nach oben

Current Behavioral Neuroscience Reports

Erschienen in:

01.03.2018 | Mood and Anxiety Disorders (C Harmer, Section Editor)

Rapid-Acting Antidepressants: Mechanistic Insights and Future Directions

verfasst von: Danielle M. Gerhard, Ronald S. Duman

Erschienen in: Current Behavioral Neuroscience Reports | Ausgabe 1/2018

Einloggen, um Zugang zu erhalten

Abstract

Purpose of Review

Ketamine produces rapid (within hours) antidepressant actions, even in patients considered treatment resistant, and even shows promise for suicidal ideation. Here, we review current research on the molecular and cellular mechanisms of ketamine and other novel rapid-acting antidepressants, and briefly explore gender differences in the pathophysiology and treatment of MDD.

Recent Findings

Ketamine, an NMDA receptor antagonist, increases BDNF release and synaptic connectivity, opposing the deficits caused by chronic stress and depression. Efforts are focused on the development of novel rapid agents that produce similar synaptic and rapid antidepressant actions, but without the side effects of ketamine. The impact of gender on the response to ketamine and other rapid-acting antidepressants is in early stages of investigation.

Summary

The discovery that ketamine produces rapid therapeutic actions for depression and suicidal ideation represents a major breakthrough and much needed alternative to currently available medications. However, novel fast acting agents with fewer side effects are needed, as well as elucidation of the efficacy of these rapid-acting antidepressants for depression in women.

Kessler RC, Chiu WT, Demler O, Walters EE. Prevalence, severity, and comorbidity of 12-Month DSM-IV disorders in the National Comorbidity Survey Replication. Arch Gen Psychiatry. 2005;62(6):617. Available from: http://archpsyc.jamanetwork.com/article.aspx?doi=10.1001/archpsyc.62.6.617 CrossRefPubMedPubMedCentral

Kessler RC. The costs of depression. Psychiatr Clin N Am. 2012;35(1):1–14. https://doi.org/10.1016/j.psc.2011.11.005.CrossRef

Murray CJL, Atkinson C, Bhalla K, Birbeck G, Burstein R, Chou D, et al. The state of US health, 1990-2010: burden of diseases, injuries, and risk factors. JAMA. 2013;310(6):591–608. Available from: http://jama.jamanetwork.com/article.aspx?doi=10.1001/jama.2013.13805 CrossRefPubMed

Simon GE. Social and economic burden of mood disorders. Biol Psychiatry. 2003;54(3):208–15.CrossRefPubMed

WHO. WHO | Depression [Internet]. Who. 2017. Available from: http://www.who.int/mediacentre/factsheets/fs369/en/

Trivedi MH, Rush AJ, Wisniewski SR, Nierenberg AA, Warden D, Ritz L, et al. Evaluation of outcomes with citalopram for depression using measurement-based care in STAR*D: implications for clinical practice. Am J Psychiatry. 2006;163(1):28–40. https://doi.org/10.1176/appi.ajp.163.1.28.CrossRefPubMed

CDC. National Violent Death Reporting System [Internet]. 2015. Available from: https://www.cdc.gov/violenceprevention/nvdrs/index.html

Hedegaard H, Warner M, Curtin SC. Increase in suicide in the United States, 1999–2014. NCHS Data Brief. 2016;241:1–8. Available from: https://www.cdc.gov/nchs/data/databriefs/db241.pdf

Seney ML, Chang LC, Oh H, Wang X, Tseng GC, Lewis DA, et al. The role of genetic sex in affect regulation and expression of GABA-related genes across species. Front Psychiatry. 2013;4(SEP) https://doi.org/10.3389/fpsyt.2013.00104.

10.

Undurraga J, Baldessarini RJ. Randomized, placebo-controlled trials of antidepressants for acute major depression: thirty-year meta-analytic review. Neuropsychopharmacology. 2012;37(4):851–64. Available from: http://www.nature.com/doifinder/10.1038/npp.2011.306 CrossRefPubMed

11.

Berman RM, Cappiello A, Anand A, D a O, Heninger GR, Charney DS, et al. Antidepressant effects of ketamine in depressed patients. Soc Biol Psychiatry. 2000;47(4):351–4. https://doi.org/10.1016/S0006-3223(99)00230-9.CrossRef

12.

Zarate CA, Singh JB, Carlson PJ, Brutsche NE, Ameli R, Luckenbaugh DA, et al. A randomized trial of an N-methyl-D-aspartate antagonist in treatment-resistant major depression. Arch Gen Psychiatry. 2006;63(8):856. Available from: http://archpsyc.jamanetwork.com/article.aspx?doi=10.1001/archpsyc.63.8.856 CrossRefPubMed

13.

Duman RS, Aghajanian GK. Synaptic dysfunction in depression: potential therapeutic targets. Science. 2012;338(6103):68–72. Available from: http://www.ncbi.nlm.nih.gov/pubmed/23042884 CrossRefPubMedPubMedCentral

14.

Savitz J, Drevets WC. Bipolar and major depressive disorder: neuroimaging the developmental-degenerative divide. Neurosci Biobehav Rev. 2009;33(5):699–771. https://doi.org/10.1016/j.neubiorev.2009.01.004.CrossRefPubMedPubMedCentral

15.

Li N, Lee B, Liu R-J, Banasr M, Dwyer JM, Iwata M, et al. mTOR-dependent synapse formation underlies the rapid antidepressant effects of NMDA antagonists. Science (80- ). 2010;329(5994):959–64. Available from: http://www.sciencemag.org/cgi/doi/10.1126/science.1190287 CrossRef

16.

Li N, Liu RJ, Dwyer JM, Banasr M, Lee B, Son H, et al. Glutamate N-methyl-D-aspartate receptor antagonists rapidly reverse behavioral and synaptic deficits caused by chronic stress exposure. Biol Psychiatry. 2011;69(8):754–61. https://doi.org/10.1016/j.biopsych.2010.12.015.CrossRefPubMedPubMedCentral

17.

Kang HJ, Voleti B, Hajszan T, Rajkowska G, Stockmeier CA, Licznerski P, et al. Decreased expression of synapse-related genes and loss of synapses in major depressive disorder. Nat Med. 2012;18(9):1413–7. Available from: http://www.nature.com/doifinder/10.1038/nm.2886 CrossRefPubMedPubMedCentral

18.

Treadway MT, Waskom ML, Dillon DG, Holmes AJ, Park MTM, Chakravarty MM, et al. Illness progression, recent stress, and morphometry of hippocampal subfields and medial prefrontal cortex in major depression. Biol Psychiatry. 2015;77(3):285–94. https://doi.org/10.1016/j.biopsych.2014.06.018.CrossRefPubMed

19.

Liston C, Miller MM, Goldwater DS, Radley JJ, Rocher AB, Hof PR, et al. Stress-induced alterations in prefrontal cortical dendritic morphology predict selective impairments in perceptual attentional set-shifting. J Neurosci. 2006;26(30):7870–4. Available from: http://www.jneurosci.org/cgi/doi/10.1523/JNEUROSCI.1184-06.2006 CrossRefPubMed

20.

Liu R-J, Aghajanian GK. Stress blunts serotonin- and hypocretin-evoked EPSCs in prefrontal cortex: role of corticosterone-mediated apical dendritic atrophy. Proc Natl Acad Sci U S A. 2008;105(1):359–64. Available from: http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=2224217&tool=pmcentrez&rendertype=abstract. https://doi.org/10.1073/pnas.0706679105.CrossRefPubMedPubMedCentral

21.

Shansky RM, Morrison JH. Stress-induced dendritic remodeling in the medial prefrontal cortex: effects of circuit, hormones and rest. Brain Res. 2009;1293:108–13. https://doi.org/10.1016/j.brainres.2009.03.062.CrossRefPubMedPubMedCentral

22.

Ota KT, Liu R-J, Voleti B, Maldonado-Aviles JG, Duric V, Iwata M, et al. REDD1 is essential for stress-induced synaptic loss and depressive behavior. Nat Med. 2014;20(5):531–5. Available from: http://www.nature.com/doifinder/10.1038/nm.3513 CrossRefPubMedPubMedCentral

23.

Colzato LS, Van der Does AJW, Kouwenhoven C, Elzinga BM, Hommel B. BDNF Val66Met polymorphism is associated with higher anticipatory cortisol stress response, anxiety, and alcohol consumption in healthy adults. Psychoneuroendocrinology. 2011;36(10):1562–9. https://doi.org/10.1016/j.psyneuen.2011.04.010.CrossRefPubMed

24.

Chen Z-Y, Jing D, Bath KG, Ieraci A, Khan T, Siao C-J, et al. Genetic variant BDNF (Val66Met) polymorphism alters anxiety-related behavior. Science (80- ). 2006;314(5796):140–3. Available from: http://www.sciencemag.org/cgi/doi/10.1126/science.1129663 CrossRef

25.

Liu RJ, Lee FS, Li XY, Bambico F, Duman RS, Aghajanian GK. Brain-derived neurotrophic factor Val66Met allele impairs basal and ketamine-stimulated synaptogenesis in prefrontal cortex. Biol Psychiatry. 2012;71(11):996–1005. https://doi.org/10.1016/j.biopsych.2011.09.030.CrossRefPubMed

26.

Egan MF, Kojima M, Callicott JH, Goldberg TE, Kolachana BS, Bertolino A, et al. The BDNF val66met polymorphism affects activity-dependent secretion of BDNF and human memory and hippocampal function. Cell. 2003;112(2):257–69. https://doi.org/10.1016/S0092-8674(03)00035-7.CrossRefPubMed

27.

Pattwell SS, Bath KG, Perez-Castro R, Lee FS, Chao MV, Ninan I. The BDNF Val66Met polymorphism impairs synaptic transmission and plasticity in the infralimbic medial prefrontal cortex. J Neurosci. 2012;32(7):2410–21. Available from: http://www.jneurosci.org/cgi/doi/10.1523/JNEUROSCI.5205-11.2012 CrossRefPubMedPubMedCentral

28.

Bath KG, Jing DQ, Dincheva I, Neeb CC, Pattwell SS, Chao MV, et al. BDNF Val66Met impairs fluoxetine-induced enhancement of adult hippocampus plasticity. Neuropsychopharmacology. 2012;37(5):1297–304. Available from: http://www.nature.com/doifinder/10.1038/npp.2011.318 CrossRefPubMedPubMedCentral

29.

Farrant M, Nusser Z. Variations on an inhibitory theme: phasic and tonic activation of GABAA receptors. Nat Rev Neurosci. 2005;6(3):215–29. Available from: http://www.nature.com/doifinder/10.1038/nrn1625 CrossRefPubMed

30.

Croarkin PE, Levinson AJ, Daskalakis ZJ. Evidence for GABAergic inhibitory deficits in major depressive disorder. Neurosci Biobehav Rev. 2011;35(3):818–25. https://doi.org/10.1016/j.neubiorev.2010.10.002.CrossRefPubMed

31.

Hasler G, van der Veen J, Tumonis T, Meyers N, Shen J, Drevets W. Reduced prefrontal glutamate/glutamine and gamma-aminobutyric acid levels in major depression determined using magnetic resonance spectroscopy. Arch Gen Psychiatry. 2007;64(2):193–200. https://doi.org/10.1001/archpsyc.64.2.193.CrossRefPubMed

32.

Sanacora G, Mason GF, Rothman DL, Behar KL, Hyder F, Petroff OA, et al. Reduced cortical gamma-aminobutyric acid levels in depressed patients determined by proton magnetic resonance spectroscopy. Arch Gen Psychiatry. 1999;56(11):1043–7. https://doi.org/10.1001/archpsyc.56.11.1043.CrossRefPubMed

33.

Guilloux J-P, Douillard-Guilloux G, Kota R, Wang X, Gardier AM, Martinowich K, et al. Molecular evidence for BDNF- and GABA-related dysfunctions in the amygdala of female subjects with major depression. Mol Psychiatry. 2012;17(11):1130–42. Available from: http://www.nature.com/doifinder/10.1038/mp.2011.113 CrossRefPubMed

34.

Karolewicz B, Maciag D, O’Dwyer G, Stockmeier CA, Feyissa AM, Rajkowska G. Reduced level of glutamic acid decarboxylase-67 kDa in the prefrontal cortex in major depression. Int J Neuropsychopharmacol. 2010;13(4):411. Available from: https://academic.oup.com/ijnp/article-lookup/doi/10.1017/S1461145709990587 CrossRefPubMed

35.

Niciu MJ, Ionescu DF, Richards EM, Zarate CA. Glutamate and its receptors in the pathophysiology and treatment of major depressive disorder. J Neural Transm. 2014;121(8):907–24. https://doi.org/10.1007/s00702-013-1130-x.CrossRefPubMed

36.

Feyissa AM, Chandran A, Stockmeier CA, Karolewicz B. Reduced levels of NR2A and NR2B subunits of NMDA receptor and PSD-95 in the prefrontal cortex in major depression. Prog Neuro-Psychopharmacology Biol Psychiatry. 2009;33(1):70–5. https://doi.org/10.1016/j.pnpbp.2008.10.005.CrossRef

37.

Klumpers UMH, Veltman DJ, Drent ML, Boellaard R, Comans EFI, Meynen G, et al. Reduced parahippocampal and lateral temporal GABAA-[11C]flumazenil binding in major depression: preliminary results. Eur J Nucl Med Mol Imaging. 2010;37(3):565–74. Available from: http://www.ncbi.nlm.nih.gov/pubmed/19890631 CrossRefPubMed

38.

Choudary PV, Molnar M, Evans SJ, Tomita H, Li JZ, Vawter MP, et al. Altered cortical glutamatergic and GABAergic signal transmission with glial involvement in depression. Proc Natl Acad Sci. 2005;102(43):15653–8. Available from: http://www.pnas.org/cgi/doi/10.1073/pnas.0507901102 CrossRefPubMedPubMedCentral

39.

• Ren Z, Pribiag H, Jefferson SJ, Shorey M, Fuchs T, Stellwagen D, et al. Bidirectional homeostatic regulation of a depression-related brain state by gamma-aminobutyric Acidergic deficits and ketamine treatment. Biol Psychiatry. 2016;80(6):457–68. https://doi.org/10.1016/j.biopsych.2016.02.009. Study demonstrating how GABAergic deficits can alter glutamatergic synaptic transmission in the prefrontal cortex.

40.

Shen Q, Lal R, Luellen BA, Earnheart JC, Andrews AM, Luscher B. γ-aminobutyric acid-type a receptor deficits cause hypothalamic-pituitary-adrenal axis hyperactivity and antidepressant drug sensitivity reminiscent of melancholic forms of depression. Biol Psychiatry. 2010;68(6):512–20. https://doi.org/10.1016/j.biopsych.2010.04.024.CrossRefPubMedPubMedCentral

41.

Maeng S, Zarate CA, Du J, Schloesser RJ, McCammon J, Chen G, et al. Cellular mechanisms underlying the antidepressant effects of ketamine: role of alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptors. Biol Psychiatry. 2008;63(4):349–52. Available from: http://www.ncbi.nlm.nih.gov/pubmed/17643398 CrossRefPubMed

42.

Lepack AE, Fuchikami M, Dwyer JM, Banasr M, Duman RS. BDNF release is required for the behavioral actions of ketamine. Int J Neuropsychopharmacol. 2015;18(1):pyu033. https://doi.org/10.1093/ijnp/pyu033.CrossRef

43.

Koike H, Iijima M, Chaki S. Involvement of AMPA receptor in both the rapid and sustained antidepressant-like effects of ketamine in animal models of depression. Behav Brain Res. 2011;224(1):107–11. https://doi.org/10.1016/j.bbr.2011.05.035.CrossRefPubMed

44.

Singh JB, Fedgchin M, Daly E, Xi L, Melman C, De Bruecker G, et al. Intravenous Esketamine in adult treatment-resistant depression: a double-blind, double-randomization, placebo-controlled study. Biol Psychiatry. 2016;80(6):424–31. https://doi.org/10.1016/j.biopsych.2015.10.018.CrossRefPubMed

45.

Yang C, Shirayama Y, Zhang J, Ren Q, Yao W, Ma M, et al. R-ketamine: a rapid-onset and sustained antidepressant without psychotomimetic side effects. Transl Psychiatry. 2015;5(9):e632. Available from: http://www.nature.com/doifinder/10.1038/tp.2015.136 CrossRefPubMedPubMedCentral

46.

Yang C, Ren Q, Qu Y, Zhang JC, Ma M, Dong C, et al. Mechanistic target of rapamycin–independent antidepressant effects of (R)-ketamine in a social defeat stress model. Biol Psychiatry. 2018;83(1):18–28. https://doi.org/10.1016/j.biopsych.2017.05.016.CrossRefPubMed

47.

Zhang JC, Li SX, Hashimoto K. R (−)-ketamine shows greater potency and longer lasting antidepressant effects than S (+)-ketamine. Pharmacol Biochem Behav. 2014;116:137–41. https://doi.org/10.1016/j.pbb.2013.11.033.CrossRefPubMed

48.

Fukumoto K, Toki H, Iijima M, Hashihayata T, Yamaguchi J, Hasimoto K, et al. Antidepressant potential of (R)-ketamine in rodent models: comparison with (S)-ketamine. J Pharmacol Exp Ther. 2017;361(1):9–16. https://doi.org/10.1124/jpet.116.239228.CrossRefPubMed

49.

•• Zanos P, Moaddel R, Morris PJ, Georgiou P, Fischell J, Elmer GI, et al. NMDAR inhibition-independent antidepressant actions of ketamine metabolites. Nature. 2016;533(7604):481–6. Available from: http://www.nature.com/doifinder/10.1038/nature17998. First studying demonstrating the rapid antidepressant potential of the ketamine metabolite (2R,6R)-hydroxynorketamine (HNK) in mice.

50.

Zhang X l, Sullivan JA, Moskal JR, Stanton PK. A NMDA receptor glycine site partial agonist, GLYX-13, simultaneously enhances LTP and reduces LTD at Schaffer collateral-CA1 synapses in hippocampus. Neuropharmacology. 2008;55(7):1238–50.CrossRefPubMedPubMedCentral

51.

Burgdorf J, Zhang X, Nicholson KL, Balster RL, David Leander J, Stanton PK, et al. GLYX-13, a NMDA receptor glycine-site functional partial agonist, induces antidepressant-like effects without ketamine-like side effects. Neuropsychopharmacology. 2013;38(5):729–42. Available from: http://www.nature.com/doifinder/10.1038/npp.2012.246 CrossRefPubMedPubMedCentral

52.

Moskal JR, Burgdorf JS, Stanton PK, Kroes RA, Disterhoft JF, Burch RM, et al. The development of rapastinel (formerly GLYX-13); a rapid acting and long lasting antidepressant. Curr Neuropharmacol. 2017;15(1):47–56. https://doi.org/10.2174/1570159X14666160321122703.CrossRefPubMedPubMedCentral

53.

Lepack AE, Bang E, Lee B, Dwyer JM, Duman RS. Fast-acting antidepressants rapidly stimulate ERK signaling and BDNF release in primary neuronal cultures. Neuropharmacology. 2016;111:242–52. https://doi.org/10.1016/j.neuropharm.2016.09.011.CrossRefPubMedPubMedCentral

54.

Liu R-J, Duman C, Kato T, Hare B, Lopresto D, Bang E, et al. GLYX-13 produces rapid antidepressant responses with key synaptic and behavioral effects distinct from ketamine. Neuropsychopharmacology. 2017;42(6):1231–42. Available from: http://www.nature.com/doifinder/10.1038/npp.2016.202

55.

• Preskorn S, Macaluso M, Mehra DV, Zammit G, Moskal JR, Burch RM. Randomized proof of concept trial of GLYX-13, an N-methyl-D-aspartate receptor glycine site partial agonist, in major depressive disorder nonresponsive to a previous antidepressant agent. J Psychiatr Pract. 2015;21(2):140–9. Available from: http://content.wkhealth.com/linkback/openurl?sid=WKPTLP:landingpage&an=00131746-201503000-00006. https://doi.org/10.1097/01.pra.0000462606.17725.93. Study demonstrating the rapid and sustained antidepressant effects of the novel rapid-acting agent GLYX-13 in a clinical population CrossRefPubMed

56.

Drevets WC, Zarate CA, Furey ML. Antidepressant effects of the muscarinic cholinergic receptor antagonist scopolamine: a review. Biol Psychiatry. 2013;73(12):1156–63. https://doi.org/10.1016/j.biopsych.2012.09.031.CrossRefPubMed

57.

Furey ML, Drevets WC. Antidepressant efficacy of the antimuscarinic drug scopolamine. Arch Gen Psychiatry. 2006;63(10):1121. Available from: http://archpsyc.jamanetwork.com/article.aspx?doi=10.1001/archpsyc.63.10.1121 CrossRefPubMedPubMedCentral

58.

Furey ML, Khanna A, Hoffman EM, Drevets WC. Scopolamine produces larger antidepressant and antianxiety effects in women than in men. Neuropsychopharmacology. 2010;35(12):2479–88. https://doi.org/10.1038/npp.2010.131.CrossRefPubMedPubMedCentral

59.

Voleti B, Navarria A, Liu RJ, Banasr M, Li N, Terwilliger R, et al. Scopolamine rapidly increases mammalian target of rapamycin complex 1 signaling, synaptogenesis, and antidepressant behavioral responses. Biol Psychiatry. 2013;74(10):742–9. https://doi.org/10.1016/j.biopsych.2013.04.025.

60.

Ghosal S, Bang E, Yue W, Hare BD, Lepack AE, Girgenti MJ, et al. Activity-dependent brain-derived neurotrophic factor release is required for the rapid antidepressant actions of scopolamine. Biol Psychiatry. 2018; 83(1):29–37. https://doi.org/10.1016/j.biopsych.2017.06.017.CrossRefPubMed

61.

Wohleb ES, Wu M, Gerhard DM, Taylor SR, Picciotto MR, Alreja M, et al. GABA interneurons mediate the rapid antidepressant-like effects of scopolamine. J Clin Invest. 2016;126(7):2482–94. https://doi.org/10.1172/JCI85033.

62.

Moghaddam B, Adams B, Verma A, Daly D. Activation of glutamatergic neurotransmission by ketamine: a novel step in the pathway from NMDA receptor blockade to dopaminergic and cognitive disruptions associated with the prefrontal cortex. J Neurosci. 1997;17(8):2921–7.PubMed

63.

Duman RS, Aghajanian GK, Sanacora G, Krystal JH. Synaptic plasticity and depression: new insights from stress and rapid-acting antidepressants. Nat Med. 2016;22(3):238–49. Available from: http://www.nature.com/doifinder/10.1038/nm.4050 CrossRefPubMedPubMedCentral

64.

Gerhard DM, Wohleb ES, Duman RS. Emerging treatment mechanisms for depression: focus on glutamate and synaptic plasticity. Drug Discov Today. 2016;21(3):454–64. https://doi.org/10.1016/j.drudis.2016.01.016.CrossRefPubMedPubMedCentral

65.

Miller OH, Moran JT, Hall BJ. Two cellular hypotheses explaining the initiation of ketamine’s antidepressant actions: direct inhibition and disinhibition. Neuropharmacology. 2016;100:17–26. https://doi.org/10.1016/j.neuropharm.2015.07.028.CrossRefPubMed

66.

Freedman R. Further investigation of ketamine. Am J Psychiatr. 2016;173(8):761–2. https://doi.org/10.1176/appi.ajp.2016.16050581.CrossRefPubMed

67.

Newport DJ, Schatzberg AF, Nemeroff CB. Whither ketamine as an antidepressant: panacea or toxin? Depress Anxiety. 2016;33(8):685–8. Available from: http://doi.wiley.com/10.1002/da.22535 CrossRefPubMed

68.

Jaso B, Niciu M, Iadarola N, Lally N, Richards E, Park M, et al. Therapeutic modulation of glutamate receptors in major depressive disorder. Curr Neuropharmacol. 2016;15(1):57–70. Available from: http://www.eurekaselect.com/openurl/content.php?genre=article&issn=1570-159X&volume=15&issue=1&spage=57. https://doi.org/10.2174/1570159X14666160321123221.

69.

Preskorn SH, Baker B, Kolluri S, Menniti FS, Krams M, Landen JW. An innovative design to establish proof of concept of the antidepressant effects of the NR2B subunit selective N-methyl-D-aspartate antagonist, CP-101,606, in patients with treatment-refractory major depressive disorder. J Clin Psychopharmacol. 2008;28(6):631–7. Available from: http://content.wkhealth.com/linkback/openurl?sid=WKPTLP:landingpage&an=00004714-200812000-00008. https://doi.org/10.1097/JCP.0b013e31818a6cea.CrossRefPubMed

70.

Domino EF. Taming the ketamine tiger. Anesthesiology. 2010;113(3):678–86. https://doi.org/10.1097/ALN.0b013e3181ed09a2.PubMed

71.

Kuehner C. Why is depression more common among women than among men? Lancet Psychiatry. 2017;4(2):146–58. https://doi.org/10.1016/S2215-0366(16)30263-2.CrossRefPubMed

72.

Mazure CM, Jones DP. Twenty years and still counting: including women as participants and studying sex and gender in biomedical research. BMC Womens Health. 2015;15(1):94. Available from: http://bmcwomenshealth.biomedcentral.com/articles/10.1186/s12905-015-0251-9 CrossRefPubMedPubMedCentral

73.

Soldin OP, Mattison DR. Sex differences in pharmacokinetics and pharmacodynamics. Clin Pharmacokinet. 2009;48(3):143–57. https://doi.org/10.2165/00003088-200948030-00001.CrossRefPubMedPubMedCentral

74.

Khan A, Brodhead AE, Schwartz KA, Kolts RL, Brown WA. Sex differences in antidepressant response in recent antidepressant clinical trials. J Clin Psychopharmacol. 2005;25(4):318–24. Available from: http://content.wkhealth.com/linkback/openurl?sid=WKPTLP:landingpage&an=00004714-200508000-00005. https://doi.org/10.1097/01.jcp.0000168879.03169.ce.CrossRefPubMed

75.

Bangasser DA, Valentino RJ. Sex differences in stress-related psychiatric disorders: neurobiological perspectives. Front Neuroendocrinol. 2014;35(3):303–19. https://doi.org/10.1016/j.yfrne.2014.03.008.CrossRefPubMedPubMedCentral

76.

Otte C, Gold SM, Penninx BW, Pariante CM, Etkin A, Fava M, et al. Major depressive disorder. Nat Rev Dis Prim. 2016;2:16065. Available from: http://www.nature.com/articles/nrdp201665 CrossRefPubMed

77.

•• Labonté B, Engmann O, Purushothaman I, Menard C, Wang J, Tan C, et al. Sex-specific transcriptional signatures in human depression. Nat Med. 2017;23(9):1102–11. Available from: http://www.nature.com/doifinder/10.1038/nm.4386. A major strength of this study is the translational experiments performed in mice. Using a viral mediated strategy to either downregulate Dusp6 or overexpress EMX1 in female and male mice, respectively, the mice exhibited increased susceptibility to chronic variable stress (CVS) and partially reproduced the depressive behaviors seen with CVS.

78.

Duman RS. Sex-specific disease-associated modules for depression. Nat Med. 2017;23(9):1015–7. Available from: http://www.nature.com/doifinder/10.1038/nm.4391 CrossRefPubMedPubMedCentral

79.

Northoff G, Walter M, Schulte RF, Beck J, Dydak U, Henning A, et al. GABA concentrations in the human anterior cingulate cortex predict negative BOLD responses in fMRI. Nat Neurosci. 2007;10(12):1515–7. Available from: http://www.nature.com/doifinder/10.1038/nn2001

80.

Sequeira A, Mamdani F, Ernst C, Vawter MP, Bunney WE, Lebel V, et al. Global brain gene expression analysis links glutamatergic and GABAergic alterations to suicide and major depression. PLoS One. 2009;4(8):e6585. https://doi.org/10.1371/journal.pone.0006585.

81.

Luscher B, Shen Q, Sahir N. The GABAergic deficit hypothesis of major depressive disorder. Mol Psychiatry. 2011;16(4):383–406. Available from: http://www.nature.com/doifinder/10.1038/mp.2010.120 CrossRefPubMed

82.

Franceschelli A, Sens J, Herchick S, Thelen C, Pitychoutis PM. Sex differences in the rapid and the sustained antidepressant-like effects of ketamine in stress-naïve and “depressed” mice exposed to chronic mild stress. Neuroscience. 2015;290:49–60. https://doi.org/10.1016/j.neuroscience.2015.01.008.CrossRefPubMed

83.

• Sarkar A, Kabbaj M. Sex differences in effects of ketamine on behavior, spine density, and synaptic proteins in socially isolated rats. Biol Psychiatry. 2016;80(6):448–56. https://doi.org/10.1016/j.biopsych.2015.12.025. Study demonstrating sex differentiated responses to chronic social isolation and subsequent ketamine treatment.

84.

Bi R, Foy MR, Vouimba RM, Thompson RF, Baudry M. Cyclic changes in estradiol regulate synaptic plasticity through the MAP kinase pathway. Proc Natl Acad Sci U S A. 2001;98(23):13391–5. Available from: http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=60881&tool=pmcentrez&rendertype=abstract. https://doi.org/10.1073/pnas.241507698.CrossRefPubMedPubMedCentral

85.

Smith CC, McMahon LL. Estradiol-induced increase in the magnitude of long-term potentiation is prevented by blocking NR2B-containing receptors. J Neurosci. 2006;26(33):8517–22. Available from: http://www.ncbi.nlm.nih.gov/pubmed/16914677 CrossRefPubMed

86.

Smith CC, Vedder LC, LL MM. Estradiol and the relationship between dendritic spines, NR2B containing NMDA receptors, and the magnitude of long-term potentiation at hippocampal CA3-CA1 synapses. Psychoneuroendocrinology. 2009;34S1:S130–S142. https://doi.org/10.1016/j.psyneuen.2009.06.003.CrossRefPubMedCentral

87.

Carrier N, Kabbaj M. Sex differences in the antidepressant-like effects of ketamine. Neuropharmacology. 2013;70:27–34. https://doi.org/10.1016/j.neuropharm.2012.12.009.CrossRefPubMed

88.

Li C-SR, Zhang S, Hung C-C, Chen C-M, Duann J-R, Lin C-P, et al. Depression in chronic ketamine users: sex differences and neural bases. Psychiatry Res. 2017;269(April):1–8. https://doi.org/10.1016/j.pscychresns.2017.09.001.

89.

Wilkinson ST, Ballard ED, Bloch MH, Mathew SJ, Murrough JW, Feder A, et al. The effect of a single dose of intravenous ketamine on suicidal ideation: a systematic review and individual participant data meta-analysis. Am J Psychiatry. 2017; Available from: http://ajp.psychiatryonline.org/doi/10.1176/appi.ajp.2017.17040472

90.

Sibille E, French B. Biological substrates underpinning diagnosis of major depression. Int J Neuropsychopharmacol. 2013;16(8):1893–909. Available from: https://academic.oup.com/ijnp/article-lookup/doi/10.1017/S1461145713000436 CrossRefPubMedPubMedCentral

91.

Chekroud AM, Zotti RJ, Shehzad Z, Gueorguieva R, Johnson MK, Trivedi MH, et al. Cross-trial prediction of treatment outcome in depression: a machine learning approach. Lancet Psychiatry. 2016;3(3):243–50. https://doi.org/10.1016/S2215-0366(15)00471-X.

92.

Chekroud AM, Gueorguieva R, Krumholz HM, Trivedi MH, Krystal JH, McCarthy G. Reevaluating the efficacy and predictability of antidepressant treatments. JAMA Psychiatry. 2017;74(4):370. Available from: http://archpsyc.jamanetwork.com/article.aspx?doi=10.1001/jamapsychiatry.2017.0025–8.CrossRefPubMed

93.

Gueorguieva R, Chekroud AM, Krystal JH. Trajectories of relapse in randomised, placebo-controlled trials of treatment discontinuation in major depressive disorder: an individual patient-level data meta-analysis. Lancet Psychiatry. 2017;4(3):230–7. https://doi.org/10.1016/S2215-0366(17)30038-X.CrossRefPubMedPubMedCentral

Titel: Rapid-Acting Antidepressants: Mechanistic Insights and Future Directions
verfasst von: Danielle M. Gerhard
Ronald S. Duman
Publikationsdatum: 01.03.2018
Verlag: Springer International Publishing
Erschienen in: Current Behavioral Neuroscience Reports / Ausgabe 1/2018
Elektronische ISSN: 2196-2979
DOI: https://doi.org/10.1007/s40473-018-0139-8

Transcranial Direct Current Stimulation for the Treatment of Depression: a Review of the Candidate Mechanisms of Action

Mood and Anxiety Disorders (C Harmer, Section Editor)

Correction to: Monoamine Oxidase a in Antisocial Personality Disorder and Borderline Personality Disorder

Correction

Intrusive Memories of Trauma in the Laboratory: Methodological Developments and Future Directions

Open Access
Mood and Anxiety Disorders (C Harmer, Section Editor)

Current Understanding of the Neural Mechanisms of Dissociation in Borderline Personality Disorder

Open Access
Personality and Impulse Control Disorders (R Lee, Section Editor)

Pathways to Neuroprediction: Opportunities and Challenges to Prediction of Treatment Response in Depression

Mood and Anxiety Disorders (C Harmer, Section Editor)

The Cognitive Neuroscience of Psychological Treatment Action in Depression and Anxiety

Mood and Anxiety Disorders (C Harmer, Section Editor)

Kompaktes Leitlinien-Wissen Neurologie (Link öffnet in neuem Fenster)

Mit medbee Pocketcards schnell und sicher entscheiden.
Leitlinien-Wissen kostenlos und immer griffbereit auf ihrem Desktop, Handy oder Tablet.

Kostenlos registrieren

Neu im Fachgebiet Neurologie

Neuartige Antikörpertherapie bremst MS über zwei Jahre hinweg

18.04.2025
AAN-Jahrestagung 2025
Nachrichten

Eine Therapie mit dem C40-Ligand-Blocker Frexalimab kann MS-Schübe und neue MRT-Läsionen über zwei Jahre hinweg verhindern. Dafür spricht die Auswertung einer offen fortgeführten Phase-2-Studie.

Positive Phase IIb-Studie zu mRNA-gestützter CAR-T bei Myasthenia gravis

17.04.2025
AAN-Jahrestagung 2025
Kongressbericht

Eine auf das B-Zell-Reifungsantigen gerichtete mRNA-basierte CAR-T-Zell-Therapie wurde jetzt in einer ersten Phase IIb-Studie zur Behandlung der generalisierten Myasthenia gravis mit Placebo verglichen.

Therapiestopp bei älteren MS-Kranken kann sich lohnen

17.04.2025
AAN-Jahrestagung 2025
Nachrichten

Eine Analyse aus Kanada bestätigt: Setzen ältere MS-Kranke die Behandlung mit Basistherapeutika ab, müssen sie kaum mit neuen Schüben und MRT-Auffälligkeiten rechnen.

Schadet Schichtarbeit dem Gehirn?

17.04.2025
AAN-Jahrestagung 2025
Kongressbericht

Eine große Registerstudie bestätigt, dass Schichtarbeit mit einem erhöhten Risiko für psychische und neurologische Erkrankungen einhergeht, sowie mit einer Volumenabnahme in Gehirnarealen, die für Depression, Angst und kognitive Funktionen relevant sind.

Update Neurologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.

Newsletter bestellen

Springer Medizin

Rapid-Acting Antidepressants: Mechanistic Insights and Future Directions

Abstract

Purpose of Review

Recent Findings

Summary

Weitere Artikel der Ausgabe 1/2018

Transcranial Direct Current Stimulation for the Treatment of Depression: a Review of the Candidate Mechanisms of Action

Correction to: Monoamine Oxidase a in Antisocial Personality Disorder and Borderline Personality Disorder

Intrusive Memories of Trauma in the Laboratory: Methodological Developments and Future Directions

Current Understanding of the Neural Mechanisms of Dissociation in Borderline Personality Disorder

Pathways to Neuroprediction: Opportunities and Challenges to Prediction of Treatment Response in Depression

The Cognitive Neuroscience of Psychological Treatment Action in Depression and Anxiety

Kompaktes Leitlinien-Wissen Neurologie (Link öffnet in neuem Fenster)

Neu im Fachgebiet Neurologie

Neuartige Antikörpertherapie bremst MS über zwei Jahre hinweg

Positive Phase IIb-Studie zu mRNA-gestützter CAR-T bei Myasthenia gravis

Therapiestopp bei älteren MS-Kranken kann sich lohnen

Schadet Schichtarbeit dem Gehirn?

Update Neurologie

Springer Medizin

Abstract

Purpose of Review

Recent Findings

Summary

Bitte loggen Sie sich ein, um Zugang zu diesem Inhalt zu erhalten