Official reprint from UpToDate®
www.uptodate.com ©2016 UpToDate®

Bipolar disorder in adults and lithium: Pharmacology, administration, and side effects

Philip G Janicak, MD
Section Editor
Paul Keck, MD
Deputy Editor
David Solomon, MD


The efficacy of lithium for treating mania was discovered in 1949, making it the first medication specifically developed to treat bipolar disorder [1]. Lithium remains a mainstay of treatment for bipolar disorder, especially for acute mania and maintenance treatment. In addition, lithium appears to reduce the risk of suicide in patients with bipolar disorder [2]. (See "Suicidal ideation and behavior in adults", section on 'Pharmacotherapy' and "Bipolar disorder in adults: Choosing maintenance treatment", section on 'Reduced risk of suicide'.)

Lithium is the third element of the periodic table and is a monovalent cation that shares certain properties with sodium, potassium, and calcium [3,4].

The pharmacology, administration, and side effects of lithium are reviewed here. Choosing a medication (including lithium) to treat acute mania, hypomania, and bipolar depression is discussed separately, as is the choice of medication for maintenance treatment of bipolar disorder, and the epidemiology, clinical manifestations, and diagnosis of bipolar disorder.

(See "Bipolar disorder in adults: Pharmacotherapy for acute mania and hypomania".)

(See "Bipolar disorder in adults: Pharmacotherapy for acute depression".)


Subscribers log in here

To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information or to purchase a personal subscription, click below on the option that best describes you:
Literature review current through: Sep 2016. | This topic last updated: Jul 16, 2016.
The content on the UpToDate website is not intended nor recommended as a substitute for medical advice, diagnosis, or treatment. Always seek the advice of your own physician or other qualified health care professional regarding any medical questions or conditions. The use of this website is governed by the UpToDate Terms of Use ©2016 UpToDate, Inc.
  1. CADE JF. Lithium salts in the treatment of psychotic excitement. Med J Aust 1949; 2:349.
  2. Cipriani A, Hawton K, Stockton S, Geddes JR. Lithium in the prevention of suicide in mood disorders: updated systematic review and meta-analysis. BMJ 2013; 346:f3646.
  3. Freeman, MP, Wiegand, CB, Gelenberg, AJ. The American Psychiatric Publishing Textbook of Psychopharmacology, 4th, Schatzberg, AF, Nemeroff CB (Eds), American Psychiatric Publishing, Inc., 2009. p.697.
  4. Malhi GS, Tanious M, Das P, Berk M. The science and practice of lithium therapy. Aust N Z J Psychiatry 2012; 46:192.
  5. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5), American Psychiatric Association, Arlington, VA 2013.
  6. Labbate, LA, Fava, M, Rosenbaum, JF, et al. Drugs for treatment of bipolar disorders. In: Handbook of Psychiatric Drug Therapy, 6th ed, Lippincott Williams & Wilkins, Philadelphia 2010. p.110.
  7. Freeman, MP, Wiegand, et al. Lithium. In: The American Psychiatric Publishing Textbook of Psychopharmacology, 4th, Schatzberg, AF, Nemeroff, CB (Eds), American Psychiatric Publishing, Inc, Washington, D.C. 2009. p.697.
  8. Zarate CA, Manji HK. Protein kinase C inhibitors: rationale for use and potential in the treatment of bipolar disorder. CNS Drugs 2009; 23:569.
  9. Cousins DA, Butts K, Young AH. The role of dopamine in bipolar disorder. Bipolar Disord 2009; 11:787.
  10. Chuang DM, Manji HK. In search of the Holy Grail for the treatment of neurodegenerative disorders: has a simple cation been overlooked? Biol Psychiatry 2007; 62:4.
  11. Chiu CT, Chuang DM. Molecular actions and therapeutic potential of lithium in preclinical and clinical studies of CNS disorders. Pharmacol Ther 2010; 128:281.
  12. Malhi GS, Tanious M, Das P, et al. Potential mechanisms of action of lithium in bipolar disorder. Current understanding. CNS Drugs 2013; 27:135.
  13. Lyoo IK, Dager SR, Kim JE, et al. Lithium-induced gray matter volume increase as a neural correlate of treatment response in bipolar disorder: a longitudinal brain imaging study. Neuropsychopharmacology 2010; 35:1743.
  14. Gildengers AG, Butters MA, Aizenstein HJ, et al. Longer lithium exposure is associated with better white matter integrity in older adults with bipolar disorder. Bipolar Disord 2015; 17:248.
  15. Germaná C, Kempton MJ, Sarnicola A, et al. The effects of lithium and anticonvulsants on brain structure in bipolar disorder. Acta Psychiatr Scand 2010; 122:481.
  16. Hajek T, Cullis J, Novak T, et al. Hippocampal volumes in bipolar disorders: opposing effects of illness burden and lithium treatment. Bipolar Disord 2012; 14:261.
  17. Simonetti A, Sani G, Dacquino C, et al. Hippocampal subfield volumes in short- and long-term lithium-treated patients with bipolar I disorder. Bipolar Disord 2016; 18:352.
  18. Hajek T, Bauer M, Simhandl C, et al. Neuroprotective effect of lithium on hippocampal volumes in bipolar disorder independent of long-term treatment response. Psychol Med 2014; 44:507.
  19. Swann AC, Bowden CL, Calabrese JR, et al. Differential effect of number of previous episodes of affective disorder on response to lithium or divalproex in acute mania. Am J Psychiatry 1999; 156:1264.
  20. Swann AC, Bowden CL, Morris D, et al. Depression during mania. Treatment response to lithium or divalproex. Arch Gen Psychiatry 1997; 54:37.
  21. McElroy SL, Keck PE Jr, Pope HG Jr, et al. Clinical and research implications of the diagnosis of dysphoric or mixed mania or hypomania. Am J Psychiatry 1992; 149:1633.
  22. Freeman TW, Clothier JL, Pazzaglia P, et al. A double-blind comparison of valproate and lithium in the treatment of acute mania. Am J Psychiatry 1992; 149:108.
  23. American Psychiatric Association. Practice guideline for the treatment of patients with bipolar disorder (revision). Am J Psychiatry 2002; 159:1.
  24. Scherk H, Pajonk FG, Leucht S. Second-generation antipsychotic agents in the treatment of acute mania: a systematic review and meta-analysis of randomized controlled trials. Arch Gen Psychiatry 2007; 64:442.
  25. Thummel, KE, et, al. Design and optimization of dosage regimens: pharmacokinetic data (appendix II). In: Goodman & Gilman's Pharmacological Basis of Therapeutics, 11th ed, Brunton, LL, Lazo, JS, Parker, KL (Eds), McGraw-Hill, New York 2006.
  26. MedicinesComplete [Internet database]. Pharmaceutical Press, London, 2010 http://www.medicinescomplete.com (Accessed on September 28, 2010).
  27. DRUGDEX® System [Internet database]. Greenwood Village, CO, Thomson Reuters (Healthcare) Inc, 2002-2010. (Accessed September 28, 2010).
  28. Alda, M. Pharmacokinetics of lithium. In: Lithium in Neuropsychiatry, Bauer, et al (Eds), Informa UK Ltd, United Kingdom 2006. p.321.
  29. Griswold KS, Pessar LF. Management of bipolar disorder. Am Fam Physician 2000; 62:1343.
  30. Glick ID, Suppes T, DeBattista C, et al. Psychopharmacologic treatment strategies for depression, bipolar disorder, and schizophrenia. Ann Intern Med 2001; 134:47.
  31. Drugs for psychiatric disorders. Treat Guidel Med Lett 2006; 4:35.
  32. Osterberg L, Blaschke T. Adherence to medication. N Engl J Med 2005; 353:487.
  33. Nolen WA, Weisler RH. The association of the effect of lithium in the maintenance treatment of bipolar disorder with lithium plasma levels: a post hoc analysis of a double-blind study comparing switching to lithium or placebo in patients who responded to quetiapine (Trial 144). Bipolar Disord 2013; 15:100.
  34. InstaRead Lithium System. Med Lett Drugs Ther 2005; 47:82.
  35. Lauritsen BJ, Mellerup ET, Plenge P, et al. Serum lithium concentrations around the clock with different treatment regimens and the diurnal variation of the renal lithium clearance. Acta Psychiatr Scand 1981; 64:314.
  36. Ott M, Stegmayr B, Renberg ES, Werneke U. Lithium intoxication: Incidence, clinical course and renal function - a population-based retrospective cohort study. J Psychopharmacol 2016.
  37. Jefferson JW. A clinician's guide to monitoring kidney function in lithium-treated patients. J Clin Psychiatry 2010; 71:1153.
  38. Ng F, Mammen OK, Wilting I, et al. The International Society for Bipolar Disorders (ISBD) consensus guidelines for the safety monitoring of bipolar disorder treatments. Bipolar Disord 2009; 11:559.
  39. Malhi GS. Lithium therapy in bipolar disorder: a balancing act? Lancet 2015; 386:415.
  40. Grandjean EM, Aubry JM. Lithium: updated human knowledge using an evidence-based approach: part III: clinical safety. CNS Drugs 2009; 23:397.
  41. Freeman MP, Freeman SA. Lithium: clinical considerations in internal medicine. Am J Med 2006; 119:478.
  42. Wingo AP, Wingo TS, Harvey PD, Baldessarini RJ. Effects of lithium on cognitive performance: a meta-analysis. J Clin Psychiatry 2009; 70:1588.
  43. McKnight RF, Adida M, Budge K, et al. Lithium toxicity profile: a systematic review and meta-analysis. Lancet 2012; 379:721.
  44. Baek JH, Kinrys G, Nierenberg AA. Lithium tremor revisited: pathophysiology and treatment. Acta Psychiatr Scand 2014; 129:17.
  45. Lazarus JH. Lithium and thyroid. Best Pract Res Clin Endocrinol Metab 2009; 23:723.
  46. Shapiro HI, Davis KA. Hypercalcemia and "primary" hyperparathyroidism during lithium therapy. Am J Psychiatry 2015; 172:12.
  47. Jain AE, Lacy T. Psychotropic drugs in pregnancy and lactation. J Psychiatr Pract 2005; 11:177.
  48. Kloos AL, Dubin-Rhodin A, Sackett JC, et al. The impact of mood disorders and their treatment on the pregnant woman, the fetus, and the infant. Curr Psychiatry Rep 2010; 12:96.
  49. Galbally M, Snellen M, Walker S, Permezel M. Management of antipsychotic and mood stabilizer medication in pregnancy: recommendations for antenatal care. Aust N Z J Psychiatry 2010; 44:99.
  50. ACOG Committee on Practice Bulletins--Obstetrics. ACOG Practice Bulletin: Clinical management guidelines for obstetrician-gynecologists number 92, April 2008 (replaces practice bulletin number 87, November 2007). Use of psychiatric medications during pregnancy and lactation. Obstet Gynecol 2008; 111:1001.
  51. Yonkers KA, Wisner KL, Stowe Z, et al. Management of bipolar disorder during pregnancy and the postpartum period. Am J Psychiatry 2004; 161:608.
  52. Cohen LS, Wang B, Nonacs R, et al. Treatment of mood disorders during pregnancy and postpartum. Psychiatr Clin North Am 2010; 33:273.
  53. Altshuler LL, Cohen L, Szuba MP, et al. Pharmacologic management of psychiatric illness during pregnancy: dilemmas and guidelines. Am J Psychiatry 1996; 153:592.
  54. Gentile S. Drug treatment for mood disorders in pregnancy. Curr Opin Psychiatry 2011; 24:34.