Putative Mechanisms of Action and Clinical Use of Lithium in Children and Adolescents: A Critical Review

Simone Pisano; Marco Pozzi; Gennaro Catone; Giulia Scrinzi; Emilio Clementi; Giangennaro Coppola; Annarita Milone; Carmela Bravaccio; Paramala Santosh; Gabriele Masi

doi:10.2174/1570159X16666171219142120

Putative Mechanisms of Action and Clinical Use of Lithium in Children and Adolescents: A Critical Review

Simone Pisano, Marco Pozzi, Gennaro Catone, Giulia Scrinzi, Emilio Clementi, Giangennaro Coppola, Annarita Milone, Carmela Bravaccio, Paramala Santosh, Gabriele Masi

Research output: Contribution to journal › Review article › peer-review

21 Citations (Scopus)

Abstract

BACKGROUND: Lithium is a first-line treatment for bipolar disorder in adults, but its mechanism of action is still far from clear. Furthermore, evidences of its use in pediatric populations are sparse, not only for bipolar disorders, but also for other possible indications. OBJECTIVES: To provide a synthesis of published data on the possible mechanisms of action of lithium, as well as on its use in pediatric samples, including pharmacokinetics, efficacy, and safety data. METHODS: Clinical trials in pediatric samples with at least one standardized measure of efficacy/ effectiveness were included in this review. We considered: i) randomized and open label trials, ii) combination studies iii) augmentation studies iv) case series including at least 5 patients. RESULTS: Different and non-alternative mechanisms of action can explain the clinical efficacy of lithium. Clinical studies in pediatric samples suggest that lithium is effective in managing manic symptoms/episodes of bipolar disorder, both in the acute phase and as maintenance strategy. Efficacy on depressive symptoms/phases of bipolar disorder is much less clear, while studies do not support its use in unipolar depression and severe mood dysregulation. Conversely, it may be effective on aggression in the context of conduct disorder. Other possible indications, with limited published evidence, are the acute attacks in Kleine-Levin syndrome, behavioral symptoms of X-fragile syndrome, and the management of clozapine- or chemotherapy- induced neutropenia. Generally, lithium resulted relatively safe. CONCLUSIONS: Lithium seems an effective and well-tolerated medication in pediatric bipolar disorder and aggression, while further evidences are needed for other clinical indications.

Original language	English
Pages (from-to)	318-341
Number of pages	24
Journal	Current Neuropharmacology
Volume	17
Issue number	4
DOIs	https://doi.org/10.2174/1570159X16666171219142120
Publication status	Published - 1 Jan 2019

Keywords

adolescents
Children
efficacy
lithium
mechanism of action
pharmacokinetics
safety.

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

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title = "Putative Mechanisms of Action and Clinical Use of Lithium in Children and Adolescents: A Critical Review",

abstract = "BACKGROUND: Lithium is a first-line treatment for bipolar disorder in adults, but its mechanism of action is still far from clear. Furthermore, evidences of its use in pediatric populations are sparse, not only for bipolar disorders, but also for other possible indications. OBJECTIVES: To provide a synthesis of published data on the possible mechanisms of action of lithium, as well as on its use in pediatric samples, including pharmacokinetics, efficacy, and safety data. METHODS: Clinical trials in pediatric samples with at least one standardized measure of efficacy/ effectiveness were included in this review. We considered: i) randomized and open label trials, ii) combination studies iii) augmentation studies iv) case series including at least 5 patients. RESULTS: Different and non-alternative mechanisms of action can explain the clinical efficacy of lithium. Clinical studies in pediatric samples suggest that lithium is effective in managing manic symptoms/episodes of bipolar disorder, both in the acute phase and as maintenance strategy. Efficacy on depressive symptoms/phases of bipolar disorder is much less clear, while studies do not support its use in unipolar depression and severe mood dysregulation. Conversely, it may be effective on aggression in the context of conduct disorder. Other possible indications, with limited published evidence, are the acute attacks in Kleine-Levin syndrome, behavioral symptoms of X-fragile syndrome, and the management of clozapine- or chemotherapy- induced neutropenia. Generally, lithium resulted relatively safe. CONCLUSIONS: Lithium seems an effective and well-tolerated medication in pediatric bipolar disorder and aggression, while further evidences are needed for other clinical indications.",

keywords = "adolescents, Children, efficacy, lithium, mechanism of action, pharmacokinetics, safety.",

author = "Simone Pisano and Marco Pozzi and Gennaro Catone and Giulia Scrinzi and Emilio Clementi and Giangennaro Coppola and Annarita Milone and Carmela Bravaccio and Paramala Santosh and Gabriele Masi",

year = "2019",

month = jan,

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doi = "10.2174/1570159X16666171219142120",

language = "English",

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pages = "318--341",

journal = "Current Neuropharmacology",

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TY - JOUR

T1 - Putative Mechanisms of Action and Clinical Use of Lithium in Children and Adolescents

T2 - A Critical Review

AU - Pisano, Simone

AU - Pozzi, Marco

AU - Catone, Gennaro

AU - Scrinzi, Giulia

AU - Clementi, Emilio

AU - Coppola, Giangennaro

AU - Milone, Annarita

AU - Bravaccio, Carmela

AU - Santosh, Paramala

AU - Masi, Gabriele

PY - 2019/1/1

Y1 - 2019/1/1

N2 - BACKGROUND: Lithium is a first-line treatment for bipolar disorder in adults, but its mechanism of action is still far from clear. Furthermore, evidences of its use in pediatric populations are sparse, not only for bipolar disorders, but also for other possible indications. OBJECTIVES: To provide a synthesis of published data on the possible mechanisms of action of lithium, as well as on its use in pediatric samples, including pharmacokinetics, efficacy, and safety data. METHODS: Clinical trials in pediatric samples with at least one standardized measure of efficacy/ effectiveness were included in this review. We considered: i) randomized and open label trials, ii) combination studies iii) augmentation studies iv) case series including at least 5 patients. RESULTS: Different and non-alternative mechanisms of action can explain the clinical efficacy of lithium. Clinical studies in pediatric samples suggest that lithium is effective in managing manic symptoms/episodes of bipolar disorder, both in the acute phase and as maintenance strategy. Efficacy on depressive symptoms/phases of bipolar disorder is much less clear, while studies do not support its use in unipolar depression and severe mood dysregulation. Conversely, it may be effective on aggression in the context of conduct disorder. Other possible indications, with limited published evidence, are the acute attacks in Kleine-Levin syndrome, behavioral symptoms of X-fragile syndrome, and the management of clozapine- or chemotherapy- induced neutropenia. Generally, lithium resulted relatively safe. CONCLUSIONS: Lithium seems an effective and well-tolerated medication in pediatric bipolar disorder and aggression, while further evidences are needed for other clinical indications.

AB - BACKGROUND: Lithium is a first-line treatment for bipolar disorder in adults, but its mechanism of action is still far from clear. Furthermore, evidences of its use in pediatric populations are sparse, not only for bipolar disorders, but also for other possible indications. OBJECTIVES: To provide a synthesis of published data on the possible mechanisms of action of lithium, as well as on its use in pediatric samples, including pharmacokinetics, efficacy, and safety data. METHODS: Clinical trials in pediatric samples with at least one standardized measure of efficacy/ effectiveness were included in this review. We considered: i) randomized and open label trials, ii) combination studies iii) augmentation studies iv) case series including at least 5 patients. RESULTS: Different and non-alternative mechanisms of action can explain the clinical efficacy of lithium. Clinical studies in pediatric samples suggest that lithium is effective in managing manic symptoms/episodes of bipolar disorder, both in the acute phase and as maintenance strategy. Efficacy on depressive symptoms/phases of bipolar disorder is much less clear, while studies do not support its use in unipolar depression and severe mood dysregulation. Conversely, it may be effective on aggression in the context of conduct disorder. Other possible indications, with limited published evidence, are the acute attacks in Kleine-Levin syndrome, behavioral symptoms of X-fragile syndrome, and the management of clozapine- or chemotherapy- induced neutropenia. Generally, lithium resulted relatively safe. CONCLUSIONS: Lithium seems an effective and well-tolerated medication in pediatric bipolar disorder and aggression, while further evidences are needed for other clinical indications.

KW - adolescents

KW - Children

KW - efficacy

KW - lithium

KW - mechanism of action

KW - pharmacokinetics

KW - safety.

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U2 - 10.2174/1570159X16666171219142120

DO - 10.2174/1570159X16666171219142120

M3 - Review article

C2 - 29256353

AN - SCOPUS:85064925505

SN - 1875-6190

VL - 17

SP - 318

EP - 341

JO - Current Neuropharmacology

JF - Current Neuropharmacology

IS - 4

ER -

Putative Mechanisms of Action and Clinical Use of Lithium in Children and Adolescents: A Critical Review

Abstract

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