Hostname: page-component-848d4c4894-75dct Total loading time: 0 Render date: 2024-05-24T13:42:29.943Z Has data issue: false hasContentIssue false

Novel antidepressant drugs: Beyond monoamine targets

Published online by Cambridge University Press:  30 September 2021

Xenia Gonda
Affiliation:
Department of Psychiatry and Psychotherapy, Semmelweis University, Budapest, Hungary NAP-2-SE New Antidepressant Target Research Group, Hungarian Brain Research Program, Semmelweis University, Budapest, Hungary MTA-SE Neuropsychopharmacology and Neurochemistry Research Group, Hungarian Academy of Sciences, Semmelweis University, Budapest, Hungary
Peter Dome
Affiliation:
Department of Psychiatry and Psychotherapy, Semmelweis University, Budapest, Hungary Nyiro Gyula National Institute of Psychiatry and Addictions, Budapest, Hungary
Joanna C. Neill
Affiliation:
Division of Pharmacy and Optometry, University of Manchester, Manchester, United Kingdom Medical Psychedelics Working Group, Drug Science, Manchester, United Kingdom
Frank I. Tarazi*
Affiliation:
Department of Psychiatry and Neuroscience Program, Harvard Medical School, McLean Hospital, Belmont, Massachusetts, USA
*
* Author for correspondence: Frank I. Tarazi Email: ftarazi@hms.harvard.edu

Abstract

Treatment of major depressive disorder (MDD) including treatment-resistant depression (TRD) remains a major unmet need. Although there are several classes of dissimilar antidepressant drugs approved for MDD, the current drugs have either limited efficacy or are associated with undesirable side effects and withdrawal symptoms. The efficacy and side effects of antidepressant drugs are mainly attributed to their actions on different monoamine neurotransmitters (serotonin, norepinephrine, and dopamine). Development of new antidepressants with novel targets beyond the monoamine pathways may fill the unmet need in treatment of MDD and TRD. The recent approval of intranasal Esketamine (glutamatergic agent) in conjunction with an oral antidepressant for the treatment of adult TRD patients was the first step toward expanding beyond the monoamine targets. Several other glutamatergic (AXS-05, REL-1017, AV-101, SLS-002, AGN24175, and PCN-101) and GABAergic (brexanolone, zuranolone, and ganaxolone) drugs are currently in different stages of clinical development for MDD, TRD and other indications. The renaissance of psychedelic drugs and the emergence of preliminary positive clinical trial results with psilocybin, Ayahuasca, 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT), and lysergic acid diethylamide (LSD) may pave the way towards establishing this class of drugs as effective therapies for MDD, TRD and other neuropsychiatric disorders. Going beyond the monoamine targets appears to be an effective strategy to develop novel antidepressant drugs with superior efficacy, safety, and tolerability for the improved treatment of MDD and TRD.

Type
Review
Copyright
© The Author(s), 2021. Published by Cambridge University Press

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Malhi, GS, Mann, JJ. Depression. Lancet. 2018;392:22992312.CrossRefGoogle ScholarPubMed
Cosci, F, Mansueto, G, Fava, GA. Relapse prevention in recurrent major depressive disorder. A comparison of different treatment options based on clinical experience and a critical review of the literature. Int J Psychiatry Clin Pract. 2020;24:18.CrossRefGoogle Scholar
American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. 5th ed. Washington, DC: American Psychiatric Publishing; 2013.Google Scholar
Fava, M, Davidson, KG. Definition and epidemiology of treatment-resistant depression. Psychiatr Clin North Am. 1996;19:179200.CrossRefGoogle ScholarPubMed
Russell, JM, Hawkins, K, Ozminkowski, RJ, et al. The cost consequences of treatment-resistant depression. J Clin Psychiatry. 2004;65:341347.CrossRefGoogle ScholarPubMed
Cuijpers, P, Karyotaki, E, Eckshtain, D, et al. Psychotherapy for depression across different age groups: a systematic review and meta-analysis. JAMA Psychiatry. 2020;77(7):694702.Google ScholarPubMed
Cook, IA, Espinoza, R, Leuchter, AF. Neuromodulation for depression: invasive and noninvasive (deep brain stimulation, transcranial magnetic stimulation, trigeminal nerve stimulation). Neurosurg Clin N Am. 2014;25(1):103116.CrossRefGoogle ScholarPubMed
Dupuy, JM, Ostacher, MJ, Huffman, J, et al. A critical review of pharmacotherapy for major depressive disorder. Int J Neuropsychopharmacol. 2011;14(10):14171431.CrossRefGoogle ScholarPubMed
Nierenberg, AA. Current perspectives on the diagnosis and treatment of major depressive disorder. Am J Manag Care. 2001;7(Suppl 11):S353S366.Google ScholarPubMed
Baldessarini, RJ. Drug therapy of depression and anxiety disorders. In: Brunton, LL, Lazo, JS, Parker, KL, eds. Goodman and Gilman’s: The Pharmacological Basis of Therapeutics. 11th ed. New York: McGraw-Hill Press; 2005: 429459.Google Scholar
Taylor, C, Fricker, AD, Devi, LA, Gomes, I. Mechanisms of action of antidepressants: from neurotransmitter systems to signaling pathways. Cell Signal. 2005;17(5):549557.CrossRefGoogle ScholarPubMed
Harmer, CJ, Duman, RS, Cowen, PJ. How do antidepressants work? New perspectives for refining future treatment approaches. Lancet Psychiatry. 2017;4:409418.CrossRefGoogle ScholarPubMed
Hu, XH, Bull, SA, Hunkeler, EM, et al. Incidence and duration of side effects and those rated as bothersome with selective serotonin reuptake inhibitor treatment for depression: patient report vs physician estimate. J Clin Psychiatry. 2004;65:959965.CrossRefGoogle Scholar
Thase, ME, Haight, BR, Richard, N, et al. Remission rates following antidepressant therapy with bupropion or selective serotonin reuptake inhibitors: meta-analysis of original data from 7 randomized controlled trials. J Clin Psychiatry. 2005;66:974981.CrossRefGoogle ScholarPubMed
Sir, A, D’Souza, RF, Uguz, S, et al. Randomized trial of sertraline versus venlafaxine XR in major depression: efficacy and discontinuation symptoms. J Clin Psychiatry. 2005;66:13121320.Google ScholarPubMed
Sanacora, G, Treccani, G, Popoli, M. Towards a glutamate hypothesis of depression: an emerging frontier of neuropsychopharmacology for mood disorders. Neuropharmacology. 2012;62:6377.CrossRefGoogle ScholarPubMed
Hashimoto, K, Sawa, A, Iyo, M. Increased levels of glutamate in brains from patients with mood disorders. Biol Psychiatry. 2007;62:13101316.CrossRefGoogle ScholarPubMed
Sanacora, G, Zarate, CA, Krystal, JH, Manji, HK. Targeting the glutamatergic system to develop novel, improved therapeutics for mood disorders. Nat Rev Drug Discov. 2008;7:426437.CrossRefGoogle ScholarPubMed
Beneyto, M, Kristiansen, LV, Oni-Orisan, A, et al. Abnormal glutamate receptor expression in the medial temporal lobe in schizophrenia and mood disorders. Neuropsychopharmacol. 2007;32:18881902.CrossRefGoogle ScholarPubMed
Koolschijn, PC, van Haren, NE, Lensvelt-Mulders, GJ, et al. Brain volume abnormalities in major depressive disorder: a meta-analysis of magnetic resonance imaging studies. Hum Brain Mapp. 2009;30:37193735.CrossRefGoogle ScholarPubMed
Musazzi, L, Treccani, G, Popoli, M. Glutamate hypothesis of depression and its consequences for antidepressant treatments. Expert Rev Neurother. 2012;12:11691172.CrossRefGoogle ScholarPubMed
Hashimoto, K. Rapid-acting antidepressant ketamine, its metabolites and other candidates: a historical overview and future perspective. Psychiatry Clin Neurosci. 2019;73:613627.CrossRefGoogle ScholarPubMed
De Berardis, D, Tomasetti, C, Pompili, M, et al. An update on glutamatergic system in suicidal depression and on the role of esketamine. Curr Top Med Chem. 2020;20:554584.CrossRefGoogle ScholarPubMed
Hausman, C, Meffert, BN, Mosich, MK, Heinz, AJ. Impulsivity and cognitive flexibility as neuropsychological markers for suicidality: a multi-modal investigation among military veterans with alcohol use disorder and PTSD. Arch Suicide Res. 2020;24:313326.CrossRefGoogle ScholarPubMed
Krystal, JH, Sanacora, G, Duman, RS. Rapid-acting glutamatergic antidepressants: the path to ketamine and beyond. Biol Psychiatry. 2013;73:11331141.CrossRefGoogle ScholarPubMed
Duman, RS, Aghajanian, GK, Sanacora, G, Krystal, JH. Synaptic plasticity and depression: new insights from stress and rapid-acting antidepressants. Nat Med. 2016;22:238249.CrossRefGoogle ScholarPubMed
Zanos, P, Gould, TD. Mechanisms of ketamine action as an antidepressant. Mol Psychiatry. 2018;23:801811.CrossRefGoogle ScholarPubMed
Yang, C, Yang, J, Luo, A, Hashimoto, K. Molecular and cellular mechanisms underlying the antidepressant effects of ketamine enantiomers and its metabolites. Transl Psychiatry. 2019;9:280.CrossRefGoogle ScholarPubMed
Abdallah, CG, Averill, LA, Gueorguieva, R, et al. Modulation of the antidepressant effects of ketamine by the mTORC1 inhibitor rapamycin. Neuropsychopharmacology. 2020;45(6):990997.CrossRefGoogle ScholarPubMed
Williams, NR, Heifets, BD, Blasey, C, et al. Attenuation of antidepressant effects of ketamine by opioid receptor antagonism. Am J Psychiatry. 2018;175(12):12051215.CrossRefGoogle ScholarPubMed
Berman, RM, Cappiello, A, Anand, A, et al. Antidepressant effects of ketamine in depressed patients. Biol Psychiatry. 2000;47:351354.CrossRefGoogle ScholarPubMed
Zarate, CA, Singh, JB, Carlson, PJ, et al. A randomized trial of an N-methyl-d-aspartate antagonist in treatment-resistant major depression. Arch Gen Psychiatry. 2006;63:856864.CrossRefGoogle ScholarPubMed
Zarate, CA, Brutsche, NE, Ibrahim, L, et al. Replication of ketamine’s antidepressant efficacy in bipolar depression: a randomized controlled add-on trial. Biol Psychiatry. 2012;71:939946.CrossRefGoogle ScholarPubMed
Wilkinson, ST, Ballard, ED, Bloch, MH, 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. 2018;175:150158.CrossRefGoogle ScholarPubMed
Kadriu, B, Musazzi, L, Henter, ID, et al. Glutamatergic neurotransmission: pathway to developing novel rapid-acting antidepressant treatments. Int J Neuropsychopharmacol. 2019;22:119135.CrossRefGoogle ScholarPubMed
Kryst, J, Kawalec, P, Pilc, A. Efficacy and safety of intranasal esketamine for the treatment of major depressive disorder. Expert Opin Pharmacother. 2020;21:920.CrossRefGoogle ScholarPubMed
Correia-Melo, FS, Leal, GC, Carvalho, MS, et al. Comparative study of esketamine and racemic ketamine in treatment-resistant depression: protocol for a non-inferiority clinical trial. Medicine (Baltimore). 2018;97:e12414.CrossRefGoogle ScholarPubMed
Singh, JB, Fedgchin, M, Daly, EJ, et al. A double-blind, randomized, placebo-controlled, dose-frequency study of intravenous ketamine in patients with treatment-resistant depression. Am J Psychiatry. 2016;173:816826.Google ScholarPubMed
Daly, EJ, Singh, JB, Fedgchin, M, et al. Efficacy and safety of intranasal esketamine adjunctive to oral antidepressant therapy in treatment-resistant depression: a randomized clinical trial. JAMA Psychiatry. 2018;75:139148.CrossRefGoogle ScholarPubMed
Daly, EJ, Trivedi, MH, Janik, A, et al. Efficacy of esketamine nasal spray plus oral antidepressant treatment for relapse prevention in patients with treatment-resistant depression: a randomized clinical trial. JAMA Psychiatry. 2019;76(9):893903.CrossRefGoogle ScholarPubMed
Canuso, CM, Singh, JB, Fedgchin, M, et al. Efficacy and safety of intranasal esketamine for the rapid reduction of symptoms of depression and suicidality in patients at imminent risk for suicide: results of a double-blind, randomized, placebo-controlled study. Am J Psychiatry. 2018;175:620630.CrossRefGoogle ScholarPubMed
Fedgchin, M, Trivedi, M, Daly, EJ, et al. Efficacy and safety of fixed-dose esketamine nasal spray combined with a new oral antidepressant in treatment-resistant depression: results of a randomized, double-blind, active-controlled study (TRANSFORM-1). Int J Neuropsychopharmacol. 2019;22:616630.CrossRefGoogle ScholarPubMed
Ochs-Ross, R, Daly, EJ, Zhang, Y, et al. Efficacy and safety of esketamine nasal spray plus an oral antidepressant in elderly patients with treatment-resistant depression-TRANSFORM-3. Am J Geriatr Psychiatry. 2020;28:121141.Google ScholarPubMed
Wajs, E, Aluisio, L, Holder, R, et al. Esketamine nasal spray plus oral antidepressant in patients with treatment-resistant depression: assessment of long-term safety in a Phase 3, open-label study (SUSTAIN-2). J Clin Psychiatry. 2020;81(3):19m12891.CrossRefGoogle Scholar
Bahr, R, Lopez, A, Rey, JA. Intranasal esketamine (Spravato™) for use in treatment-resistant depression in conjunction with an oral antidepressant. P T. 2019;44(6):340375.Google ScholarPubMed
Nguyen, L, Thomas, KL, Lucke-Wold, BP, et al. Dextromethorphan: an update on its utility for neurological and neuropsychiatric disorders. Pharmacol Ther. 2016;159:122.CrossRefGoogle ScholarPubMed
Axsome Therpaeutics Press Release. AXS-05 Achieves Primary Endpoint in Phase 2 Trial in Major Depressive Disorder; January 7, 2019.Google Scholar
Axsome Therpaeutics Press Release. Axsome Therapeutics Announces AXS-05 Achieves Primary Endpoint in GEMINI Phase 3 Trial in Major Depressive Disorder; December 16, 2019.Google Scholar
Axsome Therpaeutics Press Release. Axsome Therapeutics Announces Positive Results from the COMET-SI Trial of AXS-05 in Patients with Major Depressive Disorder Who have suicidal Ideation; December 8, 2020.Google Scholar
Fogaca, MV, Fukumoto, K, Franklin, T, et al. N-methyl-d-aspartate receptor antagonist d-methadone produces rapid, mTORC1-dependent antidepressant effects. Neuropsychopharmacology. 2019;44:22302238.CrossRefGoogle ScholarPubMed
Bernstein, G, Davis, K, Mills, C, et al. Characterization of the safety and pharmacokinetic profile of d-methadone, a novel N-methyl-d-aspartate receptor antagonist in healthy, opioid-naive subjects: results of two phase 1 studies. J Clin Psychopharmacol. 2019;39:226237.CrossRefGoogle ScholarPubMed
Gorman, AL, Elliott, KJ, Inturrisi, CE. The d- and l-isomers of methadone bind to the non-competitive site on the N-methyl-d-aspartate (NMDA) receptor in rat forebrain and spinal cord. Neurosci Lett. 1997;223:58.CrossRefGoogle Scholar
Relmada Therpaeutics Press Release. Relmada Therapeutics Announces Top-Line Results from REL-1017 Phase 2 Study in Individuals with Treatment Resistant Depression; October 15, 2019.Google Scholar
Relmada Therpaeutics Press Release. Relmada Therapeutics Announces Initiation of Second Pivotal Phase 3 Study of REL-1017 as Adjunctive Treatment for Patients with Major Depressive Disorder; April 1, 2021.Google Scholar
Zanos, P, Piantadosi, SC, Wu, HQ, et al. The prodrug 4-chlorokynurenine causes ketamine-like antidepressant effects, but not side effects, by NMDA/GlycineB-site inhibition. J Pharmacol Exp Ther. 2015;355(1):7685.CrossRefGoogle Scholar
VistaGen Therapeutics Press Release. VistaGen Reports Topline Phase 2 Results for AV-101 as an Adjunctive Treatment of Major Depressive Disorder; November 14, 2019.Google Scholar
Lapidus, KA, Levitch, CF, Perez, AM, et al. A randomized controlled trial of intranasal ketamine in major depressive disorder. Biol Psychiatry. 2014;76(12):970976.CrossRefGoogle ScholarPubMed
Burgdorf, J, Zhang, XL, Nicholson, KL, 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):729742.CrossRefGoogle ScholarPubMed
Burgdorf, J, Zhang, XL, Weiss, C, et al. The long-lasting antidepressant effects of rapastinel (GLYX-13) are associated with a metaplasticity process in the medial prefrontal cortex and hippocampus. Neuroscience. 2015;308:202211.CrossRefGoogle ScholarPubMed
Preskorn, S, Macaluso, M, Mehra, DO, et al. 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):140149.CrossRefGoogle ScholarPubMed
Allergan Press Release. Allergan Announces Phase 3 Results for Rapastinel as an Adjunctive Treatment of Major Depressive Disorder (MDD); March 6, 2019.Google Scholar
Pothula, S, Liu, R-J, Wu, M, et al. Positive modulation of NMDA receptors by AGN-241751 exerts rapid antidepressant-like effects via excitatory neurons. Neuropsychopharmacology. 2021;46:799808.CrossRefGoogle ScholarPubMed
Yang, C, Shirayama, Y, Zhang, J-C, et al. R-ketamine: a rapid-onset and sustained antidepressant without psychotomimetic side effects. Transl Psychiatry. 2015;5:e632.CrossRefGoogle ScholarPubMed
Perception Neuroscience Press Release. Perception Neuroscience’s PCN-101 (R-Ketamine) Demonstrates Tolerability in Phase 1 Single Ascending Dose Study; February 19, 2021.Google Scholar
Leal, GC, Bandeira, ID, Correia-Melo, FS, et al. Intravenous arketamine for treatment-resistant depression: open-label pilot study. Eur Arch Psychiatry Clin Neurosci. 2021;271:577582.CrossRefGoogle ScholarPubMed
Watanabe, M, Maemura, K, Kanbara, K, et al. GABA and GABA receptors in the central nervous system and other organs. Int Rev Cytol. 2002;213:147.CrossRefGoogle ScholarPubMed
Sigel, E, Steinmann, ME. Structure, function and modulation of GABAA receptors. J Biol Chem. 2012;287:4022440231.Google Scholar
Sanacora, G, Mason, GF, Rothman, DL, et al. Reduced cortical gamma-aminobutyric acid levels in depressed patients determined by proton magnetic resonance spectroscopy. Arch Gen Psychiatry. 1999;56(11):10431047.Google ScholarPubMed
Bhagwagar, Z, Wylezinska, M, Jezzard, P, et al. Low GABA concentrations in occipital cortex and anterior cingulate cortex in medication-free, recovered depressed patients. Int J Neuropsychopharmacol. 2008;11(2):255260.CrossRefGoogle ScholarPubMed
Luscher, B, Shen, Q, Sahir, N. The GABAergic deficit hypothesis of major depressive disorder. Mol Psychiatry. 2011;16:383406.Google ScholarPubMed
Sanacora, G, Mason, GF, Rothman, DL, Krystal, JH. Increased occipital cortex GABA concentrations in depressed patients after therapy with selective serotonin reuptake inhibitors. Am J Psychiatry. 2002;159(4):663665.CrossRefGoogle ScholarPubMed
Esel, E, KOse, K, Hacimusalar, Y, et al. The effects of electroconvulsive therapy on GABAergic function in major depressive patients. J ECT. 2008;24(3):224248.CrossRefGoogle ScholarPubMed
Dubin, MJ, Mao, X, Banerjee, S, et al. Elevated prefrontal cortex GABA in patients with major depressive disorder after TMS treatment measured with proton magnetic resonance spectroscopy. J Psychiatry Neurosci. 2016;41(3):E37E45.CrossRefGoogle ScholarPubMed
Akk, G, Covey, DF, Evers, AS, et al. Mechanisms of neurosteroid interactions with GABA(A) receptors. Pharmacol Ther. 2007;116:3557.CrossRefGoogle ScholarPubMed
Schule, C, Nothdurfter, C, Rupprecht, R. The role of allopregnanolone in depression and anxiety. Prog Neurobiol. 2014;113:7987.Google ScholarPubMed
Osborne, LM, Gispen, F, Sanyal, A, et al. Lower allopregnanolone during pregnancy predicts postpartum depression: an exploratory study. Psychoneuroendocrinology. 2017;79:116121.CrossRefGoogle ScholarPubMed
Uzunova, V, Sheline, Y, Davis, JM, et al. Increase in the cerebrospinal fluid content of neurosteroids in patients with unipolar major depression who are receiving fluoxetine or fluvoxamine. Proc Natl Acad Sci USA. 1998;95:32393244.CrossRefGoogle ScholarPubMed
Evans, J, Sun, Y, McGregor, A, Connor, B. Allopregnanolone regulates neurogenesis and depressive/anxiety-like behaviour in a social isolation rodent model of chronic stress. Neuropharmacology. 2012;63(8):13151326.CrossRefGoogle Scholar
Kanes, SJ, Colquhoun, H, Doherty, J, et al. Open-label, proof-of-concept study of brexanolone in the treatment of severe postpartum depression. Hum Psychopharmacol. 2017;32:16.CrossRefGoogle ScholarPubMed
Meltzer-Brody, S, Colquhoun, H, Riesenberg, R, et al. Brexanolone injection in post-partum depression: two multicentre, doubleblind, randomized, placebo-controlled, phase 3 trials. Lancet. 2018;392:10581070.CrossRefGoogle ScholarPubMed
Althaus, AL, Ackley, MA, Belfort, GM, et al. Preclinical characterization of zuranolone (SAGE-217), a selective neuroactive steroid GABA(A) receptor positive allosteric modulator. Neuropharmacology 2020;181:108333.Google Scholar
Abramian, AM, Comenencia-Ortiz, E, Modgil, A, et al. Neurosteroids promote phosphorylation and membrance insertion of extrasynaptic GABAA receptors. Proc Natl Acad Sci USA. 2014;111(19):71327137.Google Scholar
Gunduz-Bruce, H, Silber, C, Kaul, I, et al. Trial of SAGE-217 in patients with major depressive disorder. N Engl J Med. 2019;381:903911.CrossRefGoogle ScholarPubMed
Sage Therapeutics Press Release. Sage Therapeutics Reports Topline Results from Pivotal Phase 3 MOUNTAIN Study of SAGE-217 in Major Depressive Disorder; December 5, 2019.Google Scholar
Sage Therapeutics and Biogen Press Release. Sage Therapeutics and Biogen Announce Positive Pivotal Phase 3 Results for Zuranolone, an Investigational Two-Week, Once-Daily Therapeutic Being Evaluated for Major Depressive Disorder; June 15, 2021.Google Scholar
Frieder, A, Fersh, M, Hainline, R, Deligiannidis, KM. Pharmacotherapy of postpartum depression: current approaches and novel drug development. CNS Drugs. 2019;33(3):265282.CrossRefGoogle ScholarPubMed
Carter, RB, Wood, PL, Wieland, S, et al. Characterization of the anticonvulsant properties of ganaxolone (CCD 1042; 3alpha-hydroxy-3beta-methyl-5alpha-pregnan-20-one), a selective, high-affinity, steroid modulator of the gamma-aminobutyric acid(A) receptor. J Pharmacol Exp Ther. 1997;280(3):12841295.Google Scholar
Dichtel, LE, Nyer, M, Dording, C, et al. Effects of open-label, adjunctive ganaxolone on presistent depression despite adequate antidepressant treatment in postmenopausal women: a pilot study. J Clin Psychiatry. 2020;81(4):19m12887.CrossRefGoogle Scholar
Marinus Pharmaceuticals Press Release. Marinus Pharmaceuticals Announces Data from Magnolia and Amaryllis Phase 2 Studies in Women with Postpartum Depression; July 23, 2019.Google Scholar
Nutt, D, Carhart-Harris, R. The current status of psychedelics in psychiatry. JAMA Psychiatry. 2021;78(2):121122.CrossRefGoogle ScholarPubMed
Nutt, D, Erritzoe, D, Carhart-Harris, R. Psychedelic psychiatry’s brave new world. Cell. 2020;181(1):2428.CrossRefGoogle ScholarPubMed
Madsen, MK, Fisher, PM, Burmester, D, et al. Psychedelic effects of psilocybin correlate with serotonin 2A receptor occupancy and plasma psilocybin levels. Neuropsychopharmacology. 2019;44(7):13281334.Google ScholarPubMed
Vollenweider, FX, Preller, KH. Psychedelic drugs: neurobiology and potential for treatment of psychiatric disorders. Nat Rev Neurosci. 2020;21(11):611624.CrossRefGoogle ScholarPubMed
Carhart-Harris, RL, Roseman, L, Bolstridge, M, et al. Psilocybin for treatment-resistant depression: fMRI-measured brain mechanisms. Nat Sci Rep. 2017;7(1):13187.Google ScholarPubMed
Morales-Garcia, JA, Calleja-Conde, J, Lopez-Moreno, JA, et al. N,N-dimethyltryptamine compound found in the hallucinogenic tea ayahuasca, regulates adult neurogenesis in vitro and in vivo. Transl Psychiatry. 2020;10(1):331.CrossRefGoogle ScholarPubMed
Goldberg, SB, Pace, BT, Nicholas, CR, et al. The experimental effects of psilocybin on symptoms of anxiety and depression: a meta-analysis. Psychiatry Res. 2020;284:112749.Google ScholarPubMed
Carhart-Harris, RL, Bolstridge, M, Day, CMJ, et al. Psilocybin with psychological support for treatment-resistant depression: six-month follow-up. Psychopharmacology. 2018;235(2):399408.Google ScholarPubMed
Davis, AK, Barrett, FS, May, DG, et al. Effects of psilocybin-assisted therapy on major depressive disorder: a randomized clinical trial. JAMA Psychiatry. 2020; 78:e203285.Google Scholar
Carhart-Harris, RL, Giribaldi, B, Watts, R, et al. Trial of psilocybin versus escitalopram for depression. N Engl J Med. 2021;384:14021411.Google ScholarPubMed
Sanches, RF, de Lima Osório, F, Dos Santos, RG, et al. Antidepressant effects of a single dose of ayahuasca in patients with recurrent depression: a SPECT study. J Clin Psychopharmacol. 2016;36(1):7781.CrossRefGoogle ScholarPubMed
Palhano-Fontes, F, Barreto, D, Onias, H, et al. Rapid antidepressant effects of the psychedelic ayahuasca in treatment-resistant depression: a randomized placebo-controlled trial. Psychol Med. 2019;49(4):655663.CrossRefGoogle ScholarPubMed
Davis, AK, So, S, Lancelotta, R, et al. 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT) used in a naturalistic group setting is associated with unintended improvements in depression and anxiety. Am J Drug Alcohol Abuse. 2019;45(2):161169.CrossRefGoogle Scholar
Grof, S, Goodman, LE, Richards, WA, Kurland, AA. LSD-assisted psychotherapy in patients with terminal cancer. Int Pharmacopsychiatry. 1973;8(3):129144.CrossRefGoogle ScholarPubMed
Gasser, P, Holstein, D, Michel, Y, et al. Safety and efficacy of lysergic acid diethylamide-assisted psychotherapy for anxiety associated with life-threatening diseases. J Nerv Ment Dis. 2014;202(7):513520.CrossRefGoogle ScholarPubMed
Fuentes, JJ, Fonseca, F, Elices, M, et al. Therapeutic use of LSD in psychiatry: a systematic review of randomized-controlled clinical trials. Front Psychiatry. 2020;10:943.Google ScholarPubMed
Muttoni, S, Ardissino, M, John, C. Classical psychedelics for the treatment of depression and anxiety: a systematic review. J Affect Disord. 2019;258:1124.CrossRefGoogle ScholarPubMed
Egede, LE, Bishu, KG, Walker, RJ, Dismuke, CE. Impact of diagnosed depression on healthcare costs in adults with and without diabetes: United States, 2004-2011. J Affect Disord. 2016;195:119126.CrossRefGoogle ScholarPubMed
Ross, EL, Soeteman, DI. Cost-effectiveness of esketamine nasal spray for patients with treatment-resistant depression in the United States. Psychiatr Serv. 2020;71(10):988997.CrossRefGoogle ScholarPubMed
Shukla, AK, Jhai, R, Sadasivam, B. Brexanolone: panacea for postpartum depression? Reply to: ‘Intravenous brexanolone for postpartum depression: what it is, how well does it work, and will it be used?’ Ther Adv Psychopharmacol. 2021;11:2045125321997293.Google ScholarPubMed