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Cited by 73Bipolar Disorder and TreatmentSchizophrenia research and treatmentTreatment of Major Depression

The association of the effect of lithium in the maintenance treatment of bipolar disorder with lithium plasma levels: a post hoc analysis of a double‐blind study comparing switching to lithium or placebo in patients who responded to quetiapine (Trial 144)

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Nolen, Willem A, Weisler, Richard H·2013·Bipolar Disorders
DOI 10.1111/bdi.12027
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Abstract

Nolen WA, Weisler RH. The association of the effect of lithium in the maintenance treatment of bipolar disorder with lithium plasma levels: a post hoc analysis of a double‐blind study comparing switching to lithium or placebo in patients who responded to quetiapine (Trial 144). Bipolar Disord 2012: 00: 000–000. © 2012 John Wiley & Sons A/S.Published by Blackwell Publishing Ltd. Objectives: There is no robust proof that the efficacy of lithium in the prevention of manic and depressive episodes in bipolar disorder depends on its plasma level. This analysis aimed to compare the effect of lithium within the presumed therapeutic range of 0.6–1.2 mEq/L and below 0.6 mEq/L with that of placebo. Methods: We carried out a post hoc analysis of a double‐blind trial in which patients aged ≥18 years with bipolar I disorder (DSM‐IV) who had achieved stabilization from a manic, depressive, or mixed episode during open‐label treatment with quetiapine were randomized to continue quetiapine or to switch to lithium or placebo for up to 104 weeks. Of patients randomized to lithium, 201 obtained median lithium levels between 0.6 and 1.2 mEq/L, and 137 obtained median lithium levels <0.6 mEq/L. Their outcomes were compared with those of patients receiving placebo (n = 404). The primary outcome was time to recurrence of any mood event; additional outcomes included time to recurrence of a manic or depressive event. Results: Times to recurrence of any mood event as well as a manic or depressive event were significantly longer for the lithium 0.6–1.2 mEq/L group versus placebo and versus lithium <0.6 mEq/L, with no differences between lithium <0.6 mEq/L and placebo. Conclusions: The results support and expand previous findings that lithium should be dosed high enough to achieve plasma levels ≥0.6 mEq/L in order to achieve an effect in the prevention of both manic and depressive recurrences of bipolar I disorder. A major limitation is that the composition of the two lithium groups was not based on randomization.

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  • Factors associated with overall good prognosis of bipolar disorder include good treatment adherence, lack of early adversity, intermediate age at onset, good social support, and the absence of spontaneous rapid cycling or features of a personality disorder.

    “Factors associated with overall good prognosis of BD include good treatment adherence, lack of early adversity, intermediate age at onset, good social support, and the absence of spontaneous rapid cycling406, 407 or features of a personality disorder.408”

    From Canadian Network for Mood and Anxiety Treatments ( <scp>CANMAT</scp> ) and International Society for Bipolar Disorders ( <scp>ISBD</scp> ) 2018 guidelines for the management of patients with bipolar disorder (2018) · cites this paper as [406]

    The Efficacy measures and Discussion sections mention rapid cycling only as a variable adjusted for in analyses of lithium treatment; they do not say that its absence predicts a good overall prognosis. The Discussion speculates that nonadherence may have contributed to lower lithium levels, but does not establish the claimed prognostic association. Searches for rapid cycling, personality disorder, early adversity, age at onset, and social support found no passage supporting the attributed claim (page numbers unavailable). (LLM, conf=0.72)

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Authors
Nolen, W. A., & Weisler, R. H.
Affiliations
  • University Medical Center Groningen (NL)
  • University of North Carolina at Chapel Hill (US)
Corresponding author
Nolen, Willem A
ORCID
Nolen, Willem A
Venue
Bipolar Disorders
Publisher
Wiley
Published
2012-12-10
Volume
15
Issue
1
Pages
100-109
ISSN
  • 1398-5647 (ISSN-L)
  • 1399-5618
DOI
10.1111/bdi.12027
OpenAlex
W2112515572
Cited by
73
References
27
Citations by year
2026: 2 · 2025: 3 · 2024: 6 · 2023: 5 · 2022: 4 · 2021: 8 · 2020: 5 · 2019: 4 · 2018: 2 · 2017: 6 · 2016: 4 · 2015: 5 · 2014: 15 · 2013: 4
FWCI
5.45
Type
journal article
Language
en
Open access
Licence
Locations
  • Bipolar Disorders (publishedVersion, other-oa)
  • PubMed (publishedVersion)
  • University of Groningen research database (University of Groningen / Centre for Information Technology) (submittedVersion, other-oa)
Funders
AstraZeneca
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, bipolar I disorder, maintenance therapy, quetiapine, depression recurrence, therapeutic drug monitoring, lithium dosing
MeSH terms
Quetiapine Fumarate, Adult, Bipolar Disorder, Dibenzothiazepines, Dose-Response Relationship, Drug, Double-Blind Method, Female, Humans, International Cooperation, Male, Middle Aged, Psychiatric Status Rating Scales, Time Factors, Antipsychotic Agents, Outcome Assessment, Health Care, Lithium Chloride, Antimanic Agents, Statistics, Nonparametric, Drug Substitution

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