{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T23:09:14Z","timestamp":1782947354782,"version":"3.54.5"},"reference-count":49,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2024,11,13]],"date-time":"2024-11-13T00:00:00Z","timestamp":1731456000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"the Italian Ministry of Health"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Brain Sciences"],"abstract":"<jats:p>Objectives: This systematic review evaluates the anti-suicidal properties of Lithium in children and adolescents with Bipolar Disorder (BD), addressing gaps in evidence regarding its efficacy and safety in reducing suicidality and self-harming behaviors. Methods: A comprehensive literature search was conducted across PubMed, Web of Science, and Scopus up to February 2024. Eligible studies were those focusing on patients aged 25 years or younger, examining Lithium therapy and its impact on suicidal ideation and behaviors. The review included randomized controlled trials, longitudinal prospective and retrospective studies, and cross-sectional studies, while excluding expert opinions and case reports. Results: Evidence generally supports the efficacy of Lithium in reducing suicidal ideation and self-harming behaviors in youth with BD, though results are mixed. Randomized controlled trials demonstrated its effectiveness in mitigating suicidal thoughts during acute manic episodes, with effects persisting post-treatment. Longitudinal studies suggested that Lithium might offer superior outcomes compared to other mood stabilizers, although its specific impact on suicidality remains inconclusive. Cross-sectional studies and retrospective analyses reveal associations between Lithium use and reduced self-harming behaviors, but causality remains uncertain. While mood-stabilizing effects of Lithium offer potential benefits for reducing suicidality in youth, evidence on its direct impact on emotional dysregulation (ED) and long-term efficacy is limited. Variability in individual responses and adherence issues underscore the need for further research. Future studies should include larger, diverse samples, focus on ED symptoms, and explore Lithium mechanisms in suicidality prevention. Conclusions: Lithium remains a promising treatment for mood stabilization and reduction in suicidality in youth with BD.<\/jats:p>","DOI":"10.3390\/brainsci14111139","type":"journal-article","created":{"date-parts":[[2024,11,13]],"date-time":"2024-11-13T09:59:11Z","timestamp":1731491951000},"page":"1139","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Efficacy and Safety of Lithium for Suicide and Suicide-Related Behaviors in Youth: A Review of the Literature"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0435-2962","authenticated-orcid":false,"given":"Gianluca","family":"Sesso","sequence":"first","affiliation":[{"name":"IMT School for Advanced Studies, 55100 Lucca, Italy"},{"name":"Developmental Psychiatry and Psychopharmacology, IRCCS Stella Maris Foundation, 56128 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"Bargnesi","sequence":"additional","affiliation":[{"name":"Department of Clinical and Experimental Medicine, University of Pisa, 56126 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"Olzi","sequence":"additional","affiliation":[{"name":"Department of Clinical and Experimental Medicine, University of Pisa, 56126 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giulia","family":"Mutti","sequence":"additional","affiliation":[{"name":"Department of Clinical and Experimental Medicine, University of Pisa, 56126 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefano","family":"Berloffa","sequence":"additional","affiliation":[{"name":"Developmental Psychiatry and Psychopharmacology, IRCCS Stella Maris Foundation, 56128 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4164-3101","authenticated-orcid":false,"given":"Valentina","family":"Viglione","sequence":"additional","affiliation":[{"name":"Developmental Psychiatry and Psychopharmacology, IRCCS Stella Maris Foundation, 56128 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5492-8929","authenticated-orcid":false,"given":"Pamela","family":"Fantozzi","sequence":"additional","affiliation":[{"name":"Developmental Psychiatry and Psychopharmacology, IRCCS Stella Maris Foundation, 56128 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-0854-2297","authenticated-orcid":false,"given":"Greta","family":"Tolomei","sequence":"additional","affiliation":[{"name":"Developmental Psychiatry and Psychopharmacology, IRCCS Stella Maris Foundation, 56128 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fulvio","family":"Guccione","sequence":"additional","affiliation":[{"name":"Developmental Psychiatry and Psychopharmacology, IRCCS Stella Maris Foundation, 56128 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3170-1187","authenticated-orcid":false,"given":"Annarita","family":"Milone","sequence":"additional","affiliation":[{"name":"Developmental Psychiatry and Psychopharmacology, IRCCS Stella Maris Foundation, 56128 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7770-926X","authenticated-orcid":false,"given":"Gabriele","family":"Masi","sequence":"additional","affiliation":[{"name":"Developmental Psychiatry and Psychopharmacology, IRCCS Stella Maris Foundation, 56128 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,11,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"318","DOI":"10.2174\/1570159X16666171219142120","article-title":"Putative Mechanisms of Action and Clinical Use of Lithium in Children and Adolescents: A Critical Review","volume":"17","author":"Pisano","year":"2017","journal-title":"Curr. Neuropharmacol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1016\/S2215-0366(14)70314-1","article-title":"Comparative efficacy and tolerability of pharmacological treatments in the maintenance treatment of bipolar disorder: A systematic review and network meta-analysis","volume":"1","author":"Miura","year":"2014","journal-title":"Lancet Psychiatry"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"f3646","DOI":"10.1136\/bmj.f3646","article-title":"Lithium in the prevention of suicide in mood disorders: Updated systematic review and meta-analysis","volume":"346","author":"Cipriani","year":"2013","journal-title":"BMJ"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"405","DOI":"10.4088\/JCP.v59n0802","article-title":"Lithium treatment and risk of suicidal behavior in bipolar disorder patients","volume":"59","author":"Tondo","year":"1998","journal-title":"J. Clin. Psychiatry"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1186\/s40345-024-00326-x","article-title":"Prevention of suicidal behavior with lithium treatment in patients with recurrent mood disorders","volume":"12","author":"Tondo","year":"2024","journal-title":"Int. J. Bipolar Disord."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"e65","DOI":"10.1017\/S204579602200049X","article-title":"Effects of lithium on suicide and suicidal behaviour: A systematic review and meta-analysis of randomised trials","volume":"31","author":"Nabi","year":"2022","journal-title":"Epidemiol. Psychiatr. Sci."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"e199","DOI":"10.1192\/bjo.2022.605","article-title":"Lithium in the prevention of suicide in adults: Systematic review and meta-analysis of clinical trials","volume":"8","author":"Riblet","year":"2022","journal-title":"BJPsych Open"},{"key":"ref_8","first-page":"66","article-title":"Special considerations: Use of lithium in children, adolescents, and elderly populations","volume":"59","author":"Tueth","year":"1998","journal-title":"J. Clin. Psychiatry"},{"key":"ref_9","first-page":"21938","article-title":"Updated Meta-Analysis of Epidemiologic Studies of Pediatric Bipolar Disorder","volume":"80","author":"Moreira","year":"2019","journal-title":"J. Clin. Psychiatry"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"885","DOI":"10.1542\/peds.2015-0743","article-title":"Lithium in the Acute Treatment of Bipolar I Disorder: A Double-Blind, Placebo-Controlled Study","volume":"136","author":"Findling","year":"2015","journal-title":"Pediatrics"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1089\/cap.2012.0063","article-title":"Post-acute effectiveness of lithium in pediatric bipolar I disorder","volume":"23","author":"Findling","year":"2013","journal-title":"J. Child Adolesc. Psychopharmacol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"507","DOI":"10.1111\/bdi.12094","article-title":"Suicidal ideation and suicide attempts in children and adolescents with bipolar disorder: A systematic review of prevalence and incidence rates, correlates, and targeted interventions","volume":"15","author":"Hauser","year":"2013","journal-title":"Bipolar Disord."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"583","DOI":"10.1111\/bdi.12690","article-title":"Efficacy and tolerability of lithium for the treatment of acute mania in children with bipolar disorder: A systematic review: A report from the ISBD-IGSLi joint task force on lithium treatment","volume":"20","author":"Duffy","year":"2018","journal-title":"Bipolar Disord."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Vita, G., N\u00f6hles, V.B., Ostuzzi, G., Barbui, C., Tedeschi, F., Heuer, F.H., Keller, A., DelBello, M.P., Welge, J.A., and Blom, T.J. (2024). Systematic Review and Network Meta-Analysis: Efficacy and Safety of Antipsychotics vs. Antiepileptics or Lithium for Acute Mania in Children and Adolescents. J. Am. Acad. Child Adolesc. Psychiatry.","DOI":"10.1016\/j.jaac.2024.07.920"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1097\/01.chi.0000194569.70912.a7","article-title":"Open-label lithium for the treatment of adolescents with bipolar depression","volume":"45","author":"Patel","year":"2006","journal-title":"J. Am. Acad. Child Adolesc. Psychiatry"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"999","DOI":"10.1016\/j.jaac.2015.09.016","article-title":"Depression and Suicidality Outcomes in the Treatment of Early Age Mania Study","volume":"54","author":"Salpekar","year":"2015","journal-title":"J. Am. Acad. Child Adolesc. Psychiatry"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"268","DOI":"10.1177\/02698811221104058","article-title":"Systematic review and meta-analysis of augmentation and combination treatments for early-stage treatment-resistant depression","volume":"37","author":"Scott","year":"2023","journal-title":"J. Psychopharmacol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1111\/bdi.13378","article-title":"Multi-trial, aggregated, individual participant data mega-analysis of short-term antidepressant versus mood stabilizer monotherapy of bipolar type II major depressive episode","volume":"26","author":"Amsterdam","year":"2024","journal-title":"Bipolar Disord."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1089\/cap.2008.044","article-title":"of Lithium in Youths with Severe Mood Dysregulation","volume":"19","author":"Dickstein","year":"2009","journal-title":"J. Child Adolesc. Psychopharmacol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"649","DOI":"10.1001\/archpsyc.57.7.649","article-title":"A double-blind placebo-controlled study of lithium in hospitalized aggressive children and adolescents with conduct disorder","volume":"57","author":"Malone","year":"2000","journal-title":"Arch. Gen. Psychiatry"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"192","DOI":"10.1016\/j.psychres.2009.01.022","article-title":"Pharmacological response in juvenile bipolar disorder subtypes: A naturalistic retrospective examination","volume":"177","author":"Masi","year":"2010","journal-title":"Psychiatry Res."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1655","DOI":"10.1212\/WNL.0000000000002104","article-title":"Lithium therapy in Kleine-Levin syndrome: An open-label, controlled study in 130 patients","volume":"85","author":"Groos","year":"2015","journal-title":"Neurology"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1097\/DBP.0b013e31817dc447","article-title":"Open-label treatment trial of lithium to target the underlying defect in fragile X syndrome","volume":"29","author":"Sumis","year":"2008","journal-title":"J. Dev. Behav. Pediatr."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1017\/S1092852900016230","article-title":"Anti-suicidal and self-harm properties of lithium carbonate","volume":"13","author":"Masters","year":"2008","journal-title":"CNS Spectr."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"831","DOI":"10.1017\/S1092852900015571","article-title":"Update: New uses for lithium and anticonvulsants","volume":"12","author":"Rosenberg","year":"2007","journal-title":"CNS Spectr."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1146","DOI":"10.1016\/j.jaac.2019.06.013","article-title":"Lithium Versus Other Mood-Stabilizing Medications in a Longitudinal Study of Youth Diagnosed with Bipolar Disorder","volume":"59","author":"Hafeman","year":"2020","journal-title":"J. Am. Acad. Child Adolesc. Psychiatry"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1281","DOI":"10.1038\/s41467-023-36973-4","article-title":"Regional clozapine, ECT and lithium usage inversely associated with excess suicide rates in male adolescents","volume":"14","author":"Andersson","year":"2023","journal-title":"Nat. Commun."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"382","DOI":"10.1089\/cap.2013.0120","article-title":"Clinical characteristics associated with lithium use among adolescents with bipolar disorder","volume":"24","author":"Ko","year":"2014","journal-title":"J. Child Adolesc. Psychopharmacol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1002\/hup.900","article-title":"Pharmacotherapy in the community-based treatment of children with bipolar I disorder","volume":"23","author":"Jerrell","year":"2008","journal-title":"Hum. Psychopharmacol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1007\/s11920-016-0715-0","article-title":"Suicidal Behavior in Mood Disorders: Response to Pharmacological Treatment","volume":"18","author":"Tondo","year":"2016","journal-title":"Curr. Psychiatry Rep."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Masi, G., Pisano, S., Sesso, G., Mazzullo, C., Berloffa, S., Fantozzi, P., Narzisi, A., Placini, F., Valente, E., and Viglione, V. (2023). Persistent Non-Suicidal Self-Injury and Suicidality in Referred Adolescents: A Longitudinal Study Exploring the Role of Cyclothymic Temperament. Brain Sci., 13.","DOI":"10.3390\/brainsci13050755"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"706","DOI":"10.24869\/psyd.2022.706","article-title":"The Effect of Emotional Dysregulation and Impulsivity on Suicidality in Patients with Bipolar Disorder","volume":"34","author":"Kulacaoglu","year":"2022","journal-title":"Psychiatr. Danub."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1186\/s12991-023-00481-y","article-title":"Facts and myths about the use of lithium for bipolar disorder in routine clinical practice: An expert consensus paper","volume":"22","author":"Fiorillo","year":"2023","journal-title":"Ann. Gen. Psychiatry"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1038","DOI":"10.1097\/01.CHI.0000070247.24125.24","article-title":"Lithium treatment of acute mania in adolescents: A large open trial","volume":"42","author":"Kafantaris","year":"2003","journal-title":"J. Am. Acad. Child Adolesc. Psychiatry"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"984","DOI":"10.1097\/01.chi.0000129223.89433.74","article-title":"Lithium treatment of acute mania in adolescents: A placebo-controlled discontinuation study","volume":"43","author":"Kafantaris","year":"2004","journal-title":"J. Am. Acad. Child Adolesc. Psychiatry"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1097\/01.chi.0000155981.83865.ea","article-title":"Double-blind 18-month trial of lithium versus divalproex maintenance treatment in pediatric bipolar disorder","volume":"44","author":"Findling","year":"2005","journal-title":"J. Am. Acad. Child Adolesc. Psychiatry"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"336","DOI":"10.1089\/cap.2006.16.336","article-title":"A one-year open-label trial of risperidone augmentation in lithium nonresponder youth with preschool-onset bipolar disorder","volume":"16","author":"Pavuluri","year":"2006","journal-title":"J. Child Adolesc. Psychopharmacol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"515","DOI":"10.1001\/archgenpsychiatry.2011.1508","article-title":"A randomized controlled trial of risperidone, lithium, or divalproex sodium for initial treatment of bipolar I disorder, manic or mixed phase, in children and adolescents","volume":"69","author":"Geller","year":"2012","journal-title":"Arch. Gen. Psychiatry"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"974","DOI":"10.1016\/j.jaac.2015.09.019","article-title":"Double TEAM: Enhancing Response and Treating Depression in Patients with Bipolar Disorder During a Mixed or Manic Episode","volume":"54","author":"Kowatch","year":"2015","journal-title":"J. Am. Acad. Child Adolesc. Psychiatry"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"386","DOI":"10.1111\/j.1399-5618.2004.00149.x","article-title":"A prospective 4-5 year follow-up of juvenile onset bipolar disorder","volume":"6","author":"Jairam","year":"2004","journal-title":"BIPOLAR Disord."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1177\/070674370304800110","article-title":"The index manic episode in juvenile-onset bipolar disorder: The pattern of recovery","volume":"48","author":"Jairam","year":"2003","journal-title":"Can. J. Psychiatry."},{"key":"ref_42","first-page":"36","article-title":"Bipolar affective disorder in adolescence: A 10-year study","volume":"21","author":"Bashir","year":"1987","journal-title":"Aust. N. Z. J. Psychiatry"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"2749","DOI":"10.2147\/NDT.S172654","article-title":"Lithium treatment in bipolar adolescents: A follow-up naturalistic study","volume":"14","author":"Masi","year":"2018","journal-title":"Neuropsychiatr. Dis. Treat."},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Masi, G., Berloffa, S., Muratori, P., Mucci, M., Viglione, V., Villafranca, A., Inguaggiato, E., Levantini, V., Placini, F., and Pfanner, C. (2020). A Naturalistic Study of Youth Referred to a Tertiary Care Facility for Acute Hypomanic or Manic Episode. Brain Sci., 10.","DOI":"10.3390\/brainsci10100689"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"221","DOI":"10.3109\/13651501.2015.1061017","article-title":"Antidepressant drugs and teenage suicide in Hungary: Time trend and seasonality analysis","volume":"19","author":"Otuyelu","year":"2015","journal-title":"Int. J. Psychiatry Clin. Pract."},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Janiri, D., Moccia, L., Conte, E., Palumbo, L., Chieffo, D.P.R., Fredda, G., Menichincheri, R.M., Balbi, A., Kotzalidis, G.D., and Sani, G. (2021). Emotional dysregulation, temperament and lifetime suicidal ideation among youths with mood disorders. J. Pers. Med., 11.","DOI":"10.3390\/jpm11090865"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"796","DOI":"10.1001\/jamapsychiatry.2023.1390","article-title":"Association of Bipolar Disorder Diagnosis with Suicide Mortality Rates in Adolescents in Sweden","volume":"80","author":"Andersson","year":"2023","journal-title":"JAMA Psychiatry"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"485","DOI":"10.1089\/cap.2021.0039","article-title":"A Randomized, Double-Blind, Controlled Trial of Lithium Versus Quetiapine for the Treatment of Acute Mania in Youth with Early Course Bipolar Disorder","volume":"31","author":"Patino","year":"2021","journal-title":"J. Child Adolesc. Psychopharmacol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1089\/cap.2010.0084","article-title":"Dosing strategies for lithium monotherapy in children and adolescents with bipolar I disorder","volume":"21","author":"Findling","year":"2011","journal-title":"J. Child Adolesc. Psychopharmacol."}],"container-title":["Brain Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-3425\/14\/11\/1139\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T16:31:40Z","timestamp":1760113900000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-3425\/14\/11\/1139"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,11,13]]},"references-count":49,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2024,11]]}},"alternative-id":["brainsci14111139"],"URL":"https:\/\/doi.org\/10.3390\/brainsci14111139","relation":{},"ISSN":["2076-3425"],"issn-type":[{"value":"2076-3425","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,11,13]]}}}