Download PDF
Pharmacopsychiatry 2018; 51(05): 189-193
DOI: 10.1055/a-0575-4179
Review
© Georg Thieme Verlag KG Stuttgart · New York

Lithium Treatment in Children and Adolescents

Anne Duffy
1   Department of Psychiatry, Queens University, Kingston Ontario
2   Mood Disorders Center of Ottawa, Ottawa Ontario
,
Paul Grof
2   Mood Disorders Center of Ottawa, Ottawa Ontario
3   Department of Psychiatry, University of Toronto, Toronto, Ontario
› Author Affiliations
Further Information

Publication History

received 23 January 2018
revised 26 January 2018

accepted 07 February 2018

Publication Date:
28 February 2018 (online)

Also available at
    Permissions and Reprints

Abstract

Introduction There is a resurgence of interest in lithium treatment of bipolar disorders in part related to its unique anti-suicidal and neuroprotective effects.

Methods This is a narrative review of key studies pertaining to the effectiveness and tolerability of lithium treatment in pediatric populations.

Results Evidence supports that lithium is an effective and generally well-tolerated acute treatment for pediatric mania compared to placebo. Lithium may be less effective than risperidone for treating chronic mixed/manic symptoms in young children but comparable to anticonvulsants. However, in comparison, risperidone was associated with higher weight gain and prolactin levels. There is a lack of evidence inform maintenance treatment in children who benefit from lithium. Other indications that require further study include treatment of refractory or recurrent major depression in children at confirmed familial risk of bipolar disorder, as well as the treatment of acute suicidal ideation/behavior and refractory aggression.

Discussion There is inadequate data about the full variety of benefit and tolerability of lithium treatment in pediatric patients. However, given the potential for protection against suicide and neurotoxic effects of illness, further studies should be a priority.

Key words

lithium treatment - children and adolescents - narrative review
 

  • References

  • 1 Annell AL. Manic-depressive illness in children and effect of treatment with lithium carbonate. Acta Paedopsychiatr 1969; 36: 292-301
    PubMedGoogle Scholar
  • 2 Cipriani A, Hawton K, Stockton S. et al. Lithium in the prevention of suicide in mood disorders: Updated systematic review and meta-analysis. BMJ 2013; 346: f3646
    CrossrefPubMedGoogle Scholar
  • 3 Girlanda F, Cipriani A, Agrimi E. et al. Effectiveness of lithium in subjects with treatment-resistant depression and suicide risk: Results and lessons of an underpowered randomised clinical trial. BMC Res Notes 2014; 7: 731
    CrossrefPubMedGoogle Scholar
  • 4 BALANCE investigators and collaborators . Geddes JR, Goodwin GM. et al. Lithium plus valproate combination therapy versus monotherapy for relapse prevention in bipolar I disorder (BALANCE): A randomised open-label trial. Lancet 2010; 375: 385-395
    CrossrefPubMedGoogle Scholar
  • 5 Smith KA, Cipriani A. Lithium and suicide in mood disorders: Updated meta-review of the scientific literature. Bipolar Disord 2017; 19: 575-586
    CrossrefPubMedGoogle Scholar
  • 6 Hayes JF, Marston L, Walters K. et al. Lithium vs. valproate vs. olanzapine vs. quetiapine as maintenance monotherapy for bipolar disorder: A population-based UK cohort study using electronic health records. World Psychiatry 2016; 15: 53-58
    CrossrefPubMedGoogle Scholar
  • 7 Kessing LV, Hellmund G, Geddes JR. et al. Valproate v. lithium in the treatment of bipolar disorder in clinical practice: Observational nationwide register-based cohort study. Br J Psychiatry 2011; 199: 57-63
    CrossrefPubMedGoogle Scholar
  • 8 Geller B, Tillman R. Prepubertal and early adolescent bipolar I disorder: Review of diagnostic validation by Robins and Guze criteria. J Clin Psychiatry 2005; 66 (Suppl. 07) 21-28
    PubMedGoogle Scholar
  • 9 Grof P, Alda M, Grof E. et al. Lithium response and genetics of affective disorders. J Affect Disord 1994; 32: 85-95
    CrossrefPubMedGoogle Scholar
  • 10 Grof P, Hux M, Grof E. et al. Prediction of response to stabilizing lithium treatment. Pharmacopsychiatria 1983; 16: 195-200
    Article in Thieme ConnectPubMedGoogle Scholar
  • 11 Grof P, Duffy A, Alda M. et al. Lithium response across generations. Acta Psychiatr Scand 2009; 120: 378-385
    CrossrefPubMedGoogle Scholar
  • 12 Duffy A, Horrocks J, Doucette S. et al. The developmental trajectory of bipolar disorder. Br J Psychiatry 2014; 204: 122-128
    CrossrefPubMedGoogle Scholar
  • 13 Grof P, Alda M. Discrepancies in the efficacy of lithium. Arch Gen Psychiatry 2000; 57: 191
    CrossrefPubMedGoogle Scholar
  • 14 Grof P, Muller-Oerlinghausen B. A critical appraisal of lithiumʼs efficacy and effectiveness: The last 60 years. Bipolar Disord 2009; 11 (Suppl. 02) 10-19
    CrossrefPubMedGoogle Scholar
  • 15 Grof P, Alda M, Grof E. et al. The challenge of predicting response to stabilising lithium treatment. The importance of patient selection. Br J Psychiatry Suppl 1993; 21: 16-19
    PubMedGoogle Scholar
  • 16 Grof P. Selecting effective long-term treatment for bipolar patients: Monotherapy and combinations. J Clin Psychiatry 2003; 64 (Suppl. 05) 53-61
    CrossrefPubMedGoogle Scholar
  • 17 Kessing LV, Gerds TA, Feldt-Rasmussen B. et al. Use of lithium and anticonvulsants and the rate of chronic kidney disease: A nationwide population-based study. JAMA Psychiatry 2015; 72: 1182-1191
    CrossrefPubMedGoogle Scholar
  • 18 Wang J, Wang FW, Kessinger A. The natural history and outcomes of the patients with carcinosarcoma involving kidney and renal pelvis. Adv Urol 2011; 2011: 693964
    PubMedGoogle Scholar
  • 19 Baldessarini RJ, Tondo L, Hennen J. Lithium treatment and suicide risk in major affective disorders: Update and new findings. J Clin Psychiatry 2003; 64 (Suppl. 05) 44-52
    PubMedGoogle Scholar
  • 20 Malhi GS, Outhred T. Therapeutic mechanisms of lithium in bipolar disorder: Recent advances and current understanding. CNS Drugs 2016; 30: 931-949
    CrossrefPubMedGoogle Scholar
  • 21 Malhi GS, McAulay C, Gershon S. et al. The lithium battery: Assessing the neurocognitive profile of lithium in bipolar disorder. Bipolar Disord 2016; 18: 102-115
    CrossrefPubMedGoogle Scholar
  • 22 Hayes JF, Marston L, Walters K. et al. Adverse renal, endocrine, hepatic, and metabolic events during maintenance mood stabilizer treatment for bipolar disorder: A population-based cohort study. PLoS Med 2016; 13: e1002058
    CrossrefPubMedGoogle Scholar
  • 23 Locher C, Koechlin H, Zion SR. et al. Efficacy and safety of selective serotonin reuptake inhibitors, serotonin-norepinephrine reuptake inhibitors, and placebo for common psychiatric disorders among children and adolescents: A systematic review and meta-analysis. JAMA Psychiatry 2017; 74: 1011-1020
    CrossrefPubMedGoogle Scholar
  • 24 Rice F. Genetics of childhood and adolescent depression: Insights into etiological heterogeneity and challenges for future genomic research. Genome Med 2010; 2: 68
    CrossrefPubMedGoogle Scholar
  • 25 Duffy A, Goodday S, Passos IC. et al. Changing the bipolar illness trajectory. Lancet Psychiatry 2017; 4: 11-13
    CrossrefPubMedGoogle Scholar
  • 26 Eunice Kennedy Shriver National Institute of Child Health and Human Development. Best Pharmaceuticals for Children Act. Available from: https://bpca.nichd.nih.gov/Pages/default.aspx
    PubMed
  • 27 McKnew DH, Cytryn L, Buchsbaum MS. et al. Lithium in children of lithium-responding parents. Psychiatry Res 1981; 4: 171-180
    CrossrefPubMedGoogle Scholar
  • 28 DeLong GR, Nieman GW. Lithium-induced behavior changes in children with symptoms suggesting manic-depressive illness. Psychopharmacol Bull 1983; 19: 258-265
    PubMedGoogle Scholar
  • 29 Brumback RA, Weinberg WA. Mania in childhood. II. Therapeutic trial of lithium carbonate and further description of manic-depressive illness in children. Am J Dis Child 1977; 131: 1122-1126
    CrossrefPubMedGoogle Scholar
  • 30 Kowatch RA, Suppes T, Carmody TJ. et al. Effect size of lithium, divalproex sodium, and carbamazepine in children and adolescents with bipolar disorder. J Am Acad Child Adolesc Psychiatry 2000; 39: 713-720
    CrossrefPubMedGoogle Scholar
  • 31 Findling RL, Robb A, McNamara NK. et al. Lithium in the acute treatment of bipolar I disorder: A double-blind, placebo-controlled study. Pediatrics 2015; 136: 885-894
    CrossrefPubMedGoogle Scholar
  • 32 Geller B, Luby JL, Joshi P. et al. 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: 515-528
    CrossrefPubMedGoogle Scholar
  • 33 Vitiello B, Riddle MA, Yenokyan G. et al. Treatment moderators and predictors of outcome in the Treatment of Early Age Mania (TEAM) study. J Am Acad Child Adolesc Psychiatry 2012; 51: 867-878
    CrossrefPubMedGoogle Scholar
  • 34 Walkup JT, Wagner KD, Miller L. et al. Treatment of early-age mania: Outcomes for partial and nonresponders to initial treatment. J Am Acad Child Adolesc Psychiatry 2015; 54: 1008-1019
    CrossrefPubMedGoogle Scholar
  • 35 Findling RL, McNamara NK, Youngstrom EA. et al. Double-blind 18-month trial of lithium versus divalproex maintenance treatment in pediatric bipolar disorder. J Am Acad Child Adolesc Psychiatry 2005; 44: 409-417
    CrossrefPubMedGoogle Scholar
  • 36 Pavuluri MN, Henry DB, Carbray JA. et al. Open-label prospective trial of risperidone in combination with lithium or divalproex sodium in pediatric mania. J Affect Disord 2004; 82 (Suppl. 01) S103-S111
    CrossrefPubMedGoogle Scholar
  • 37 Duffy A, Patten S, Goodday S. et al. Efficacy and tolerability of lithium in treating acute mania in youth with bipolar disorder: Protocol for a systematic review. Int J Bipolar Disord 2017; 5: 22
    CrossrefPubMedGoogle Scholar
  • 38 Grof P, Duffy A, Cavazzoni P. et al. Is response to prophylactic lithium a familial trait?. J Clin Psychiatry 2002; 63: 942-947
    CrossrefPubMedGoogle Scholar
  • 39 Duffy A, Alda M, Milin R. et al. A consecutive series of treated affected offspring of parents with bipolar disorder: Is response associated with the clinical profile?. Can J Psychiatry 2007; 52: 369-376
    CrossrefPubMedGoogle Scholar
  • 40 Leibenluft E. Severe mood dysregulation, irritability, and the diagnostic boundaries of bipolar disorder in youths. Am J Psychiatry 2011; 168: 129-142
    CrossrefPubMedGoogle Scholar
  • 41 Duffy A. The early natural history of bipolar disorder: what we have learned from longitudinal high-risk research. Can J Psychiatry 2010; 55: 477-485
    CrossrefPubMedGoogle Scholar
  • 42 Gottesman II, Laursen TM, Bertelsen A. et al. Severe mental disorders in offspring with 2 psychiatrically ill parents. Arch Gen Psychiatry 2010; 67: 252-257
    CrossrefPubMedGoogle Scholar
  • 43 Duffy A, Alda M, Kutcher S. et al. Psychiatric symptoms and syndromes among adolescent children of parents with lithium-responsive or lithium-nonresponsive bipolar disorder. Am J Psychiatry 1998; 155: 431-433
    CrossrefPubMedGoogle Scholar
  • 44 Mesman E, Nolen WA, Reichart CG. et al. The Dutch bipolar offspring study: 12-year follow-up. Am J Psychiatry 2013; 170: 542-549
    CrossrefPubMedGoogle Scholar
  • 45 Vandeleur CL, Strippoli MF, Castelao E. et al. The Lausanne-Geneva cohort study of offspring of parents with mood disorders: Methodology, findings, current sample characteristics, and perspectives. Soc Psychiatry Psychiatr Epidemiol 2017; 52: 1041-1058
    CrossrefPubMedGoogle Scholar
  • 46 Egeland JA, Endicott J, Hostetter AM. et al. A 16-year prospective study of prodromal features prior to BPI onset in well Amish children. J Affect Disord 2012; 142: 186-192
    CrossrefPubMedGoogle Scholar
  • 47 Birmaher B, Axelson D, Monk K. et al. Lifetime psychiatric disorders in school-aged offspring of parents with bipolar disorder: The Pittsburgh Bipolar Offspring study. Arch Gen Psychiatry 2009; 66: 287-296
    CrossrefPubMedGoogle Scholar
  • 48 Schou M, Baastrup PC, Grof P. et al. Pharmacological and clinical problems of lithium prophylaxis. Br J Psychiatry 1970; 116: 615-619
    CrossrefPubMedGoogle Scholar
  • 49 Schou M. TK Baastrup P. Studies on the course of current endongeneous affective disorders. J Int Pharmacopsychiat 1970; 5: 100-106
    PubMedGoogle Scholar
  • 50 Yatham LN, Kennedy SH, Parikh SV. et al. Canadian Network for Mood and Anxiety Treatments (CANMAT) and International Society for Bipolar Disorders (ISBD) collaborative update of CANMAT guidelines for the management of patients with bipolar disorder: Update 2013. Bipolar Disord 2013; 15: 1-44
    PubMedGoogle Scholar
  • 51 Duffy A. Interventions for youth at risk of bipolar disorder. Curr Treat Options Psychiatry 2014; 1: 37-47
    PubMedGoogle Scholar
  • 52 Deshauer D, Grof E, Alda M. et al. Patterns of DST positivity in remitted affective disorders. Biol Psychiatry 1999; 45: 1023-1029
    CrossrefPubMedGoogle Scholar
  • 53 Duffy A. Early identification of recurrent mood disorders in youth: The importance of a developmental approach. Evid Based Ment Health 2015; 18: 7-9
    CrossrefPubMedGoogle Scholar
  • 54 Duffy A, Horrocks J, Doucette S. et al. Childhood anxiety: An early predictor of mood disorders in offspring of bipolar parents. J Affect Disord 2013; 150: 363-369
    CrossrefPubMedGoogle Scholar
  • 55 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: 1247-1255
    CrossrefPubMedGoogle Scholar
  • 56 Cross-Disorder Group of the Psychiatric Genomics Consortium . Identification of risk loci with shared effects on five major psychiatric disorders: A genome-wide analysis. Lancet 2013; 381: 1371-1379
    CrossrefPubMedGoogle Scholar
  • 57 Masi G, Milone A, Manfredi A. et al. Effectiveness of lithium in children and adolescents with conduct disorder: A retrospective naturalistic study. CNS Drugs 2009; 23: 59-69
    CrossrefPubMedGoogle Scholar
  • 58 Duffy A, Grof P, Robertson C. et al. The implications of genetics studies of major mood disorders for clinical practice. J Clin Psychiatry 2000; 61: 630-637
    CrossrefPubMedGoogle Scholar
  • 59 Grof P, Duffy A, Cavazzoni P. et al Is response to prophylactic lithium a familial trait?. The J Clin Psychiatry 2002; 63: 942-947
    PubMedGoogle Scholar