428
Views
8
CrossRef citations to date
0
Altmetric
Drug Discovery Case History

Lamotrigine as a mood stabilizer: insights from the pre-clinical evidence

, &
Pages 179-190 | Received 15 Aug 2018, Accepted 27 Nov 2018, Published online: 07 Dec 2018

References

  • Calabrese JR, Bowden CL, Sachs GS, et al. A double-blind placebo-controlled study of lamotrigine monotherapy in outpatients with bipolar I depression. Lamictal 602 Study Group. J Clin Psychiatry. 1999;60:79–88.
  • Weisler RH, Calabrese JR, Bowden CL, et al. Discovery and development of lamotrigine for bipolar disorder: a story of serendipity, clinical observations, risk taking, and persistence. J Affective Disorders. 2008;108:1–9.
  • Reynolds EH, Chanarin I, Milner G, et al. Anticonvulsant therapy, folic acid and vitamin b 12 metabolism and mental symptoms. Epilepsia. 1966;7:261–270.
  • Fischer J, Ganellin CR, Ganesan A, et al. Standalone drugs. analog. drug discov. II. Weinheim, Germany: Wiley-VCH Verlag GmbH & Co. KGaA; 2010. p. 29–59.
  • Baxter MG, Elphick AR, Miller AA, et al. 1,2,4-triazine derivatives, pharmaceutical compositions and intermediates used for their preparation. EP21121, 1981.
  • Sander JWAS, Patsalos PN. An assessment of serum and red blood cell folate concentrations in patients with epilepsy on lamotrigine therapy. Epilepsy Res. 1992;13:89–92.
  • Leach MJ, Marden CM, Miller AA. Pharmacological Studies on Lamotrigine, A Novel Potential Antiepileptic Drug. Epilepsia. 1986;27:490–497.
  • Brodie MJ. Lamotrigine. Lancet. 1992;339:1397–1400.
  • Cheung H, Kamp D, Harris E. An in vitro investigation of the action of lamotrigine on neuronal voltage-activated sodium channels. Epilepsy Res. 1992;13:107–112.
  • Prabhavalkar KS, Poovanpallil NB, Bhatt LK. Management of bipolar depression with lamotrigine: an antiepileptic mood stabilizer. Front Pharmacol. 2015 Oct 23;6:242. doi:10.3389/fphar.2015.00242. eCollection 2015.
  • Xie X, Lancaster B, Peakman T, et al. Interaction of the antiepileptic drug lamotrigine with recombinant rat brain type IIA Na+ channels and with native Na+ channels in rat hippocampal neurones. Pfl?Gers Arch Eur J Physiol. 1995;430:437–446.
  • Cunningham MO, Jones RSG. The anticonvulsant, lamotrigine decreases spontaneous glutamate release but increases spontaneous GABA release in the rat entorhinal cortex in vitro. Neuropharmacology. 2000;39:2139–2146.
  • Cohen AF, Ashby L, Crowley D, et al. Lamotrigine (BW430C), a potential anticonvulsant. Effects on the central nervous system in comparison with phenytoin and diazepam. Br. J. Clin. Pharmacol. 1985;20:619–629.
  • Smith D, Baker G, Davies G, et al. Outcomes of add-on treatment with lamotrigine in partial epilepsy. Epilepsia. 34:312–322.
  • Rapoport SI, Basselin M, Kim H-W, et al. Bipolar disorder and mechanisms of action of mood stabilizers. Brain Res Rev. 2009;61:185–209.
  • Perlis RH, Dennehy EB, Miklowitz DJ, et al. Retrospective age at onset of bipolar disorder and outcome during two-year follow-up: results from the STEP-BD study. Bipolar Disord. 2009;11:391–400.
  • Bauer M, Glenn T, Rasgon N, et al. Association between age of onset and mood in bipolar disorder: comparison of subgroups identified by cluster analysis and clinical observation. J Psychiatr Res. 2010;44:1170–1175.
  • Novick DM, Swartz HA, Frank E. Suicide attempts in bipolar I and bipolar II disorder: a review and meta-analysis of the evidence. Bipolar Disord. 2010;12:1–9.
  • Undurraga J, Baldessarini RJ, Valenti M, et al. Suicidal risk factors in bipolar i and ii disorder patients. J Clin Psychiatry. 2012;73:778–782.
  • Whiteford HA, Degenhardt L, Rehm J, et al. Global burden of disease attributable to mental and substance use disorders: findings from the global burden of disease study 2010. Lancet. 2013;382:1575–1586.
  • Ghaemi SN, Dalley S. The bipolar spectrum: conceptions and misconceptions. Aust N Z J Psychiatry. 2014;48:314–324.
  • Krishnan KRR. Psychiatric and medical comorbidities of bipolar disorder. Psychosom Med. 2005;67:1–8.
  • Kupfer DJ. The increasing medical burden in bipolar disorder. JAMA. 2005;293:2528.
  • Sierra P, Livianos L, Rojo L. Quality of life for patients with bipolar disorder: relationship with clinical and demographic variables. Bipolar Disord. 2005;7:159–165.
  • Angst F, Stassen HH, Clayton PJ, et al. Mortality of patients with mood disorders: follow-up over 34–38 years. J Affect Disord. 2002;68:167–181.
  • American Psychiatric Association. Diagnostic and statistical manual of mental disorders. 5th ed. Arlington: American Psychiatric Association; 2013.
  • Fries GR, Pfaffenseller B, Stertz L, et al. Staging and neuroprogression in bipolar disorder. Curr Psychiatry Rep. 2012;14:667–675.
  • Kapczinski F, Pvs M, Balanzá-Martinez V, et al. Staging systems in bipolar disorder: an international society for bipolar disorders task force report. Acta Psychiatr Scand. 2014;130:354–363.
  • Zarate CA, Tohen M, Fletcher K. Cycling into depression from a first episode of mania: a case-comparison study. Am J Psychiatry. 2001;158:1524–1526.
  • Sachs GS, Gardner-Schuster EE. Adjunctive treatment of acute mania: a clinical overview. Acta Psychiatr Scand. 2007;116:27–34.
  • Judd LL, Akiskal HS, Schettler PJ, et al. The long-term natural history of the weekly symptomatic status of bipolar I disorder. Arch Gen Psychiatry. 2002;59:530–537.
  • Post RM, Denicoff KD, Leverich GS, et al. Morbidity in 258 bipolar outpatients followed for 1 year with daily prospective ratings on the NIMH life chart method. J Clin Psychiatry. 2003;64:680–90 quiz ;738–9.
  • Kupka RW, Altshuler LL, Nolen WA, et al. Three times more days depressed than manic or hypomanic in both bipolar I and bipolar II disorder. Bipolar Disord. 2007;9:531–535.
  • Baldessarini RJ, Salvatore P, Khalsa H-MK, et al. Morbidity in 303 first-episode bipolar I disorder patients. Bipolar Disord. 2010;12:264–270.
  • Bauer M, Ritter P, Grunze H, et al. Treatment options for acute depression in bipolar disorder. Bipolar Disord. 2012;14:37–50.
  • Yatham LN, Calabrese JR, Kusumakar V. Bipolar depression: criteria for treatment selection, definition of refractoriness, and treatment options. Bipolar Disord. 2003;5:85–97.
  • De Fruyt J, Deschepper E, Audenaert K, et al. Second generation antipsychotics in the treatment of bipolar depression: a systematic review and meta-analysis. J Psychopharmacol. 2012;26:603–617.
  • Ghaemi SN, Boiman EE, Goodwin FK. Diagnosing bipolar disorder and the effect of antidepressants: a naturalistic study. J Clin Psychiatry. 2000;61: 804–808. quiz 809.
  • Perlis RH, Miyahara S, Marangell LB, et al. Long-Term implications of early onset in bipolar disorder: data from the first 1000 participants in the systematic treatment enhancement program for bipolar disorder (STEP-BD). Biol Psychiatry. 2004;55:875–881.
  • Ghaemi SN, Ko JY, Goodwin FK. The bipolar spectrum and the antidepressant view of the world. J Psychiatr Pract. 2001;7:287–297.
  • Ghaemi SN, Ko JY, Goodwin FK. “Cade’s disease” and beyond: misdiagnosis, antidepressant use, and a proposed definition for bipolar spectrum disorder. Can J Psychiatry. 2002;47:125–134.
  • Delvecchio G, Fossati P, Boyer P, et al. Common and distinct neural correlates of emotional processing in bipolar disorder and major depressive disorder: a voxel-based meta-analysis of functional magnetic resonance imaging studies. Eur Neuropsychopharmacol. 2012;22:100–113.
  • Hirschfeld RM. Differential diagnosis of bipolar disorder and major depressive disorder. J Affect Disord. 2014;169:S12–S16.
  • Normann C, Hummel B, Schärer LO, et al. Lamotrigine as adjunct to paroxetine in acute depression: a placebo-controlled, double-blind study. J Clin Psychiatry. 2002;63:337–344.
  • Barbee JG, Thompson TR, Jamhour NJ, et al. A double-blind placebo-controlled trial of lamotrigine as an antidepressant augmentation agent in treatment-refractory unipolar depression. J Clin Psychiatry. 2011;72:1405–1412.
  • Zavodnick AD, Ali R. Lamotrigine in the treatment of unipolar depression with and without comorbidities: a literature review. Psychiatr Q. 2012;83:371–383.
  • Grunze HCR. Anticonvulsants in bipolar disorder. J Ment Heal. 2010;19:127–141.
  • Weisler R, Risner M, Ascher J, et al. Use of lamotrigine in the treatment of bipolar disorder. Philadelphia (PA): Am. Psychiatr. Assoc. Annu. Meet; 1994.
  • Calabrese JR, Bowden CL, McElroy SL, et al. Spectrum of activity of lamotrigine in treatment-refractory bipolar disorder. Am J Psychiatry. 1999;156:1019–1023.
  • Calabrese JR, Bowden CL, Sachs G, et al. A placebo-controlled 18-month trial of lamotrigine and lithium maintenance treatment in recently depressed patients with bipolar I disorder. J Clin Psychiatry. 2003;64:1013–1024.
  • Calabrese JR, Suppes T, Bowden CL, et al. A double-blind, placebo-controlled, prophylaxis study of lamotrigine in rapid-cycling bipolar disorder. lamictal 614 study group. J Clin Psychiatry. 2000;61:841–850.
  • Goldsmith DR, Wagstaff AJ, Ibbotson T, et al. Lamotrigine: a review of its use in bipolar disorder. Drugs. 2003;63:2029–2050.
  • Post RM, Leverich GS, Denicoff KD, et al. Alternative approaches to refractory depression in bipolar illness. Depress Anxiety. 1997;5:175–189.
  • Post RM, Tasman A, Goldfinger SM, et al. Alternatives to lithium for bipolar affective illness. Wahshington (DC): American Psychiatric Press; 1990.
  • Post RM, Denicoff KD, Frye MA, et al. A history of the use of anticonvulsants as mood stabilizers in the last two decades of the 20th century. Neuropsychobiology. 1998;38:152–166.
  • Calabrese JR, Shelton MD, Rapport DJ, et al. Current research on rapid cycling bipolar disorder and its treatment. J Affect Disord. 2001;67:241–255.
  • Calabrese JR, Rapport DJ, Youngstrom EA, et al. New data on the use of lithium, divalproate, and lamotrigine in rapid cycling bipolar disorder. Eur Psychiatry. 2005;20:92–95.
  • Weisler RH, Cutler AJ, Ballenger JC, et al. The use of antiepileptic drugs in bipolar disorders: a review based on evidence from controlled trials. CNS Spectr. 2006;11:788–799.
  • Redmond JR, Jamison KL, Bowden CL. Lamotrigine combined with divalproex or lithium for bipolar disorder: a case series. CNS Spectr. 2006;11:915–918.
  • Ichim L, Berk M, Brook S. Lamotrigine compared with lithium in mania: a double-blind randomized controlled trial. Ann. Clin. Psychiatry. 2000;12:5–10.
  • Waszkielewicz AM, Gunia A, Szkaradek N, et al. Ion channels as drug targets in central nervous system disorders. Curr Med Chem. 2013;20:1241–1285.
  • Tikhonov DB, Zhorov BS. Mechanism of sodium channel block by local anesthetics, antiarrhythmics, and anticonvulsants. J Gen Physiol. 2017;149:465–481.
  • Bölcskei H, Tarnawa I, Kocsis P. Voltage-gated sodium channel blockers, 2001–2006: an overview. Med Chem Res. 2008;17:356–368.
  • Tarnawa I, Bölcskei H, Kocsis P. Blockers of voltage-gated sodium channels for the treatment of central nervous system diseases. Recent Pat CNS Drug Discov. 2007;2:57–78.
  • Hainsworth AH, Stefani A, Calabresi P, et al. Sipatrigine (BW 619C89) is a neuroprotective agent and a sodium channel and calcium channel inhibitor. CNS Drug Rev. 2006;6:111–134.
  • Muir KW, Hamilton SJ, Lunnon MW, et al. Safety and tolerability of 619C89 after acute stroke. Cerebrovasc Dis. 1998;8:31–37.
  • Foreman MM, Hanania T, Stratton SC, et al. In vivo pharmacological effects of JZP-4, a novel anticonvulsant, in models for anticonvulsant, antimania and antidepressant activity. Pharmacol Biochem Behav. 2008;89:523–534.
  • Foreman MM, Hanania T, Eller M. Anxiolytic effects of lamotrigine and JZP-4 in the elevated plus maze and in the four plate conflict test. Eur J Pharmacol. 2009;602:316–320.
  • Trezise DJ, John VH, Xie XM. Voltage- and use-dependent inhibition of Na + channels in rat sensory neurones by 4030W92, a new antihyperalgesic agent. Br J Pharmacol. 1998;124:953–963.
  • Muir KW, Holzapfel L, Lees KR. Phase II clinical trial of sipatrigine (619C89) by continuous infusion in acute stroke. Cerebrovasc Dis. 2000;10:431–436.
  • Bialer M, Johannessen SI, Levy RH, et al. Progress report on new antiepileptic drugs: a summary of the Ninth Eilat Conference (EILAT IX). Epilepsy Res. 2009;83:1–43.
  • Vohora D, Saraogi P, Yazdani MA, et al. Recent advances in adjunctive therapy for epilepsy: focus on sodium channel blockers as third-generation antiepileptic drugs. Drugs Today. 2010;46:265.
  • de Miranda AS, Andreatini R, Teixeira AL Animal models of mania: essential tools to better understand bipolar disorder. anim. model. study hum. dis. 2nd Ed. San Diego: Elsevier; 2017. p. 1131–1143.
  • Gould TD, Einat H. Animal models of bipolar disorder and mood stabilizer efficacy: A critical need for improvement. Neurosci Biobehav Rev. 2007;31:825–831.
  • Cryan JF, Markou A, Lucki I. Assessing antidepressant activity in rodents: recent developments and future needs. Trends Pharmacol Sci. 2002;23:238–245.
  • Ali A, Pillai KK, Pal SN. Effects of folic acid and lamotrigine therapy in some rodent models of epilepsy and behaviour. J Pharm Pharmacol. 2003;55:387–391.
  • Bourin M, Masse F, Hascoët M. Evidence for the activity of lamotrigine at 5-HT(1A) receptors in the mouse forced swimming test. J Psychiatry Neurosci. 2005;30:275–282.
  • Bourin M, Lambert O, Guitton B. Treatment of acute mania?from clinical trials to recommendations for clinical practice. Hum Psychopharmacol Clin Exp. 2005;20:15–26.
  • Vinod KY, Subhash MN. Lamotrigine induced selective changes in 5-HT(1A) receptor mediated response in rat brain. Neurochem Int. 2002;40:315–319.
  • Shim S, El Mansari M, Blier P. Modulation of the antidepressant-like effects of sustained administration of carisbamate and lamotrigine on monoaminergic systems: electrophysiological studies in the rat brain. J Pharmacol Exp Ther. 2013;347:487–496.
  • Ahmad S, Fowler LJ, Whitton PS. Effect of acute and chronic lamotrigine on basal and stimulated extracellular 5-hydroxytryptamine and dopamine in the hippocampus of the freely moving rat. Br J Pharmacol. 2004;142:136–142.
  • D’Souza UM, Powell-Smith G, Haddley K, et al. Allele-specific expression of the serotonin transporter and its transcription factors following lamotrigine treatment in vitro. Am J Med Genet Part B Neuropsychiatr Genet. 2013;162:474–483.
  • Consoni FT, Vital MABF, Andreatini R. Dual monoamine modulation for the antidepressant-like effect of lamotrigine in the modified forced swimming test. Eur Neuropsychopharmacol. 2006;16:451–458.
  • Millan MJ, Lejeune F, Gobert A. Reciprocal autoreceptor and heteroreceptor control of serotonergic, dopaminergic and noradrenergic transmission in the frontal cortex: relevance to the actions of antidepressant agents. J Psychopharmacol. 2000;14:114–138.
  • Kaster MP, Raupp I, Binfaré RW, et al. Antidepressant-like effect of lamotrigine in the mouse forced swimming test: evidence for the involvement of the noradrenergic system. Eur J Pharmacol. 2007;565:119–124.
  • Ostadhadi S, Ahangari M, Nikoui V, et al. Pharmacological evidence for the involvement of the NMDA receptor and nitric oxide pathway in the antidepressant-like effect of lamotrigine in the mouse forced swimming test. Biomed Pharmacother. 2016;82:713–721.
  • Du J, Suzuki K, Wei Y, et al. The anticonvulsants lamotrigine, riluzole, and valproate differentially regulate AMPA receptor membrane localization: relationship to clinical effects in mood disorders. Neuropsychopharmacology. 2007;32:793–802.
  • Waldmeier PC, Baumann PA, Wicki P, et al. Similar potency of carbamazepine, oxcarbazepine, and lamotrigine in inhibiting the release of glutamate and other neurotransmitters. Neurology. 1995;45:1907–1913.
  • Prica C, Hascoet M, Bourin M. Antidepressant-like effect of lamotrigine is reversed by veratrine: a possible role of sodium channels in bipolar depression. Behav Brain Res. 2008;191:49–54.
  • Contestabile A. Roles of NMDA receptor activity and nitric oxide production in brain development. Brain Res Brain Res Rev. 2000;32:476–509.
  • Esplugues JV. NO as a signalling molecule in the nervous system. Br J Pharmacol. 2002;135:1079–1095.
  • Harkin AJ, Bruce KH, Craft B, et al. Nitric oxide synthase inhibitors have antidepressant-like properties in mice. 1. Acute treatments are active in the forced swim test. Eur. J. Pharmacol 1999;372:207–213.
  • Da Silva GD, Matteussi As.dos Santos Ar, et al. Evidence for dual effects of nitric oxide in the forced swimming test and in the tail suspension test in mice. Neuroreport 2000;11:3699–3702.
  • Volke V, Wegener G, Bourin M, et al. Antidepressant- and anxiolytic-like effects of selective neuronal NOS inhibitor 1-(2-trifluoromethylphenyl)-imidazole in mice. Behav Brain Res. 2003;140:141–147.
  • Duman RS. Role of neurotrophic factors in the etiology and treatment of mood disorders. Neuromolecular Med. 2004;5:11–25.
  • Chang YC, Rapoport SI, Rao JS. Chronic administration of mood stabilizers upregulates BDNF and bcl-2 expression levels in rat frontal cortex. Neurochem Res. 2009;34:536–541.
  • Abelaira HM, Réus GZ, Ribeiro KF, et al. Effects of acute and chronic treatment elicited by lamotrigine on behavior, energy metabolism, neurotrophins and signaling cascades in rats. Neurochem Int. 2011;59:1163–1174.
  • Li N, He X, Qi X, et al. The mood stabilizer lamotrigine produces antidepressant behavioral effects in rats: role of brain-derived neurotrophic factor. J Psychopharmacol. 2010;24:1772–1778.
  • Hajszan T, Dow A, Warner-Schmidt JL, et al. Remodeling of hippocampal spine synapses in the rat learned helplessness model of depression. Biol Psychiatry. 2009;65:392–400.
  • Li N, He X, Zhang Y, et al. Brain-derived neurotrophic factor signalling mediates antidepressant effects of lamotrigine. Int. J. Neuropsychopharmacol. 2011;14:1091–1098.
  • Sun R, Li N, Li T. VEGF regulates antidepressant effects of lamotrigine. Eur Neuropsychopharmacol. 2012;22:424–430.
  • Abelaira HM, Réus GZ, Ribeiro KF, et al. Lamotrigine treatment reverses depressive-like behavior and alters BDNF levels in the brains of maternally deprived adult rats. Pharmacol Biochem Behav. 2012;101:348–353.
  • Chuang D-M. The antiapoptotic actions of mood stabilizers: molecular mechanisms and therapeutic potentials. Ann N Y Acad Sci. 2005;1053:195–204.
  • Chalovich EM, Zhu J, Caltagarone J, et al. Functional repression of cAMP response element in 6-hydroxydopamine-treated neuronal cells. J Biol Chem. 2006;281:17870–17881.
  • Knable MB, Barci BM, Webster MJ, et al. Molecular abnormalities of the hippocampus in severe psychiatric illness: postmortem findings from the Stanley Neuropathology Consortium. Mol Psychiatry. 2004;9:609–620,544.
  • Dean B, Gray L, Scarr E. Regionally specific changes in levels of cortical S100beta in bipolar 1 disorder but not schizophrenia. Aust N Z J Psychiatry. 2006;40:217–224.
  • Eren I, Naziroğlu M, Demirdaş A. Protective effects of lamotrigine, aripiprazole and escitalopram on depression-induced oxidative stress in rat brain. Neurochem Res. 2007;32:1188–1195.
  • Bakare A, Shao L, Cui J, et al. Mood stabilizing drugs lamotrigine and olanzapine increase expression and activity of glutathione s-transferase in primary cultured rat cerebral cortical cells. Neurosci Lett. 2009;455:70–73.
  • Goldstein BI, Kemp DE, Soczynska JK, et al. Inflammation and the phenomenology, pathophysiology, comorbidity, and treatment of bipolar disorder. J Clin Psychiatry. 2009;70:1078–1090.
  • Leboyer M, Soreca I, Scott J, et al. Can bipolar disorder be viewed as a multi-system inflammatory disease? J. Affect Disord. 2012;141:1–10.
  • Barbosa IG, Machado-Vieira R, Soares JC, et al. The immunology of bipolar disorder. Neuroimmunomodulation. 2014;21:117–122.
  • Barbosa IG, Vaz GN, Rocha NP, et al. Plasma levels of tumor necrosis factor superfamily molecules are increased in bipolar disorder. Clin Psychopharmacol Neurosci. 2017;15:269–275.
  • Strange RC, Spiteri MA, Ramachandran S, et al. Glutathione-S-transferase family of enzymes. Mutat Res. 2001;482:21–26.
  • Cross DAE, Alessi DR, Cohen P, et al. Inhibition of glycogen synthase kinase-3 by insulin mediated by protein kinase B. Nature. 1995;378:785–789.
  • Hashimoto K, Sawa A, Iyo M. Increased levels of glutamate in brains from patients with mood disorders. Biol Psychiatry. 2007;62:1310–1316.
  • Rao JS, Harry GJ, Rapoport SI, et al. Increased excitotoxicity and neuroinflammatory markers in postmortem frontal cortex from bipolar disorder patients. Mol Psychiatry. 2010;15:384–392.
  • Basselin M, Villacreses NE, Lee H-J, et al. Chronic lithium administration attenuates up-regulated brain arachidonic acid metabolism in a rat model of neuroinflammation. J Neurochem. 2007;102:761–772.
  • Lee H-J, Rao JS, Chang L, et al. Chronic N-methyl-D-aspartate administration increases the turnover of arachidonic acid within brain phospholipids of the unanesthetized rat. J Lipid Res. 2008;49:162–168.
  • Rao JS, Ertley RN, Rapoport SI, et al. Chronic NMDA administration to rats up-regulates frontal cortex cytosolic phospholipase A2 and its transcription factor, activator protein-2. J Neurochem. 2007;102:1918–1927.
  • Kim H-W, Rapoport SI, Rao JS. Altered arachidonic acid cascade enzymes in postmortem brain from bipolar disorder patients. Mol Psychiatry. 2011;16:419–428.
  • Lee H-J, Ertley RN, Rapoport SI, et al. Chronic administration of lamotrigine downregulates COX-2 mRNA and protein in rat frontal cortex. Neurochem Res. 2008;33:861–866.
  • Dumuis A, Sebben M, Haynes L, et al. NMDA receptors activate the arachidonic acid cascade system in striatal neurons. Nature. 1988;336:68–70.
  • Ramadan E, Basselin M, Rao JS, et al. Lamotrigine blocks NMDA receptor-initiated arachidonic acid signalling in rat brain: implications for its efficacy in bipolar disorder. Int. J. Neuropsychopharmacol. 2012;15:931–943.
  • Valvassori SS, Budni J, Varela RB, et al. Contributions of animal models to the study of mood disorders. Rev Bras Psiquiatr. 2013;35:S121–S131.
  • Arban R, Maraia G, Brackenborough K, et al. Evaluation of the effects of lamotrigine, valproate and carbamazepine in a rodent model of mania. Behav Brain Res. 2005;158:123–132.
  • Dencker D, Dias R, Pedersen ML, et al. Effect of the new antiepileptic drug retigabine in a rodent model of mania. Epilepsy Behav. 2008;12:49–53.
  • Brody SA, Geyer MA, Large CH. Lamotrigine prevents ketamine but not amphetamine-induced deficits in prepulse inhibition in mice. Psychopharmacology (Berl). 2003;169:240–246.
  • Flood DG, Choinski M, Marino MJ, et al. Mood stabilizers increase prepulse inhibition in DBA/2NCrl mice. Psychopharmacology (Berl). 2009;205:369–377.
  • Paylor R, Crawley JN. Inbred strain differences in prepulse inhibition of the mouse startle response. Psychopharmacology (Berl). 1997;132:169–180.
  • Ison JR, Hoffman HS. Reflex modification in the domain of startle: II. The anomalous history of a robust and ubiquitous phenomenon. Psychol Bull 1983;94:3–17.
  • Braff DL, Geyer MA. Sensorimotor gating and schizophrenia. Human and animal model studies. Arch Gen Psychiatry 1990;47:181–188.
  • Perry W, Minassian A, Feifel D, et al. Sensorimotor gating deficits in bipolar disorder patients with acute psychotic mania. Biol Psychiatry. 2001;50:418–424.
  • Braff DL, Geyer MA, Swerdlow NR. Human studies of prepulse inhibition of startle: normal subjects, patient groups, and pharmacological studies. Psychopharmacology (Berl). 2001;156:234–258.
  • Tremblay M, Winstanley CA. Anticonvulsant medications attenuate amphetamine-induced deficits in behavioral inhibition but not decision making under risk on a rat gambling task. Behav Brain Res. 2016;314:143–151.
  • Christodoulou T, Lewis M, Ploubidis GB, et al. The relationship of impulsivity to response inhibition and decision-making in remitted patients with bipolar disorder. Eur Psychiatry. 2006;21:270–273.
  • Yechiam E, Hayden EP, Bodkins M, et al. Decision making in bipolar disorder: a cognitive modeling approach. Psychiatry Res. 2008;161:142–152.
  • Labudda K, Frigge K, Horstmann S, et al. Decision making in patients with temporal lobe epilepsy. Neuropsychologia. 2009;47:50–58.
  • Delazer M, Zamarian L, Bonatti E, et al. Decision making under ambiguity and under risk in mesial temporal lobe epilepsy. Neuropsychologia. 2010;48:194–200.
  • Delazer M, Zamarian L, Bonatti E, et al. Decision making under ambiguity in temporal lobe epilepsy: does the location of the underlying structural abnormality matter? Epilepsy Behav. 2011;20:34–37.
  • Yamano M, Akamatsu N, Tsuji S, et al. Decision-making in temporal lobe epilepsy examined with the Iowa gambling task. Epilepsy Res. 2011;93:33–38.
  • Maksimovic M, Vekovischeva OY, Aitta-Aho T, et al. Chronic treatment with mood-stabilizers attenuates abnormal hyperlocomotion of glua1-subunit deficient mice. In Clelland JD, editor. PLoS One. 2014. Vol. 9, e100188.
  • Maksimovic M, Aitta-Aho T, Korpi ER. Reversal of novelty-induced hippocampal c-fos expression in gluA1 subunit-deficient mice by chronic treatment targeting glutamatergic transmission. Eur J Pharmacol. 2014;745:36–45.
  • Fountoulakis KN, Kelsoe JR, Akiskal H. Receptor targets for antidepressant therapy in bipolar disorder: an overview. J Affect Disord. 2012;138:222–238.
  • Fountoulakis KN, Gazouli M, Kelsoe J, et al. The pharmacodynamic properties of lurasidone and their role in its antidepressant efficacy in bipolar disorder. Eur Neuropsychopharmacol. 2015;25:335–342.
  • Zheng W, Thorne N, McKew JC. Phenotypic screens as a renewed approach for drug discovery. Drug Discov Today. 2013;18:1067–1073.
  • Costantino L, Barlocco D. Challenges in the design of multitarget drugs against multifactorial pathologies: a new life for medicinal chemistry? Future. Med Chem. 2013;5:5–7.
  • Berrettini WH. Are schizophrenic and bipolar disorders related? A review of family and molecular studies. Biol Psychiatry. 2000;48:531–538.
  • Walker J, Curtis V, Murray RM. Schizophrenia and bipolar disorder: similarities in pathogenic mechanisms but differences in neurodevelopment. Int Clin Psychopharmacol. 2002;17(Suppl 3):S11–9.
  • Boteva K, Lieberman J. Reconsidering the classification of schizophrenia and manic depressive illness-a critical analysis and new conceptual model. World J Biol Psychiatry. 2003;4:81–92.
  • Ishibashi T, Horisawa T, Tokuda K, et al. Pharmacological profile of lurasidone, a novel antipsychotic agent with potent 5-hydroxytryptamine 7 (5-HT7) and 5-HT1A receptor activity. J Pharmacol Exp Ther. 2010;334:171–181.
  • Muneer A. The treatment of adult bipolar disorder with aripiprazole: a systematic review. Cureus. 2016;8:e562.
  • Macdonald KJ, Young LT. Newer antiepileptic drugs in bipolar disorder: rationale for use and role in therapy. CNS Drugs. 2002;16:549–562.

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.