Lithium induced hypercalcemia: an expert opinion and management algorithm

Zoltan Kovacs; Peter Vestergaard; Rasmus W. Licht; Sune P. V. Straszek; Anne Sofie Hansen; Allan H. Young; Anne Duffy; Bruno Müller-Oerlinghausen; Florian Seemueller; Gabriele Sani; Janusz Rubakowski; Josef Priller; Lars Vedel Kessing; Leonardo Tondo; Martin Alda; Mirko Manchia; Paul Grof; Phillip Ritter; Tomas Hajek; Ute Lewitzka; Veerle Bergink; Michael Bauer; René Ernst Nielsen

doi:10.1186/s40345-022-00283-3

Lithium induced hypercalcemia: an expert opinion and management algorithm

Zoltan Kovacs, Peter Vestergaard, Rasmus W. Licht, Sune P. V. Straszek, Anne Sofie Hansen, Allan H. Young, Anne Duffy, Bruno Müller-Oerlinghausen, Florian Seemueller, Gabriele Sani, Janusz Rubakowski, Josef Priller, Lars Vedel Kessing, Leonardo Tondo, Martin Alda, Mirko Manchia, Paul Grof, Phillip Ritter, Tomas Hajek, Ute LewitzkaVeerle Bergink, Michael Bauer, René Ernst Nielsen

Medicine

Research output: Contribution to journal › Article › peer-review

12 Citations (Scopus)

Abstract

Background: Lithium is the gold standard prophylactic treatment for bipolar disorder. Most clinical practice guidelines recommend regular calcium assessments as part of monitoring lithium treatment, but easy-to-implement specific management strategies in the event of abnormal calcium levels are lacking. Methods: Based on a narrative review of the effects of lithium on calcium and parathyroid hormone (PTH) homeostasis and its clinical implications, experts developed a step-by-step algorithm to guide the initial management of emergent hypercalcemia during lithium treatment. Results: In the event of albumin-corrected plasma calcium levels above the upper limit, PTH and calcium levels should be measured after two weeks. Measurement of PTH and calcium levels should preferably be repeated after one month in case of normal or high PTH level, and after one week in case of low PTH level, independently of calcium levels. Calcium levels above 2.8 mmol/l may require a more acute approach. If PTH and calcium levels are normalized, repeated measurements are suggested after six months. In case of persistent PTH and calcium abnormalities, referral to an endocrinologist is suggested since further examination may be needed. Conclusions: Standardized consensus driven management may diminish the potential risk of clinicians avoiding the use of lithium because of uncertainties about managing side-effects and consequently hindering some patients from receiving an optimal treatment.

Original language	English
Article number	34
Journal	International Journal of Bipolar Disorders
Volume	10
Issue number	1
DOIs	https://doi.org/10.1186/s40345-022-00283-3
Publication status	Published - Dec 2022

Bibliographical note

Funding Information:
ZK has nothing to declare. PV has nothing to declare. RWL has within the last three years received speaker fees from Lundbeck, Janssen-Cilag and Teva, and fees from Janssen-Cilag for advisory board activity. SS has within the last three years received speakers fees from Lundbeck. ASH has nothing to declare. AY independent research is funded by the National Institute for Health and Care Research (NIHR) Maudsley Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King's College London. The views expressed are those of the author(s) and not necessarily those of the NIHR or the Department of Health and Social Care. AD has nothing to declare. BMO has nothing to declare. FS has received speaking fees for Janssen-Cilag, Aristo, Lundbeck, Servier and has acted as advisor to Janssen-Cilag and Lundbeck . GS has nothing to delclare . JR has nothing to declare . JP has nothing to declare . LVK has the last three years been a consultant for Lundbeck and Teva. LT has nothing to declare . MA has nothing to declare . MM has nothing to declare . PG has nothing to declare . PR has nothing to declare . TH has nothing to declare . UL has received research grants from BMBF, AFSP, BMG, ulinsky Foundation, Janssen-Cilag; honoraria for lecturing from Janssen-Cilag; honoraria for advisory board activity from Janssen-Cilag . VB has nothing to declare . MB has received research grants from Deutsche Forschungsgemeinschaft (DFG), Bundesministerium für Bildung und Forschung (BMBF), and European Commission. He has received honoraria for lecturing from Aristo, Janssen-Cilag, Janssen Pharmaceutica NV, and Servier Deutschland. He has served as a consultant for Biogen, GH Research, Janssen-Cilag, Livanova, Novartis, and Sunovion. REN has within the last three years been an investigator for Compass Pharmaceuticals, Janssen-Cilag, Sage and Boehringer-Ingelheim for clinical trials, has received speaking fees from Lundbeck, Teva Pharmaceuticals, Janssen-Cilag and Otsuka Pharmaceuticals, and has acted as advisor to Lundbeck and Janssen-Cilag.

Publisher Copyright:
© 2022, The Author(s).

ASJC Scopus Subject Areas

Psychiatry and Mental health
Biological Psychiatry

PubMed: MeSH publication types

Journal Article

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1186/s40345-022-00283-3

Cite this

Kovacs, Z., Vestergaard, P., W. Licht, R., P. V. Straszek, S., Hansen, A. S., H. Young, A., Duffy, A., Müller-Oerlinghausen, B., Seemueller, F., Sani, G., Rubakowski, J., Priller, J., Vedel Kessing, L., Tondo, L., Alda, M., Manchia, M., Grof, P., Ritter, P., Hajek, T., ... Nielsen, R. E. (2022). Lithium induced hypercalcemia: an expert opinion and management algorithm. International Journal of Bipolar Disorders, 10(1), Article 34. https://doi.org/10.1186/s40345-022-00283-3

Kovacs, Z, Vestergaard, P, W. Licht, R, P. V. Straszek, S, Hansen, AS, H. Young, A, Duffy, A, Müller-Oerlinghausen, B, Seemueller, F, Sani, G, Rubakowski, J, Priller, J, Vedel Kessing, L, Tondo, L, Alda, M, Manchia, M, Grof, P, Ritter, P, Hajek, T, Lewitzka, U, Bergink, V, Bauer, M & Nielsen, RE 2022, 'Lithium induced hypercalcemia: an expert opinion and management algorithm', International Journal of Bipolar Disorders, vol. 10, no. 1, 34. https://doi.org/10.1186/s40345-022-00283-3

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title = "Lithium induced hypercalcemia: an expert opinion and management algorithm",

abstract = "Background: Lithium is the gold standard prophylactic treatment for bipolar disorder. Most clinical practice guidelines recommend regular calcium assessments as part of monitoring lithium treatment, but easy-to-implement specific management strategies in the event of abnormal calcium levels are lacking. Methods: Based on a narrative review of the effects of lithium on calcium and parathyroid hormone (PTH) homeostasis and its clinical implications, experts developed a step-by-step algorithm to guide the initial management of emergent hypercalcemia during lithium treatment. Results: In the event of albumin-corrected plasma calcium levels above the upper limit, PTH and calcium levels should be measured after two weeks. Measurement of PTH and calcium levels should preferably be repeated after one month in case of normal or high PTH level, and after one week in case of low PTH level, independently of calcium levels. Calcium levels above 2.8 mmol/l may require a more acute approach. If PTH and calcium levels are normalized, repeated measurements are suggested after six months. In case of persistent PTH and calcium abnormalities, referral to an endocrinologist is suggested since further examination may be needed. Conclusions: Standardized consensus driven management may diminish the potential risk of clinicians avoiding the use of lithium because of uncertainties about managing side-effects and consequently hindering some patients from receiving an optimal treatment.",

author = "Zoltan Kovacs and Peter Vestergaard and {W. Licht}, Rasmus and {P. V. Straszek}, Sune and Hansen, {Anne Sofie} and {H. Young}, Allan and Anne Duffy and Bruno M{\"u}ller-Oerlinghausen and Florian Seemueller and Gabriele Sani and Janusz Rubakowski and Josef Priller and {Vedel Kessing}, Lars and Leonardo Tondo and Martin Alda and Mirko Manchia and Paul Grof and Phillip Ritter and Tomas Hajek and Ute Lewitzka and Veerle Bergink and Michael Bauer and Nielsen, {Ren{\'e} Ernst}",

note = "Funding Information: ZK has nothing to declare. PV has nothing to declare. RWL has within the last three years received speaker fees from Lundbeck, Janssen-Cilag and Teva, and fees from Janssen-Cilag for advisory board activity. SS has within the last three years received speakers fees from Lundbeck. ASH has nothing to declare. AY independent research is funded by the National Institute for Health and Care Research (NIHR) Maudsley Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King's College London. The views expressed are those of the author(s) and not necessarily those of the NIHR or the Department of Health and Social Care. AD has nothing to declare. BMO has nothing to declare. FS has received speaking fees for Janssen-Cilag, Aristo, Lundbeck, Servier and has acted as advisor to Janssen-Cilag and Lundbeck . GS has nothing to delclare . JR has nothing to declare . JP has nothing to declare . LVK has the last three years been a consultant for Lundbeck and Teva. LT has nothing to declare . MA has nothing to declare . MM has nothing to declare . PG has nothing to declare . PR has nothing to declare . TH has nothing to declare . UL has received research grants from BMBF, AFSP, BMG, ulinsky Foundation, Janssen-Cilag; honoraria for lecturing from Janssen-Cilag; honoraria for advisory board activity from Janssen-Cilag . VB has nothing to declare . MB has received research grants from Deutsche Forschungsgemeinschaft (DFG), Bundesministerium f{\"u}r Bildung und Forschung (BMBF), and European Commission. He has received honoraria for lecturing from Aristo, Janssen-Cilag, Janssen Pharmaceutica NV, and Servier Deutschland. He has served as a consultant for Biogen, GH Research, Janssen-Cilag, Livanova, Novartis, and Sunovion. REN has within the last three years been an investigator for Compass Pharmaceuticals, Janssen-Cilag, Sage and Boehringer-Ingelheim for clinical trials, has received speaking fees from Lundbeck, Teva Pharmaceuticals, Janssen-Cilag and Otsuka Pharmaceuticals, and has acted as advisor to Lundbeck and Janssen-Cilag. Publisher Copyright: {\textcopyright} 2022, The Author(s).",

year = "2022",

month = dec,

doi = "10.1186/s40345-022-00283-3",

language = "English",

volume = "10",

journal = "International Journal of Bipolar Disorders",

issn = "2194-7511",

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TY - JOUR

T1 - Lithium induced hypercalcemia

T2 - an expert opinion and management algorithm

AU - Kovacs, Zoltan

AU - Vestergaard, Peter

AU - W. Licht, Rasmus

AU - P. V. Straszek, Sune

AU - Hansen, Anne Sofie

AU - H. Young, Allan

AU - Duffy, Anne

AU - Müller-Oerlinghausen, Bruno

AU - Seemueller, Florian

AU - Sani, Gabriele

AU - Rubakowski, Janusz

AU - Priller, Josef

AU - Vedel Kessing, Lars

AU - Tondo, Leonardo

AU - Alda, Martin

AU - Manchia, Mirko

AU - Grof, Paul

AU - Ritter, Phillip

AU - Hajek, Tomas

AU - Lewitzka, Ute

AU - Bergink, Veerle

AU - Bauer, Michael

AU - Nielsen, René Ernst

N1 - Funding Information: ZK has nothing to declare. PV has nothing to declare. RWL has within the last three years received speaker fees from Lundbeck, Janssen-Cilag and Teva, and fees from Janssen-Cilag for advisory board activity. SS has within the last three years received speakers fees from Lundbeck. ASH has nothing to declare. AY independent research is funded by the National Institute for Health and Care Research (NIHR) Maudsley Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King's College London. The views expressed are those of the author(s) and not necessarily those of the NIHR or the Department of Health and Social Care. AD has nothing to declare. BMO has nothing to declare. FS has received speaking fees for Janssen-Cilag, Aristo, Lundbeck, Servier and has acted as advisor to Janssen-Cilag and Lundbeck . GS has nothing to delclare . JR has nothing to declare . JP has nothing to declare . LVK has the last three years been a consultant for Lundbeck and Teva. LT has nothing to declare . MA has nothing to declare . MM has nothing to declare . PG has nothing to declare . PR has nothing to declare . TH has nothing to declare . UL has received research grants from BMBF, AFSP, BMG, ulinsky Foundation, Janssen-Cilag; honoraria for lecturing from Janssen-Cilag; honoraria for advisory board activity from Janssen-Cilag . VB has nothing to declare . MB has received research grants from Deutsche Forschungsgemeinschaft (DFG), Bundesministerium für Bildung und Forschung (BMBF), and European Commission. He has received honoraria for lecturing from Aristo, Janssen-Cilag, Janssen Pharmaceutica NV, and Servier Deutschland. He has served as a consultant for Biogen, GH Research, Janssen-Cilag, Livanova, Novartis, and Sunovion. REN has within the last three years been an investigator for Compass Pharmaceuticals, Janssen-Cilag, Sage and Boehringer-Ingelheim for clinical trials, has received speaking fees from Lundbeck, Teva Pharmaceuticals, Janssen-Cilag and Otsuka Pharmaceuticals, and has acted as advisor to Lundbeck and Janssen-Cilag. Publisher Copyright: © 2022, The Author(s).

PY - 2022/12

Y1 - 2022/12

N2 - Background: Lithium is the gold standard prophylactic treatment for bipolar disorder. Most clinical practice guidelines recommend regular calcium assessments as part of monitoring lithium treatment, but easy-to-implement specific management strategies in the event of abnormal calcium levels are lacking. Methods: Based on a narrative review of the effects of lithium on calcium and parathyroid hormone (PTH) homeostasis and its clinical implications, experts developed a step-by-step algorithm to guide the initial management of emergent hypercalcemia during lithium treatment. Results: In the event of albumin-corrected plasma calcium levels above the upper limit, PTH and calcium levels should be measured after two weeks. Measurement of PTH and calcium levels should preferably be repeated after one month in case of normal or high PTH level, and after one week in case of low PTH level, independently of calcium levels. Calcium levels above 2.8 mmol/l may require a more acute approach. If PTH and calcium levels are normalized, repeated measurements are suggested after six months. In case of persistent PTH and calcium abnormalities, referral to an endocrinologist is suggested since further examination may be needed. Conclusions: Standardized consensus driven management may diminish the potential risk of clinicians avoiding the use of lithium because of uncertainties about managing side-effects and consequently hindering some patients from receiving an optimal treatment.

AB - Background: Lithium is the gold standard prophylactic treatment for bipolar disorder. Most clinical practice guidelines recommend regular calcium assessments as part of monitoring lithium treatment, but easy-to-implement specific management strategies in the event of abnormal calcium levels are lacking. Methods: Based on a narrative review of the effects of lithium on calcium and parathyroid hormone (PTH) homeostasis and its clinical implications, experts developed a step-by-step algorithm to guide the initial management of emergent hypercalcemia during lithium treatment. Results: In the event of albumin-corrected plasma calcium levels above the upper limit, PTH and calcium levels should be measured after two weeks. Measurement of PTH and calcium levels should preferably be repeated after one month in case of normal or high PTH level, and after one week in case of low PTH level, independently of calcium levels. Calcium levels above 2.8 mmol/l may require a more acute approach. If PTH and calcium levels are normalized, repeated measurements are suggested after six months. In case of persistent PTH and calcium abnormalities, referral to an endocrinologist is suggested since further examination may be needed. Conclusions: Standardized consensus driven management may diminish the potential risk of clinicians avoiding the use of lithium because of uncertainties about managing side-effects and consequently hindering some patients from receiving an optimal treatment.

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Lithium induced hypercalcemia: an expert opinion and management algorithm

Abstract

Bibliographical note

ASJC Scopus Subject Areas

PubMed: MeSH publication types

UN SDGs

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