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Association between lithium serum level, mood state, and patient-reported adverse drug reactions during long-term lithium treatment: a naturalistic follow-up study

Authors

  • Ingeborg Wilting,

    1. Utrecht University, Faculty of Science, Utrecht Institute for Pharmaceutical Sciences, Division of Pharmacoepidemiology and Pharmacotherapy
    2. Department of Clinical Pharmacy, University Medical Center Utrecht, Utrecht
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  • Eibert R Heerdink,

    1. Utrecht University, Faculty of Science, Utrecht Institute for Pharmaceutical Sciences, Division of Pharmacoepidemiology and Pharmacotherapy
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  • Peter-Paul A Mersch,

    1. Department of Psychiatry, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
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  • Johannes A Den Boer,

    1. Department of Psychiatry, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
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  • Antoine C G Egberts,

    1. Utrecht University, Faculty of Science, Utrecht Institute for Pharmaceutical Sciences, Division of Pharmacoepidemiology and Pharmacotherapy
    2. Department of Clinical Pharmacy, University Medical Center Utrecht, Utrecht
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  • Willem A Nolen

    1. Department of Psychiatry, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
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  • The authors of this paper do not have any commercial associations that might pose a conflict of interest in connection with this manuscript.

Corresponding author:
Prof. Dr. Antoine C. G.
Egberts Utrecht University, Faculty of Science Utrecht Institute for Pharmaceutical Sciences Division of Pharmacoepidemiology and Pharmacotherapy
P.O. Box 80082 3508 TB Utrecht, The Netherlands
Fax: +31-30-2539166
e-mail: a.c.g.egberts@uu.nl

Abstract

Objectives:  To assess the association between mood state and the prevalence and the severity of lithium adverse drug reactions (ADRs).

Methods:  A 26-year follow-up study was conducted among patients ≥18 years treated at the outpatient lithium clinic of the University Medical Center Groningen, The Netherlands, between November 1973 and December 2000. At each monthly scheduled visit, patients were questioned by a research nurse in a standardized manner about the presence and the severity of nine specific ADRs that frequently occur as a consequence of lithium treatment and that can be identified by the patients themselves. In addition, lithium serum level was measured and mood state was rated at each visit.

Results:  A total of 186 patients participated and the median duration of follow-up was 5.7 years (interquartile range 2.2–11.8 years). We observed an increased prevalence and severity of ADRs with increased lithium serum level (p < 0.05), also when adjusting for mood state. The prevalence and the severity of ADRs increased with decreasing mood state into the depressive range and decreased with mood state increasing into the manic range (p < 0.05), also when adjusting for lithium serum level. Taking into account the intraindividual dependency of the data resulted in a statistically significant (p < 0.001) association between, respectively, lithium serum level, mood state, and the prevalence and severity of ADRs.

Conclusions:  Both physicians and researchers need to be aware that lithium serum level and mood state are independently associated with patient reporting and severity scoring of ADRs, which may complicate objective assessment of ADRs.

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