What is the optimal serum lithium level in the long‐term treatment of bipolar disorder – a review?

Severus, W. Emanuel; Kleindienst, Nikolaus; Seemüller, Florian; Frangou, Sophia; Möller, Hans‐Jürgen; Greil, Waldemar

doi:10.1111/j.1399-5618.2007.00475.x

Cited by 116 publications

(57 citation statements)

References 25 publications

(67 reference statements)

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“…Mice were given lithium orally for 10 days before tumor inoculation, to achieve serum levels comparable to therapeutic doses in humans being treated for bipolar disorder (30,31). As shown in Fig.…”

Section: Resultsmentioning

confidence: 99%

“…Oral administration of lithium chloride using doses comparable in humans treated for bipolar disorder (30,31) resulted in a statistically significant growth inhibition of human colorectal cancer xenografts containing a single mutant PIK3CA allele compared with isogenic xenografts with a single wild-type PIK3CA allele. Interestingly, increased levels of phosphorylated GSK3␤ (Ser-9) and augmented sensitivity to GSK3␤ inhibitors have been described in the SKOV-3 ovarian cancer cell line (26), and this cell line has also been shown to contain an oncogenic PIK3CA mutation (32).…”

Section: Discussionmentioning

confidence: 98%

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Knockin of mutant PIK3CA activates multiple oncogenic pathways

Gustin

Karakas

Weiss

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

155

199

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The phosphatidylinositol 3-kinase subunit PIK3CA is frequently mutated in human cancers. Here we used gene targeting to ''knock in'' PIK3CA mutations into human breast epithelial cells to identify new therapeutic targets associated with oncogenic PIK3CA. Mutant PIK3CA knockin cells were capable of epidermal growth factor and mTOR-independent cell proliferation that was associated with AKT, ERK, and GSK3␤ phosphorylation. Paradoxically, the GSK3␤ inhibitors lithium chloride and SB216763 selectively decreased the proliferation of human breast and colorectal cancer cell lines with oncogenic PIK3CA mutations and led to a decrease in the GSK3␤ target gene CYCLIN D1. Oral treatment with lithium preferentially inhibited the growth of nude mouse xenografts of HCT-116 colon cancer cells with mutant PIK3CA compared with isogenic HCT-116 knockout cells containing only wild-type PIK3CA. Our findings suggest GSK3␤ is an important effector of mutant PIK3CA, and that lithium, an FDA-approved therapy for bipolar disorders, has selective antineoplastic properties against cancers that harbor these mutations.GSK3␤ ͉ lithium ͉ mTOR ͉ phosphatidylinositol 3-kinase ͉ cancer

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 98%

Knockin of mutant PIK3CA activates multiple oncogenic pathways

Gustin

Karakas

Weiss

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

155

199

View full text Add to dashboard Cite

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“…Although effective, this substance requires specific care as it has a narrow therapeutic range, high risk of intoxication (9)(10)(11)(12) and slow onset of action, is subject to serum variation levels due to pharmacological interactions, and presents elimination and dosage-plasma level variations among people (7) . The serum monitoring of lithium carbonate levels is important for treatment effectiveness and patients' safety (9)(10)(11)(12) . Therefore, it is necessary to investigate whether this is being regularly carried out at psychological healthcare services.…”

Section: Introductionmentioning

confidence: 99%

“…The whole context shows that adherence to treatment (3)(4)8) , knowledge about the drug therapy (6)(7)(8) and serum monitoring of lithium carbonate levels (9,(10)(11)(12) are essential for the safety of patients who make use of this medication. These aspects are strictly related to the nursing practice, which plays a unique role in patients' For the collection of data, a review of medical records and structured interviews were performed, using a guide developed by the authors of the study with questions about socio-demographic information and patients' treatment, as well as a test evaluating patients' adherence to drug therapy (13) including lithium carbonate, and a scale to evaluate the interviewees' knowledge concerning the prescribed drug therapy (14) .…”

Section: Introductionmentioning

confidence: 99%

Bipolar disorder and medication: adherence, patients' knowledge and serum monitoring of lithium carbonate

Souza

Vedana

Mercedes

et al. 2013

Rev. Latino-Am. Enfermagem

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Objectives: this study featured patients with affective bipolar disorder who were making use of lithium and received care at an outpatient care center located in a country town in the state of Sao Paulo in 2009; it assessed the adherence and knowledge of these patients in relation to the medication prescribed to them and verified the proportion of blood tests performed per year in the service, for each individual, to measure lithium levels in the blood. Method: descriptive study with quantitative approach, involving 36 participants. Structured interviews and review of medical records were used for data collection and descriptive statistics for data analysis. Results: difficulties in reporting the dosage of the medication prescribed and a high rate of non-adherence were identified among the participants. None of the participants in the study was submitted to two tests a year to measure lithium levels in the blood, which is the minimum proportion of tests recommended by the literature for maintenance treatment using lithium carbonate. Conclusion: this study highlights the critical factors for the promotion of patients' safety in monitoring lithium drug therapy.

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“…Lithium is known to target nerve cells and is still being used for the treatment of nervous disorders (1). However, a multiplicity of cell responses is elicited by lithium outside the nervous system and has profound effects on a variety of processes, including metabolism, cell proliferation and development (2,3).…”

Section: Introductionmentioning

confidence: 99%

Lithium induces mortality in medulloblastoma cell lines

et al. 2010

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Abstract. Lithium is the main therapeutic agent for the treatment of bipolar disorders but nerve cells are not the sole target of this drug. Indeed, lithium has been reported to target numerous cell types and to affect cell proliferation, differentiation and death. Lithium targets a variety of enzymes among which there is GSK-3ß and a number of cell responses elicited by lithium are mediated by the Wnt pathway that is involved in medulloblastoma (MB) pathogenesis. We studied the in vitro effects of lithium on two different MB cell lines: D283MED and DAOY. High doses of lithium inhibited GSK3-ß, decreased cell proliferation and induced nonapoptotic cell death in both cell lines independently by intracellular levels of ß-catenin that is consistently high only in D283MED. At clinical doses, the anti-neoplastic effects were observed only in this cell line, highlighting the importance of a specific molecular background in determining the target therapy response. In conclusion, lithium could be a promising drug in MB, but an accurate molecular profile predictive of drug response still needs to be clarified.

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What is the optimal serum lithium level in the long‐term treatment of bipolar disorder – a review?

Abstract: In the long-term treatment of bipolar disorder clinicians should initially aim for serum lithium levels of 0.6-0.75 mmol/L, while higher levels may benefit patients with predominantly manic symptoms.

Cited by 116 publications

References 25 publications

Knockin of mutant PIK3CA activates multiple oncogenic pathways

Knockin of mutant PIK3CA activates multiple oncogenic pathways

Bipolar disorder and medication: adherence, patients' knowledge and serum monitoring of lithium carbonate

Lithium induces mortality in medulloblastoma cell lines

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