Bipolar disorder: a review of current U.S. Food and Drug Administration approved pharmacotherapy


  • Aashal B. Shah Department of Pharmacology, New Civil Hospital, Government Medical College, Surat, Gujarat, India
  • Preeti P. Yadav Department of Pharmacology, New Civil Hospital, Government Medical College, Surat, Gujarat, India
  • Mayur A. Chaudhari Department of Pharmacology, New Civil Hospital, Government Medical College, Surat, Gujarat, India
  • Jayant Rai Department of Pharmacology, New Civil Hospital, Government Medical College, Surat, Gujarat, India
  • Naresh D. Kantharia Department of Pharmacology, New Civil Hospital, Government Medical College, Surat, Gujarat, India



Bipolar disorder, U.S. Food and Drug Administration, Mood stabilizers, Atypical antipsychotics, Adverse effects, Bipolar depression


Bipolar disorder (BD) is a chronic disorder which usually has its onset in early adulthood. At one end of the spectrum is depression and at other is mania. Like many psychiatric illnesses, it is not treatable but its symptoms are completely manageable with medications. Commonly used drugs are mood stabilizers and atypical antipsychotics along with adjunctive medications such as anxiolytics and antidepressants. In general, a combination of these drugs is used for treatment. These drugs have significant adverse effects which add to the burden of the disease. Presently, there are 11 US Food and Drug Administration - approved drugs for management of acute mania, 3 for bipolar depression and 7 for bipolar maintenance. This review article details the use of these drugs in BD.


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.

Fagiolini A, Forgione R, Maccari M, Cuomo A, Morana B, Dell’Osso MC, et al. Prevalence, chronicity, burden and borders of bipolar disorder. J Affect Disord. 2013;148(2-3):161-9.

Segurado R, Detera-Wadleigh SD, Levinson DF, Lewis CM, Gill M, Nurnberger JI Jr, et al. Genome scan meta-analysis of schizophrenia and bipolar disorder, part III: bipolar disorder. Am J Hum Genet. 2003;73(1):49-62.

Lahera G, Freund N, Sáiz-Ruiz J. Salience and dysregulation of the dopaminergic system. Rev Psiquiatr Salud Ment. 2013;6(1):45-51.

Hashimoto K, Sawa A, Iyo M. Increased levels of glutamate in brains from patients with mood disorders. Biol Psychiatry. 2007;62(11):1310-6.

Benes FM, Berretta S. GABAergic interneurons: implications for understanding schizophrenia and bipolar disorder. Neuropsychopharmacology. 2001;25(1):1-27.

Strakowski SM, Adler CM, Almeida J, Altshuler LL, Blumberg HP, Chang KD, et al. The functional neuroanatomy of bipolar disorder: a consensus model. Bipolar Disord. 2012;14(4):313-25.

Ketter TA. American Psychiatry Publishing Textbook of Psychiatry. 6th Edition. Washington, DC: American Psychiatry Publishing Inc.; 2015: 311-52.

Johnson CP, Follmer RL, Oguz I, Warren LA, Christensen GE, Fiedorowicz JG, et al. Brain abnormalities in bipolar disorder detected by quantitative T1? mapping. Mol Psychiatry. 2015;20(2):201-6.

Chen JJ, Huang H, Zhao LB, Zhou DZ, Yang YT, Zheng P, et al. Sex-specific urinary biomarkers for diagnosing bipolar disorder. PLoS One. 2014;9(12):e115221.

McIntyre RS, Mancini DA, Lin P, Jordan J. Treating bipolar disorder. Evidence-based guidelines for family medicine. Can Fam Physician. 2004;50:388-94.

Cole N, Parker G. Cade’s identification of lithium for manic-depressive illness – the prospector who found a gold nugget. J Nerv Ment Dis. 2012;200(12):1101-4.

Shorter E. The history of lithium therapy. Bipolar Disord. 2009;11 Suppl 2:4-9.

Bender RE, Alloy LB. Life stress and kindling in bipolar disorder: review of the evidence and integration with emerging biopsychosocial theories. Clin Psychol Rev. 2011;31(3):383-98.

Severus E, Taylor MJ, Sauer C, Pfennig A, Ritter P, Bauer M, et al. Lithium for prevention of mood episodes in bipolar disorders: systematic review and meta-analysis. Int J Bipolar Disord. 2014;2:15.

Ahmadi-Abhari SA, Ghaeli P, Fahimi F, Esfahanian F, Farsam H, Dehpour AR, et al. Risk factors of thyroid abnormalities in bipolar patients receiving lithium: a case control study. BMC Psychiatry. 2003;3:4.

Deodhar SD, Singh B, Pathak CM, Sharan P, Kulhara P. Thyroid functions in lithium-treated psychiatric patients: a cross-sectional study. Biol Trace Elem Res. 1999;67(2):151-63.

Bogazzi F, Bartalena L, Brogioni S, Scarcello G, Burelli A, Campomori A, et al. Comparison of radioiodine with radioiodine plus lithium in the treatment of Graves’ hyperthyroidism. J Clin Endocrinol Metab. 1999;84(2):499-503.

Albert U, De Cori D, Aguglia A, Barbaro F, Lanfranco F, Bogetto F, et al. Lithium-associated hyperparathyroidism and hypercalcaemia: a case-control cross-sectional study. J Affect Disord. 2013;151(2):786-90.

Werneke U, Ott M, Renberg ES, Taylor D, Stegmayr B. A decision analysis of long-term lithium treatment and the risk of renal failure. Acta Psychiatr Scand. 2012;126(3):186-97.

Galbally M, Roberts M, Buist A; Perinatal Psychotropic Review Group. Mood stabilizers in pregnancy: a systematic review. Aust N Z J Psychiatry. 2010;44(11):967-77.

American Psychiatric Association. Practice guideline for the treatment of patients with bipolar disorder (revision). Am J Psychiatry. 2002;159 4 Suppl:1-50.

Suppes T, Dennehy EB, Hirschfeld RM, Altshuler LL, Bowden CL, Calabrese JR, et al. The Texas implementation of medication algorithms: update to the algorithms for treatment of bipolar I disorder. J Clin Psychiatry. 2005;66(7):870-86.

BALANCE investigators and collaborators, Geddes JR, Goodwin GM, Rendell J, Azorin JM, Cipriani A, 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.

Tohen M, Ketter TA, Zarate CA, Suppes T, Frye M, Altshuler L, et al. Olanzapine versus divalproex sodium for the treatment of acute mania and maintenance of remission: a 47-week study. Am J Psychiatry. 2003;160(7):1263-71.

Conley EL, Coley KC, Pollock BG, Dapos SV, Maxwell R, Branch RA. Prevalence and risk of thrombocytopenia with valproic acid: experience at a psychiatric teaching hospital. Pharmacotherapy. 2001;21(11):1325-30.

Joffe H, Cohen LS, Suppes T, McLaughlin WL, Lavori P, Adams JM, et al. Valproate is associated with new-onset oligoamenorrhea with hyperandrogenism in women with bipolar disorder. Biol Psychiatry. 2006;59(11):1078-86.

Chapman SA, Wacksman GP, Patterson BD. Pancreatitis associated with valproic acid: a review of the literature. Pharmacotherapy. 2001;21(12):1549-60.

Chopra A, Kolla BP, Mansukhani MP, Netzel P, Frye MA. Valproate-induced hyperammonemic encephalopathy: an update on risk factors, clinical correlates and management. Gen Hosp Psychiatry. 2012;34(3):290-8.

Weisler RH, Keck PE Jr, Swann AC, Cutler AJ, Ketter TA, Kalali AH; SPD Study Group. Extended-release carbamazepine capsules as monotherapy for acute mania in bipolar disorder: a multicenter, randomized, double-blind, placebo-controlled trial. J Clin Psychiatry. 2005;66(3):323-30.

Simko J, Horacek J. Carbamazepine and risk of hypothyroidism: a prospective study. Acta Neurol Scand. 2007;116(5):317-21.

Geddes JR, Calabrese JR, Goodwin GM. Lamotrigine for treatment of bipolar depression: independent meta-analysis and meta-regression of individual patient data from five randomised trials. Br J Psychiatry. 2009;194(1):4-9.

Calabrese JR, Sullivan JR, Bowden CL, Suppes T, Goldberg JF, Sachs GS, et al. Rash in multicenter trials of lamotrigine in mood disorders: clinical relevance and management. J Clin Psychiatry. 2002;63(11):1012-9.

Holmes LB, Baldwin EJ, Smith CR, Habecker E, Glassman L, Wong SL, et al. Increased frequency of isolated cleft palate in infants exposed to lamotrigine during pregnancy. Neurology. 2008;70:2152-8.

Yildiz A, Vieta E, Leucht S, Baldessarini RJ. Efficacy of antimanic treatments: meta-analysis of randomized, controlled trials. Neuropsychopharmacology. 2011;36(2):375-89.

Tarsy D, Lungu C, Baldessarini RJ. Epidemiology of tardive dyskinesia before and during the era of modern antipsychotic drugs. Handb Clin Neurol. 2011;100:601-16.

Soares-Weiser K, Maayan N, McGrath J. Vitamin E for neuroleptic-induced tardive dyskinesia. Cochrane Database Syst Rev. 2011:CD000209.

Kramer MS, Gorkin R, DiJohnson C. Treatment of neuroleptic-induced akathisia with propranolol: a controlled replication study. Hillside J Clin Psychiatry. 1989;11(2):107-19.

Strawn JR, Keck PE Jr, Caroff SN. Neuroleptic malignant syndrome. Am J Psychiatry. 2007;164:870-6.

Muench J, Hamer AM. Adverse effects of antipsychotic medications. Am Fam Physician. 2010;81:617-22.

Haddad PM, Wieck A. Antipsychotic-induced hyperprolactinaemia: mechanisms, clinical features and management. Drugs. 2004;64(20):2291-314.

Meaney AM, Smith S, Howes OD, O’Brien M, Murray RM, O’Keane V. Effects of long-term prolactin-raising antipsychotic medication on bone mineral density in patients with schizophrenia. Br J Psychiatry. 2004;184:503-8.

Meaney AM, O’Keane V. Bone mineral density changes over a year in young females with schizophrenia: relationship to medication and endocrine variables. Schizophr Res. 2007;93(1-3):136-43.

Tikk K, Sookthai D, Fortner RT, Johnson T, Rinaldi S, Tjønneland A, et al. Circulating prolactin and in situ breast cancer risk in the European epic cohort: a case-control study. Breast Cancer Res. 2015;17:49.

Pallava A, Chadda RK, Sood M, Lakshmy R. Metabolic syndrome in schizophrenia: a comparative study of antipsychotic-free/naïve and antipsychotic-treated patients from india. Nord J Psychiatry. 2012;66(3):215-21.

American Diabetes Association; American Psychiatric Association; American Association of Clinical Endocrinologists; North American Association for the Study of Obesity. Consensus development conference on antipsychotic drugs and obesity and diabetes. Diabetes Care. 2004;27:596-601.

Correll CU, Frederickson AM, Kane JM, Manu P. Equally increased risk for metabolic syndrome in patients with bipolar disorder and schizophrenia treated with second-generation antipsychotics. Bipolar Disord. 2008;10(7):788-97.

Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. Executive summary of the Third Report of the National Cholesterol Education Program (NCEP) expert panel on detection, evaluation, and treatment of high blood cholesterol in adults (Adult Treatment Panel iii). JAMA. 2001;285(19):2486-97.

Wilson DR, D’Souza L, Sarkar N, Newton M, Hammond C. New-onset diabetes and ketoacidosis with atypical antipsychotics. Schizophr Res. 2003;59(1):1-6.

Gentile S. Long-term treatment with atypical antipsychotics and the risk of weight gain: a literature analysis. Drug Saf. 2006;29(4):303-19.

Habermann F, Fritzsche J, Fuhlbrück F, Wacker E, Allignol A, Weber-Schoendorfer C, et al. Atypical antipsychotic drugs and pregnancy outcome: a prospective, cohort study. J Clin Psychopharmacol. 2013;33(4):453-62.

Tohen M, Greil W, Calabrese JR, Sachs GS, Yatham LN, Oerlinghausen BM, et al. Olanzapine versus lithium in the maintenance treatment of bipolar disorder: a 12-month, randomized, double-blind, controlled clinical trial. Am J Psychiatry. 2005;162(7):1281-90.

Ketter TA, Houston JP, Adams DH, Risser RC, Meyers AL, Williamson DJ, et al. Differential efficacy of olanzapine and lithium in preventing manic or mixed recurrence in patients with bipolar I disorder based on number of previous manic or mixed episodes. J Clin Psychiatry. 2006;67(1):95-101.

Ramaswamy K, Kozma CM, Nasrallah H. Risk of diabetic ketoacidosis after exposure to risperidone or olanzapine. Drug Saf. 2007;30(7):589-99.

Rendell JM, Gijsman HJ, Bauer MS, Goodwin GM, Geddes GR. Risperidone alone or in combination for acute mania. Cochrane Database Syst Rev. 2006:CD004043.

Muneer A. Pharmacotherapy of bipolar disorder with quetiapine: a recent literature review and an update. Clin Psychopharmacol Neurosci. 2015;13(1):25-35.

Suppes T, Datto C, Minkwitz M, Nordenhem A, Walker C, Darko D. Effectiveness of the extended release formulation of quetiapine as monotherapy for the treatment of acute bipolar depression. J Affect Disord. 2014;168:485-93.

Newcomer JW. Second-generation (atypical) antipsychotics and metabolic effects: a comprehensive literature review. CNS Drugs. 2005;19 Suppl 1:1-93.

Taylor D. Ziprasidone in the management of schizophrenia: the QT interval issue in context. CNS Drugs. 2003;17(6):423-30.

Rezayat AA, Hebrani P, Behdani F, Salaran M, Marvast MN. Comparison the effectiveness of aripiprazole and risperidone for the treatment of acute bipolar mania. J Res Med Sci. 2014;19(8):733-8.

Li X, Tang Y, Wang C. Adjunctive aripiprazole versus placebo for antipsychotic-induced hyperprolactinemia: meta-analysis of randomized controlled trials. PLoS One. 2013;8(8):e70179.

Asenapine: a less effective, yet, more dangerous neuroleptic! Prescrire Int. 2012;21(131):229-32.

Chwieduk CM, Scott LJ. Asenapine: a review of its use in the management of mania in adults with bipolar I disorder. CNS Drugs. 2011;25(3):251-67.

Tohen M, Vieta E, Calabrese J, Ketter TA, Sachs G, Bowden C, et al. Efficacy of olanzapine and olanzapine-fluoxetine combination in the treatment of bipolar I depression. Arch Gen Psychiatry. 2003;60(11):1079-88.

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.

Loebel A, Cucchiaro J, Silva R, Kroger H, Sarma K, Xu J, et al. Lurasidone as adjunctive therapy with lithium or valproate for the treatment of bipolar I depression: a randomized, double-blind, placebo-controlled study. Am J Psychiatry. 2014;171(2):169-77.

Loebel A, Cucchiaro J, Silva R, Kroger H, Hsu J, Sarma K, et al. Lurasidone monotherapy in the treatment of bipolar I depression: a randomized, double-blind, placebo-controlled study. Am J Psychiatry. 2014;171(2):160-8.

Citrome L, Ketter TA, Cucchiaro J, Loebel A. Clinical assessment of lurasidone benefit and risk in the treatment of bipolar I depression using number needed to treat, number needed to harm, and likelihood to be helped or harmed. J Affect Disord. 2014;155:20-7.




How to Cite

Shah, A. B., Yadav, P. P., Chaudhari, M. A., Rai, J., & Kantharia, N. D. (2017). Bipolar disorder: a review of current U.S. Food and Drug Administration approved pharmacotherapy. International Journal of Basic & Clinical Pharmacology, 4(4), 623–631.



Review Articles