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Current Antipsychotics pp 187–212Cite as

Antipsychotics in the Treatment of Bipolar Disorder

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Part of the book series: Handbook of Experimental Pharmacology ((HEP,volume 212))

Abstract

Atypical antipsychotics have an important role in the acute and maintenance treatment of bipolar disorder. While robust evidence supports the efficacy of these agents in the treatment of mania and in the prevention of manic relapse, few atypical antipsychotics have shown efficacy in the treatment or prevention of depressive episodes. These agents pose a lower risk of extrapyramidal side effects compared to typical neuroleptics, but carry a significant liability for weight gain and other metabolic side effects such as hyperglycemia and hyperlipidemia. More comparative effectiveness studies are needed to assess the optimal treatment regimens, including the relative benefits and risks of antipsychotics versus mood stabilizers. The exploration of the molecular mechanisms of antipsychotics has helped to shed further light on the underlying neurobiology of bipolar disorder, since these compounds target systems thought to be key to the pathophysiology of bipolar disorder. In addition to modulating monoaminergic neurotransmission, atypical antipsychotics appear to share properties with mood-stabilizing agents known to alter intracellular signal transduction leading to changes in neuronal activity and gene expression. Atypical antipsychotic drugs have been shown to exhibit neuroprotective properties that are mediated by upregulation of trophic and cellular resilience factors. Building on our understanding of existing therapeutics, especially as it relates to underlying disease pathology, newer “plasticity enhancing” strategies hold promise for future treatments of bipolar disorder.

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References

  • Amrollahi Z, Rezaei F, Salehi B, Modabbernia AH, Maroufi A, Esfandiari GR et al (2011) Double-blind, randomized, placebo-controlled 6-week study on the efficacy and safety of the tamoxifen adjunctive to lithium in acute bipolar mania. J Affect Disord 129(1–3):327–331

    PubMed  CAS  Google Scholar 

  • APA (2002) Practice guideline for the treatment of patients with bipolar disorder (revision). Am J Psychiatry 159(4 Suppl):1–50

    Google Scholar 

  • Beaulieu JM, Gainetdinov RR (2011) The physiology, signaling, and pharmacology of dopamine receptors. Pharmacol Rev 63(1):182–217

    PubMed  CAS  Google Scholar 

  • Beaulieu JM, Gainetdinov RR, Caron MG (2007) The Akt-GSK-3 signaling cascade in the actions of dopamine. Trends Pharmacol Sci 28(4):166–172

    PubMed  CAS  Google Scholar 

  • Beaulieu JM, Gainetdinov RR, Caron MG (2009) Akt/GSK3 signaling in the action of psychotropic drugs. Annu Rev Pharmacol Toxicol 49:327–347

    PubMed  CAS  Google Scholar 

  • Beckford-Ball J (2006) An overview of the new NICE guidelines on bipolar disorder. Nurs Times 102(34):23–24

    Google Scholar 

  • Benyamina A, Samalin L (2012) Atypical antipsychotic-induced mania/hypomania: a review of recent case reports and clinical studies. Int J Psychiatry Clin Pract 16(1):2–7

    PubMed  CAS  Google Scholar 

  • Berk M, Dodd S, Kauer-Sant’anna M, Malhi GS, Bourin M, Kapczinski F et al (2007) Dopamine dysregulation syndrome: implications for a dopamine hypothesis of bipolar disorder. Acta Psychiatr Scand Suppl 434:41–49

    PubMed  Google Scholar 

  • Berwaerts J, Lane R, Nuamah IF, Lim P, Remmerie B, Hough DW (2011) Paliperidone extended-release as adjunctive therapy to lithium or valproate in the treatment of acute mania: a randomized, placebo-controlled study. J Affect Disord 129(1–3):252–260

    PubMed  CAS  Google Scholar 

  • Blier P, Blondeau C (2011) Neurobiological bases and clinical aspects of the use of aripiprazole in treatment-resistant major depressive disorder. J Affect Disord 128(Suppl 1):S3–10

    PubMed  CAS  Google Scholar 

  • Bowden CL, Grunze H, Mullen J, Brecher M, Paulsson B, Jones M et al (2005) A randomized, double-blind, placebo-controlled efficacy and safety study of quetiapine or lithium as monotherapy for mania in bipolar disorder. J Clin Psychiatry 66(1):111–121

    PubMed  CAS  Google Scholar 

  • Bowden CL, Vieta E, Ice KS, Schwartz JH, Wang PP, Versavel M (2010) Ziprasidone plus a mood stabilizer in subjects with bipolar I disorder: a 6-month, randomized, placebo-controlled, double-blind trial. J Clin Psychiatry 71(2):130–137

    PubMed  CAS  Google Scholar 

  • Calabrese JR, Elhaj O, Gajwani P, Gao K (2005a) Clinical highlights in bipolar depression: focus on atypical antipsychotics. J Clin Psychiatry 66(Suppl 5):26–33

    PubMed  CAS  Google Scholar 

  • Calabrese JR, Keck PE Jr, Macfadden W, Minkwitz M, Ketter TA, Weisler RH et al (2005b) A randomized, double-blind, placebo-controlled trial of quetiapine in the treatment of bipolar I or II depression. Am J Psychiatry 162(7):1351–1360

    PubMed  Google Scholar 

  • Calabrese J, Stet L, Kotari H (2010) Asenapine as adjunctive treatment for bipolar mania: results of a placebo-controlled 12-week study and 40-week extension. Eur Psychiatry (Supplement 1): 1447

    Google Scholar 

  • Chang KD (2008) The use of atypical antipsychotics in pediatric bipolar disorder. J Clin Psychiatry 69(Suppl 4):4–8

    PubMed  CAS  Google Scholar 

  • Chen G, Zeng WZ, Yuan PX, Huang LD, Jiang YM, Zhao ZH et al (1999) The mood-stabilizing agents lithium and valproate robustly increase the levels of the neuroprotective protein bcl-2 in the CNS. J Neurochem 72(2):879–882

    PubMed  CAS  Google Scholar 

  • Chen G, Henter ID, Manji HK (2010) Translational research in bipolar disorder: emerging insights from genetically based models. Mol Psychiatry 15(9):883–895

    PubMed  CAS  Google Scholar 

  • Cipriani A, Barbui C, Salanti G, Rendell J, Brown R, Stockton S et al (2011) Comparative efficacy and acceptability of antimanic drugs in acute mania: a multiple-treatments meta-analysis. Lancet 378:1306–15

    PubMed  CAS  Google Scholar 

  • Collo G, Zanetti S, Missale C, Spano P (2008) Dopamine D3 receptor-preferring agonists increase dendrite arborization of mesencephalic dopaminergic neurons via extracellular signal-regulated kinase phosphorylation. Eur J Neurosci 28(7):1231–1240

    PubMed  Google Scholar 

  • Corya SA, Perlis RH, Keck PE Jr, Lin DY, Case MG, Williamson DJ et al (2006) A 24-week open-label extension study of olanzapine-fluoxetine combination and olanzapine monotherapy in the treatment of bipolar depression. J Clin Psychiatry 67(5):798–806

    PubMed  CAS  Google Scholar 

  • Councill JH, Tucker ES, Haskell GT, Maynard TM, Meechan DW, Hamer RM et al (2006) Limited influence of olanzapine on adult forebrain neural precursors in vitro. Neuroscience 140(1):111–122

    PubMed  CAS  Google Scholar 

  • Cousins DA, Young AH (2007) The armamentarium of treatments for bipolar disorder: a review of the literature. Int J Neuropsychopharmacol 10(3):411–431

    PubMed  CAS  Google Scholar 

  • Cousins DA, Butts K, Young AH (2009) The role of dopamine in bipolar disorder. Bipolar Disord 11(8):787–806

    PubMed  CAS  Google Scholar 

  • Creson TK, Yuan P, Manji HK, Chen G (2009) Evidence for involvement of ERK, PI3K, and RSK in induction of Bcl-2 by valproate. J Mol Neurosci 37(2):123–134

    PubMed  CAS  Google Scholar 

  • Cruz N, Sanchez-Moreno J, Torres F, Goikolea JM, Valenti M, Vieta E (2009) Efficacy of modern antipsychotics in placebo-controlled trials in bipolar depression: a meta-analysis. Int J Neuropsychopharmacol 13(1):5–14

    PubMed  Google Scholar 

  • Deutch AY, Ongur D, Duman RS (1995) Antipsychotic drugs induce Fos protein in the thalamic paraventricular nucleus: a novel locus of antipsychotic drug action. Neuroscience 66(2):337–346

    PubMed  CAS  Google Scholar 

  • Di Benedetto B, Kuhn R, Nothdurfter C, Rein T, Wurst W, Rupprecht R (2011) N-desalkylquetiapine activates ERK1/2 to induce GDNF release in C6 glioma cells: A putative cellular mechanism for quetiapine as antidepressant. Neuropharmacology 62(1):209–16

    PubMed  Google Scholar 

  • DiazGranados N, Zarate CA Jr (2008) A review of the preclinical and clinical evidence for protein kinase C as a target for drug development for bipolar disorder. Curr Psychiatry Rep 10(6):510–519

    PubMed  Google Scholar 

  • Dwivedi Y, Pandey GN (1999) Effects of treatment with haloperidol, chlorpromazine, and clozapine on protein kinase C (PKC) and phosphoinositide-specific phospholipase C (PI-PLC) activity and on mRNA and protein expression of PKC and PLC isozymes in rat brain. J Pharmacol Exp Ther 291(2):688–704

    PubMed  CAS  Google Scholar 

  • Einat H, Yuan P, Gould TD, Li J, Du J, Zhang L et al (2003) The role of the extracellular signal-regulated kinase signaling pathway in mood modulation. J Neurosci 23(19):7311–7316

    PubMed  CAS  Google Scholar 

  • Einat H, Yuan P, Manji HK (2005) Increased anxiety-like behaviors and mitochondrial dysfunction in mice with targeted mutation of the Bcl-2 gene: further support for the involvement of mitochondrial function in anxiety disorders. Behav Brain Res 165(2):172–180

    PubMed  CAS  Google Scholar 

  • Fraguas D, Correll CU, Merchan-Naranjo J, Rapado-Castro M, Parellada M, Moreno C et al (2010) Efficacy and safety of second-generation antipsychotics in children and adolescents with psychotic and bipolar spectrum disorders: comprehensive review of prospective head-to-head and placebo-controlled comparisons. Eur Neuropsychopharmacol 21(8):621–645

    PubMed  Google Scholar 

  • Freyberg Z, Ferrando SJ, Javitch JA (2010) Roles of the Akt/GSK-3 and Wnt signaling pathways in schizophrenia and antipsychotic drug action. Am J Psychiatry 167(4):388–396

    PubMed  Google Scholar 

  • Fumagalli F, Molteni R, Bedogni F, Gennarelli M, Perez J, Racagni G et al (2004) Quetiapine regulates FGF-2 and BDNF expression in the hippocampus of animals treated with MK-801. Neuroreport 15(13):2109–2112

    PubMed  CAS  Google Scholar 

  • Gao K, Kemp DE, Ganocy SJ, Gajwani P, Xia G, Calabrese JR (2008) Antipsychotic-induced extrapyramidal side effects in bipolar disorder and schizophrenia: a systematic review. J Clin Psychopharmacol 28(2):203–209

    PubMed  Google Scholar 

  • Gentile S (2007) Atypical antipsychotics for the treatment of bipolar disorder: more shadows than lights. CNS Drugs 21(5):367–387

    PubMed  CAS  Google Scholar 

  • Giese AA (2009) Closing the gap between guidelines for bipolar disorder treatment and clinical practice. Am J Psychiatry 166(11):1205–1206

    PubMed  Google Scholar 

  • Goodwin FK (2007) Manic-depressive illness: bipolar disorders and recurrent depression, 2nd edn. Oxford University Press, Oxford

    Google Scholar 

  • Goodwin FK, Jamison KR (2007) Manic-depressive illness: bipolar disorders and recurrent depression, 2nd edn. Oxford University Press, Oxford

    Google Scholar 

  • Gould TD, Picchini AM, Einat H, Manji HK (2006) Targeting glycogen synthase kinase-3 in the CNS: implications for the development of new treatments for mood disorders. Curr Drug Targets 7(11):1399–1409, Review. PubMed PMID: 17100580

    PubMed  CAS  Google Scholar 

  • Green W, Patil P, Marsden CA, Bennett GW, Wigmore PM (2006) Treatment with olanzapine increases cell proliferation in the subventricular zone and prefrontal cortex. Brain Res 1070(1):242–245

    PubMed  CAS  Google Scholar 

  • Hammonds MD, Shim SS (2009) Effects of 4-week treatment with lithium and olanzapine on levels of brain-derived neurotrophic factor, B-cell CLL/lymphoma 2 and phosphorylated cyclic adenosine monophosphate response element-binding protein in the sub-regions of the hippocampus. Basic Clin Pharmacol Toxicol 105(2):113–119

    PubMed  CAS  Google Scholar 

  • He J, Xu H, Yang Y, Zhang X, Li XM (2004) Neuroprotective effects of olanzapine on methamphetamine-induced neurotoxicity are associated with an inhibition of hyperthermia and prevention of Bcl-2 decrease in rats. Brain Res 1018(2):186–192

    PubMed  CAS  Google Scholar 

  • He J, Xu H, Yang Y, Rajakumar D, Li X, Li XM (2006) The effects of chronic administration of quetiapine on the phencyclidine-induced reference memory impairment and decrease of Bcl-XL/Bax ratio in the posterior cingulate cortex in rats. Behav Brain Res 168(2):236–242

    PubMed  CAS  Google Scholar 

  • Hirschfeld RM, Keck PE Jr, Kramer M, Karcher K, Canuso C, Eerdekens M et al (2004) Rapid antimanic effect of risperidone monotherapy: a 3-week multicenter, double-blind, placebo-controlled trial. Am J Psychiatry 161(6):1057–1065

    PubMed  Google Scholar 

  • Hunsberger J, Austin DR, Henter ID, Chen G (2009) The neurotrophic and neuroprotective effects of psychotropic agents. Dialogues Clin Neurosci 11(3):333–348

    PubMed  Google Scholar 

  • Hunsberger JG, Machado-Vieira R, Austin DR, Zarate C, Chuang DM, Chen G et al (2011) Bax inhibitor 1, a modulator of calcium homeostasis, confers affective resilience. Brain Res 1403:19–27

    PubMed  CAS  Google Scholar 

  • Inestrosa NC, Arenas E (2010) Emerging roles of Wnts in the adult nervous system. Nat Rev Neurosci 11(2):77–86

    PubMed  CAS  Google Scholar 

  • Jarskog LF, Gilmore JH, Selinger ES, Lieberman JA (2000) Cortical bcl-2 protein expression and apoptotic regulation in schizophrenia. Biol Psychiatry 48(7):641–650

    PubMed  CAS  Google Scholar 

  • Jarskog LF, Selinger ES, Lieberman JA, Gilmore JH (2004) Apoptotic proteins in the temporal cortex in schizophrenia: high Bax/Bcl-2 ratio without caspase-3 activation. Am J Psychiatry 161(1):109–115

    PubMed  Google Scholar 

  • Jensen NH, Rodriguiz RM, Caron MG, Wetsel WC, Rothman RB, Roth BL (2008) N-desalkylquetiapine, a potent norepinephrine reuptake inhibitor and partial 5-HT1A agonist, as a putative mediator of quetiapine’s antidepressant activity. Neuropsychopharmacology 33(10):2303–2312

    PubMed  CAS  Google Scholar 

  • Jiao S, Li Z (2011) Nonapoptotic function of BAD and BAX in long-term depression of synaptic transmission. Neuron 70(4):758–772

    PubMed  CAS  Google Scholar 

  • Jonas E (2006) BCL-xL regulates synaptic plasticity. Mol Interv 6(4):208–222

    PubMed  CAS  Google Scholar 

  • Jonas EA (2009) Molecular participants in mitochondrial cell death channel formation during neuronal ischemia. Exp Neurol 218(2):203–212

    PubMed  CAS  Google Scholar 

  • Kapur S, Mann JJ (1992) Role of the dopaminergic system in depression. Biol Psychiatry 32(1):1–17

    PubMed  CAS  Google Scholar 

  • Kato T (2007) Molecular genetics of bipolar disorder and depression. Psychiatry Clin Neurosci 61(1):3–19

    PubMed  CAS  Google Scholar 

  • Keck PE Jr, Versiani M, Potkin S, West SA, Giller E, Ice K (2003) Ziprasidone in the treatment of acute bipolar mania: a three-week, placebo-controlled, double-blind, randomized trial. Am J Psychiatry 160(4):741–748

    PubMed  Google Scholar 

  • Keck PE Jr, Calabrese JR, McIntyre RS, McQuade RD, Carson WH, Eudicone JM et al (2007) Aripiprazole monotherapy for maintenance therapy in bipolar I disorder: a 100-week, double-blind study versus placebo. J Clin Psychiatry 68(10):1480–1491

    PubMed  CAS  Google Scholar 

  • Keilhoff G, Grecksch G, Bernstein HG, Roskoden T, Becker A (2010) Risperidone and haloperidol promote survival of stem cells in the rat hippocampus. Eur Arch Psychiatry Clin Neurosci 260(2):151–162

    PubMed  Google Scholar 

  • Khanna S, Vieta E, Lyons B, Grossman F, Eerdekens M, Kramer M (2005) Risperidone in the treatment of acute mania: double-blind, placebo-controlled study. Br J Psychiatry 187:229–234

    PubMed  Google Scholar 

  • Kim I, Xu W, Reed JC (2008) Cell death and endoplasmic reticulum stress: disease relevance and therapeutic opportunities. Nat Rev Drug Discov 7(12):1013–1030

    PubMed  CAS  Google Scholar 

  • Kim HW, Rapoport SI, Rao JS (2010) Altered expression of apoptotic factors and synaptic markers in postmortem brain from bipolar disorder patients. Neurobiol Dis 37(3):596–603

    PubMed  CAS  Google Scholar 

  • Kinon BJ, Stauffer VL, Kollack-Walker S, Chen L, Sniadecki J (2008) Olanzapine versus aripiprazole for the treatment of agitation in acutely ill patients with schizophrenia. J Clin Psychopharmacol 28(6):601–607

    PubMed  CAS  Google Scholar 

  • Kusumakar V (2002) Antidepressants and antipsychotics in the long-term treatment of bipolar disorder. J Clin Psychiatry 63(Suppl 10):23–28

    PubMed  CAS  Google Scholar 

  • Lee R, Kermani P, Teng KK, Hempstead BL (2001) Regulation of cell survival by secreted proneurotrophins. Science 294(5548):1945–1948

    PubMed  CAS  Google Scholar 

  • Levy B, Manove E (2011) Functional outcome in bipolar disorder: the big picture. Depress Res Treat 2012:949248

    PubMed  Google Scholar 

  • Li X, Jope RS (2010) Is glycogen synthase kinase-3 a central modulator in mood regulation? Neuropsychopharmacology 35(11):2143–2154

    PubMed  CAS  Google Scholar 

  • Lien R, Flaisher-Grinberg S, Cleary C, Hejny M, Einat H (2008) Behavioral effects of Bcl-2 deficiency: implications for affective disorders. Pharmacol Rep 60(4):490–498

    PubMed  CAS  Google Scholar 

  • Lieberman JA, Bymaster FP, Meltzer HY, Deutch AY, Duncan GE, Marx CE, Aprille JR, Dwyer DS, Li XM, Mahadik SP, Duman RS, Porter JH, Modica-Napolitano JS, Newton SS, Csernansky JG (2008) Antipsychotic drugs: comparison in animal models of efficacy, neurotransmitter regulation, and neuroprotection. Pharmacol Rev 60(3):358–403, Review. Erratum in: Pharmacol Rev. 2008 Dec;60(4):582. PubMed PMID: 18922967

    PubMed  CAS  Google Scholar 

  • Lipina TV, Kaidanovich-Beilin O, Patel S, Wang M, Clapcote SJ, Liu F et al (2011) Genetic and pharmacological evidence for schizophrenia-related Disc1 interaction with GSK-3. Synapse 65(3):234–248

    PubMed  CAS  Google Scholar 

  • Luo C, Xu H, Li XM (2004) Post-stress changes in BDNF and Bcl-2 immunoreactivities in hippocampal neurons: effect of chronic administration of olanzapine. Brain Res 1025(1–2):194–202

    PubMed  CAS  Google Scholar 

  • Macfadden W, Alphs L, Haskins JT, Turner N, Turkoz I, Bossie C et al (2009) A randomized, double-blind, placebo-controlled study of maintenance treatment with adjunctive risperidone long-acting therapy in patients with bipolar I disorder who relapse frequently. Bipolar Disord 11(8):827–839

    PubMed  CAS  Google Scholar 

  • Machado-Vieira R, Pivovarova NB, Stanika RI, Yuan P, Wang Y, Zhou R et al (2011) The Bcl-2 gene polymorphism rs956572AA increases inositol 1,4,5-trisphosphate receptor-mediated endoplasmic reticulum calcium release in subjects with bipolar disorder. Biol Psychiatry 69(4):344–352

    PubMed  CAS  Google Scholar 

  • Maeng S, Hunsberger JG, Pearson B, Yuan P, Wang Y, Wei Y et al (2008) BAG1 plays a critical role in regulating recovery from both manic-like and depression-like behavioral impairments. Proc Natl Acad Sci U S A 105(25):8766–8771

    PubMed  CAS  Google Scholar 

  • Malkesman O, Austin DR, Tragon T, Henter ID, Reed JC, Pellecchia M, et al (2011) Targeting the BH3-interacting domain death agonist to develop mechanistically unique antidepressants. Mol Psychiatry

    Google Scholar 

  • Marcus R, Khan A, Rollin L, Morris B, Timko K, Carson W et al (2011) Efficacy of aripiprazole adjunctive to lithium or valproate in the long-term treatment of patients with bipolar I disorder with an inadequate response to lithium or valproate monotherapy: a multicenter, double-blind, randomized study. Bipolar Disord 13(2):133–144

    PubMed  CAS  Google Scholar 

  • McIntyre RS, Brecher M, Paulsson B, Huizar K, Mullen J (2005) Quetiapine or haloperidol as monotherapy for bipolar mania–a 12-week, double-blind, randomised, parallel-group, placebo-controlled trial. Eur Neuropsychopharmacol 15(5):573–585

    PubMed  CAS  Google Scholar 

  • McIntyre RS, Cohen M, Zhao J, Alphs L, Macek TA, Panagides J (2009) Asenapine versus olanzapine in acute mania: a double-blind extension study. Bipolar Disord 11(8):815–826

    PubMed  CAS  Google Scholar 

  • McIntyre RS, Cohen M, Zhao J, Alphs L, Macek TA, Panagides J (2010) Asenapine in the treatment of acute mania in bipolar I disorder: a randomized, double-blind, placebo-controlled trial. J Affect Disord 122(1–2):27–38

    PubMed  CAS  Google Scholar 

  • McQuade R, Marcus R, Sanchez R (2003) Aripiprazole vs placebo in acute mania: safety and tolerability pooled analysis. Paper presented at the 5th International Conference on Bipolar Disorder, Pittsburgh, PA

    Google Scholar 

  • Merlo S, Canonico PL, Sortino MA (2011) Distinct effects of pramipexole on the proliferation of adult mouse sub-ventricular zone-derived cells and the appearance of a neuronal phenotype. Neuropharmacology 60(6):892–900

    PubMed  CAS  Google Scholar 

  • Montezinho LP, Castro MM, Duarte CB, Penschuck S, Geraldes CF, Mork A (2006) The interaction between dopamine D2-like and beta-adrenergic receptors in the prefrontal cortex is altered by mood-stabilizing agents. J Neurochem 96(5):1336–1348

    PubMed  CAS  Google Scholar 

  • Mullen J, Devine N, Sweitzer D (2003) Quetiapine adjunctive therapy for acute mania associated with bipolar disorder (SIAM) Paper presented at the 156th Annual Meeting of the American Psychiatric Association, San Francisco, CA

    Google Scholar 

  • Nasrallah HA, Hopkins T, Pixley SK (2010) Differential effects of antipsychotic and antidepressant drugs on neurogenic regions in rats. Brain Res 1354:23–29

    PubMed  CAS  Google Scholar 

  • Newton SS, Duman RS (2007) Neurogenic actions of atypical antipsychotic drugs and therapeutic implications. CNS Drugs 21(9):715–725

    PubMed  CAS  Google Scholar 

  • Nikolaus S, Antke C, Muller HW (2009) In vivo imaging of synaptic function in the central nervous system: II Mental and affective disorders. Behav Brain Res 204(1):32–66

    PubMed  Google Scholar 

  • O'Brien WT, Klein PS (2007) Regulation of glycogen synthase kinase-3 in patients with affective disorders. Biol Psychiatry 61(2):139–141

    PubMed  Google Scholar 

  • Pearlson GD, Wong DF, Tune LE, Ross CA, Chase GA, Links JM et al (1995) In vivo D2 dopamine receptor density in psychotic and nonpsychotic patients with bipolar disorder. Arch Gen Psychiatry 52(6):471–477

    PubMed  CAS  Google Scholar 

  • Pereira M, Martynhak BJ, Baretta IP, Correia D, Siba IP, Andreatini R (2011) Antimanic-like effect of tamoxifen is not reproduced by acute or chronic administration of medroxyprogesterone or clomiphene. Neurosci Lett 500(2):95–98

    PubMed  CAS  Google Scholar 

  • Perlis RH, Welge JA, Vornik LA, Hirschfeld RM, Keck PE Jr (2006) Atypical antipsychotics in the treatment of mania: a meta-analysis of randomized, placebo-controlled trials. J Clin Psychiatry 67(4):509–516

    PubMed  CAS  Google Scholar 

  • Pinsonneault JK, Han DD, Burdick KE, Kataki M, Bertolino A, Malhotra AK et al (2011) Dopamine transporter gene variant affecting expression in human brain is associated with bipolar disorder. Neuropsychopharmacology 36(8):1644–1655

    PubMed  CAS  Google Scholar 

  • Popovic D, Reinares M, Amann B, Salamero M, Vieta E (2010) Number needed to treat analyses of drugs used for maintenance treatment of bipolar disorder. Psychopharmacology (Berl) 213(4):657–667

    Google Scholar 

  • Potkin SG, Keck PE Jr, Segal S, Ice K, English P (2005) Ziprasidone in acute bipolar mania: a 21-day randomized, double-blind, placebo-controlled replication trial. J Clin Psychopharmacol 25(4):301–310

    PubMed  CAS  Google Scholar 

  • Prieto E, Mico JA, Meana JJ, Majadas S (2010) Neurobiological bases of quetiapine antidepresant effect in the bipolar disorder. Actas Esp Psiquiatr 38(1):22–32

    PubMed  CAS  Google Scholar 

  • Quiroz JA, Yatham LN, Palumbo JM, Karcher K, Kushner S, Kusumakar V (2010) Risperidone long-acting injectable monotherapy in the maintenance treatment of bipolar I disorder. Biol Psychiatry 68(2):156–162

    PubMed  CAS  Google Scholar 

  • Roh MS, Seo MS, Kim Y, Kim SH, Jeon WJ, Ahn YM et al (2007) Haloperidol and clozapine differentially regulate signals upstream of glycogen synthase kinase 3 in the rat frontal cortex. Exp Mol Med 39(3):353–360

    PubMed  CAS  Google Scholar 

  • Rybakowski J (2005) Maintenance treatment of bipolar disorders. Neuro Endocrinol Lett 26(Suppl 1):49–65

    PubMed  Google Scholar 

  • Sachs GS, Grossman F, Ghaemi SN, Okamoto A, Bowden CL (2002) Combination of a mood stabilizer with risperidone or haloperidol for treatment of acute mania: a double-blind, placebo-controlled comparison of efficacy and safety. Am J Psychiatry 159(7):1146–1154

    PubMed  Google Scholar 

  • Sachs G, Chengappa KN, Suppes T, Mullen JA, Brecher M, Devine NA et al (2004) Quetiapine with lithium or divalproex for the treatment of bipolar mania: a randomized, double-blind, placebo-controlled study. Bipolar Disord 6(3):213–223

    PubMed  CAS  Google Scholar 

  • Sachs G, Sanchez R, Marcus R, Stock E, McQuade R, Carson W et al (2006) Aripiprazole in the treatment of acute manic or mixed episodes in patients with bipolar I disorder: a 3-week placebo-controlled study. J Psychopharmacol 20(4):536–546

    PubMed  CAS  Google Scholar 

  • Samuels BA, Hen R (2011) Neurogenesis and affective disorders. Eur J Neurosci 33(6):1152–1159

    PubMed  Google Scholar 

  • Scheffer RE, Tripathi A, Kirkpatrick FG, Schultz T (2011) Guidelines for treatment-resistant mania in children with bipolar disorder. J Psychiatr Pract 17(3):186–193

    PubMed  Google Scholar 

  • Sklar P, Ripke S, Scott LJ, Andreassen OA, Cichon S, Craddock N et al (2011) Large-scale genome-wide association analysis of bipolar disorder identifies a new susceptibility locus near ODZ4. Nat Genet 43(10):977–83

    CAS  Google Scholar 

  • Smith LA, Cornelius V, Warnock A, Bell A, Young AH (2007) Effectiveness of mood stabilizers and antipsychotics in the maintenance phase of bipolar disorder: a systematic review of randomized controlled trials. Bipolar Disord 9(4):394–412

    PubMed  CAS  Google Scholar 

  • Smulevich AB, Khanna S, Eerdekens M, Karcher K, Kramer M, Grossman F (2005) Acute and continuation risperidone monotherapy in bipolar mania: a 3-week placebo-controlled trial followed by a 9-week double-blind trial of risperidone and haloperidol. Eur Neuropsychopharmacol 15(1):75–84

    PubMed  CAS  Google Scholar 

  • Suppes T, Brown E, Schuh LM, Baker RW, Tohen M (2005a) Rapid versus non-rapid cycling as a predictor of response to olanzapine and divalproex sodium for bipolar mania and maintenance of remission: post hoc analyses of 47-week data. J Affect Disord 89(1–3):69–77

    PubMed  CAS  Google Scholar 

  • Suppes T, Dennehy EB, Hirschfeld RM, Altshuler LL, Bowden CL, Calabrese JR et al (2005b) The Texas implementation of medication algorithms: update to the algorithms for treatment of bipolar I disorder. J Clin Psychiatry 66(7):870–886

    PubMed  Google Scholar 

  • Suppes T, Vieta E, Liu S, Brecher M, Paulsson B (2009) 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 166(4):476–488

    PubMed  Google Scholar 

  • Surja AA, Tamas RL, El-Mallakh RS (2006) Antipsychotic medications in the treatment of bipolar disorder. Curr Drug Targets 7(9):1217–1224

    PubMed  CAS  Google Scholar 

  • Sutton LP, Rushlow WJ (2011) Regulation of Akt and Wnt signaling by the group II metabotropic glutamate receptor antagonist LY341495 and agonist LY379268. J Neurochem 117(6):973–983

    PubMed  CAS  Google Scholar 

  • Thase ME, Macfadden W, Weisler RH, Chang W, Paulsson B, Khan A et al (2006) Efficacy of quetiapine monotherapy in bipolar I and II depression: a double-blind, placebo-controlled study (the BOLDER II study). J Clin Psychopharmacol 26(6):600–609

    PubMed  CAS  Google Scholar 

  • Thase ME, Jonas A, Khan A, Bowden CL, Wu X, McQuade RD et al (2008) Aripiprazole monotherapy in nonpsychotic bipolar I depression: results of 2 randomized, placebo-controlled studies. J Clin Psychopharmacol 28(1):13–20

    PubMed  CAS  Google Scholar 

  • Tohen M, Vieta E (2009) Antipsychotic agents in the treatment of bipolar mania. Bipolar Disord 11(Suppl 2):45–54

    PubMed  CAS  Google Scholar 

  • Tohen M, Sanger TM, McElroy SL, Tollefson GD, Chengappa KN, Daniel DG et al (1999) Olanzapine versus placebo in the treatment of acute mania Olanzapine HGEH Study Group. Am J Psychiatry 156(5):702–709

    PubMed  CAS  Google Scholar 

  • Tohen M, Jacobs TG, Grundy SL, McElroy SL, Banov MC, Janicak PG et al (2000) Efficacy of olanzapine in acute bipolar mania: a double-blind, placebo-controlled study The Olanzipine HGGW Study Group. Arch Gen Psychiatry 57(9):841–849

    PubMed  CAS  Google Scholar 

  • Tohen M, Chengappa KN, Suppes T, Zarate CA Jr, Calabrese JR, Bowden CL et al (2002) Efficacy of olanzapine in combination with valproate or lithium in the treatment of mania in patients partially nonresponsive to valproate or lithium monotherapy. Arch Gen Psychiatry 59(1):62–69

    PubMed  CAS  Google Scholar 

  • Tohen M, Vieta E, Calabrese J, Ketter TA, Sachs G, Bowden C et al (2003) Efficacy of olanzapine and olanzapine-fluoxetine combination in the treatment of bipolar I depression. Arch Gen Psychiatry 60(11):1079–1088

    PubMed  CAS  Google Scholar 

  • Tohen M, Greil W, Calabrese JR, Sachs GS, Yatham LN, Oerlinghausen BM et al (2005) Olanzapine versus lithium in the maintenance treatment of bipolar disorder: a 12-month, randomized, double-blind, controlled clinical trial. Am J Psychiatry 162(7):1281–1290

    PubMed  Google Scholar 

  • Tohen M, Calabrese JR, Sachs GS, Banov MD, Detke HC, Risser R et al (2006) Randomized, placebo-controlled trial of olanzapine as maintenance therapy in patients with bipolar I disorder responding to acute treatment with olanzapine. Am J Psychiatry 163(2):247–256

    PubMed  Google Scholar 

  • Toprac MG, Dennehy EB, Carmody TJ, Crismon ML, Miller AL, Trivedi MH et al (2006) Implementation of the texas medication algorithm project patient and family education program. J Clin Psychiatry 67(9):1362–1372

    PubMed  Google Scholar 

  • Tran-Johnson TK, Sack DA, Marcus RN, Auby P, McQuade RD, Oren DA (2007) Efficacy and safety of intramuscular aripiprazole in patients with acute agitation: a randomized, double-blind, placebo-controlled trial. J Clin Psychiatry 68(1):111–119

    PubMed  CAS  Google Scholar 

  • Vestergaard P (1992) Treatment and prevention of mania: a Scandinavian perspective. Neuropsychopharmacology 7(4):249–259

    PubMed  CAS  Google Scholar 

  • Vieta E, Suppes T, Eggens I, Persson I, Paulsson B, Brecher M (2008a) Efficacy and safety of quetiapine in combination with lithium or divalproex for maintenance of patients with bipolar I disorder (international trial 126). J Affect Disord 109(3):251–263

    PubMed  CAS  Google Scholar 

  • Vieta E, T’Joen C, McQuade RD, Carson WH Jr, Marcus RN, Sanchez R et al (2008b) Efficacy of adjunctive aripiprazole to either valproate or lithium in bipolar mania patients partially nonresponsive to valproate/lithium monotherapy: a placebo-controlled study. Am J Psychiatry 165(10):1316–1325

    PubMed  Google Scholar 

  • Vieta E, Nuamah IF, Lim P, Yuen EC, Palumbo JM, Hough DW et al (2010) A randomized, placebo- and active-controlled study of paliperidone extended release for the treatment of acute manic and mixed episodes of bipolar I disorder. Bipolar Disord 12(3):230–243

    PubMed  CAS  Google Scholar 

  • Vieta E, Gunther O, Locklear J, Ekman M, Miltenburger C, Chatterton ML et al (2011) Effectiveness of psychotropic medications in the maintenance phase of bipolar disorder: a meta-analysis of randomized controlled trials. Int J Neuropsychopharmacol 14(8):1029–1049

    PubMed  CAS  Google Scholar 

  • Wagstaff AJ, Easton J, Scott LJ (2005) Intramuscular olanzapine: a review of its use in the management of acute agitation. CNS Drugs 19(2):147–164

    PubMed  CAS  Google Scholar 

  • Walburn J, Gray R, Gournay K, Quraishi S, David AS (2001) Systematic review of patient and nurse attitudes to depot antipsychotic medication. Br J Psychiatry 179:300–307

    PubMed  CAS  Google Scholar 

  • Weisler R, Dunn J, English P (2003) Ziprasidone in adjunctive treatment of acute bipolar mania: a randomized, placebo-controlled trial. Paper presented at the 16th congress of the European College of Neuro-psychopharmacology, Prague, Czech Republic

    Google Scholar 

  • Weisler RH, Nolen WA, Neijber A, Hellqvist A, Paulsson B (2010) Continuation of quetiapine versus switching to placebo or lithium for maintenance treatment of bipolar I disorder (Trial 144: a randomized controlled study). J Clin Psychiatry 72(11):1452–1464

    Google Scholar 

  • Yatham LN, Grossman F, Augustyns I, Vieta E, Ravindran A (2003) Mood stabilisers plus risperidone or placebo in the treatment of acute mania. International, double-blind, randomised controlled trial. Br J Psychiatry 182:141–147

    PubMed  Google Scholar 

  • Yildiz A, Guleryuz S, Ankerst DP, Ongur D, Renshaw PF (2008) Protein kinase C inhibition in the treatment of mania: a double-blind, placebo-controlled trial of tamoxifen. Arch Gen Psychiatry 65(3):255–263

    PubMed  CAS  Google Scholar 

  • Yildiz A, Vieta E, Leucht S, Baldessarini RJ (2011) Efficacy of antimanic treatments: meta-analysis of randomized, controlled trials. Neuropsychopharmacology 36(2):375–389

    PubMed  CAS  Google Scholar 

  • Youle RJ, Strasser A (2008) The BCL-2 protein family: opposing activities that mediate cell death. Nat Rev Mol Cell Biol 9(1):47–59

    PubMed  CAS  Google Scholar 

  • Yuan PX, Huang LD, Jiang YM, Gutkind JS, Manji HK, Chen G (2001) The mood stabilizer valproic acid activates mitogen-activated protein kinases and promotes neurite growth. J Biol Chem 276(34):31674–31683

    PubMed  CAS  Google Scholar 

  • Yuan P, Zhou R, Wang Y, Li X, Li J, Chen G et al (2010) Altered levels of extracellular signal-regulated kinase signaling proteins in postmortem frontal cortex of individuals with mood disorders and schizophrenia. J Affect Disord 124(1–2):164–169

    PubMed  CAS  Google Scholar 

  • Zarate CA, Manji HK (2009) Protein kinase C inhibitors: rationale for use and potential in the treatment of bipolar disorder. CNS Drugs 23(7):569–582

    PubMed  CAS  Google Scholar 

  • Zarate CA Jr, Singh JB, Carlson PJ, Quiroz J, Jolkovsky L, Luckenbaugh DA et al (2007) Efficacy of a protein kinase C inhibitor (tamoxifen) in the treatment of acute mania: a pilot study. Bipolar Disord 9(6):561–570

    PubMed  CAS  Google Scholar 

  • Zhou R, Gray NA, Yuan P, Li X, Chen J, Chen G et al (2005) The anti-apoptotic, glucocorticoid receptor cochaperone protein BAG-1 is a long-term target for the actions of mood stabilizers. J Neurosci 25(18):4493–4502

    PubMed  CAS  Google Scholar 

  • Zupancic ML (2011) Role of atypical antipsychotics in rapid cycling bipolar disorder: a review of the literature. Ann Clin Psychiatry 23(2):141–149

    PubMed  Google Scholar 

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Authors and Affiliations

  1. Janssen Pharmaceutical Research and Development, L.L.C., 1125 Trenton-Harbourton Road, Titusville, NJ, 08560, USA

    Jaskaran Singh, Guang Chen & Carla M. Canuso

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  1. Jaskaran Singh
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  2. Guang Chen
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  3. Carla M. Canuso
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Correspondence to Carla M. Canuso .

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  1. Institut für Pharmakologie, Universität, Neuroscience Research, Abbott GmbH & Co. KG, Knollstraße, Ludwigshafen, 67061, Germany

    Gerhard Gross

  2. Dept. Psychiatry, University of California San Diego, Gilman Drive 9500, La Jolla, 92093-0804, California, USA

    Mark A. Geyer

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Singh, J., Chen, G., Canuso, C.M. (2012). Antipsychotics in the Treatment of Bipolar Disorder. In: Gross, G., Geyer, M. (eds) Current Antipsychotics. Handbook of Experimental Pharmacology, vol 212. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-25761-2_8

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