Title:Putative Mechanisms of Action and Clinical Use of Lithium in Children and Adolescents: A Critical Review
Volume: 17
Issue: 4
Author(s): Simone Pisano*, Marco Pozzi, Gennaro Catone, Giulia Scrinzi, Emilio Clementi, Giangennaro Coppola, Annarita Milone, Carmela Bravaccio, Paramala Santosh and Gabriele Masi
Affiliation:
- Clinic of Child and Adolescent Neuropsychiatry, Department of Medicine and Surgery, University of Salerno, Salerno,Italy
Keywords:
Children, adolescents, lithium, efficacy, safety, pharmacokinetics, mechanism of action.
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.
