Skip to main content Accessibility help

We use cookies to distinguish you from other users and to provide you with a better experience on our websites. Close this message to accept cookies or find out how to manage your cookie settings.

Close cookie message
×
Hostname: page-component-cd9895bd7-lnqnp Total loading time: 0 Render date: 2024-12-27T07:52:19.691Z Has data issue: false hasContentIssue false

Chapter 19 - Treatment-Resistant Depression: Pharmacological Approach

Published online by Cambridge University Press:  16 May 2024

By
Alexandre Paim Diaz ,
Joao Quevedo ,
Marsal Sanches  and
Jair C. Soares
Edited by
Allan Young ,
Marsal Sanches ,
Jair C. Soares  and
Mario Juruena
Allan Young
Affiliation:
Institute of Psychiatry, King's College London
Marsal Sanches
Affiliation:
Baylor College of Medicine, Texas
Jair C. Soares
Affiliation:
McGovern Medical School, The University of Texas
Mario Juruena
Affiliation:
King's College London
Get access

Summary

There is no consensus for the concept of treatment-resistant depression (TRD). Although some authors argue considering TRD a depression subtype is not supported by evidence, its impact on the individual and society is clear. This chapter discusses the concept of TRD, presents evidence about its neurobiology, pharmacological interventions, and describes drugs currently under investigation. Among the pharmacological strategies to manage TRD, guidelines include increasing the antidepressant dose, switching to another new antidepressant, combining two or more antidepressants, and augmentation of the current medication. Several new components have been investigated for TRD targeting, for instance, the glutamatergic system, inflammatory system, the opioid system, the cholinergic system, dopaminergic system, and neurotrophin signaling. Finally, machine-learning techniques using clinical and neurobiological data provide promising information about treatment outcomes prediction that could change the current approach to a more personalized one.

Keywords

treatment-resistantdepressionneurobiologyinterventionspharmacology
Type
Chapter
Information
Clinical Textbook of Mood Disorders , pp. 193 - 205
Publisher: Cambridge University Press
Print publication year: 2024

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

Haskovec, L, Rysanek, K. The action of reserpine in imipramine-resistant depressive patients. Clinical and biochemical study. Psychopharmacologia. 1967;11(1):18–30.CrossRefGoogle ScholarPubMed
Drago, F, Motta, A, Grossi, E. Intravenous maprotiline in severe and resistant primary depression: a double-blind comparison with clomipramine. J Int Med Res. 1983;11(2):78–84.CrossRefGoogle ScholarPubMed
Decker, HS. The Making of DSM-III: A Diagnostic Manual’s Conquest of American Psychiatry. New York: Oxford University Press, 2013.Google Scholar
Hardy, P. [Concept of resistant depression]. Encephale. 1986;12:Spec No:191–6.Google ScholarPubMed
Malhi, GS, Byrow, Y. Is treatment-resistant depression a useful concept? Evid Based Ment Health. 2016;19(1):1–3.CrossRefGoogle ScholarPubMed
Rybak, YE, Lai, KSP, Ramasubbu, R, et al. et al. Treatment-resistant major depressive disorder: Canadian expert consensus on definition and assessment. Depress Anxiety. 2021;38(4):456–67.CrossRefGoogle ScholarPubMed
Dodd, S, Bauer, M, Carvalho, AF, et al. A clinical approach to treatment resistance in depressed patients: what to do when the usual treatments don’t work well enough? World J Biol Psychiatry. 2021:22(7):483–94.CrossRefGoogle Scholar
National Institute of Mental Health. Major depression. 2017. Available from: www.nimh.nih.gov/health/statistics/major-depression.Google Scholar
Gronemann, FH, Petersen, J, Alulis, S, et al. Treatment patterns in patients with treatment-resistant depression in Danish patients with major depressive disorder. J Affect Disord. 2021;287:204–13.CrossRefGoogle ScholarPubMed
Gaynes, BN, Warden, D, Trivedi, MH, et al. What did STAR*D teach us? Results from a large-scale, practical, clinical trial for patients with depression. Psychiatr Serv. 2009;60(11):1439–45.CrossRefGoogle ScholarPubMed
Gaynes, BN, Rush, AJ, Trivedi, MH, et al. The STAR*D study: treating depression in the real world. Cleve Clin J Med. 2008;75(1):57–66.CrossRefGoogle ScholarPubMed
Mojtabai, R. Nonremission and time to remission among remitters in major depressive disorder: revisiting STAR*D. Depress Anxiety. 2017;34(12):1123–33.CrossRefGoogle ScholarPubMed
Thomas, L, Kessler, D, Campbell, J, et al. Prevalence of treatment-resistant depression in primary care: cross-sectional data. Br J Gen Pract. 2013;63(617):e852-8.CrossRefGoogle ScholarPubMed
Zhdanava, M, Pilon, D, Ghelerter, I, et al. The prevalence and national burden of treatment-resistant depression and major depressive disorder in the United States. J Clin Psychiatry. 2021;82(2).CrossRefGoogle ScholarPubMed
Madsen, KB, Plana-Ripoll, O, Musliner, KL, et al. Cause-specific life years lost in individuals with treatment-resistant depression: a Danish nationwide register-based cohort study. J Affect Disord. 2021;280(Pt A):250–7.CrossRefGoogle ScholarPubMed
Gronemann, FH, Jorgensen, MB, Nordentoft, M, Andersen, PK, Osler, M. Treatment-resistant depression and risk of all-cause mortality and suicidality in Danish patients with major depression. J Psychiatr Res. 2021;135:197–202.CrossRefGoogle ScholarPubMed
Brenner, P, Reutfors, J, Nijs, M, Andersson, TM. Excess deaths in treatment-resistant depression. Ther Adv Psychopharmacol. 2021;11:20451253211006508.CrossRefGoogle ScholarPubMed
Caraci, F, Calabrese, F, Molteni, R, et al. International Union of Basic and Clinical Pharmacology CIV: the neurobiology of treatment-resistant depression: from antidepressant classifications to novel pharmacological targets. Pharmacol Rev. 2018;70(3):475–504.CrossRefGoogle ScholarPubMed
Ceruso, A, Martinez-Cengotitabengoa, M, Peters-Corbett, A, Diaz-Gutierrez, MJ, Martinez-Cengotitabengoa, M. Alterations of the HPA axis observed in patients with major depressive disorder and their relation to early life stress: a systematic review. Neuropsychobiology. 2020;79(6):417–27.CrossRefGoogle ScholarPubMed
LeMoult, J, Humphreys, KL, Tracy, A, et al. Meta-analysis: exposure to early life stress and risk for depression in childhood and adolescence. J Am Acad Child Adolesc Psychiatry. 2020;59(7):842–55.CrossRefGoogle ScholarPubMed
Juruena, MF, Cleare, AJ, Papadopoulos, AS, et al. Different responses to dexamethasone and prednisolone in the same depressed patients. Psychopharmacology (Berl). 2006;189(2):225–35.CrossRefGoogle ScholarPubMed
Allen, AP, Naughton, M, Dowling, J, et al. Kynurenine pathway metabolism and the neurobiology of treatment-resistant depression: comparison of multiple ketamine infusions and electroconvulsive therapy. J Psychiatr Res. 2018;100:24–32.CrossRefGoogle ScholarPubMed
Fabbri, C, Corponi, F, Albani, D, et al. Pleiotropic genes in psychiatry: calcium channels and the stress-related FKBP5 gene in antidepressant resistance. Prog Neuropsychopharmacol Biol Psychiatry. 2018;81:203–10.CrossRefGoogle ScholarPubMed
Fabbri, C, Marsano, A, Albani, D, et al. PPP3CC gene: a putative modulator of antidepressant response through the B-cell receptor signaling pathway. Pharmacogenomics J. 2014;14(5):463–72.CrossRefGoogle ScholarPubMed
Zarate, CA Jr, 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(8):856–64.CrossRefGoogle ScholarPubMed
Marcantoni, WS, Akoumba, BS, Wassef, M, et al. A systematic review and meta-analysis of the efficacy of intravenous ketamine infusion for treatment resistant depression: January 2009–January 2019. J Affect Disord. 2020;277:831–41.CrossRefGoogle ScholarPubMed
Carlson, PJ, Diazgranados, N, Nugent, AC, et al. Neural correlates of rapid antidepressant response to ketamine in treatment-resistant unipolar depression: a preliminary positron emission tomography study. Biol Psychiatry. 2013;73(12):1213–21.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(2):119–35.CrossRefGoogle ScholarPubMed
Du, J, Machado-Vieira, R, Maeng, S, et al. Enhancing AMPA to NMDA throughput as a convergent mechanism for antidepressant action. Drug Discov Today Ther Strateg. 2006;3(4):519–26.CrossRefGoogle ScholarPubMed
Pizzagalli, DA. Depression, stress, and anhedonia: toward a synthesis and integrated model. Annu Rev Clin Psychol. 2014;10:393–423.CrossRefGoogle Scholar
Sternat, T, Katzman, MA. Neurobiology of hedonic tone: the relationship between treatment-resistant depression, attention-deficit hyperactivity disorder, and substance abuse. Neuropsychiatr Dis Treat. 2016;12:2149–64.Google ScholarPubMed
McMakin, DL, Olino, TM, Porta, G, et al. Anhedonia predicts poorer recovery among youth with selective serotonin reuptake inhibitor treatment-resistant depression. J Am Acad Child Adolesc Psychiatry. 2012;51(4):404–11.CrossRefGoogle ScholarPubMed
Iob, E, Kirschbaum, C, Steptoe, A. Persistent depressive symptoms, HPA-axis hyperactivity, and inflammation: the role of cognitive-affective and somatic symptoms. Mol Psychiatry. 2020;25(5):1130–40.CrossRefGoogle ScholarPubMed
Edwards, SJ, Hamilton, V, Nherera, L, Trevor, N. Lithium or an atypical antipsychotic drug in the management of treatment-resistant depression: a systematic review and economic evaluation. Health Technol Assess. 2013;17(54):1–190.CrossRefGoogle ScholarPubMed
Nelson, JC, Baumann, P, Delucchi, K, Joffe, R, Katona, C. A systematic review and meta-analysis of lithium augmentation of tricyclic and second generation antidepressants in major depression. J Affect Disord. 2014;168:269–75.CrossRefGoogle ScholarPubMed
Zhou, X, Keitner, GI, Qin, B, et al. Atypical antipsychotic augmentation for treatment-resistant depression: a systematic review and network meta-analysis. Int J Neuropsychopharmacol. 2015;18(11):pyv060.CrossRefGoogle ScholarPubMed
Zhou, X, Ravindran, AV, Qin, B, et al. Comparative efficacy, acceptability, and tolerability of augmentation agents in treatment-resistant depression: systematic review and network meta-analysis. J Clin Psychiatry. 2015;76(4):e487-98.CrossRefGoogle ScholarPubMed
Luan, S, Wan, H, Zhang, L, Zhao, H. Efficacy, acceptability, and safety of adjunctive aripiprazole in treatment-resistant depression: a meta-analysis of randomized controlled trials. Neuropsychiatr Dis Treat. 2018;14:467–77.CrossRefGoogle ScholarPubMed
Citrome, L, Ota, A, Nagamizu, K, et al. The effect of brexpiprazole (OPC-34712) and aripiprazole in adult patients with acute schizophrenia: results from a randomized, exploratory study. Int Clin Psychopharmacol. 2016;31(4):192–201.CrossRefGoogle ScholarPubMed
Kishi, T, Sakuma, K, Nomura, I, et al. Brexpiprazole as adjunctive treatment for major depressive disorder following treatment failure with at least one antidepressant in the current episode: a systematic review and meta-analysis. Int J Neuropsychopharmacol. 2019;22(11):698–709.CrossRefGoogle ScholarPubMed
Skelin, I, Fikre-Merid, M, Diksic, M. Both acute and subchronic treatments with pindolol, a 5-HT(1A) and beta(1) and beta(2) adrenoceptor antagonist, elevate regional serotonin synthesis in the rat brain: an autoradiographic study. Neurochem Int. 2012;61(8):1417–23.CrossRefGoogle Scholar
Artigas, F, Celada, P, Laruelle, M, Adell, A. How does pindolol improve antidepressant action? Trends Pharmacol Sci. 2001;22(5):224–8.CrossRefGoogle ScholarPubMed
Liu, Y, Zhou, X, Zhu, D, et al. Is pindolol augmentation effective in depressed patients resistant to selective serotonin reuptake inhibitors? A systematic review and meta-analysis. Hum Psychopharmacol. 2015;30(3):132–42.CrossRefGoogle ScholarPubMed
Luan, S, Wan, H, Wang, S, Li, H, Zhang, B. Efficacy and safety of olanzapine/fluoxetine combination in the treatment of treatment-resistant depression: a meta-analysis of randomized controlled trials. Neuropsychiatr Dis Treat. 2017;13:609–20.CrossRefGoogle ScholarPubMed
Bavaresco, DV, Uggioni, MLR, Ferraz, SD, et al. Efficacy of infliximab in treatment-resistant depression: a systematic review and meta-analysis. Pharmacol Biochem Behav. 2020;188:172838.CrossRefGoogle ScholarPubMed
Kryst, J, Kawalec, P, Mitoraj, AM, et al. Efficacy of single and repeated administration of ketamine in unipolar and bipolar depression: a meta-analysis of randomized clinical trials. Pharmacol Rep. 2020;72(3):543–62.CrossRefGoogle ScholarPubMed
Papadimitropoulou, K, Vossen, C, Karabis, A, Donatti, C, Kubitz, N. Comparative efficacy and tolerability of pharmacological and somatic interventions in adult patients with treatment-resistant depression: a systematic review and network meta-analysis. Curr Med Res Opin. 2017;33(4):701–11.CrossRefGoogle ScholarPubMed
Davies, P, Ijaz, S, Williams, CJ, et al. Pharmacological interventions for treatment-resistant depression in adults. Cochrane Database Syst Rev. 2019;12:CD010557.Google ScholarPubMed
Lee, Y, Brietzke, E, Cao, B, et al. Development and implementation of guidelines for the management of depression: a systematic review. Bull World Health Organ. 2020;98(10):683-97 H.CrossRefGoogle ScholarPubMed
Simons, P, Cosgrove, L, Shaughnessy, AF, Bursztajn, H. Antipsychotic augmentation for major depressive disorder: a review of clinical practice guidelines. Int J Law Psychiatry. 2017;55:64–71.CrossRefGoogle ScholarPubMed
Malhi, GS, Hitching, R, Berk, M, et al. Pharmacological management of unipolar depression. Acta Psychiatr Scand Suppl. 2013(443):6–23.CrossRefGoogle ScholarPubMed
Kennedy, SH, Lam, RW, McIntyre, RS, et al. Canadian Network for Mood and Anxiety Treatments (CANMAT) 2016 Clinical Guidelines for the Management of Adults with Major Depressive Disorder: Section 3. Pharmacological Treatments. Can J Psychiatry. 2016;61(9):540–60.Google Scholar
Bauer, M, Severus, E, Moller, HJ, Young, AH, Disorders WTFoUD. Pharmacological treatment of unipolar depressive disorders: summary of WFSBP guidelines. Int J Psychiatry Clin Pract. 2017;21(3):166–76.CrossRefGoogle ScholarPubMed
Bennabi, D, Charpeaud, T, Yrondi, A, et al. Clinical guidelines for the management of treatment-resistant depression: French recommendations from experts, the French Association for Biological Psychiatry and Neuropsychopharmacology and the Foundation FondaMental. BMC Psychiatry. 2019;19(1):262.CrossRefGoogle ScholarPubMed
Dold, M, Kasper, S. Evidence-based pharmacotherapy of treatment-resistant unipolar depression. Int J Psychiatry Clin Pract. 2017;21(1):13–23.CrossRefGoogle ScholarPubMed
MacQueen, G, Santaguida, P, Keshavarz, H, et al. Systematic review of clinical practice guidelines for failed antidepressant treatment response in major depressive disorder, dysthymia, and subthreshold depression in adults. Can J Psychiatry. 2017;62(1):11–23.CrossRefGoogle ScholarPubMed
Henssler, J, Kurschus, M, Franklin, J, Bschor, T, Baethge, C. Trajectories of acute antidepressant efficacy: how long to wait for response? A systematic review and meta-analysis of long-term, placebo-controlled acute treatment trials. J Clin Psychiatry. 2018;79(3).Google Scholar
National institutes of Health. Recruiting studies | treatment resistant depression. 2021. Available from: https://clinicaltrials.gov/ct2/results?cond=Treatment+Resistant+Depression&Search=Apply&recrs=a&age_v=&gndr=&type=&rslt=.Google Scholar
Henter, ID, Park, LT, Zarate, CA Jr. Novel glutamatergic modulators for the treatment of mood disorders: current status. CNS Drugs. 2021;35(5):527–43.CrossRefGoogle ScholarPubMed
Wilkinson, ST, Sanacora, G. A new generation of antidepressants: an update on the pharmaceutical pipeline for novel and rapid-acting therapeutics in mood disorders based on glutamate/GABA neurotransmitter systems. Drug Discov Today. 2019;24(2):606–15.CrossRefGoogle ScholarPubMed
Stahl, SM. Dextromethorphan/bupropion: a novel oral NMDA (N-methyl-d-aspartate) receptor antagonist with multimodal activity. CNS Spectr. 2019;24(5):461–6.CrossRefGoogle ScholarPubMed
Hanrahan, B, Carson, RP. Ethosuximide. Treasure Island, FL: StatPearls Publishing, 2021.Google Scholar
Yang, Y, Cui, Y, Sang, K, et al. Ketamine blocks bursting in the lateral habenula to rapidly relieve depression. Nature. 2018;554(7692):317–22.CrossRefGoogle ScholarPubMed
Chevalier, G, Siopi, E, Guenin-Mace, L, et al. Effect of gut microbiota on depressive-like behaviors in mice is mediated by the endocannabinoid system. Nat Commun. 2020;11(1):6363.CrossRefGoogle ScholarPubMed
Chinna Meyyappan, A, Forth, E, Wallace, CJK, Milev, R. Effect of fecal microbiota transplant on symptoms of psychiatric disorders: a systematic review. BMC Psychiatry. 2020;20(1):299.CrossRefGoogle ScholarPubMed
Zhang, Y, Huang, R, Cheng, M, et al. Gut microbiota from NLRP3-deficient mice ameliorates depressive-like behaviors by regulating astrocyte dysfunction via circHIPK2. Microbiome. 2019;7(1):116.CrossRefGoogle ScholarPubMed
Szabo, A. Psychedelics and immunomodulation: novel approaches and therapeutic opportunities. Front Immunol. 2015;6:358.CrossRefGoogle ScholarPubMed
Lima da Cruz, RV, Moulin, TC, Petiz, LL, Leao, RN. A single dose of 5-MeO-DMT stimulates cell proliferation, neuronal survivability, morphological and functional changes in adult mice ventral dentate gyrus. Front Mol Neurosci. 2018;11:312.CrossRefGoogle ScholarPubMed
Vollenweider, FX, Preller, KH. Psychedelic drugs: neurobiology and potential for treatment of psychiatric disorders. Nat Rev Neurosci. 2020;21(11):611–24.CrossRefGoogle ScholarPubMed
Daniel, DG, Daniel, NG, Daniel, DT, Flynn, LC, Allen, MH. The effect of propofol on a forced swim test in mice at 24 hours. Curr Ther Res Clin Exp. 2020;92:100590.CrossRefGoogle ScholarPubMed
Daniel, DG, Daniel, NG, Daniel, DT, Flynn, LC, Allen, MH. The effect of acutely administered propofol on forced swim test outcomes in mice. Innov Clin Neurosci. 2019;16(9–10):22–6.Google ScholarPubMed
Vane, JR, Botting, RM. The mechanism of action of aspirin. Thromb Res. 2003;110(5–6):255–8.CrossRefGoogle ScholarPubMed
Hu, K, Sjolander, A, Lu, D, et al. Aspirin and other non-steroidal anti-inflammatory drugs and depression, anxiety, and stress-related disorders following a cancer diagnosis: a nationwide register-based cohort study. BMC Med. 2020;18(1):238.CrossRefGoogle ScholarPubMed
Bhatt, S, Pundarikakshudu, K, Patel, P, et al. Beneficial effect of aspirin against interferon-alpha-2b-induced depressive behavior in Sprague Dawley rats. Clin Exp Pharmacol Physiol. 2016;43(12):1208–15.CrossRefGoogle ScholarPubMed
Wu, H, Lv, W, Pan, Q, et al. Simvastatin therapy in adolescent mice attenuates HFD-induced depression-like behavior by reducing hippocampal neuroinflammation. J Affect Disord. 2019;243:83–95.CrossRefGoogle ScholarPubMed
Wilde, MI, Benfield, P. Tianeptine. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic efficacy in depression and coexisting anxiety and depression. Drugs. 1995;49(3):411–39.Google ScholarPubMed
Wlaz, P, Kasperek, R, Wlaz, A, et al. NMDA and AMPA receptors are involved in the antidepressant-like activity of tianeptine in the forced swim test in mice. Pharmacol Rep. 2011;63(6):1526–32.Google ScholarPubMed
Zeier, Z, Carpenter, LL, Kalin, NH, et al. Clinical implementation of pharmacogenetic decision support tools for antidepressant drug prescribing. Am J Psychiatry. 2018;175(9):873–86.CrossRefGoogle ScholarPubMed
Zubenko, GS, Sommer, BR, Cohen, BM. On the marketing and use of pharmacogenetic tests for psychiatric treatment. JAMA Psychiatry. 2018;75(8):769–70.CrossRefGoogle ScholarPubMed
Webb, CA, Trivedi, MH, Cohen, ZD, et al. Personalized prediction of antidepressant v. placebo response: evidence from the EMBARC study. Psychol Med. 2019;49(7):1118–27.CrossRefGoogle ScholarPubMed
Zhdanov, A, Atluri, S, Wong, W, et al. Use of machine learning for predicting escitalopram treatment outcome from electroencephalography recordings in adult patients with depression. JAMA Netw Open. 2020;3(1):e1918377.CrossRefGoogle ScholarPubMed
Wu, W, Zhang, Y, Jiang, J, et al. An electroencephalographic signature predicts antidepressant response in major depression. Nat Biotechnol. 2020;38(4):439–47.CrossRefGoogle ScholarPubMed
Michel, CM, Pascual-Leone, A. Predicting antidepressant response by electroencephalography. Nat Biotechnol. 2020;38(4):417–9.CrossRefGoogle ScholarPubMed
Dichtel, LE, Carpenter, LL, Nyer, M, et al. Low-dose testosterone augmentation for antidepressant-resistant major depressive disorder in women: an 8-week randomized placebo-controlled study. Am J Psychiatry. 2020;177(10):965–73.CrossRefGoogle ScholarPubMed
Umbricht, D, Niggli, M, Sanwald-Ducray, P, et al. randomized, double-blind, placebo-controlled trial of the mGlu2/3 negative allosteric modulator decoglurant in partially refractory major depressive disorder. J Clin Psychiatry. 2020;81(4).CrossRefGoogle ScholarPubMed
Popova, V, Daly, DJ, Trivedi, M, et al. Efficacy and safety of flexibly dosed esketamine nasal spray combined with a newly initiated oral antidepressant in treatment-resistant depression: a randomized double-blind active-controlled study. Am J Psychiatry. 2019;176(6):428–38.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):655–63.CrossRefGoogle 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(2):139–48.Google ScholarPubMed
Miyaoka, T, Kanayama, M, Wake, R, et al. Clostridium butyricum MIYAIRI 588 as adjunctive therapy for treatment-resistant major depressive disorder: a prospective open-label trial. Clin Neuropharmacol. 2018;41(5):151–5.CrossRefGoogle ScholarPubMed
Mathew, SJ, Gueorguieva, R, Brandt, C, Fava, M, Sanacora, G. A randomized, double-blind, placebo-controlled, sequential parallel comparison design trial of adjunctive riluzole for treatment-resistant major depressive disorder. Neuropsychopharmacology. 2017;42(13):2567–74.CrossRefGoogle ScholarPubMed
Husain, MI, Chaudhry, IB, Husain, N, et al. Minocycline as an adjunct for treatment-resistant depressive symptoms: a pilot randomised placebo-controlled trial. J Psychopharmacol. 2017;31(9):1166–75.CrossRefGoogle ScholarPubMed
Mehdi, SM, Atlas, SE, Qadir, S, et al. Double-blind, randomized crossover study of intravenous infusion of magnesium sulfate versus 5% dextrose on depressive symptoms in adults with treatment-resistant depression. Psychiatry Clin Neurosci. 2017;71(3):204–11.CrossRefGoogle ScholarPubMed
Sanacora, G, Johnson, MR, Khan, A, et al. Adjunctive lanicemine (AZD6765) in patients with major depressive disorder and history of inadequate response to antidepressants: a randomized, placebo-controlled study. Neuropsychopharmacology. 2017;42(4):844–53.CrossRefGoogle ScholarPubMed

Save book to Kindle

To save this book to your Kindle, first ensure [email protected] is added to your Approved Personal Document E-mail List under your Personal Document Settings on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part of your Kindle email address below. Find out more about saving to your Kindle.

Note you can select to save to either the @free.kindle.com or @kindle.com variations. ‘@free.kindle.com’ emails are free but can only be saved to your device when it is connected to wi-fi. ‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.

Find out more about the Kindle Personal Document Service.

Available formats
×

Save book to Dropbox

To save content items to your account, please confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account. Find out more about saving content to Dropbox.

Available formats
×

Save book to Google Drive

To save content items to your account, please confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account. Find out more about saving content to Google Drive.

Available formats
×