical practice received a score of 43%, and monitoring and auditing criteria were found in 48% of clinical practice guidelines.

The authors suggest that the quality of patient monitoring may improve if the clinical practice guidelines are improved, as many healthcare professionals use the guidelines in their monitoring of patients taking lithium.


Nederlof M, Kupka RW, Braam AM, Egberts ACG, Heerdink ER. Evaluation of clarity of presentation and applicability of monitoring instructions for patients using lithium in clinical practice guidelines for treatment of bipolar disorder [published online August 13, 2018]. Bipolar Disord. doi:10.1111/bdi.12681