Abstract
Lithium preparations have been successfully used to treat bipolar disorder (BD), and remain the best established long-term treatment for the disorder. In fact, lithium is a cornerstone of treatment to minimize the risk of recurrences and improve inter-episodic symptomatology. We reviewed the available evidence for the use of lithium in the treatment of BD, including its efficacy, limitations, and potential benefits also in consideration of the different formulations available. We also overviewed salient comparative aspects regarding the long-term alternative use of anticonvulsants, antidepressants, and antipsychotics in BD patients. The available evidence indicates that BD patients should be treated primarily with lithium, combined in some cases with antipsychotics especially in acute treatments, and sometimes, because of intolerance or inefficacy of lithium, with anticonvulsants. The use of adjunctive antidepressants should be limited to episodes of breakthrough depression. Lithium should be offered to the majority of BD patients as initial treatment especially when suicide ideation or behavior is present with adequate information about its long-term benefits and its potential side effects. Many patients can tolerate lithium without concomitant use of antidepressants, which may worsen the course of the illness or antipsychotics, which may cause severe long-term side effects.
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Merikangas KR, Jin R, He JP, Kessler RC, Lee S, Sampson NA, et al. Prevalence and correlates of bipolar spectrum disorder in the world mental health survey initiative. Arch Gen Psychiatry. 2011;68(3):241–51.
Angst J, Grobler C. Unipolar mania: a necessary diagnostic concept. Eur Arch Psychiatry Clin Neurosci. 2015;265(4):273–80.
Perlis RH, Ostacher MJ, Patel JK, Marangell LB, Zhang H, Wisniewski SR, et al. Predictors of recurrence in bipolar disorder: primary outcomes from the systematic treatment enhancement program for bipolar disorder (STEP-BD). Am J Psychiatry. 2006;163(2):217–24.
Judd LL, Akiskal HS, Schettler PJ, Endicott J, Maser J, Solomon DA, et al. The long-term natural history of the weekly symptomatic status of bipolar I disorder. Arch Gen Psychiatry. 2002;59(6):530–7.
Forte A, Baldessarini RJ, Tondo L, Vazquez GH, Pompili M, Girardi P. Long-term morbidity in bipolar-I, bipolar-II, and unipolar major depressive disorders. J Affect Disord. 2015;178:71–8.
Price AL, Marzani-Nissen GR. Bipolar disorders: a review. Am Fam Physician. 2012;85(5):483–93.
Miura T, Noma H, Furukawa TA, Mitsuyasu H, Tanaka S, Stockton S, et al. Comparative efficacy and tolerability of pharmacological treatments in the maintenance treatment of bipolar disorder: a systematic review and network meta-analysis. Lancet Psychiatry. 2014;1(5):351–9.
Baldessarini RJ, Tondo L. Lithium in psychiatry. Rev Neuropsiquiatr. 2013;76(4):189–203.
Goodwin GM, Haddad PM, Ferrier IN, Aronson JK, Barnes T, Cipriani A, et al. Evidence-based guidelines for treating bipolar disorder: revised third edition recommendations from the British Association for Psychopharmacology. J Psychopharmacol. 2016;30(6):495–553.
Grande I, Berk M, Birmaher B, Vieta E. Bipolar disorder. Lancet. 2016;387(10027):1561–72.
Cade JF. Lithium salts in the treatment of psychotic excitement. Med J Aust. 1949;2(10):349–52.
Geddes JR, Miklowitz DJ. Treatment of bipolar disorder. Lancet. 2013;381(9878):1672–82.
Malhi GS, Tanious M, Berk M. Mania: diagnosis and treatment recommendations. Curr Psychiatry Rep. 2012;14(6):676–86.
Berk M, Brnabic A, Dodd S, Kelin K, Tohen M, Malhi GS, et al. Does stage of illness impact treatment response in bipolar disorder? Empirical treatment data and their implication for the staging model and early intervention. Bipolar Disord. 2011;13(1):87–98.
Yatham LN, Kennedy SH, Parikh SV, Schaffer A, Beaulieu S, Alda M, 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):1–44.
Fountoulakis KN, Yatham L, Grunze H, Vieta E, Young A, Blier P, et al. The International College of Neuro-Psychopharmacology (CINP) treatment guidelines for bipolar disorder in adults (CINP-BD-2017), part 2: review, grading of the evidence, and a precise algorithm. Int J Neuropsychopharmacol. 2016;. doi:10.1093/ijnp/pyw100.
Hayes J, Prah P, Nazareth I, King M, Walters K, Petersen I, et al. Prescribing trends in bipolar disorder: cohort study in the United Kingdom THIN primary care database 1995–2009. PLoS One. 2011;6(12):e28725.
Bastiampillai T, Sharfstein SS, Allison S. Increasing the use of lithium and clozapine in US suicide prevention. JAMA Psychiatry. 2017;. doi:10.1001/jamapsychiatry.2016.3866.
Malhi GS, Outhred T. Therapeutic mechanisms of lithium in bipolar disorder: recent advances and current understanding. CNS Drugs. 2016;30(10):931–49.
Oedegaard KJ, Alda M, Anand A, Andreassen OA, Balaraman Y, Berrettini WH, et al. The Pharmacogenomics of Bipolar Disorder study (PGBD): identification of genes for lithium response in a prospective sample. BMC Psychiatry. 2016;16:129.
Keck PE, Orsulak PJ, Cutler AJ, Sanchez R, Torbeyns A, Marcus RN, et al. Aripiprazole monotherapy in the treatment of acute bipolar I mania: a randomized, double-blind, placebo- and lithium-controlled study. J Affect Disord. 2009;112(1–3):36–49.
Ostacher MJ, Suppes T, Swann AC, Eudicone JM, Landsberg W, Baker RA, et al. Patterns of response to aripiprazole, lithium, haloperidol, and placebo across factor scores of mania. Int J Bipolar Disord. 2015;3:11.
Storosum JG, Wohlfarth T, Schene A, Elferink A, van Zwieten BJ, van den Brink W. Magnitude of effect of lithium in short-term efficacy studies of moderate to severe manic episode. Bipolar Disord. 2007;9(8):793–8.
Pfennig A, Bschor T, Falkai P, Bauer M. The diagnosis and treatment of bipolar disorder: recommendations from the current s3 guideline. Dtsch Arztebl Int. 2013;110(6):92–100.
Licht RW. Drug treatment of mania: a critical review. Acta Psychiatr Scand. 1998;97(6):387–97.
Pope HG Jr, McElroy SL, Keck PE Jr, Hudson JI. Valproate in the treatment of acute mania. A placebo-controlled study. Arch Gen Psychiatry. 1991;48(1):62–8.
Baron M, Gershon ES, Rudy V, Jonas WZ, Buchsbaum M. Lithium carbonate response in depression. Prediction by unipolar/bipolar illness, average-evoked response, catechol-O-methyl transferase, and family history. Arch Gen Psychiatry. 1975;32(9):1107–11.
Goodwin FK, Murphy DL, Bunney WE Jr. Lithium-carbonate treatment in depression and mania. A longitudinal double-blind study. Arch Gen Psychiatry. 1969;21(4):486–96.
Haeberle A, Greil W, Russmann S, Grohmann R. Mono- and combination drug therapies in hospitalized patients with bipolar depression. Data from the European drug surveillance program AMSP. BMC Psychiatry. 2012;12:153.
McElroy SL, Weisler RH, Chang W, Olausson B, Paulsson B, Brecher M, et al. A double-blind, placebo-controlled study of quetiapine and paroxetine as monotherapy in adults with bipolar depression (EMBOLDEN II). J Clin Psychiatry. 2010;71(2):163–74.
Young AH, McElroy SL, Bauer M, Philips N, Chang W, Olausson B, et al. A double-blind, placebo-controlled study of quetiapine and lithium monotherapy in adults in the acute phase of bipolar depression (EMBOLDEN I). J Clin Psychiatry. 2010;71(2):150–62.
Pacchiarotti I, Bond DJ, Baldessarini RJ, et al. The International Society for Bipolar Disorders (ISBD) task force report on antidepressant use in bipolar disorders. Am J Psychiatry. 2013;170(11):1249–62.
Maina G, Albert U, Rosso G, Bogetto F. Olanzapine or lamotrigine addition to lithium in remitted bipolar disorder patients with anxiety disorder comorbidity: a randomized, single-blind, pilot study. J Clin Psychiatry. 2008;69(4):609–16.
Kemp DE, Gao K, Ganocy SJ, Elhaj O, Bilali SR, Conroy C, et al. A 6-month, double-blind, maintenance trial of lithium monotherapy versus the combination of lithium and divalproex for rapid-cycling bipolar disorder and Co-occurring substance abuse or dependence. J Clin Psychiatry. 2009;70(1):113–21.
Wang Z, Gao K, Kemp DE, Chan PK, Serrano MB, Conroy C, et al. Lamotrigine adjunctive therapy to lithium and divalproex in depressed patients with rapid cycling bipolar disorder and a recent substance use disorder: a 12-week, double-blind, placebo-controlled pilot study. Psychopharmacol Bull. 2010;43(4):5–21.
Popovic D, Reinares M, Amann B, Salamero M, Vieta E. Number needed to treat analyses of drugs used for maintenance treatment of bipolar disorder. Psychopharmacology (Berl). 2011;213(4):657–67.
Koukopoulos A, Reginaldi D, Tondo L, Visioli C, Baldessarini RJ. Course sequences in bipolar disorder: depressions preceding or following manias or hypomanias. J Affect Disord. 2013;151(1):105–10.
Popovic D, Reinares M, Goikolea JM, Bonnin CM, Gonzalez-Pinto A, Vieta E. Polarity index of pharmacological agents used for maintenance treatment of bipolar disorder. Eur Neuropsychopharmacol. 2012;22(5):339–46.
Kusumakar V. Antidepressants and antipsychotics in the long-term treatment of bipolar disorder. J Clin Psychiatry. 2002;63(Suppl 10):23–8.
Sylvia LG, Shelton RC, Kemp DE, Bernstein EE, Friedman ES, Brody BD, et al. Medical burden in bipolar disorder: findings from the Clinical and Health Outcomes Initiative in Comparative Effectiveness for Bipolar Disorder study (Bipolar CHOICE). Bipolar Disord. 2015;17(2):212–23.
Carvalho AF, Quevedo J, McIntyre RS, Soeiro-de-Souza MG, Fountoulakis KN, Berk M, et al. Treatment implications of predominant polarity and the polarity index: a comprehensive review. Int J Neuropsychopharmacol. 2014;. doi:10.1093/ijnp/pyu079.
Grandjean EM, Aubry JM. Lithium: updated human knowledge using an evidence-based approach: Part I: clinical efficacy in bipolar disorder. CNS Drugs. 2009;23(3):225–40.
Geddes JR, Burgess S, Hawton K, Jamison K, Goodwin GM. Long-term lithium therapy for bipolar disorder: systematic review and meta-analysis of randomized controlled trials. Am J Psychiatry. 2004;161(2):217–22.
Vieta E, Gunther O, Locklear J, Ekman M, Miltenburger C, Chatterton ML, et al. Effectiveness of psychotropic medications in the maintenance phase of bipolar disorder: a meta-analysis of randomized controlled trials. Int J Neuropsychopharmacol. 2011;14(8):1029–49.
Suppes T, Baldessarini RJ, Faedda GL, Tondo L, Tohen M. Discontinuation of maintenance treatment in bipolar disorder: risks and implications. Harv Rev Psychiatry. 1993;1(3):131–44.
Biel MG, Peselow E, Mulcare L, Case BG, Fieve R. Continuation versus discontinuation of lithium in recurrent bipolar illness: a naturalistic study. Bipolar Disord. 2007;9(5):435–42.
Baldessarini RJ, Tondo L, Faedda GL, Suppes TR, Floris G, Rudas N. Effects of the rate of discontinuing lithium maintenance treatment in bipolar disorders. J Clin Psychiatry. 1996;57(10):441–8.
Baldessarini RJ, Tondo L, Davis P, Pompili M, Goodwin FK, Hennen J. Decreased risk of suicides and attempts during long-term lithium treatment: a meta-analytic review. Bipolar Disord. 2006;8(5 Pt 2):625–39.
Smith EG, Sondergard L, Lopez AG, Andersen PK, Kessing LV. Association between consistent purchase of anticonvulsants or lithium and suicide risk: a longitudinal cohort study from Denmark, 1995–2001. J Affect Disord. 2009;117(3):162–7.
Baldessarini RJ, Tondo L. Suicidal risks during treatment of bipolar disorder patients with lithium vs. anticonvulsants. Pharmacopsychiatry. 2009;4:72–5.
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.
Guzzetta F, Tondo L, Centorrino F, Baldessarini RJ. Lithium treatment reduces suicide risk in recurrent major depressive disorder. J Clin Psychiatry. 2007;68(3):380–3.
Hayes JF, Pitman A, Marston L, Walters K, Geddes JR, King M, et al. Self-harm, unintentional injury, and suicide in bipolar disorder during maintenance mood stabilizer treatment: a UK Population-Based Electronic Health Records Study. JAMA Psychiatry. 2016;73(6):630–7.
Muller-Oerlinghausen B, Lewitzka U. Lithium reduces pathological aggression and suicidality: a mini-review. Neuropsychobiology. 2010;62(1):43–9.
Muller-Oerlinghausen B. Arguments for the specificity of the antisuicidal effect of lithium. Eur Arch Psychiatry Clin Neurosci. 2001;251(Suppl 2):II72–5.
Tondo L, Baldessarini RJ. Suicidal behavior in mood disorders: response to pharmacological treatment. Curr Psychiatry Rep. 2016;18(9):88.
Baldessarini RJ, Tondo L. Lithium and suicidal risk. Bipolar Disord. 2008;10(1):114–5.
Suppes T, Baldessarini RJ, Faedda GL, Tohen M. Risk of recurrence following discontinuation of lithium treatment in bipolar disorder. Arch Gen Psychiatry. 1991;48(12):1082–8.
Tondo L, Baldessarini RJ, 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):405–14.
Lewitzka U, Bauer M, Felber W, Muller-Oerlinghausen B. Anti-suicidal effect of lithium: current state of research and its clinical implications for the long-term treatment of affective disorders. Nervenarzt. 2013;84(3):294–306.
Berk M, Conus P, Kapczinski F, Andreazza AC, Yucel M, Wood SJ, et al. From neuroprogression to neuroprotection: implications for clinical care. Med J Aust. 2010;193(4 Suppl):S36–40.
Lyoo IK, Kim MJ, Stoll AL, Demopulos CM, Parow AM, Dager SR, et al. Frontal lobe gray matter density decreases in bipolar I disorder. Biol Psychiatry. 2004;55(6):648–51.
McDonald C. brain structural effects of psychopharmacological treatment in bipolar disorder. Curr Neuropharmacol. 2015;13(4):445–57.
Regenold WT. Lithium and increased cortical gray matter-more tissue or more water? Biol Psychiatry. 2008;63(3):e17 (author reply e9).
Simonetti A, Sani G, Dacquino C, Piras F, De Rossi P, Caltagirone C, et al. Hippocampal subfield volumes in short- and long-term lithium-treated patients with bipolar I disorder. Bipolar Disord. 2016;18(4):352–62.
Kessing LV, Forman JL, Andersen PK. Does lithium protect against dementia? Bipolar Disord. 2010;12(1):87–94.
Nunes PV, Forlenza OV, Gattaz WF. Lithium and risk for Alzheimer’s disease in elderly patients with bipolar disorder. Br J Psychiatry. 2007;190:359–60.
Libro R, Bramanti P, Mazzon E. The role of the Wnt canonical signaling in neurodegenerative diseases. Life Sci. 2016;158:78–88.
Zeng Z, Wang H, Shang F, Zhou L, Little PJ, Quirion R, et al. Lithium ions attenuate serum-deprivation-induced apoptosis in PC12 cells through regulation of the Akt/FoxO1 signaling pathways. Psychopharmacology (Berl). 2016;233(5):785–94.
Malhi GS, McAulay C, Gershon S, Gessler D, Fritz K, Das P, et al. The lithium battery: assessing the neurocognitive profile of lithium in bipolar disorder. Bipolar Disord. 2016;18(2):102–15.
Viguera AC, Nonacs R, Cohen LS, Tondo L, Murray A, Baldessarini RJ. Risk of recurrence of bipolar disorder in pregnant and nonpregnant women after discontinuing lithium maintenance. Am J Psychiatry. 2000;157(2):179–84.
Viguera AC, Whitfield T, Baldessarini RJ, Newport DJ, Stowe Z, Reminick A, et al. Risk of recurrence in women with bipolar disorder during pregnancy: prospective study of mood stabilizer discontinuation. Am J Psychiatry. 2007;164(12):1817–24 (quiz 923).
Uguz F, Sharma V. Mood stabilizers during breastfeeding: a systematic review of the recent literature. Bipolar Disord. 2016;18(4):325–33.
Stewart DE. Clinical practice. Depression during pregnancy. N Engl J Med. 2011;365(17):1605–11.
Boden R, Lundgren M, Brandt L, Reutfors J, Andersen M, Kieler H. Risks of adverse pregnancy and birth outcomes in women treated or not treated with mood stabilisers for bipolar disorder: population based cohort study. BMJ. 2012;345:e7085.
Rosso G, Albert U, Di Salvo G, Scata M, Todros T, Maina G. Lithium prophylaxis during pregnancy and the postpartum period in women with lithium-responsive bipolar I disorder. Arch Womens Ment Health. 2016;19(2):429–32.
Viguera AC, Newport DJ, Ritchie J, Stowe Z, Whitfield T, Mogielnicki J, et al. Lithium in breast milk and nursing infants: clinical implications. Am J Psychiatry. 2007;164(2):342–5.
Diaz-Caneja CM, Moreno C, Llorente C, Espliego A, Arango C, Moreno D. Practitioner review: long-term pharmacological treatment of pediatric bipolar disorder. J Child Psychol Psychiatry. 2014;55(9):959–80.
Dols A, Kessing LV, Strejilevich SA, Rej S, Tsai SY, Gildengers AG, et al. Do current national and international guidelines have specific recommendations for older adults with bipolar disorder? A brief report. Int J Geriatr Psychiatry. 2016;31(12):1295–300.
Albert U, De Cori D, Blengino G, Bogetto F, Maina G. Lithium treatment and potential long-term side effects: a systematic review of the literature. Riv Psichiatr. 2014;49(1):12–21.
McKnight RF, Adida M, Budge K, Stockton S, Goodwin GM, Geddes JR. Lithium toxicity profile: a systematic review and meta-analysis. Lancet. 2012;379(9817):721–8.
Price LH, Heninger GR. Lithium in the treatment of mood disorders. N Engl J Med. 1994;331(9):591–8.
Azab AN, Shnaider A, Osher Y, Wang D, Bersudsky Y, Belmaker RH. Lithium nephrotoxicity. Int J Bipolar Disord. 2015;3(1):28.
Gelenberg AJ, Jefferson JW. Lithium tremor. J Clin Psychiatry. 1995;56(7):283–7.
Gitlin M. Lithium side effects and toxicity: prevalence and management strategies. Int J Bipolar Disord. 2016;4(1):27.
Wingo AP, Wingo TS, Harvey PD, Baldessarini RJ. Effects of lithium on cognitive performance: a meta-analysis. J Clin Psychiatry. 2009;70(11):1588–97.
Jafferany M. Lithium and skin: dermatologic manifestations of lithium therapy. Int J Dermatol. 2008;47(11):1101–11.
Lazarus JH. Lithium and thyroid. Best Pract Res Clin Endocrinol Metab. 2009;23(6):723–33.
Malhi GS, Tanious M, Gershon S. The lithiumeter: a measured approach. Bipolar Disord. 2011;13(3):219–26.
Young AH, Hammond JM. Lithium in mood disorders: increasing evidence base, declining use? Br J Psychiatry. 2007;191:474–6.
Tondo L, Abramowicz M, Alda M, Bauer M, Bocchetta A, Bolzani L, et al. Long-term lithium treatment in bipolar disorder: effects on glomerular filtration rate and other metabolic parameters. Int J Bipolar Disord. 2016 (in press).
Shine B, McKnight RF, Leaver L, Geddes JR. Long-term effects of lithium on renal, thyroid, and parathyroid function: a retrospective analysis of laboratory data. Lancet. 2015;386(9992):461–8.
Bendz H, Schon S, Attman PO, Aurell M. Renal failure occurs in chronic lithium treatment but is uncommon. Kidney Int. 2010;77(3):219–24.
Grunfeld JP, Rossier BC. Lithium nephrotoxicity revisited. Nat Rev Nephrol. 2009;5(5):270–6.
Close H, Reilly J, Mason JM, Kripalani M, Wilson D, Main J, et al. Renal failure in lithium-treated bipolar disorder: a retrospective cohort study. PLoS One. 2014;9(3):e90169.
Kirkham E, Skinner J, Anderson T, Bazire S, Twigg MJ, Desborough JA. One lithium level >1.0 mmol/L causes an acute decline in eGFR: findings from a retrospective analysis of a monitoring database. BMJ Open. 2014;4(11):e006020.
Aiff H, Attman PO, Aurell M, Bendz H, Ramsauer B, Schon S, et al. Effects of 10 to 30 years of lithium treatment on kidney function. J Psychopharmacol. 2015;29(5):608–14.
Jonczyk-Potoczna K, Abramowicz M, Chlopocka-Wozniak M, Strzelczuk-Judka L, Michalak M, Czekalski SP, et al. Renal sonography in bipolar patients on long-term lithium treatment. J Clin Ultrasound. 2016;44(6):354–9.
Aprahamian I, Santos FS, dos Santos B, Talib L, Diniz BS, Radanovic M, et al. Long-term, low-dose lithium treatment does not impair renal function in the elderly: a 2-year randomized, placebo-controlled trial followed by single-blind extension. J Clin Psychiatry. 2014;75(7):e672–8.
Singh LK, Nizamie SH, Akhtar S, Praharaj SK. Improving tolerability of lithium with a once-daily dosing schedule. Am J Ther. 2011;18(4):288–91.
Murru A, Pacchiarotti I, Amann BL, Nivoli AM, Vieta E, Colom F. Treatment adherence in bipolar I and schizoaffective disorder, bipolar type. J Affect Disord. 2013;151(3):1003–8.
Gitlin MJ, Cochran SD, Jamison KR. Maintenance lithium treatment: side effects and compliance. J Clin Psychiatry. 1989;50(4):127–31.
Sylvia LG, Reilly-Harrington NA, Leon AC, Kansky CI, Calabrese JR, Bowden CL, et al. Medication adherence in a comparative effectiveness trial for bipolar disorder. Acta Psychiatr Scand. 2014;129(5):359–65.
Lostia AM, Mazzarini L, Pacchiarotti I, Lionetto L, De Rossi P, Sanna L, et al. Serum levels of risperidone and its metabolite, 9-hydroxyrisperidone: correlation between drug concentration and clinical response. Ther Drug Monit. 2009;31(4):475–81.
Malhi GS, Tanious M, Das P, Berk M. The science and practice of lithium therapy. Aust N Z J Psychiatry. 2012;46(3):192–211.
Tohen M, Jacobs TG, Feldman PD. Onset of action of antipsychotics in the treatment of mania. Bipolar Disord. 2000;2(3 Pt 2):261–8.
Licht RW. Lithium: still a major option in the management of bipolar disorder. CNS Neurosci Ther. 2012;18(3):219–26.
Musenga A, Saracino MA, Sani G, Raggi MA. Antipsychotic and antiepileptic drugs in bipolar disorder: the importance of therapeutic drug monitoring. Curr Med Chem. 2009;16(12):1463–81.
Baird-Gunning J, Lea-Henry T, Hoegberg LC, Gosselin S, Roberts DM. Lithium Poisoning. J Intensive Care Med. 2017;32:249–63.
Kirkham E, Bazire S, Anderson T, Wood J, Grassby P, Desborough JA. Impact of active monitoring on lithium management in Norfolk. Ther Adv Psychopharmacol. 2013;3(5):260–5.
Durbano F, Mencacci C, Dorigo D, Riva M, Buffa G. The long-term efficacy and tolerability of carbolithium once a day: an interim analysis at 6 months. Clin Ter. 2002;153(3):161–6.
Ljubicic D, Letica-Crepulja M, Vitezic D, Bistrovic IL, Ljubicic R. Lithium treatments: single and multiple daily dosing. Can J Psychiatry. 2008;53(5):323–31.
Bowden CL. Key treatment studies of lithium in manic-depressive illness: efficacy and side effects. J Clin Psychiatry. 1998;59(Suppl 6):13–9 (discussion 20).
Girardi P, Brugnoli R, Manfredi G, Sani G. Lithium in bipolar disorder: optimizing therapy using prolonged-release formulations. Drugs R D. 2016;16(4):293–302.
Vieta E, Grunze H. Bipolar disorder–a focus on depression. N Engl J Med. 2011;364(16):1581 (author reply 2).
Goodwin GM, Consensus Group of the British Association for P. Evidence-based guidelines for treating bipolar disorder: revised second edition–recommendations from the British Association for Psychopharmacology. J Psychopharmacol. 2009;23(4):346–88.
Grunze H, Vieta E, Goodwin GM, Bowden C, Licht RW, Moller HJ, et al. The World Federation of Societies of Biological Psychiatry (WFSBP) guidelines for the biological treatment of bipolar disorders: update 2012 on the long-term treatment of bipolar disorder. World J Biol Psychiatry. 2013;14(3):154–219.
Ghaemi SN, Lenox MS, Baldessarini RJ. Effectiveness and safety of long-term antidepressant treatment in bipolar disorder. J Clin Psychiatry. 2001;62(7):565–9.
Ghaemi SN, Hsu DJ, Soldani F, Goodwin FK. Antidepressants in bipolar disorder: the case for caution. Bipolar Disord. 2003;5(6):421–33.
Grande I, de Arce R, Jimenez-Arriero MA, Lorenzo FG, Valverde JI, Balanza-Martinez V, et al. Patterns of pharmacological maintenance treatment in a community mental health services bipolar disorder cohort study (SIN-DEPRES). Int J Neuropsychopharmacol. 2013;16(3):513–23.
Kukopulos A, Reginaldi D, Laddomada P, Floris G, Serra G, Tondo L. Course of the manic-depressive cycle and changes caused by treatments. Pharmakopsychiatry. 1980;13:156–67.
Kotzalidis GD, Rapinesi C, Savoja V, Cuomo I, Simonetti A, Ambrosi E, et al. Neurobiological evidence for the primacy of mania hypothesis. Curr Neuropharmacol. 2017;15(3):339–52.
Koukopoulos A, Ghaemi SN. The primacy of mania: a reconsideration of mood disorders. Eur Psychiatry. 2009;24(2):125–34.
Sani G, Simonetti A, Reginaldi D, Koukopoulos AE, Del Casale A, Manfredi G, et al. Free interval duration: clinical evidence of the primary role of excitement in bipolar disorder. Curr Neuropharmacol. 2017;15(3):394–401.
Wehr TA, Sack DA, Rosenthal NE, Cowdry RW. Rapid cycling affective disorder: contributing factors and treatment responses in 51 patients. Am J Psychiatry. 1988;145(2):179–84.
Koukopoulos A, Sani G, Koukopoulos AE, Minnai GP, Girardi P, Pani L, et al. Duration and stability of the rapid-cycling course: a long-term personal follow-up of 109 patients. J Affect Disord. 2003;73(1–2):75–85.
Schneck CD, Miklowitz DJ, Miyahara S, Araga M, Wisniewski S, Gyulai L, et al. The prospective course of rapid-cycling bipolar disorder: findings from the STEP-BD. Am J Psychiatry. 2008;165(3):370–7 (quiz 410).
El-Mallakh RS, Ghaemi SN, Sagduyu K, Thase ME, Wisniewski SR, Nierenberg AA, et al. Antidepressant-associated chronic irritable dysphoria (ACID) in STEP-BD patients. J Affect Disord. 2008;111(2–3):372–7.
Sani G, Napoletano F, Vohringer PA, Sullivan M, Simonetti A, Koukopoulos A, et al. Mixed depression: clinical features and predictors of its onset associated with antidepressant use. Psychother Psychosom. 2014;83(4):213–21.
Stone M, Laughren T, Jones ML, Levenson M, Holland PC, Hughes A, et al. Risk of suicidality in clinical trials of antidepressants in adults: analysis of proprietary data submitted to US Food and Drug Administration. BMJ. 2009;339:b2880.
Leon AC, Solomon DA, Li C, Fiedorowicz JG, Coryell WH, Endicott J, et al. Antidepressants and risks of suicide and suicide attempts: a 27-year observational study. J Clin Psychiatry. 2011;72(5):580–6.
Tondo L, Hennen J, Baldessarini RJ. Lower suicide risk with long-term lithium treatment in major affective illness: a meta-analysis. Acta Psychiatr Scand. 2001;104(3):163–72.
Centorrino F, Fogarty KV, Cimbolli P, Salvatore P, Thompson TA, Sani G, et al. Aripiprazole: initial clinical experience with 142 hospitalized psychiatric patients. J Psychiatr Pract. 2005;11(4):241–7.
Cipriani A, Barbui C, Salanti G, Rendell J, Brown R, Stockton S, et al. Comparative efficacy and acceptability of antimanic drugs in acute mania: a multiple-treatments meta-analysis. Lancet. 2011;378(9799):1306–15.
Nierenberg AA, McElroy SL, Friedman ES, Ketter TA, Shelton RC, Deckersbach T, et al. Bipolar CHOICE (Clinical Health Outcomes Initiative in Comparative Effectiveness): a pragmatic 6-month trial of lithium versus quetiapine for bipolar disorder. J Clin Psychiatry. 2016;77(1):90–9.
Buoli M, Serati M, Altamura AC. Is the combination of a mood stabilizer plus an antipsychotic more effective than mono-therapies in long-term treatment of bipolar disorder? A systematic review. J Affect Disord. 2014;152–154:12–8.
Ketter TA, Miller S, Dell’Osso B, Wang PW. Treatment of bipolar disorder: review of evidence regarding quetiapine and lithium. J Affect Disord. 2016;191:256–73.
Jones PB, Barnes TR, Davies L, Dunn G, Lloyd H, Hayhurst KP, et al. Randomized controlled trial of the effect on quality of life of second- vs first-generation antipsychotic drugs in schizophrenia: Cost Utility of the Latest Antipsychotic Drugs in Schizophrenia Study (CUtLASS 1). Arch Gen Psychiatry. 2006;63(10):1079–87.
Lieberman JA, Stroup TS, McEvoy JP, Swartz MS, Rosenheck RA, Perkins DO, et al. Effectiveness of antipsychotic drugs in patients with chronic schizophrenia. N Engl J Med. 2005;353(12):1209–23.
Geddes J, Freemantle N, Harrison P, Bebbington P. Atypical antipsychotics in the treatment of schizophrenia: systematic overview and meta-regression analysis. BMJ. 2000;321(7273):1371–6.
Tarsy D, Baldessarini RJ. Epidemiology of tardive dyskinesia: is risk declining with modern antipsychotics? Mov Disord. 2006;21(5):589–98.
Centorrino F, Fogarty KV, Sani G, Salvatore P, Cimbolli P, Baldessarini RJ. Antipsychotic drug use: McLean Hospital, 2002. Hum Psychopharmacol. 2005;20(5):355–8.
Tohen M, Calabrese JR, Sachs GS, Banov MD, Detke HC, Risser R, et al. Randomized, placebo-controlled trial of olanzapine as maintenance therapy in patients with bipolar I disorder responding to acute treatment with olanzapine. Am J Psychiatry. 2006;163(2):247–56.
Suppes T, Vieta E, Liu S, Brecher M, Paulsson B, Trial I. Maintenance treatment for patients with bipolar I disorder: results from a north american study of quetiapine in combination with lithium or divalproex (trial 127). Am J Psychiatry. 2009;166(4):476–88.
Keck PE Jr, Calabrese JR, McQuade RD, Carson WH, Carlson BX, Rollin LM, et al. A randomized, double-blind, placebo-controlled 26-week trial of aripiprazole in recently manic patients with bipolar I disorder. J Clin Psychiatry. 2006;67(4):626–37.
Bowden CL, Vieta E, Ice KS, Schwartz JH, Wang PP, Versavel M. Ziprasidone plus a mood stabilizer in subjects with bipolar I disorder: a 6-month, randomized, placebo-controlled, double-blind trial. J Clin Psychiatry. 2010;71(2):130–7.
McIntyre RS, Cohen M, Zhao J, Alphs L, Macek TA, Panagides J. Asenapine for long-term treatment of bipolar disorder: a double-blind 40-week extension study. J Affect Disord. 2010;126(3):358–65.
Lindstrom L, Lindstrom E, Nilsson M, Hoistad M. Maintenance therapy with second generation antipsychotics for bipolar disorder—a systematic review and meta-analysis. J Affect Disord. 2017;213:138–50.
Spina E, Perugi G. Antiepileptic drugs: indications other than epilepsy. Epileptic Disord. 2004;6(2):57–75.
Emrich HM. Studies with oxcarbazepine in acute mania. Int Clin Psychopharmacol. 1990;5:83–8.
Perugi G, Toni C, Ruffolo G, Sartini S, Simonini E, Akiskal H. Clinical experience using adjunctive gabapentin in treatment-resistant bipolar mixed states. Pharmacopsychiatry. 1999;32(4):136–41.
Lerer B, Moore N, Meyendorff E, Cho SR, Gershon S. Carbamazepine versus lithium in mania: a double-blind study. J Clin Psychiatry. 1987;48(3):89–93.
Greil W, Ludwig-Mayerhofer W, Erazo N, Schochlin C, Schmidt S, Engel RR, et al. Lithium versus carbamazepine in the maintenance treatment of bipolar disorders–a randomised study. J Affect Disord. 1997;43(2):151–61.
Hartong EG, Moleman P, Hoogduin CA, Broekman TG, Nolen WA, LitCar G. Prophylactic efficacy of lithium versus carbamazepine in treatment-naive bipolar patients. J Clin Psychiatry. 2003;64(2):144–51.
Kleindienst N, Greil W. Differential efficacy of lithium and carbamazepine in the prophylaxis of bipolar disorder: results of the MAP study. Neuropsychobiology. 2000;42(Suppl 1):2–10.
Freeman TW, Clothier JL, Pazzaglia P, Lesem MD, Swann AC. A double-blind comparison of valproate and lithium in the treatment of acute mania. Am J Psychiatry. 1992;149(1):108–11.
Davis LL, Bartolucci A, Petty F. Divalproex in the treatment of bipolar depression: a placebo-controlled study. J Affect Disord. 2005;85(3):259–66.
Ghaemi SN, Gilmer WS, Goldberg JF, Zablotsky B, Kemp DE, Kelley ME, et al. Divalproex in the treatment of acute bipolar depression: a preliminary double-blind, randomized, placebo-controlled pilot study. J Clin Psychiatry. 2007;68(12):1840–4.
Smith LA, Cornelius VR, Azorin JM, Perugi G, Vieta E, Young AH, et al. Valproate for the treatment of acute bipolar depression: systematic review and meta-analysis. J Affect Disord. 2010;122(1–2):1–9.
EMA. http://www.ema.europa.eu/ema/index.jsp?curl=pages/medicines/human/referrals/Valproate_and_related_substances/human_referral_prac_000032.jsp&mid=WC0b01ac05805c516f. Accessed 14 Nov 2016.
Ballenger JC, Post RM. Carbamazepine in manic-depressive illness: a new treatment. Am J Psychiatry. 1980;137(7):782–90.
Goldsmith DR, Wagstaff AJ, Ibbotson T, Perry CM. Lamotrigine: a review of its use in bipolar disorder. Drugs. 2003;63(19):2029–50.
Coxhead N, Silverstone T, Cookson J. Carbamazepine versus lithium in the prophylaxis of bipolar affective disorder. Acta Psychiatr Scand. 1992;85(2):114–8.
Denicoff KD, Smith-Jackson EE, Disney ER, Ali SO, Leverich GS, Post RM. Comparative prophylactic efficacy of lithium, carbamazepine, and the combination in bipolar disorder. J Clin Psychiatry. 1997;58(11):470–8.
Calabrese JR, Shelton MD, Rapport DJ, Youngstrom EA, Jackson K, Bilali S, et al. A 20-month, double-blind, maintenance trial of lithium versus divalproex in rapid-cycling bipolar disorder. Am J Psychiatry. 2005;162(11):2152–61.
Investigators B, collaborators, Geddes JR, Goodwin GM, Rendell J, Azorin JM, 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(9712):385–95.
Calabrese JR, Suppes T, Bowden CL, Sachs GS, Swann AC, McElroy SL, et al. A double-blind, placebo-controlled, prophylaxis study of lamotrigine in rapid-cycling bipolar disorder. Lamictal 614 Study Group. J Clin Psychiatry. 2000;61(11):841–50.
Goodwin GM, Bowden CL, Calabrese JR, Grunze H, Kasper S, White R, et al. A pooled analysis of 2 placebo-controlled 18-month trials of lamotrigine and lithium maintenance in bipolar I disorder. J Clin Psychiatry. 2004;65(3):432–41.
Kessing LV, Sondergard L, Forman JL, Andersen PK. Lithium treatment and risk of dementia. Arch Gen Psychiatry. 2008;65(11):1331–5.
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Prof. Gabriele Sani has acted as consultant of Lundbeck, Angelini and Janseen and is on the speaker/advisory board of Angelini and Lundbeck. Prof. Giulio Perugi has acted as consultant of Eli Lilly, Lundbeck, and Angelini; received grant/research support from Lundbeck; is on the speaker/advisory board of Sanofi Aventis, Angelini, Eli Lilly, Lundbeck, FB-Health. Prof. Leonardo Tondo has acted as a consultant for Angelini.
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Sani, G., Perugi, G. & Tondo, L. Treatment of Bipolar Disorder in a Lifetime Perspective: Is Lithium Still the Best Choice?. Clin Drug Investig 37, 713–727 (2017). https://doi.org/10.1007/s40261-017-0531-2
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DOI: https://doi.org/10.1007/s40261-017-0531-2