Potential novel treatments for bipolar depression

  • Carlos A. ZarateJr
  • Husseini K. Manji
Part of the Milestones in Drug Therapy book series (MDT)


Existing pharmacological treatments for bipolar disorder (BPD), a severe recurrent mood disorder, is in general insufficient for many patients. Despite adequate doses and treatment duration, many individuals afflicted with this disease continue to experience mood episode relapses, residual symptoms, and functional impairment. In contrast to the manic phase of the illness where a fairly large variety of effective treatments are available, in bipolar depression effective therapeutics are scarce. This is especially troubling because the long-term course of BPD is dominated by recurrent depressive episodes and lingering depressive symptoms rather than hypomanic/manic episodes. Novel therapeutics—that is, drugs that do not include the existing antipsychotic, antiepileptic, and antidepressant medications—currently being studied to determine their efficacy and safety in bipolar depression include modafinil, pramipexole, N-acetyl cysteine (NAC), scopolamine, agomelatine, riluzole, memantine, ketamine, AMPA potentiators, ketoconazole, mifepristone, celecoxib, creatine, and uridine RG2417. Further study of these drugs will investigate their clinical utility in bipolar depression, and further our understanding of relevant drug targets.


Bipolar Disorder Major Depressive Disorder AMPA Receptor Mood Stabilizer Biol Psychiatry 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


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  1. 1.
    Sachs GS, Nierenberg AA, Calabrese JR, Marangell LB, Wisniewski SR, Gyulai L, Friedman ES, Bowden CL, Fossey MD, Ostacher MJ et al (2007) Effectiveness of adjunctive antidepressant treatment for bipolar depression. N Engl J Med 356: 1711–1722PubMedCrossRefGoogle Scholar
  2. 2.
    Judd LL, Akiskal HS, Schettler PJ, Endicott J, Maser J, Solomon DA, Leon AC, Rice JA, Keller MB (2002) The long-term natural history of the weekly symptomatic status of bipolar I disorder. Arch Gen Psychiatry 59: 530–537PubMedCrossRefGoogle Scholar
  3. 3.
    Montgomery P, Richardson AJ (2008) Omega-3 fatty acids for bi-polar disorder. Cochrane Database Syst Rev 16: CDD005169Google Scholar
  4. 4.
    Keck PE Jr, Mintz J, McElroy SL, Freeman MP, Suppes T, Frye MA, Altshuler LL, Kupka R, Nolen WA, Leverich GS et al (2006) Double-blind, randomized, placebo-controlled trials of ethyleicosapentanoate in the treatment of bipolar depression and rapid cycling bipolar disorder. Biol Psychiatry 60: 1020–1022PubMedCrossRefGoogle Scholar
  5. 5.
    Littner M, Johnson SF, McCall VW, Anderson WM, Davila D, Hartse SK, Kushida CA, Wise MS, Hirshkowitz M, Woodson BT et al (2001) Practice parameters for the treatment of narcolepsy: an update for 2000. Sleep 24: 451–466PubMedGoogle Scholar
  6. 6.
    Ballon JS, Feifel D (2006) A systematic review of modafinil: Potential clinical uses and mechanisms of action. J Clin Psychiatry 67: 554–566PubMedGoogle Scholar
  7. 7.
    Frye MA, Grunze H, Suppes T, McElroy SL, Keck PE Jr, Walden J, Leverich GS, Altshuler LL, Nakelsky S, Hwang S et al (2007) A placebo-controlled evaluation of adjunctive modafinil in the treatment of bipolar depression. Am J Psychiatry 164: 1242–1249PubMedCrossRefGoogle Scholar
  8. 8.
    Post RM, Altshuler LL, Frye MA, Suppes T, McElroy SL, Keck PE Jr, Leverich GS, Kupka R, Nolen WA, Grunze H (2006) New findings from the Bipolar Collaborative Network: clinical implications for therapeutics. Curr Psychiatry Rep 8: 489–497PubMedCrossRefGoogle Scholar
  9. 9.
    Wolf J, Fiedler U, Anghelescu I, Schwertfeger N (2006) Manic switch in a patient with treatmentresistant bipolar depression treated with modafinil. J Clin Psychiatry 67: 1817PubMedCrossRefGoogle Scholar
  10. 10.
    Ranjan S, Chandra PS (2005) Modafinil-induced irritability and aggression? A report of 2 bipolar patients. J Clin Psychopharmacol 25: 628–629PubMedCrossRefGoogle Scholar
  11. 11.
    Zarate CA Jr, Payne JL, Singh J, Quiroz JA, Luckenbaugh DA, Denicoff KD, Charney DS, Manji HK (2004) Pramipexole for bipolar II depression: a placebo-controlled proof of concept study. Biol Psychiatry 56: 54–60PubMedCrossRefGoogle Scholar
  12. 12.
    Goldberg JF, Burdick KE, Endick CJ (2004) Preliminary randomized, double-blind, placebo-controlled trial of pramipexole added to mood stabilizers for treatment-resistant bipolar depression. Am J Psychiatry 161: 564–566PubMedCrossRefGoogle Scholar
  13. 13.
    Takata K, Kitamura Y, Kakimura J, Kohno Y, Taniguchi T (2000) Increase of bcl-2 protein in neuronal dendritic processes of cerebral cortex and hippocampus by the antiparkinsonian drugs, talipexole and pramipexole. Brain Res 872: 326–341CrossRefGoogle Scholar
  14. 14.
    Zarate CA Jr, Singh J, Manji HK (2006) Cellular plasticity cascades: targets for the development of novel therapeutics for bipolar disorder. Biol Psychiatry 59: 1006–1020PubMedCrossRefGoogle Scholar
  15. 15.
    Andreazza AC, Cassini C, Rosa AR, Leite MC, de Almeida LM, Nardin P, Cunha AB, Cereser KM, Santin A, Gottfried C et al (2007) Serum S100B and antioxidant enzymes in bipolar patients. J Psychiatr Res 41: 523–529PubMedCrossRefGoogle Scholar
  16. 16.
    Kuloglu M, Ustundag B, Atmaca M, Canatan H, Tezcan AE, Cinkiline N (2002) Lipid peroxidation and antioxidant enzyme levels in patients with schizophrenia and bipolar disorder. Cell Biochem Funct 20: 171–175PubMedCrossRefGoogle Scholar
  17. 17.
    Berk M, Copolov DL, Dean O, Lu K, Jeavons S, Schapkaitz I, Anderson-Hunt M, Bush AI (2008) N-Acetyl Cysteine for depressive symptoms in bipolar disorder-a double-blind randomized placebo-controlled trial. Biol Psychiatry 64: 468–475PubMedCrossRefGoogle Scholar
  18. 18.
    Janowsky DS, el-Yousef MK, Davis JM, Sekerke HJ (1972) A cholinergic-adrenergic hypothesis of mania and depression. Lancet 2: 632–635PubMedCrossRefGoogle Scholar
  19. 19.
    Shi J, Hattori E, Zou H, Badner JA, Christian SL, Gershon ES, Liu C (2007) No evidence for association between 19 cholinergic genes and bipolar disorder. Am J Med Genet B Neuropsychiatr Genet 144: 715–723Google Scholar
  20. 20.
    Overstreet DH (1993) The Flinders sensitive line rats: a genetic animal model of depression. Neurosci Biobehav Rev 17: 51–68PubMedCrossRefGoogle Scholar
  21. 21.
    Dilsaver SC (1986) Pathophysiology of “cholinoceptor supersensitivity” in affective disorders. Biol Psychiatry 21: 813–829PubMedCrossRefGoogle Scholar
  22. 22.
    Sokolski KN, DeMet EM (2000) Cholinergic sensitivity predicts severity of mania. Psychiatry Res 95: 195–200PubMedCrossRefGoogle Scholar
  23. 23.
    Cannon DM, Carson RE, Nugent AC, Eckelman WC, Kiesewetter DO, Williams J, Rollis D, Drevets M, Gandhi S, Solorio G et al (2006) Reduced muscarinic type 2 receptor binding in subjects with bipolar disorder. Arch Gen Psychiatry 63: 741–747PubMedCrossRefGoogle Scholar
  24. 24.
    Davis KL, Berger PA, Hollister LE, Defraites E (1978) Physostigmine in mania. Arch Gen Psychiatry 35: 119–122PubMedGoogle Scholar
  25. 25.
    Khouzam HR, Kissmeyer PM (1996) Physostigmine temporarily and dramatically reversing acute mania. Gen Hosp Psychiatry 18: 203–204PubMedCrossRefGoogle Scholar
  26. 26.
    Burt T, Sachs GS, Demopoulos C (1999) Donepezil in treatment-resistant bipolar disorder. Biol Psychiatry 45: 959–964PubMedCrossRefGoogle Scholar
  27. 27.
    Eden Evins A, Demopulos C, Nierenberg A, Culhane MA, Eisner L, Sachs GS (2006) A doubleblind, placebo-controlled trial of adjunctive donepezil in treatment-resistant mania. Bipolar Disord 8: 75–80CrossRefGoogle Scholar
  28. 28.
    Kasper S, Moises HW, Beckmann H (1981) The anticholinergic biperiden in depressive disorders. Pharmacopsychiatria 14: 195–198PubMedCrossRefGoogle Scholar
  29. 29.
    Furey ML, Drevets WC (2006) Antidepressant efficacy of the antimuscarinic drug scopolamine: a randomized, placebo-controlled clinical trial. Arch Gen Psychiatry 63: 1121–1129PubMedCrossRefGoogle Scholar
  30. 30.
    Hallam KT, Olver JS, Norman TR (2005) Melatonin sensitivity to light in monozygotic twins discordant for bipolar I disorder. Aust N Z J Psychiatry 39: 947PubMedGoogle Scholar
  31. 31.
    Lewy AJ, Nurnberger JI Jr, Wehr TA, Pack D, Becker LE, Powell RL, Newsome DA (1985) Supersensitivity to light: possible trait marker for manic-depressive illness. Am J Psychiatry 142: 725–727PubMedGoogle Scholar
  32. 32.
    Lewy AJ, Wehr TA, Goodwin FK, Newsome DA, Rosenthal NE (1981) Manic-depressive patients may be supersensitive to light. Lancet 8216: 383–384CrossRefGoogle Scholar
  33. 33.
    Nurnberger JI Jr, Adkins S, Lahiri DK, Mayeda A, Hu K, Lewy AJ, Miller A, Bowman ES, Miller MJ, Rau L et al (2000) Melatonin suppression by light in euthymic bipolar and unipolar patients. Arch Gen Psychiatry 57: 572–579PubMedCrossRefGoogle Scholar
  34. 34.
    Thomson PA, Wray NR, Thomson AM, Dunbar DR, Grassie MA, Condie A, Walker MT, Smith DJ, Pulford DJ, Muir W et al (2005) Sex-specific association between bipolar affective disorder in women and GPR50, an X-linked orphan G protein-coupled receptor. Mol Psychiatry 10: 470–478PubMedCrossRefGoogle Scholar
  35. 35.
    Alaerts M, Venken T, Lenaerts AS, De Zutter S, Norrback KF, Adolfsson R, Del-Favero J (2006) Lack of association of an insertion/deletion polymorphism in the G protein-coupled receptor 50 with bipolar disorder in a Northern Swedish population. Psychiatr Genet 16: 235–236PubMedCrossRefGoogle Scholar
  36. 36.
    Hallam KT, Olver JS, Horgan JE, McGrath C, Norman TR (2005) Low doses of lithium carbonate reduce melatonin light sensitivity in healthy volunteers. Int J Neuropsychopharmacol 8: 255–259PubMedCrossRefGoogle Scholar
  37. 37.
    Hallam KT, Olver JS, Norman TR (2005) Effect of sodium valproate on nocturnal melatonin sensitivity to light in healthy volunteers. Neuropsychopharmacology 30: 1400–1404PubMedGoogle Scholar
  38. 38.
    Bersani G, Garavani A (2000) Melatonin add-on in manic patients with treatment resistant insomnia. Biol Psychiatry 24: 185–191Google Scholar
  39. 39.
    Leibenluft E, Feldman-Naim S, Turner EH, Wehr TA, Rosenthal NE (1997) Effects of exogenous melatonin administration and withdrawal in five patients with rapid-cycling bipolar disorder. J Clin Psychiatry 58: 383–388PubMedGoogle Scholar
  40. 40.
    Banasr M, Soumier A, Hery M, Mocaer E, Daszuta A (2006) Agomelatine, a new antidepressant, induces regional changes in hippocampal neurogenesis. Biol Psychiatry 59: 1087–1096PubMedCrossRefGoogle Scholar
  41. 41.
    Bertaina-Anglade V, laRochelle CD, Boyer PA, Mocaer E (2006) Antidepressant-like effects of agomelatine (S 20098) in the learned helplessness model. Behav Pharmacol 17: 703–713PubMedCrossRefGoogle Scholar
  42. 42.
    Papp M, Gruca P, Boyer PA, Mocaer E (2003) Effect of agomelatine in the chronic mild stress model of depression in the rat. Neuropsychopharmacology 28: 694–703PubMedCrossRefGoogle Scholar
  43. 43.
    Millan MJ, Brocco M, Gobert A, Dekeyne A (2005) Anxiolytic properties of agomelatine, an antidepressant with melatoninergic and serotonergic properties: role of 5-HT2C receptor blockade. Psychopharmacology (Berl) 177: 448–458CrossRefGoogle Scholar
  44. 44.
    Montgomery SA, Kasper S (2007) Severe depression and antidepressants: focus on a pooled analysis of placebo-controlled studies on agomelatine. Int Clin Psychopharmacol 22: 283–291PubMedCrossRefGoogle Scholar
  45. 45.
    Calabrese JR, Guelfi JD, Perdrizet-Chevalier C (2007) Agomelatine adjunctive therapy for acute bipolar depression: preliminary open data. Bipolar Disord 9: 628–635PubMedCrossRefGoogle Scholar
  46. 46.
    Sanacora G, Zarate CA Jr, Krystal JH, Manji HK (2008) Targeting the glutamatergic system to develop novel, improved therapeutics for mood disorders. Nat Rev Drug Discov 7: 426–437PubMedCrossRefGoogle Scholar
  47. 47.
    Bannerman DM, Good MA, Butcher SP, Ramsay M, Morris RG (1995) Distinct components of spatial learning revealed by prior training and NMDA receptor blockade. Nature 378: 182–186PubMedCrossRefGoogle Scholar
  48. 48.
    Collingridge GL (1994) Long-term potentiation. A question of reliability. Nature 371: 652–653PubMedCrossRefGoogle Scholar
  49. 49.
    Collingridge GL, Bliss TV (1995) Memories of NMDA receptors and LTP. Trends Neurosci 18: 54–56PubMedCrossRefGoogle Scholar
  50. 50.
    Watkins J, Collingridge G (1994) Phenylglycine derivatives as antagonists of metabotropic glutamate receptors. Trends Pharmacol Sci 15: 333–342PubMedCrossRefGoogle Scholar
  51. 51.
    Du J, Suzuki K, Wei Y, Wang Y, Blumenthal R, Chen Z, Falke C, Zarate CA Jr, Manji HK (2007) The anticonvulsants lamotrigine, riluzole, and valproate differentially regulate AMPA receptor membrane localization: relationship to clinical effects in mood disorders. Neuropsychopharmacology 32: 793–802PubMedCrossRefGoogle Scholar
  52. 52.
    Fumagalli E, Funicello M, Rauen T, Gobbi M, Mennini T (2008) Riluzole enhances the activity of glutamate transporters GLAST, GLT1 and EAAC1. Eur J Pharmacol 578: 171–176PubMedCrossRefGoogle Scholar
  53. 53.
    Mizuta I, Ohta M, Ohta K, Nishimura M, Mizuta E, Kuno S (2001) Riluzole stimulates nerve growth factor, brain-derived neurotrophic factor and glial cell line-derived neurotrophic factor synthesis in cultured mouse astrocytes. Neurosci Lett 310: 117–120PubMedCrossRefGoogle Scholar
  54. 54.
    Sanacora G, Kendell SF, Levin Y, Simen AA, Fenton LR, Coric V, Krystal JH (2007) Preliminary evidence of riluzole efficacy in antidepressant-treated patients with residual depressive symptoms. Biol Psychiatry 61: 822–825PubMedCrossRefGoogle Scholar
  55. 55.
    Zarate CA Jr, Payne JL, Quiroz JA, Sporn J, Denicoff KD, Luckenbaugh DA, Chandra PS, Charney DS, Manji HK (2004) An open-label trial of riluzole in patients with treatment-resistant major depression. Am J Psychiatry 161: 171–174PubMedCrossRefGoogle Scholar
  56. 56.
    Zarate CA Jr, Quiroz JA, Singh J, Denicoff KD, De Jesus G, Luckenbaugh DA, Charney DS, Manji HK (2005) An open-label trial of the glutamate-modulating agent riluzole in combination with lithium for the treatment of bipolar depression. Biol Psychiatry 57: 430–432PubMedCrossRefGoogle Scholar
  57. 57.
    Lourenco Da Silva A, Hoffmann A, Dietrich MO, Dall’Igna OP, Souza DO, Lara DR (2003) Effect of riluzole on MK-801 and amphetamine-induced hyperlocomotion. Neuropsychobiology 48: 27–30CrossRefGoogle Scholar
  58. 58.
    Moryl E, Danysz W, Quack G (1993) Potential antidepressive properties of amantadine, memantine and bifemelane. Pharmacol Toxicol 72: 394–397PubMedCrossRefGoogle Scholar
  59. 59.
    Rogoz Z, Skuza G, Maj J, Danysz W (2002) Synergistic effect of uncompetitive NMDA receptor antagonists and antidepressant drugs in the forced swimming test in rats. Neuropharmacology 42: 1024–1030PubMedCrossRefGoogle Scholar
  60. 60.
    Zarate CA Jr, Singh JB, Quiroz JA, De Jesus G, Denicoff KD, Luckenbaugh DA, Manji HK, Charney DS (2006) A double-blind, placebo-controlled study of memantine in the treatment of major depression. Am J Psychiatry 163: 153–155PubMedCrossRefGoogle Scholar
  61. 61.
    Teng CT, Demetrio FN (2006) Memantine may acutely improve cognition and have a mood stabilizing effect in treatment-resistant bipolar disorder. Rev Bras Psiquiatr 28: 252–254PubMedCrossRefGoogle Scholar
  62. 62.
    Berman RM, Cappiello A, Anand A, Oren DA, Heninger GR, Charney DS, Krystal JH (2000) Antidepressant effects of ketamine in depressed patients. Biol Psychiatry 47: 351–354PubMedCrossRefGoogle Scholar
  63. 63.
    Zarate CA Jr, Singh JB, Carlson PJ, Brutsche NE, Ameli R, Luckenbaugh DA, Charney DS, Manji HK (2006) A randomized trial of an N-methyl-D-aspartate antagonist in treatment-resistant major depression. Arch Gen Psychiatry 63: 856–864PubMedCrossRefGoogle Scholar
  64. 64.
    Maeng S, Zarate CA Jr, Du J, Schloesser RJ, McCammon J, Chen G, Manji HK (2008) Cellular mechanisms underlying the antidepressant effects of ketamine: role of alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptors. Biol Psychiatry 63: 349–352PubMedCrossRefGoogle Scholar
  65. 65.
    Black MD (2005) Therapeutic potential of positive AMPA modulators and their relationship to AMPA receptor subunits. A review of preclinical data. Psychopharmacology (Berl) 179: 154–163CrossRefGoogle Scholar
  66. 66.
    Du J, Quiroz JA, Yuan P, Zarate CA Jr, Manji HK (2004) Bipolar disorder: involvement of sig-naling cascades and AMPA receptor trafficking at synapses. Neuron Glia Biol 1: 231–243PubMedCrossRefGoogle Scholar
  67. 67.
    Du J, Gray NA, Falke C, Chen W, Yuan P, Szabo ST, Einat H, Manji HK (2004) Modulation of synaptic plasticity by antimanic agents: the role of AMPA glutamate receptor subunit 1 synaptic expression. J Neurosci 24: 6578–6589PubMedCrossRefGoogle Scholar
  68. 68.
    Quiroz JA, Singh J, Gould TD, Denicoff KD, Zarate CA Jr, Manji HK (2004) Emerging experimental therapeutics for bipolar disorder: clues from the molecular pathophysiology. Mol Psychiatry 9: 756–776PubMedCrossRefGoogle Scholar
  69. 69.
    Brown ES, Bobadilla L, Rush AJ (2001) Ketoconazole in bipolar patients with depressive symptoms: a case series and literature review. Bipolar Disord 3: 23–29PubMedCrossRefGoogle Scholar
  70. 70.
    Raven PW, O’Dwyer AM, Taylor NF, Checkley SA (1996) The relationship between the effects of metyrapone treatment on depressed mood and urinary steroid profiles. Psychoneuroendocrinology 21: 277–286PubMedCrossRefGoogle Scholar
  71. 71.
    Wolkowitz OM, Reus VI, Manfredi F, Ingbar J, Brizendine L, Weingartner H (1993) Ketoconazole administration in hypercortisolemic depression. Am J Psychiatry 150: 810–812PubMedGoogle Scholar
  72. 72.
    Young AH, Gallagher P, Watson S, Del-Estal D, Owen BM, Ferrier IN (2004) Improvements in neurocognitive function and mood following adjunctive treatment with mifepristone (RU-486) in bipolar disorder. Neuropsychopharmacology 29: 1538–1545PubMedCrossRefGoogle Scholar
  73. 73.
    Carroll BJ, Rubin RT (2008) Mifepristone in psychotic depression? Biol Psychiatry 63: E1PubMedCrossRefGoogle Scholar
  74. 74.
    Rothschild AJ (2003) Challenges in the treatment of depression with psychotic features. Biol Psychiatry 53: 680–690PubMedCrossRefGoogle Scholar
  75. 75.
    Gould TD, Manji HK (2004) The molecular medicine revolution and psychiatry: bridging the gap between basic neuroscience research and clinical psychiatry. J Clin Psychiatry 65: 598–604PubMedCrossRefGoogle Scholar
  76. 76.
    Gould TD, Manji HK (2005) Glycogen synthase kinase-3: a putative molecular target for lithium mimetic drugs. Neuropsychopharmacology 30: 1223–1237PubMedGoogle Scholar
  77. 77.
    Gould TD, Einat H, Bhat R, Manji HK (2004) AR-A014418, a selective GSK-3 inhibitor, produces antidepressant-like effects in the forced swim test. Int J Neuropsychopharmacol 7: 387–390PubMedCrossRefGoogle Scholar
  78. 78.
    Gould TD, Zarate CA Jr, Manji HK (2004) Glycogen synthase kinase-3: a target for novel bipolar disorder treatments. J Clin Psychiatry 65: 10–21PubMedGoogle Scholar
  79. 79.
    Myint AM, Steinbusch HW, Goeghegan L, Luchtman D, Kim YK, Leonard BE (2007) Effect of the COX-2 inhibitor celecoxib on behavioural and immune changes in an olfactory bulbectomised rat model of depression. Neuroimmunomodulation 14: 65–71PubMedCrossRefGoogle Scholar
  80. 80.
    Muller N, Schwarz MJ, Dehning S, Douhe A, Cerovecki A, Goldstein-Muller B, Spellman I, Hetzel G, Maino K, Kleindienst N et al (2006) The cyclooxygenase-2 inhibitor celecoxib has therapeutic effects in major depression: results of a double-blind, randomized, placebo controlled, add-on pilot study to reboxetine. Mol Psychiatry 11: 680–684PubMedCrossRefGoogle Scholar
  81. 81.
    Nery FG, Monkul ES, Hatch JP, Fonseca M, Zunta-Soares GB, Frey BN, Bowden CL, Soares JC (2008) Celecoxib as an adjunct in the treatment of depressive or mixed episodes of bipolar disorder: a double-blind, randomized, placebo-controlled study. Hum Psychopharmacol 23: 87–94PubMedCrossRefGoogle Scholar
  82. 82.
    Velentgas P, West W, Cannuscio CC, Watson DJ, Walker AM (2006) Cardiovascular risk of selective cyclooxygenase-2 inhibitors and other non-aspirin non-steroidal anti-inflammatory medications. Pharmacoepidemiol Drug Saf 15: 641–652PubMedCrossRefGoogle Scholar
  83. 83.
    Roitman S, Green T, Osher Y, Karni N, Levine J (2007) Creatine monohydrate in resistant depression: a preliminary study. Bipolar Disord 9: 754–758PubMedCrossRefGoogle Scholar
  84. 84.
    Zarate CA Jr, Manji HK (2008) Bipolar disorder: candidate drug targets. Mt Sinai J Med 75: 226–247PubMedCrossRefGoogle Scholar
  85. 85.
    Zarate CA Jr, Singh J, Carlson PJ, Quiroz JA, Jolkovsky L, Luckenbaugh DA, Manji HK (2007) Efficacy of a protein kinase C inhibitor (tamoxifen) in the treatment of acute mania: a pilot study. Bipolar Disord 9: 561–570PubMedCrossRefGoogle Scholar
  86. 86.
    Wolkowitz OM, Reus VI, Keebler A, Nelson N, Friedland M, Brizendine L, Roberts E (1999) Double-blind treatment of major depression with dehydroepiandrosterone. Am J Psychiatry 156: 646–649PubMedGoogle Scholar

Copyright information

© Birkhäuser Verlag/Switzerland 2009

Authors and Affiliations

  • Carlos A. ZarateJr
    • 1
  • Husseini K. Manji
    • 1
  1. 1.Laboratory of Molecular Pathophysiology & Experimental Therapeutics, Mood and Anxiety Disorders Research ProgramNational Institute of Mental Health, National Institutes of HealthBethesdaUSA

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