Key considerations in the pharmacological management of treatment-resistant depression

References

• Hasin DS, Sarvet AL, Meyers JL, et al. Epidemiology of adult DSM-5 major depressive disorder and its specifiers in the United States. JAMA Psychiatry. 2018;75:336–346.
   PubMed Web of Science ®Google Scholar
• World Health Organization. Depression and Other Common Mental Disorders: global Health Estimates. Geneva, Switzerland: World Health Organization; 2017.
   Google Scholar
• Cuijpers P, Vogelzangs N, Twisk J, et al. Comprehensive meta-analysis of excess mortality in depression in the general community versus patients with specific illnesses. Am J Psychiatry. 2014;171:453–462.
   PubMed Web of Science ®Google Scholar
• Moore TJ, Mattison DR. Adult utilization of psychiatric drugs and differences by sex, age, and race. JAMA Intern Med. 2017;177:274–275.
   PubMed Web of Science ®Google Scholar
• McIntyre RS, Filteau MJ, Martin L, et al. Treatment-resistant depression: definitions, review of the evidence, and algorithmic approach. J Affect Disord. 2014 Mar;156:1–7.
   PubMed Web of Science ®Google Scholar
• Thase ME. Treatment-resistant depression: prevalence, risk factors, and treatment strategies. J Clin Psychiatry. 2011 May;72(5):e18.
   PubMedGoogle Scholar
• Dunner DL, Rush AJ, Russell JM, et al. Prospective, long-term, multicenter study of the naturalistic outcomes of patients with treatment-resistant depression. J Clin Psychiatry. 2006;67:688–695.
   PubMed Web of Science ®Google Scholar
• Milev RV, Giacobbe P, Kennedy SH, et al. Canadian Network for Mood and Anxiety Treatments (CANMAT) 2016 clinical guidelines for the management of adults with major depressive disorder: section 4. Can J Psychiatry. 2016;61:561–575.
   PubMed Web of Science ®Google Scholar
• Wijkstra J, Lijmer J, Burger H, et al. Pharmacological treatment for psychotic depression. Cochrane Database Syst Rev. 2015;CD004044. doi: https://doi.org/10.1002/14651858.CD004044.pub4
   Google Scholar
• Bennabi D, Haffen E, Van Waes V. Vortioxetine for cognitive enhancement in major depression: from animal models to clinical research. Front Psychiatry. 2019;10:771.
   PubMed Web of Science ®Google Scholar
• Patel K, Allen S, Haque MN, et al. Bupropion: a systematic review and meta-analysis of effectiveness as an antidepressant. Ther Adv Psychopharmacol. 2016;6:99–144.
   PubMed Web of Science ®Google Scholar
• Lunn MPT, Hughes RAC, Wiffen PJ. Duloxetine for treating painful neuropathy, chronic pain or fibromyalgia. Cochrane Database Syst Rev. 2014;CD007115.
   PubMed Web of Science ®Google Scholar
• Serafini G, Gonda X, Canepa G, et al. Extreme sensory processing patterns show a complex association with depression, and impulsivity, alexithymia, and hopelessness. J Affect Disord. 2017;210:249–257.
   PubMed Web of Science ®Google Scholar
• McGrath PJ, Stewart JW, Harrison W, et al. Predictive value of symptoms of atypical depression for differential drug treatment outcome. J Clin Psychopharmacol. 1992;12:197–202.
   PubMed Web of Science ®Google Scholar
• McGrath PJ, Stewart JW, Janal MN, et al. A placebo-controlled study of fluoxetine versus imipramine in the acute treatment of atypical depression. Am J Psychiatry. 2000;157:344–350.
   PubMed Web of Science ®Google Scholar
• Gold PW, Chrousos GP. Organization of the stress system and its dysregulation in melancholic and atypical depression: high vs low CRH/NE states. Mol Psychiatry. 2002;7:254–275.
   PubMed Web of Science ®Google Scholar
• Hillemacher T, Frieling H. Pharmacotherapeutic options for co-morbid depression and alcohol dependence. Expert Opin Pharmacother. 2019;20:547–569.
   PubMed Web of Science ®Google Scholar
• Pettinati HM, Oslin DW, Kampman KM, et al. A double-blind, placebo-controlled trial combining sertraline and naltrexone for treating co-occurring depression and alcohol dependence. Am J Psychiatry. 2010;167:668–675.
   PubMed Web of Science ®Google Scholar
• Taylor RW, Marwood L, Oprea E, et al. Pharmacological augmentation in unipolar depression: a guide to the guidelines. Int J Neuropsychopharmacol. 2020;23:587–625.
   PubMed Web of Science ®Google Scholar
• Rush AJ, Trivedi MH, Wisniewski SR, et al. Bupropion-SR, sertraline, or venlafaxine-XR after failure of SSRIs for depression. N Engl J Med. 2006 Mar 23;354(12):1231–1242. .
   PubMed Web of Science ®Google Scholar
• Fava M, Rush AJ, Wisniewski SR, et al. A comparison of mirtazapine and nortriptyline following two consecutive failed medication treatments for depressed outpatients: a STAR*D report. Am J Psychiatry. 2006;163:1161–1172.
   PubMed Web of Science ®Google Scholar
• Thase ME, Rush AJ, Howland RH, et al. Double-blind switch study of imipramine or sertraline treatment of antidepressant-resistant chronic depression. Arch Gen Psychiatry. 2002;59:233–239.
   PubMed Web of Science ®Google Scholar
• Thase ME, Frank E, Mallinger AG, et al. Treatment of imipramine-resistant recurrent depression, III: efficacy of monoamine oxidase inhibitors. J Clin Psychiatry. 1992 Jan;53(1):5–11.
   PubMed Web of Science ®Google Scholar
• Relling MV, Klein TE. CPIC: clinical Pharmacogenetics Implementation Consortium of the Pharmacogenomics Research Network. Clin Pharmacol Ther. 2011;89:464–467.
   PubMed Web of Science ®Google Scholar
• Hamilton SP. The promise of psychiatric pharmacogenomics. Biol Psychiatry. 2015;77:29–35.
   PubMed Web of Science ®Google Scholar
• Papakostas GI, Fava M, Thase ME. Treatment of SSRI-resistant depression: a meta-analysis comparing within- versus across-class switches. Biol Psychiatry. 2008;63:699–704.
   PubMed Web of Science ®Google Scholar
• Mohamed S, Johnson GR, Chen P, et al. Effect of antidepressant switching vs augmentation on remission among patients with major depressive disorder unresponsive to antidepressant treatment: the VAST-D randomized clinical trial. JAMA. 2017;318:132–145.
   PubMed Web of Science ®Google Scholar
• Lomas J, Llewellyn A, Soares M, et al. The clinical and cost effectiveness of vortioxetine for the treatment of a major depressive episode in patients with failed prior antidepressant therapy: a critique of the evidence. Pharmacoeconomics. 2016;34:901–912.
   PubMed Web of Science ®Google Scholar
• Gonda X, Sharma SS, Tarazi FI. Vortioxetine: a novel antidepressant for the treatment of major depressive disorder. Expert Opin Drug Discov. 2019;14:81–89.
   PubMed Web of Science ®Google Scholar
• Koesters M, Ostuzzi G, Guaiana G, et al. Vortioxetine for depression in adults. Cochrane Database Syst Rev. 2017;7:CD011520.
   PubMedGoogle Scholar
• Stahl SM. Prescriber’s Guide (Stahl’s Essential Psychopharmacology). Cambridge, UK: Cambridge University Press; 2021.
   Google Scholar
• Carpenter LL, Yasmin S, Price LH. A double-blind, placebo-controlled study of antidepressant augmentation with mirtazapine. Biol Psychiatry. 2002;51:183–188.
   PubMed Web of Science ®Google Scholar
• Kessler DS, MacNeill SJ, Tallon D, et al. Mirtazapine added to SSRIs or SNRIs for treatment resistant depression in primary care: phase III randomised placebo controlled trial (MIR). BMJ. 2018;363:k4218.
   PubMedGoogle Scholar
• Bauer M, Ricken AM, Severus E, et al. Role of lithium augmentation in the management of major depressive disorder. CNS Drugs. 2014;28:331–342.
   PubMed Web of Science ®Google Scholar
• Nierenberg AA, Fava M, Trivedi MH, et al. A comparison of lithium and T(3) augmentation following two failed medication treatments for depression: a STAR*D report. Am J Psychiatry. 2006;163:1519–1530.
   PubMed Web of Science ®Google Scholar
• Nelson JC, Baumann P, Delucchi K, et al. A systematic review and meta-analysis of lithium augmentation of tricyclic and second generation antidepressants in major depression. J Affect Disord. 2014;168:269–275.
   PubMed Web of Science ®Google Scholar
• 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:e487–98.
   PubMed Web of Science ®Google Scholar
• Guzzetta F, Tondo L, Centorrino F, et al. Lithium treatment reduces suicide risk in recurrent major depressive disorder. J Clin Psychiatry. 2007;68:380–383.
   PubMed Web of Science ®Google Scholar
• Han C, Wang S-M, Kato M, et al. Second-generation antipsychotics in the treatment of major depressive disorder: current evidence. Expert Rev Neurother. 2013;13:851–870.
   PubMed Web of Science ®Google Scholar
• Keitner GI, Garlow SJ, Ryan CE, et al. A randomized, placebo-controlled trial of risperidone augmentation for patients with difficult-to-treat unipolar, non-psychotic major depression. J Psychiatr Res. 2009;43:205–214.
   PubMed Web of Science ®Google Scholar
• Mahmoud RA, Pandina GJ, Turkoz I, et al. Risperidone for treatment-refractory major depressive disorder: a randomized trial. Ann Intern Med. 2007;147:593–602.
   PubMed Web of Science ®Google Scholar
• Schmidt AW, Lebel LA, Howard HR, et al. Ziprasidone: a novel antipsychotic agent with a unique human receptor binding profile. Eur J Pharmacol. 2001;425:197–201.
   PubMed Web of Science ®Google Scholar
• Papakostas GI, Fava M, Baer L, et al. Ziprasidone augmentation of escitalopram for major depressive disorder: efficacy results from a randomized, double-blind, placebo-controlled study. Am J Psychiatry. 2015;172:1251–1258.
   PubMed Web of Science ®Google Scholar
• Berent D, Zboralski K, Orzechowska A, et al. Thyroid hormones association with depression severity and clinical outcome in patients with major depressive disorder. Mol Biol Rep. 2014;41:2419–2425.
   PubMed Web of Science ®Google Scholar
• Altshuler LL, Bauer M, Frye MA, et al. Does thyroid supplementation accelerate tricyclic antidepressant response? A review and meta-analysis of the literature. Am J Psychiatry. 2001;158:1617–1622.
   PubMed Web of Science ®Google Scholar
• Aronson R, Offman HJ, Joffe RT, et al. Triiodothyronine augmentation in the treatment of refractory depression. A meta-analysis. Arch Gen Psychiatry. 1996;53: 842–848.
   PubMed Web of Science ®Google Scholar
• Cooper-Kazaz R, Lerer B. Efficacy and safety of triiodothyronine supplementation in patients with major depressive disorder treated with specific serotonin reuptake inhibitors. Int J Neuropsychopharmacol. 2008;11:685–699.
   PubMed Web of Science ®Google Scholar
• McIntyre RS, Lee Y, Zhou AJ, et al. The efficacy of psychostimulants in major depressive episodes: a systematic review and meta-analysis. J Clin Psychopharmacol. 2017;37:412–418.
   PubMed Web of Science ®Google Scholar
• Goss AJ, Kaser M, Costafreda SG, et al. Modafinil augmentation therapy in unipolar and bipolar depression: a systematic review and meta-analysis of randomized controlled trials. J Clin Psychiatry. 2013;74:1101–1117.
   PubMed Web of Science ®Google Scholar
• Insel T, Cuthbert B, Garvey M, et al. Research domain criteria (RDoC): toward a new classification framework for research on mental disorders. Am J Psychiatry. 2010 Jul;167(7):748–751. .
   PubMed Web of Science ®Google Scholar
• Nummenmaa L, Tuominen L. Opioid system and human emotions. Br J Pharmacol. 2018;175:2737–2749.
   PubMed Web of Science ®Google Scholar
• Serafini G, Adavastro G, Canepa G, et al. The efficacy of buprenorphine in major depression, treatment-resistant depression and suicidal behavior: a systematic review. Int J Mol Sci. 2018;19:2410.
   PubMed Web of Science ®Google Scholar
• Dinoff A, Lynch ST, Sekhri N, et al. A meta-analysis of the potential antidepressant effects of buprenorphine versus placebo as an adjunctive pharmacotherapy for treatment-resistant depression. J Affect Disord. 2020;271:91–99.
   PubMed Web of Science ®Google Scholar
• Fava M, Thase ME, Trivedi MH, et al. Opioid system modulation with buprenorphine/samidorphan combination for major depressive disorder: two randomized controlled studies. Mol Psychiatry. 2020;25:1580–1591.
   PubMed Web of Science ®Google Scholar
• Sharma A, Gerbarg P, Bottiglieri T, et al. S-Adenosylmethionine (SAMe) for neuropsychiatric disorders: a clinician-oriented review of research. J Clin Psychiatry. 2017;78:e656–e67.
   PubMed Web of Science ®Google Scholar
• Cuomo A, Crescenzi BB, Bolognesi S, et al. S-Adenosylmethionine (SAMe) in major depressive disorder (MDD): a clinician-oriented systematic review. Ann Gen Psychiatry. 2020;19:50.
   PubMed Web of Science ®Google Scholar
• Papakostas GI, Shelton RC, Zajecka JM, et al. L-methylfolate as adjunctive therapy for SSRI-resistant major depression: results of two randomized, double-blind, parallel-sequential trials. Am J Psychiatry. 2012;169:1267–1274.
   PubMed Web of Science ®Google Scholar
• Roberts E, Carter B, Young AH. Caveat emptor: folate in unipolar depressive illness, a systematic review and meta-analysis. J Psychopharmacol. 2018;32:377–384.
   PubMed Web of Science ®Google Scholar
• Wan L, Li Y, Zhang Z, et al. Methylenetetrahydrofolate reductase and psychiatric diseases. Transl Psychiatry. 2018;8:242.
   PubMed Web of Science ®Google Scholar
• Shelton RC, Pencina MJ, Barrentine LW, et al. Association of obesity and inflammatory marker levels on treatment outcome: results from a double-blind, randomized study of adjunctive L-methylfolate calcium in patients with MDD who are inadequate responders to SSRIs. J Clin Psychiatry. 2015;76:1635–1641.
   PubMed Web of Science ®Google Scholar
• Berman RM, Cappiello A, Anand A, et al. Antidepressant effects of ketamine in depressed patients. Biol Psychiatry. 2000 Feb 15;47(4):351–354.
   PubMed Web of Science ®Google Scholar
• Zarate CA Jr., Du J, Quiroz J, et al. Regulation of cellular plasticity cascades in the pathophysiology and treatment of mood disorders: role of the glutamatergic system. Ann N Y Acad Sci. 2003 Nov;1003:273–291.
   PubMed Web of Science ®Google Scholar
• 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 Aug;63(8):856–864. .
   PubMed Web of Science ®Google Scholar
• Lener MS, Kadriu B, Zarate CA Jr. Ketamine and beyond: investigations into the potential of glutamatergic agents to treat depression. Drugs. 2017;77:381–401.
   PubMed Web of Science ®Google Scholar
• 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 Oct;3(175):150–158. .
   Google Scholar
• Swainson J, McGirr A, Blier P, et al. The Canadian Network for Mood and Anxiety Treatments (CANMAT) Task Force recommendations for the use of racemic ketamine in adults with major depressive disorder. Can J Psychiatry. 2020. epub ahead of print. doi: https://doi.org/10.1177/0706743720970860
   Google Scholar
• Gould TD, Zarate CAJ, Thompson SM. Molecular pharmacology and neurobiology of rapid-acting antidepressants. Annu Rev Pharmacol Toxicol. 2019;59:213–236.
   PubMed Web of Science ®Google Scholar
• Lener MS, Niciu MJ, Ballard ED, et al. Glutamate and gamma-aminobutyric acid systems in the pathophysiology of major depression and antidepressant response to ketamine. Biol Psychiatry. 2017;81:886–897.
   PubMed Web of Science ®Google Scholar
• Duman RS, Sanacora G, Krystal JH. Altered connectivity in depression: GABA and glutamate neurotransmitter deficits and reversal by novel treatments. Neuron. 2019;102:75–90.
   PubMed Web of Science ®Google Scholar
• Niciu MJ, Luckenbaugh DA, Ionescu DF, et al. Clinical predictors of ketamine response in treatment-resistant major depression. J Clin Psychiatry. 2014;75(5):417. .
   PubMed Web of Science ®Google Scholar
• Phelps LE, Brutsche N, Moral JR, et al. Family history of alcohol dependence and initial antidepressant response to an N-methyl-D-aspartate antagonist. Biol Psychiatry. 2009 Jan 15;65(2):181–184.
   PubMed Web of Science ®Google Scholar
• Machado-Vieira R, Gold PW, Luckenbaugh DA, et al. The role of adipokines in the rapid antidepressant effects of ketamine. Mol Psychiatry. 2017 Jan;22(1):127–133. .
   PubMed Web of Science ®Google Scholar
• Salvadore G, van der Veen JW, Zhang Y, et al. An investigation of amino-acid neurotransmitters as potential predictors of clinical improvement to ketamine in depression. Int J Neuropsychopharmacol. 2012 Sep;15(8):1063–1072. .
   PubMed Web of Science ®Google Scholar
• Duncan WC Jr., Selter J, Brutsche N, et al. Baseline delta sleep ratio predicts acute ketamine mood response in major depressive disorder. J Affect Disord. 2013 Feb 15;145(1):115–119.
   PubMed Web of Science ®Google Scholar
• Salvadore G, Cornwell BR, Sambataro F, et al. Anterior cingulate desynchronization and functional connectivity with the amygdala during a working memory task predict rapid antidepressant response to ketamine. Neuropsychopharmacology. 2010 Jun;35(7):1415–1422. .
   PubMed Web of Science ®Google Scholar
• Laje G, Lally N, Mathews D, et al. Brain-derived neurotrophic factor Val66Met polymorphism and antidepressant efficacy of ketamine in depressed patients. Biol Psychiatry. 2012 Dec 1;72(11):e27–8.
   PubMed Web of Science ®Google Scholar
• Murrough JW, Wan LB, Iacoviello B, et al. Neurocognitive effects of ketamine in treatment-resistant major depression: association with antidepressant response. Psychopharmacology (Berl). epub ahead of print Sep 2013. doi: https://doi.org/10.1007/s00213-013-3255-x
   Google Scholar
• Kadriu B, Ballard ED, Henter ID, et al. Neurobiological biomarkers of response to ketamine. Adv Pharmacol. 2020;89:195–235.
   PubMedGoogle Scholar
• Luckenbaugh DA, Niciu MJ, Ionescu DF, et al. Do the dissociative side effects of ketamine mediate its antidepressant effects? J Affect Disord. 2014 Apr;159:56–61.
   PubMed Web of Science ®Google Scholar
• Ballard ED, Zarate CA. The role of dissociation in ketamine’s antidepressant effects. Nat Commun.
   Web of Science ®Google Scholar
• Kaiser RH, Andrews-Hanna JR, Wager TD, et al. Large-scale network dysfunction in major depressive disorder: a meta-analysis of resting-state functional connectivity. JAMA Psychiatry. 2015Jun1;72(6):603–611.
   PubMed Web of Science ®Google Scholar
• Greicius MD, Flores BH, Menon V, et al. Resting-state functional connectivity in major depression: abnormally increased contributions from subgenual cingulate cortex and thalamus. Biol Psychiatry. 2007 Sep 01;62(5):429–437.
   PubMed Web of Science ®Google Scholar
• Drevets WC, Savitz J, Trimble M. The subgenual anterior cingulate cortex in mood disorders. CNS Spectr. 2008 Aug;13(8):663–681.
   PubMed Web of Science ®Google Scholar
• Pizzagalli DA. Frontocingulate dysfunction in depression: toward biomarkers of treatment response. Neuropsychopharmacology. 2011 Jan;36(1):183–206.
   PubMed Web of Science ®Google Scholar
• Scheidegger M, Walter M, Lehmann M, et al. Ketamine decreases resting state functional network connectivity in healthy subjects: implications for antidepressant drug action. PLoS One. 2012;7(9):e44799. .
   PubMed Web of Science ®Google Scholar
• Gilbert JR, Zarate CA. Electrophysiological biomarkers of antidepressant response to ketamine in treatment-resistant depression: gamma power and long-term potentiation. Pharmacol Biochem Behav. 2020;189:172856.
   PubMed Web of Science ®Google Scholar
• Garay RP, Zarate CA Jr., Charpeaud T, et al. Investigational drugs in recent clinical trials for treatment-resistant depression. Expert Rev Neurother. 2017 Jun;17(6):593–609. .
   PubMed Web of Science ®Google Scholar
• Kadriu B, Musazzi L, Henter ID, et al. Glutamatergic neurotransmission: pathway to developing novel rapid-acting antidepressant treatments. Int J Neuropsychopharmacol. 2019Feb1;22(2):119–135.
   PubMed Web of Science ®Google Scholar
• Zanos P, Thompson SM, Duman RS, et al. Convergent mechanisms underlying rapid antidepressant action. CNS Drugs. 2018 Mar;32(3):197–227.
   PubMed Web of Science ®Google Scholar
• Machado-Vieira R, Henter ID, Zarate Jr. CA Jr. New targets for rapid antidepressant action. Prog Neurobiol. 2017;152:21–37.
   PubMed Web of Science ®Google Scholar
• Rosenblat JD, Cha DS, Mansur RB, et al. Inflamed moods: a review of the interactions between inflammation and mood disorders. Prog Neuropsychopharmacol Biol Psychiatry. 2014;53:23–34.
   PubMed Web of Science ®Google Scholar
• Beurel E, Toups M, Nemeroff CB. The bidirectional relationship of depression and inflammation: double trouble. Neuron. 2020;107:234–256.
   PubMed Web of Science ®Google Scholar
• Cattaneo A, Ferrari C, Turner L, et al. Whole-blood expression of inflammasome- and glucocorticoid-related mRNAs correctly separates treatment-resistant depressed patients from drug-free and responsive patients in the BIODEP study. Transl Psychiatry. 2020;10:232.
   PubMed Web of Science ®Google Scholar
• Enache D, Pariante CM, Mondelli V. Markers of central inflammation in major depressive disorder: a systematic review and meta-analysis of studies examining cerebrospinal fluid, positron emission tomography and post-mortem brain tissue. Brain Behav Immun. 2019;81:24–40. .
   PubMed Web of Science ®Google Scholar
• Lu Y, Ho CS, Liu X, et al. Chronic administration of fluoxetine and pro-inflammatory cytokine change in a rat model of depression. PLoS One. 2017;12:e0186700.
   PubMed Web of Science ®Google Scholar
• Festa A, D’Agostino RJ, Williams K, et al. The relation of body fat mass and distribution to markers of chronic inflammation. Int J Obes Relat Metab Disord. 2001;25:1407–1415.
   PubMed Web of Science ®Google Scholar
• Rong C, Park C, Rosenblat JD, et al. Predictors of response to ketamine in treatment resistant major depressive disorder and bipolar disorder. Int J Environ Res Public Health. 2001;25(10):771.
   Google Scholar
• Giacobbe J, Benoiton B, Zunszain P, et al. The anti-inflammatory role of omega-3 polyunsaturated fatty acids metabolites in pre-clinical models of psychiatric, neurodegenerative, and neurological disorders. Front Psychiatry. 2020;11:122.
   PubMed Web of Science ®Google Scholar
• Nikkheslat N, McLaughlin AP, Hastings C, et al. Childhood trauma, HPA axis activity and antidepressant response in patients with depression. Brain Behav Immun. 2020;87:229–237.
   PubMed Web of Science ®Google Scholar
• Majidi J, Kosari-Nasab M, A-a S. Developmental minocycline treatment reverses the effects of neonatal immune activation on anxiety- and depression-like behaviors, hippocampal inflammation, and HPA axis activity in adult mice. Brain Res Bull. 2016;120:1–13.
   PubMed Web of Science ®Google Scholar
• Rosenblat JD, McIntyre RS. Efficacy and tolerability of minocycline for depression: a systematic review and meta-analysis of clinical trials. J Affect Disord. 2018;227:219–225.
   PubMed Web of Science ®Google Scholar
• Soczynska JK, Mansur RB, Brietzke E, et al. Novel therapeutic targets in depression: minocycline as a candidate treatment. Behav Brain Res. 2012;235:302–317.
   PubMed Web of Science ®Google Scholar
• Husain MI, Cullen C, Umer M, et al. Minocycline as adjunctive treatment for treatment-resistant depression: study protocol for a double blind, placebo-controlled, randomized trial (MINDEP2). BMC Psychiatry. 2020;20:173.
   PubMed Web of Science ®Google Scholar
• Faridhosseini F, Sadeghi R, Farid L, et al. Celecoxib: a new augmentation strategy for depressive mood episodes. A systematic review and meta-analysis of randomized placebo-controlled trials. 2014;29(3):216–223. Human psychopharmacology.
   PubMed Web of Science ®Google Scholar
• Berk M, Woods RL, Nelson MR, et al. Effect of aspirin vs placebo on the prevention of depression in older people: a randomized clinical trial. JAMA Psychiatry. 2020;77:1012–1020.
   PubMedGoogle Scholar
• Raison CL, Rutherford RE, Woolwine BJ, et al. A randomized controlled trial of the tumor necrosis factor antagonist infliximab for treatment-resistant depression: the role of baseline inflammatory biomarkers. JAMA Psychiatry. 2013 Jan;70(1):31–41. .
   PubMed Web of Science ®Google Scholar
• Attwells S, Setiawan E, Rusjan P, et al. Translocator protein distribution volume predicts reduction of symptoms during open-label trial of celecoxib in major depressive disorder. Biol Psychiatry. 2020;88:649–656.
   PubMed Web of Science ®Google Scholar
• Ijaz S, Davies P, Williams CJ, et al. Psychological therapies for treatment‐resistant depression in adults. Cochrane Database Syst Rev. 2018;14:CD010558.
   Google Scholar
• Van Bronswijk S, Moopen N, Beijers L, et al. Effectiveness of psychotherapy for treatment-resistant depression: a meta-analysis and meta-regression. Psychol Med. 2019;49:366–379.
   PubMed Web of Science ®Google Scholar
• McClintock SM, Kallioniemi E, Martin DM, et al. A critical review and synthesis of clinical and neurocognitive effects of noninvasive neuromodulation antidepressant therapies. Focus (Am Psychiatr Publ). 2019;17:18–29.
   PubMedGoogle Scholar
• Vlaicu A, Vlaicu MB. New neuromodulation techniques for treatment resistant depression. Int J Psychiatry Clin Pract. 2020;24:106–115.
   PubMed Web of Science ®Google Scholar
• Brouwers MC, Kho ME, Browman GP, et al. AGREE II: advancing guideline development, reporting and evaluation in health care. CMAJ. 2010;182:E839–E42.
   PubMed Web of Science ®Google Scholar
• Hasan A, Bandelow B, Yatham LN, et al. WFSBP guidelines on how to grade treatment evidence for clinical guideline development. World J Biol Psychiatry. 2019;20:2–16.
   PubMed Web of Science ®Google Scholar
• Kraus C, Kadriu B, Lanzenberger R, et al. Prognosis and improved outcomes in major depression: a review. Transl Psychiatry. 2019;9:127. .
   PubMed Web of Science ®Google Scholar
• Dold M, Bartova L, Kasper S. Treatment response of add-on esketamine nasal spray in resistant major depression in relation to add-on second-generation antipsychotic treatment. Int J Neuropsychopharmacol. 2020;23:440–445.
   PubMed Web of Science ®Google Scholar
• Fornaro M, Giosue P. Current nosology of treatment resistant depression: a controversy resistant to revision. Clin Pract Epidemiol Ment Health. 2010;6:20–24.
   PubMedGoogle Scholar
• Trivedi MH. Right patient, right treatment, right time: biosignatures and precision medicine in depression. World Psychiatry. 2016;15:237–238.
   PubMed Web of Science ®Google Scholar
• Tansey KE, Guipponi M, Hu X, et al. Contribution of common genetic variants to antidepressant response. Biol Psychiatry. 2013;73:679–682.
   PubMed Web of Science ®Google Scholar
• Pérez V, Salavert A, Espadaler J, et al. Efficacy of prospective pharmacogenetic testing in the treatment of major depressive disorder: results of a randomized, double-blind clinical trial. BMC Psychiatry. 2017;17:250.
   PubMed Web of Science ®Google Scholar
• Cai N, Choi KW, Fried EI. Reviewing the genetics of heterogeneity in depression: operationalizations, manifestations and etiologies. Hum Mol Genet. 2020;29:R10–R18.
   PubMed Web of Science ®Google Scholar
• Akil H, Gordon J, Hen R, et al. Treatment resistant depression: a multi-scale, systems biology approach. Neurosci Biobehav Rev. 2018;84:272–288.
   PubMed Web of Science ®Google Scholar
• Spellman T, Liston C. Toward circuit mechanisms of pathophysiology in depression. Am J Psychiatry. 2020;177:381–390.
   PubMed Web of Science ®Google Scholar
• Trivedi MH, McGrath PJ, Fava M, et al. Establishing moderators and biosignatures of antidepressant response in clinical care (EMBARC): rationale and design. J Psychiatr Res. 2016;78:11–23.
   PubMed Web of Science ®Google Scholar
• Thompson PM, Jahanshad N, Ching CRK, et al. ENIGMA and global neuroscience: a decade of large-scale studies of the brain in health and disease across more than 40 countries. Transl Psychiatry. 2020 Mar 20;10(1):100. .
   PubMed Web of Science ®Google Scholar
• Wu W, Zhang Y, Jiang J, et al. An electroencephalographic signature predicts antidepressant response in major depression. Nat Biotechnol. 2020;38:439–447.
   PubMed Web of Science ®Google Scholar
• Anderson KM, Collins MA, Kong R, et al. Convergent molecular, cellular, and cortical neuroimaging signatures of major depressive disorder. Proc Natl Acad Sci USA. 2020;117:25138–25149.
   PubMed Web of Science ®Google Scholar