Use of Lithium in Pediatric Bipolar Disorders and Externalizing Childhood-
related Disorders: A Systematic Review of Randomized Controlled
Trials

Delfina      Janiri; Lorenzo      Moccia; Silvia      Montanari; Valentina      Zani; Claudia      Prinari; Laura      Monti; Daniela      Chieffo; Marianna      Mazza; Alessio      Simonetti; Georgios   D.   Kotzalidis; Luigi      Janiri

doi:10.2174/1570159X21666230126153105

Abstract

Background: Lithium is the standard treatment for bipolar disorders (BD) in adults. There is a dearth of data on its use in the pediatric age. This review aimed to investigate the use of lithium in pediatric bipolar disorder (BD) and other externalizing childhood-related disorders.

Methods: We applied the Preferred Reporting Items for Systematic Reviews and Meta-analyses criteria (PRISMA) to identify randomized controlled trials evaluating the use of lithium in pediatric (BD), conduct disorder (CD), attention deficit hyperactivity disorder, oppositional defiant disorder, and disruptive mood dysregulation disorder. The primary outcome of our study was to evaluate the efficacy of lithium compared to a placebo or other pharmacological agents. The secondary outcomes were acceptability and tolerability.

Results: Twelve studies were eligible, 8 on BD and 4 on CD. Overall, 857 patients were treated with lithium. No studies for externalizing disorder diagnoses were identified. Regarding BD patients (n = 673), efficacy results suggested that lithium was superior to placebo in manic/mixed episodes but inferior to antipsychotics. Lithium efficacy ranged from 32% to 82.4%. Results on maintenance need to be expanded. Comorbidity rates with other externalizing disorders were extremely high, up to 98.6%. Results in CD patients (n= 184) suggested the efficacy of lithium, especially for aggressive behaviors. No severe adverse events directly related to lithium were reported in BD and CD; common side effects were similar to adults.

Conclusion: This systematic review supports the use of lithium in BD and CD as an efficacious and generally well‐tolerated treatment in the pediatric age. However, evidence is limited due to the paucity of available data.

Keywords: Lithium, pediatric, bipolar disorder, conduct disorder, children, externalizing disorder.

« Previous Next »

Graphical Abstract

[1]
Grof, P.; Duffy, A.; Alda, M.; Hajek, T. Lithium response across generations. Acta Psychiatr. Scand.,  2009, 120(5), 378-385.
 [http://dx.doi.org/10.1111/j.1600-0447.2009.01454.x] [PMID: 19807719]

[2]
Sani, G.; Perugi, G.; Tondo, L. Treatment of bipolar disorder in a lifetime perspective: Is lithium still the best choice? Clin. Drug Investig.,  2017, 37(8), 713-727.
 [http://dx.doi.org/10.1007/s40261-017-0531-2] [PMID: 28477315]

[3]
Cipriani, A.; Hawton, K.; Stockton, S.; Geddes, J.R. Lithium in the prevention of suicide in mood disorders: Updated systematic review and meta-analysis. BMJ,  2013, 346(jun27 4), f3646-f3646.
 [http://dx.doi.org/10.1136/bmj.f3646] [PMID: 23814104]

[4]
Baldessarini, R.J.; Tondo, L.; Vázquez, G.H.; Undurraga, J.; Bolzani, L.; Yildiz, A.; Khalsa, H.M.K.; Lai, M.; Lepri, B.; Lolich, M.; Maffei, P.M.; Salvatore, P.; Faedda, G.L.; Vieta, E.; Tohen, M. Age at onset versus family history and clinical outcomes in 1,665 international bipolar-I disorder patients. World Psychiatry,  2012, 11(1), 40-46.
 [http://dx.doi.org/10.1016/j.wpsyc.2012.01.006] [PMID: 22295008]

[5]
Van Meter, A.; Moreira, A.L.R.; Youngstrom, E. Updated metaanalysis of epidemiologic studies of pediatric bipolar disorder. J. Clin. Psychiatry,  2019, 80(3), 18r12180.
 [http://dx.doi.org/10.4088/JCP.18r12180] [PMID: 30946542]

[6]
Carragher, N.; Krueger, R.F.; Eaton, N.R.; Slade, T. Disorders without borders: Current and future directions in the meta-structure of mental disorders. Soc. Psychiatry Psychiatr. Epidemiol.,  2015, 50(3), 339-350.
 [http://dx.doi.org/10.1007/s00127-014-1004-z] [PMID: 25557024]

[7]
Brotman, M.A.; Schmajuk, M.; Rich, B.A.; Dickstein, D.P.; Guyer, A.E.; Costello, E.J.; Egger, H.L.; Angold, A.; Pine, D.S.; Leibenluft, E. Prevalence, clinical correlates, and longitudinal course of severe mood dysregulation in children. Biol. Psychiatry,  2006, 60(9), 991-997.
 [http://dx.doi.org/10.1016/j.biopsych.2006.08.042] [PMID: 17056393]

[8]
Althoff, R.R.; Crehan, E.T.; He, J.P.; Burstein, M.; Hudziak, J.J.; Merikangas, K.R. Disruptive mood dysregulation disorder at ages 13-18: results from the national comorbidity survey—adolescent supplement. J. Child Adolesc. Psychopharmacol.,  2016, 26(2), 107-113.
 [http://dx.doi.org/10.1089/cap.2015.0038] [PMID: 26771536]

[9]
Greene, R.W.; Biederman, J.; Zerwas, S.; Monuteaux, M.C.; Goring, J.C.; Faraone, S.V. Psychiatric comorbidity, family dysfunction, and social impairment in referred youth with oppositional defiant disorder. Am. J. Psychiatry,  2002, 159(7), 1214-1224.
 [http://dx.doi.org/10.1176/appi.ajp.159.7.1214] [PMID: 12091202]

[10]
Masi, G.; Milone, A.; Manfredi, A.; Pari, C.; Paziente, A.; Millepiedi, S. Comorbidity of conduct disorder and bipolar disorder in clinically referred children and adolescents. J. Child Adolesc. Psychopharmacol.,  2008, 18(3), 271-279.
 [http://dx.doi.org/10.1089/cap.2008.0051] [PMID: 18582182]

[11]
Arnold, L.E.; Demeter, C.; Mount, K.; Frazier, T.W.; Youngstrom, E.A.; Fristad, M.; Birmaher, B.; Findling, R.L.; Horwitz, S.M.; Kowatch, R.; Axelson, D.A. Pediatric bipolar spectrum disorder and ADHD: comparison and comorbidity in the LAMS clinical sample. Bipolar Disord.,  2011, 13(5-6), 509-521.
 [http://dx.doi.org/10.1111/j.1399-5618.2011.00948.x] [PMID: 22017220]

[12]
Findling, R.L.; Zhou, X.; George, P.; Chappell, P.B. Diagnostic trends and prescription patterns in disruptive mood dysregulation disorder and bipolar disorder. J. Am. Acad. Child Adolesc. Psychiatry,  2022, 61(3), 434-445.
 [http://dx.doi.org/10.1016/j.jaac.2021.05.016] [PMID: 34091008]

[13]
Malone, R.P.; Delaney, M.A.; Luebbert, J.F.; Cater, J.; Campbell, M. A double-blind placebo-controlled study of lithium in hospitalized aggressive children and adolescents with conduct disorder. Arch. Gen. Psychiatry,  2000, 57(7), 649-654.
 [http://dx.doi.org/10.1001/archpsyc.57.7.649] [PMID: 10891035]

[14]
Masi, G.; Milone, A.; Manfredi, A.; Pari, C.; Paziente, A.; Millepiedi, S. Effectiveness of lithium in children and adolescents with conduct disorder: A retrospective naturalistic study. CNS Drugs,  2009, 23(1), 59-69.
 [http://dx.doi.org/10.2165/0023210-200923010-00004] [PMID: 19062775]

[15]
Licamele, W.L.; Goldberg, R.L. The concurrent use of lithium and methylphenidate in a child. J. Am. Acad. Child Adolesc. Psychiatry,  1989, 28(5), 785-787.
 [http://dx.doi.org/10.1097/00004583-198909000-00023] [PMID: 2507515]

[16]
Campbell, M.; Adams, P.B.; Small, A.M.; Kafantaris, V.; Silva, R.R.; Shell, J.; Perry, R.; Overall, J. Lithium in hospitalized aggressive children with conduct disorder: a double-blind and placebo-controlled study. J. Am. Acad. Child Adolesc. Psychiatry,  1995, 34(4), 445-453.
 [http://dx.doi.org/10.1097/00004583-199504000-00011] [PMID: 7751258]

[17]
Duffy, A.; Heffer, N.; Goodday, S.M.; Weir, A.; Patten, S.; Malhi, G.S.; Cipriani, A. Efficacy and tolerability of lithium for the treatment of acute mania in children with bipolar disorder: A systematic review. Bipolar Disord.,  2018, 20(7), 583-593.
 [http://dx.doi.org/10.1111/bdi.12690] [PMID: 30221434]

[18]
Amerio, A.; Ossola, P.; Scagnelli, F.; Odone, A.; Allinovi, M.; Cavalli, A.; Iacopelli, J.; Tonna, M.; Marchesi, C.; Ghaemi, S.N. Safety and efficacy of lithium in children and adolescents: A systematic review in bipolar illness. Eur. Psychiatry,  2018, 54, 85-97.
 [http://dx.doi.org/10.1016/j.eurpsy.2018.07.012] [PMID: 30130637]

[19]
Sterne, J.A.C.; Savović, J.; Page, M.J.; Elbers, R.G.; Blencowe, N.S.; Boutron, I.; Cates, C.J.; Cheng, H.Y.; Corbett, M.S.; Eldridge, S.M.; Emberson, J.R.; Hernán, M.A.; Hopewell, S.; Hróbjartsson, A.; Junqueira, D.R.; Jüni, P.; Kirkham, J.J.; Lasserson, T.; Li, T.; McAleenan, A.; Reeves, B.C.; Shepperd, S.; Shrier, I.; Stewart, L.A.; Tilling, K.; White, I.R.; Whiting, P.F.; Higgins, J.P.T. RoB 2: A revised tool for assessing risk of bias in randomised trials. BMJ,  2019, 366, l4898.
 [http://dx.doi.org/10.1136/bmj.l4898] [PMID: 31462531]

[20]
Geller, B.; Cooper, T.B.; Sun, K.; Zimerman, B.; Frazier, J.; Williams, M.; Heath, J. Double-blind and placebo-controlled study of lithium for adolescent bipolar disorders with secondary substance dependency. J. Am. Acad. Child Adolesc. Psychiatry,  1998, 37(2), 171-178.
 [http://dx.doi.org/10.1097/00004583-199802000-00009] [PMID: 9473913]

[21]
Kowatch, R.A.; Suppes, T.; Carmody, T.J.; Bucci, J.P.; Hume, J.H.; Kromelis, M.; Emslie, G.J.; Weinberg, W.A.; Rush, A.J. Effect size of lithium, divalproex sodium, and carbamazepine in children and adolescents with bipolar disorder. J. Am. Acad. Child Adolesc. Psychiatry,  2000, 39(6), 713-720.
 [http://dx.doi.org/10.1097/00004583-200006000-00009] [PMID: 10846305]

[22]
Kafantaris, V.; Coletti, D.J.; Dicker, R.; Padula, G.; Pleak, R.R.; Alvir, J.O.S.E.M.J. Lithium treatment of acute mania in adolescents: a placebo-controlled discontinuation study. J. Am. Acad. Child Adolesc. Psychiatry,  2004, 43(8), 984-993.
 [http://dx.doi.org/10.1097/01.chi.0000129223.89433.74] [PMID: 15266193]

[23]
Pavuluri, M.N.; Henry, D.B.; Carbray, J.A.; Sampson, G.; Naylor, M.W.; Janicak, P.G. Open-label prospective trial of risperidone in combination with lithium or divalproex sodium in pediatric mania. J. Affect. Disord.,  2004, 82(Suppl. 1), S103-S111.
 [http://dx.doi.org/10.1016/j.jad.2004.05.017] [PMID: 15571784]

[24]
Findling, R.L.; Mcnamara, N.K.; Youngstrom, E.A.; Stansbrey, R.; Gracious, B.L.; Reed, M.D.; Calabrese, J.R. Double-blind 18-month trial of lithium versus divalproex maintenance treatment in pediatric bipolar disorder. J. Am. Acad. Child Adolesc. Psychiatry,  2005, 44(5), 409-417.
 [http://dx.doi.org/10.1097/01.chi.0000155981.83865.ea] [PMID: 15843762]

[25]
Geller, B.; Luby, J.L.; Joshi, P.; Wagner, K.D.; Emslie, G.; Walkup, J.T.; Axelson, D.A.; Bolhofner, K.; Robb, A.; Wolf, D.V.; Riddle, M.A.; Birmaher, B.; Nusrat, N.; Ryan, N.D.; Vitiello, B.; Tillman, R.; Lavori, P. 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. Arch. Gen. Psychiatry,  2012, 69(5), 515-528.
 [http://dx.doi.org/10.1001/archgenpsychiatry.2011.1508] [PMID: 22213771]

[26]
Findling, R.L.; Robb, A.; McNamara, N.K.; Pavuluri, M.N.; Kafantaris, V.; Scheffer, R.; Frazier, J.A.; Rynn, M.; DelBello, M.; Kowatch, R.A.; Rowles, B.M.; Lingler, J.; Martz, K.; Anand, R.; Clemons, T.E.; Taylor-Zapata, P. Lithium in the acute treatment of bipolar I disorder: A double-blind, placebo-controlled study. Pediatrics,  2015, 136(5), 885-894.
 [http://dx.doi.org/10.1542/peds.2015-0743] [PMID: 26459650]

[27]
Patino, L.R.; Klein, C.C.; Strawn, J.R.; Blom, T.J.; Tallman, M.J.; Adler, C.M.; Welge, J.A.; DelBello, M.P. A randomized, double-blind, controlled trial of lithium versus quetiapine for the treatment of acute mania in youth with early course bipolar disorder. J. Child Adolesc. Psychopharmacol.,  2021, 31(7), 485-493.
 [http://dx.doi.org/10.1089/cap.2021.0039] [PMID: 34520250]

[28]
Campbell, M.; Small, A.M.; Green, W.H.; Jennings, S.J.; Perry, R.; Bennett, W.G.; Anderson, L. Behavioral efficacy of haloperidol and lithium carbonate. A comparison in hospitalized aggressive children with conduct disorder. Arch. Gen. Psychiatry,  1984, 41(7), 650-656.
 [http://dx.doi.org/10.1001/archpsyc.1984.01790180020002] [PMID: 6428371]

[29]
Rifkin, A.; Karajgi, B.; Dicker, R.; Perl, E.; Boppana, V.; Hasan, N.; Pollack, S. Lithium treatment of conduct disorders in adolescents. Am. J. Psychiatry,  1997, 154(4), 554-555.
 [http://dx.doi.org/10.1176/ajp.154.4.554] [PMID: 9090346]

[30]
Walkup, J.T.; Wagner, K.D.; Miller, L.; Yenokyan, G.; Luby, J.L.; Joshi, P.T.; Axelson, D.A.; Robb, A.; Salpekar, J.A.; Wolf, D.; Sanyal, A.; Birmaher, B.; Vitiello, B.; Riddle, M.A. Treatment of early-age mania: Outcomes for partial and nonresponders to initial treatment. J. Am. Acad. Child Adolesc. Psychiatry,  2015, 54(12), 1008-1019.
 [http://dx.doi.org/10.1016/j.jaac.2015.09.015] [PMID: 26598476]

[31]
Salpekar, J.A.; Joshi, P.T.; Axelson, D.A.; Reinblatt, S.P.; Yenokyan, G.; Sanyal, A.; Walkup, J.T.; Vitiello, B.; Luby, J.L.; Wagner, K.D.; Nusrat, N.; Riddle, M.A. Depression and suicidality outcomes in the treatment of early age mania study. J. Am. Acad. Child Adolesc. Psychiatry,  2015, 54(12), 999-1007.e4.
 [http://dx.doi.org/10.1016/j.jaac.2015.09.016] [PMID: 26598475]

[32]
Vitiello, B.; Riddle, M.A.; Yenokyan, G.; Axelson, D.A.; Wagner, K.D.; Joshi, P.; Walkup, J.T.; Luby, J.; Birmaher, B.; Ryan, N.D.; Emslie, G.; Robb, A.; Tillman, R. Treatment moderators and predictors of outcome in the Treatment of Early Age Mania (TEAM) study. J. Am. Acad. Child Adolesc. Psychiatry,  2012, 51(9), 867-878.
 [http://dx.doi.org/10.1016/j.jaac.2012.07.001] [PMID: 22917200]

[33]
Findling, R.L.; McNamara, N.K.; Pavuluri, M.; Frazier, J.A.; Rynn, M.; Scheffer, R.; Kafantaris, V.; Robb, A.; DelBello, M.; Kowatch, R.A.; Rowles, B.M.; Lingler, J.; Zhao, J.; Clemons, T.; Martz, K.; Anand, R.; Taylor-Zapata, P. Lithium for the maintenance treatment of bipolar I disorder: A double-blind, placebo-controlled discontinuation study. J. Am. Acad. Child Adolesc. Psychiatry,  2019, 58(2), 287-296.e4.
 [http://dx.doi.org/10.1016/j.jaac.2018.07.901] [PMID: 30738555]

[34]
Cipriani, A.; Barbui, C.; Salanti, G.; Rendell, J.; Brown, R.; Stockton, S.; Purgato, M.; Spineli, L.M.; Goodwin, G.M.; Geddes, J.R. Comparative efficacy and acceptability of antimanic drugs in acute mania: A multiple-treatments meta-analysis. Lancet,  2011, 378(9799), 1306-1315.
 [http://dx.doi.org/10.1016/S0140-6736(11)60873-8] [PMID: 21851976]

[35]
Sani, G.; Fiorillo, A. The use of lithium in mixed states. CNS Spectr.,  2020, 25(4), 449-451.
 [http://dx.doi.org/10.1017/S1092852919001184] [PMID: 31248464]

[36]
De Filippis, S.; Cuomo, I.; Lionetto, L.; Janiri, D.; Simmaco, M.; Caloro, M.; De Persis, S.; Piazzi, G.; Simonetti, A.; Telesforo, C.L.; Sciarretta, A.; Caccia, F.; Gentile, G.; Kotzalidis, G.D.; Girardi, P. Intramuscular aripiprazole in the acute management of psychomotor agitation. Pharmacotherapy,  2013, 33(6), 603-614.
 [http://dx.doi.org/10.1002/phar.1260] [PMID: 23505124]

[37]
Duffy, A. The nature of the association between childhood ADHD and the development of bipolar disorder: A review of prospective high-risk studies. Am. J. Psychiatry,  2012, 169(12), 1247-1255.
 [http://dx.doi.org/10.1176/appi.ajp.2012.11111725] [PMID: 23212056]

[38]
Di Nicola, M.; Pepe, M.; Modica, M.; Lanzotti, P.; Panaccione, I.; Moccia, L.; Janiri, L. Mixed states in patients with substance and behavioral addictions. Psychiatr. Clin. North Am.,  2020, 43(1), 127-137.
 [http://dx.doi.org/10.1016/j.psc.2019.10.012] [PMID: 32008679]

[39]
Hafeman, D.M.; Rooks, B.; Merranko, J.; Liao, F.; Gill, M.K.; Goldstein, T.R.; Diler, R.; Ryan, N.; Goldstein, B.I.; Axelson, D.A.; Strober, M.; Keller, M.; Hunt, J.; Hower, H.; Weinstock, L.M.; Yen, S.; Birmaher, B. Lithium versus other mood-stabilizing medications in a longitudinal study of youth diagnosed with bipolar disorder. J. Am. Acad. Child Adolesc. Psychiatry,  2020, 59(10), 1146-1155.
 [http://dx.doi.org/10.1016/j.jaac.2019.06.013] [PMID: 31369795]

[40]
Hafeman, D.M.; Chang, K.D.; Garrett, A.S.; Sanders, E.M.; Phillips, M.L. Effects of medication on neuroimaging findings in bipolar disorder: an updated review. Bipolar Disord.,  2012, 14(4), 375-410.
 [http://dx.doi.org/10.1111/j.1399-5618.2012.01023.x] [PMID: 22631621]

[41]
Nolen, W.A.; Licht, R.W.; Young, A.H.; Malhi, G.S.; Tohen, M.; Vieta, E.; Kupka, R.W.; Zarate, C.; Nielsen, R.E.; Baldessarini, R.J.; Severus, E. What is the optimal serum level for lithium in the maintenance treatment of bipolar disorder? A systematic review and recommendations from the ISBD/IGSLI Task Force on treatment with lithium. Bipolar Disord.,  2019, 21(5), 394-409.
 [http://dx.doi.org/10.1111/bdi.12805] [PMID: 31112628]

[42]
Schou, M. Lithium prophylaxis: Myths and realities. Am. J. Psychiatry,  1989, 146(5), 573-576.
 [http://dx.doi.org/10.1176/ajp.146.5.573] [PMID: 2653052]

[43]
Grant, B.; Salpekar, J.A. Using lithium in children and adolescents with bipolar disorder: Efficacy, tolerability, and practical considerations. Paediatr. Drugs,  2018, 20(4), 303-314.
 [http://dx.doi.org/10.1007/s40272-018-0289-x] [PMID: 29651656]

[44]
Gitlin, M. Lithium side effects and toxicity: Prevalence and management strategies. Int. J. Bipolar Disord.,  2016, 4(1), 27.
 [http://dx.doi.org/10.1186/s40345-016-0068-y] [PMID: 27900734]

[45]
Landersdorfer, C.B.; Findling, R.L.; Frazier, J.A.; Kafantaris, V.; Kirkpatrick, C.M.J. Lithium in paediatric patients with bipolar disorder: Implications for selection of dosage regimens via population pharmacokinetics/pharmacodynamics. Clin. Pharmacokinet.,  2017, 56(1), 77-90.
 [http://dx.doi.org/10.1007/s40262-016-0430-3] [PMID: 27393139]

[46]
Amdisen, A.; Hildebrandt, J. Use of lithium in the medically ill. Psychother. Psychosom.,  1988, 49(2), 103-119.
 [http://dx.doi.org/10.1159/000288074] [PMID: 3064119]

[47]
Janiri, D.; Moccia, L.; Conte, E.; Palumbo, L.; Chieffo, D.P.R.; Fredda, G.; Menichincheri, R.M.; Balbi, A.; Kotzalidis, G.D.; Sani, G.; Janiri, L. Emotional dysregulation, temperament and lifetime suicidal ideation among youths with mood disorders. J. Pers. Med.,  2021, 11(9), 865.
 [http://dx.doi.org/10.3390/jpm11090865] [PMID: 34575642]

[48]
Ko, A.; Swampillai, B.; Timmins, V.; Scavone, A.; Collinger, K.; Goldstein, B.I. Clinical characteristics associated with lithium use among adolescents with bipolar disorder. J. Child Adolesc. Psychopharmacol.,  2014, 24(7), 382-389.
 [http://dx.doi.org/10.1089/cap.2013.0120] [PMID: 25010788]

[49]
Jiang, X.; Mio, M.; Dimick, M.K.; Zou, Y.; Sultan, A.A.; Goldstein, B.I. Association of lithium and second-generation antipsychotics with neurocognition in youth with bipolar disorder. J. Child Adolesc. Psychopharmacol.,  2022, 32(1), 61-69.
 [http://dx.doi.org/10.1089/cap.2021.0093] [PMID: 35085001]

[50]
Masi, G.; Perugi, G.; Millepiedi, S.; Mucci, M.; Pfanner, C.; Berloffa, S.; Pari, C.; Gagliano, A.; D’Amico, F.; Akiskal, H.S. Pharmacological response in juvenile bipolar disorder subtypes: A naturalistic retrospective examination. Psychiatry Res.,  2010, 177(1-2), 192-198.
 [http://dx.doi.org/10.1016/j.psychres.2009.01.022] [PMID: 20381170]

[51]
Findling, R.L.; Kafantaris, V.; Pavuluri, M.; McNamara, N.K.; Frazier, J.A.; Sikich, L.; Kowatch, R.; Rowles, B.M.; Clemons, T.E.; Taylor-Zapata, P. Post-acute effectiveness of lithium in pediatric bipolar I disorder. J. Child Adolesc. Psychopharmacol.,  2013, 23(2), 80-90.
 [http://dx.doi.org/10.1089/cap.2012.0063] [PMID: 23510444]

[52]
Tondo, L.; Baldessarini, R.J.; Hennen, J.; Floris, G.; Silvetti, F.; Tohen, M. Lithium treatment and risk of suicidal behavior in bipolar disorder patients. J. Clin. Psychiatry,  1998, 59(8), 405-414.
 [http://dx.doi.org/10.4088/JCP.v59n0802] [PMID: 9721820]

[53]
Toffol, E.; Hätönen, T.; Tanskanen, A.; Lönnqvist, J.; Wahlbeck, K.; Joffe, G.; Tiihonen, J.; Haukka, J.; Partonen, T. Lithium is associated with decrease in all-cause and suicide mortality in high-risk bipolar patients: A nationwide registry-based prospective cohort study. J. Affect. Disord.,  2015, 183, 159-165.
 [http://dx.doi.org/10.1016/j.jad.2015.04.055] [PMID: 26005778]

[54]
Manchia, M.; Sani, G.; Alda, M. Suicide Risk and Lithium. JAMA Psychiatry,  2022, 79(5), 513.
 [http://dx.doi.org/10.1001/jamapsychiatry.2022.0081] [PMID: 35262644]

[55]
Tondo, L.; Vázquez, G.H.; Baldessarini, R.J. Prevention of suicidal behavior in bipolar disorder. Bipolar Disord.,  2021, 23(1), 14-23.
 [http://dx.doi.org/10.1111/bdi.13017] [PMID: 33037692]

Rights & Permissions Print Cite

Article Metrics

34

1

Journal Information

For Authors

For Editors

For Reviewers

Explore Articles

Open Access

Open Access Articles

For Visitors

DOI https://dx.doi.org/10.2174/1570159X21666230126153105	Print ISSN 1570-159X
Publisher Name Bentham Science Publisher	Online ISSN 1875-6190

Current Neuropharmacology

Use of Lithium in Pediatric Bipolar Disorders and Externalizing Childhood- related Disorders: A Systematic Review of Randomized Controlled Trials

Abstract

Graphical Abstract

Related Journals

Related Books