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Definition and Epidemiology of Treatment Resistance in Psychiatry

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Treatment Resistance in Psychiatry

Abstract

The current chapter discusses different aspects of treatment resistance in mental disorders. We will first describe the prevalence and disease burden of mental disorders, then we will have a closer look at treatment outcomes in psychiatry, and next we will focus on treatment resistance, its impact and strategies for improvement. It will become clear that, despite the rapidly increasing knowledge base for psychiatric treatments, there are still many unknowns and points for improvement. The aim of this chapter is to introduce the major elements of this discussion needed to appreciate the more specific aspects that will be treated in the subsequent chapters that focus on specific disorders.

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References

  1. Kessler RC, Berglund P, Demler O, Jin R, Merikangas KR, Walters EE. Lifetime prevalence and age-of-onset distributions of DSM-IV disorders in the National Comorbidity Survey Replication. Arch Gen Psychiatry. 2005;62(6):593–602.

    Article  PubMed  Google Scholar 

  2. Funk M, Ivbijaro G, editors. Integrating mental health into primary care: a global perspective. Geneva: WHO Press; 2008.

    Google Scholar 

  3. World Health Organization. Health statistics and information systems [Internet]. Geneva: World Health Organization; 2018. http://www.who.int/healthinfo/global_burden_disease/en/.

    Google Scholar 

  4. Bijl RV, Ravelli A. Current and residual functional disability associated with psychopathology: findings from the Netherlands Mental Health Survey and Incidence Study (NEMESIS). Psychol Med. 2000;30(3):657–68.

    Article  CAS  PubMed  Google Scholar 

  5. WHO International Consortium in Psychiatric Epidemiology. Cross-national comparisons of the prevalences and correlates of mental disorders. Bull World Health Organ. 2000;78(4):413–26.

    Google Scholar 

  6. Hirschfeld RM, Keller MB, Panico S, Arons BS, Barlow D, Davidoff F, et al. The national depressive and manic-depressive association consensus statement on the undertreatment of depression. JAMA. 1997;277(4):333–40.

    Article  CAS  PubMed  Google Scholar 

  7. Gøtzsche PC. Deadly medicines and organised crime: how big pharma has corrupted healthcare. London: Radcliffe Publishing; 2013.

    Google Scholar 

  8. Gøtzsche PC. Antidepressants are addictive and increase the risk of relapse. BMJ. 2016;352:i574.

    Article  PubMed  Google Scholar 

  9. Turner EH, Matthews AM, Linardatos E, Tell RA, Rosenthal R. Selective publication of antidepressant trials and its influence on apparent efficacy. N Engl J Med. 2008;358(3):252–60.

    Article  CAS  PubMed  Google Scholar 

  10. Turner EH. Publication bias, with a focus on psychiatry: causes and solutions. CNS Drugs. 2013;27(6):457–68.

    Article  PubMed  Google Scholar 

  11. Turner EH, Knoepflmacher D, Shapley L. Publication bias in antipsychotic trials: an analysis of efficacy comparing the published literature to the US Food and Drug Administration database. PLoS Med. 2012;9(3):e1001189.

    Article  PubMed  PubMed Central  Google Scholar 

  12. Roest AM, de Jonge P, Williams CD, de Vries YA, Schoevers RA, Turner EH. Reporting bias in clinical trials investigating the efficacy of second-generation antidepressants in the treatment of anxiety disorders: a report of 2 meta-analyses. JAMA Psychiatry. 2015;72(5):500–10.

    Article  PubMed  Google Scholar 

  13. Cuijpers P, van Straten A, van Schaik A, Andersson G. Psychological treatment of depression in primary care: a meta-analysis. Br J Gen Pract. 2009;59(559):e51–60.

    Article  PubMed  PubMed Central  Google Scholar 

  14. Driessen E, Hollon SD, Bockting CL, Cuijpers P, Turner EH. Does publication bias inflate the apparent efficacy of psychological treatment for major depressive disorder? A systematic review and meta-analysis of US National Institutes of Health-funded trials. PLoS One. 2015;10(9):e0137864.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  15. Ioannidis JP. Defending biomedical science in an era of threatened funding. JAMA. 2017;317(24):2483–4.

    Article  PubMed  Google Scholar 

  16. Kirsch I, Deacon BJ, Huedo-Medina TB, Scoboria A, Moore TJ, Johnson BT. Initial severity and antidepressant benefits: a meta-analysis of data submitted to the Food and Drug Administration. PLoS Med. 2008;5(2):e45.

    Article  PubMed  PubMed Central  Google Scholar 

  17. Leucht S, Arbter D, Engel RR, Kissling W, Davis JM. How effective are second-generation antipsychotic drugs? A meta-analysis of placebo-controlled trials. Mol Psychiatry. 2009;14(4):429–47.

    Article  CAS  PubMed  Google Scholar 

  18. Rabinowitz J, Werbeloff N, Mandel FS, Menard F, Marangell L, Kapur S. Initial depression severity and response to antidepressants v. placebo: patient-level data analysis from 34 randomised controlled trials. Br J Psychiatry. 2016;209(5):427–8.

    Article  PubMed  Google Scholar 

  19. Fountoulakis KN, Veroniki AA, Siamouli M, Möller HJ. No role for initial severity on the efficacy of antidepressants: results of a multi-meta-analysis. Ann Gen Psychiatry. 2013;12(1):26.

    Article  PubMed  PubMed Central  Google Scholar 

  20. Gibbons RD, Hur K, Brown CH, Davis JM, Mann JJ. Benefits from antidepressants: synthesis of 6-week patient-level outcomes from double-blind placebo-controlled randomized trials of fluoxetine and venlafaxine. Arch Gen Psychiatry. 2012;69(6):572–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Melander H, Salmonson T, Abadie E, Van Zwieten-Boot B. A regulatory Apologia – a review of placebo-controlled studies in regulatory submissions of new-generation antidepressants. Eur Neuropsychopharmacol. 2008;18(9):623–7.

    Article  CAS  PubMed  Google Scholar 

  22. Baldessarini RJ, Tondo L. Suicide risk and treatments for patients with bipolar disorder. JAMA. 2003;290(11):1517–9.

    Article  CAS  PubMed  Google Scholar 

  23. Cipriani A, Pretty H, Hawton K, Geddes JR. Lithium in the prevention of suicidal behavior and all-cause mortality in patients with mood disorders: a systematic review of randomized trials. Am J Psychiatry. 2005;162(10):1805–19.

    Article  PubMed  Google Scholar 

  24. Geddes JR, Carney SM, Davies C, Furukawa TA, Kupfer DJ, Frank E, et al. Relapse prevention with antidepressant drug treatment in depressive disorders: a systematic review. Lancet. 2003;361(9358):653–61.

    Article  CAS  PubMed  Google Scholar 

  25. Hansen R, Gaynes B, Thieda P, Gartlehner G, Deveaugh-Geiss A, Krebs E, et al. Meta-analysis of major depressive disorder relapse and recurrence with second-generation antidepressants. Psychiatr Serv. 2008;59(10):1121–30.

    Article  PubMed  PubMed Central  Google Scholar 

  26. Komossa K, Depping AM, Heres S, Kissling W, Davis JM, Leucht S. Maintenance treatment with antipsychotic drugs for schizophrenia. Cochrane Database Syst Rev. 2009;4:CD008016.

    Google Scholar 

  27. Naylor CD, Chen E, Strauss B. Measured enthusiasm: does the method of reporting trial results alter perception of therapeutic effectiveness? Ann Intern Med. 1992;117(11):916–21.

    Article  CAS  PubMed  Google Scholar 

  28. Goldacre B. Bad science. London: Fourth Estate; 2008.

    Google Scholar 

  29. Weimer K, Colloca L, Enck P. Placebo effects in psychiatry: mediators and moderators. Lancet Psychiatry. 2015;2(3):246–57.

    Article  PubMed  PubMed Central  Google Scholar 

  30. Thomson R. Side effects and placebo amplification. Br J Psychiatry. 1982;140:64–8.

    Article  CAS  PubMed  Google Scholar 

  31. Gaudiano BA, Herbert JD. Methodological issues in clinical trials of antidepressant medications: perspectives from psychotherapy outcome research. Psychother Psychosom. 2005;74(1):17–25.

    Article  PubMed  Google Scholar 

  32. Gracely RH, Dubner R, Deeter WR, Wolskee PJ. Clinicians’ expectations influence placebo analgesia. Lancet. 1985;1(8419):43.

    Article  CAS  PubMed  Google Scholar 

  33. Gryll SL, Katahn M. Situational factors contributing to the placebos effect. Psychopharmacology (Berlin). 1978;57(3):253–61.

    Article  CAS  Google Scholar 

  34. McQueen D, Cohen S, St. John-Smith P, Rampes H. Rethinking placebo in psychiatry: the range of placebo effects. BJPsych Adv. 2013;19(3):162–70.

    Google Scholar 

  35. Storosum JG, Elferink AJ, van Zwieten BJ, van den Brink W, Gersons BP, van Strik R, et al. Short-term efficacy of tricyclic antidepressants revisited: a meta-analytic study. Eur Neuropsychopharmacol. 2001;11(2):173–80.

    Article  CAS  PubMed  Google Scholar 

  36. Barbui C, Furukawa TA, Cipriani A. Effectiveness of paroxetine in the treatment of acute major depression in adults: a systematic re-examination of published and unpublished data from randomized trials. CMAJ. 2008;178(3):296–305.

    Article  PubMed  PubMed Central  Google Scholar 

  37. Hansen RA, Gartlehner G, Lohr KN, Gaynes BN, Carey TS. Efficacy and safety of second-generation antidepressants in the treatment of major depressive disorder. Ann Intern Med. 2005;143(6):415–26.

    Article  CAS  PubMed  Google Scholar 

  38. Watts SE, Turnell A, Kladnitski N, Newby JM, Andrews G. Treatment-as-usual (TAU) is anything but usual: a meta-analysis of CBT versus TAU for anxiety and depression. J Affect Disord. 2015;175:152–67.

    Article  PubMed  Google Scholar 

  39. Leucht S, Tardy M, Komossa K, Heres S, Kissling W, Salanti G, et al. Antipsychotic drugs versus placebo for relapse prevention in schizophrenia: a systematic review and meta-analysis. Lancet. 2012;379(9831):2063–71.

    Article  CAS  PubMed  Google Scholar 

  40. Storosum JG, Wohlfarthe T, Schene A, Elferink A, van Zwieten BJ, van den Brink W. Magnitude of effect of lithium in short-term efficacy studies of moderate to severe manic episode. Bipolar Disord. 2007;9(8):793–8.

    Article  CAS  PubMed  Google Scholar 

  41. Scherk H, Pajonk FG, Leucht S. Second-generation antipsychotic agents in the treatment of acute mania: a systematic review and meta-analysis of randomized controlled trials. Arch Gen Psychiatry. 2007;64(4):442–55.

    Article  CAS  PubMed  Google Scholar 

  42. Davis JM, Janicak PG, Hogan DM. Mood stabilizers in the prevention of recurrent affective disorders: a meta-analysis. Acta Psychiatr Scand. 1999;100(6):406–17.

    Article  CAS  PubMed  Google Scholar 

  43. Gijsman HJ, Geddes JR, Rendell JM, Nolen WA, Goodwin GM. Antidepressants for bipolar depression: a systematic review of randomized, controlled trials. Am J Psychiatry. 2004;161(9):1537–47.

    Article  PubMed  Google Scholar 

  44. Soomro GM, Altman D, Rajagopal S, Oakley-Browne M. Selective serotonin re-uptake inhibitors (SSRIs) versus placebo for obsessive compulsive disorder (OCD). Cochrane Database Syst Rev. 2008;1:CD001765.

    Google Scholar 

  45. Hans E, Hiller W. A meta-analysis of nonrandomized effectiveness studies on outpatient cognitive behavioral therapy for adult anxiety disorders. Clin Psychol Rev. 2013;33(8):954–64.

    Article  PubMed  Google Scholar 

  46. Mitte K. A meta-analysis of the efficacy of psycho- and pharmacotherapy in panic disorder with and without agoraphobia. J Affect Disord. 2005;88(1):27–45.

    Article  PubMed  Google Scholar 

  47. Schachter HM, Pham B, King J, Langford S, Moher D. How efficacious and safe is short-acting methylphenidate for the treatment of attention-deficit disorder in children and adolescents? A meta-analysis. CMAJ. 2001;165(11):1475–88.

    CAS  PubMed  PubMed Central  Google Scholar 

  48. Faraone SV, Biederman J. Efficacy of Adderall for attention-deficit/hyperactivity disorder: a meta-analysis. J Atten Disord. 2002;6(2):69–75.

    Article  CAS  PubMed  Google Scholar 

  49. Cheng JY, Chen RY, Ko JS, Ng EM. Efficacy and safety of atomoxetine for attention-deficit/hyperactivity disorder in children and adolescents – meta-analysis and meta-regression analysis. Psychopharmacology. 2007;194(2):197–209.

    Article  CAS  PubMed  Google Scholar 

  50. Leucht S, Hierl S, Kissling W, Dold M, Davis JM. Putting the efficacy of psychiatric and general medicine medication into perspective: review of meta-analyses. Br J Psychiatry. 2012;200(2):97–106.

    Article  PubMed  Google Scholar 

  51. Bijkersma-Pot LM, Cuijpers P, Beekman AT, Schoevers RA. Comparison of efficacy of psychiatric treatment versus treatment in general medicine. Tijdschr Psychiatry. 2016;58:751–8.

    CAS  Google Scholar 

  52. Nemeroff CB, editor. Management of treatment-resistant major psychiatric disorders. Oxford: Oxford University Press; 2012.

    Google Scholar 

  53. Jakovljevic M. Creative, person-centered and narrative psychopharmacotherapy or how to prevent and overcome treatment resistance in psychiatry. Psychiatr Danub. 2015;27(3):291–301.

    PubMed  Google Scholar 

  54. Rasmussen KG, Mueller M, Kellner CH, Knapp RG, Petrides G, Rummans TA, et al. Patterns of psychotropic medication use among patients with severe depression referred for electroconvulsive therapy: data from the Consortium for Research on Electroconvulsive Therapy. J ECT. 2006;22(2):116–23.

    Article  PubMed  Google Scholar 

  55. Rush AJ, Thase ME, Dubé S. Research issues in the study of difficult-to-treat depression. Biol Psychiatry. 2003;53(8):743–53.

    Article  PubMed  Google Scholar 

  56. Breyer-Pfaff U, Gaertner HJ, Giedke H. Plasma levels, psychophysiological variables, and clinical response to amitriptyline. Psychiatry Res. 1982;6(2):223–34.

    Article  CAS  PubMed  Google Scholar 

  57. Faravelli C, Ballerini A, Ambonetti A, Broadhurst AD, Das M. Plasma levels and clinical response during treatment with clomipramine. J Affect Disord. 1984;6(1):95–107.

    Article  CAS  PubMed  Google Scholar 

  58. Moleman P. Praktische psychofarmacologie. Houten: Bohn Stafleu van Loghum; 1998.

    Google Scholar 

  59. Crossley NA, Bauer M. Acceleration and augmentation of antidepressants with lithium for depressive disorders: two meta-analyses of randomized, placebo-controlled trials. J Clin Psychiatry. 2007;68(6):935–40.

    Article  CAS  PubMed  Google Scholar 

  60. Berlim MT, Turecki G. Definition, assessment, and staging of treatment-resistant refractory major depression: a review of current concepts and methods. Can J Psychiatry. 2007;52(1):46–54.

    Article  PubMed  Google Scholar 

  61. Zevin S, Benowitz NL. Drug interactions with tobacco smoking. An update. Clin Pharmacokinet. 1999;36(6):425–38.

    Article  CAS  PubMed  Google Scholar 

  62. Ravyn D, Ravyn V, Lowney R, Nasrallah HA. CYP450 pharmacogenetic treatment strategies for antipsychotics: a review of the evidence. Schizophr Res. 2013;149(1–3):1–14.

    Article  PubMed  Google Scholar 

  63. Simoons M, Mulder H, Schoevers RA, Ruhé HG, van Roon EN. Availability of CYP2D6 genotyping results in general practitioner and community pharmacy medical records. Pharmacogenomics. 2017;18(9):843–51.

    Article  CAS  PubMed  Google Scholar 

  64. Roy-Byrne P. Treatment-refractory anxiety; definition, risk factors, and treatment challenges. Dialogues Clin Neurosci. 2015;17(2):191–206.

    PubMed  PubMed Central  Google Scholar 

  65. Craske MG, Roy-Byrne P, Stein MB, Sullivan G, Hazlett-Stevens H, Bystritsky A, et al. CBT intensity and outcome for panic disorder in a primary care setting. Behav Ther. 2006;37(2):112–9.

    Article  PubMed  Google Scholar 

  66. Julius RJ, Novitsky MA Jr, Dublin WR. Medication adherence: a review of the literature and implications for clinical practice. J Psychiatr Pract. 2009;15(1):34–44.

    Article  PubMed  Google Scholar 

  67. Fava M. Diagnosis and definition of treatment-resistant depression. Biol Psychiatry. 2003;53(8):649–59.

    Article  PubMed  Google Scholar 

  68. Berlim MT, Turecki G. What is the meaning of treatment resistant/refractory major depression (TRD)? A systematic review of current randomized trials. Eur Neuropsychopharmacol. 2007;17(11):696–707.

    Article  CAS  PubMed  Google Scholar 

  69. Bystritsky A. Treatment-resistant anxiety disorders. Mol Psychiatry. 2006;11(9):805–14.

    Article  CAS  PubMed  Google Scholar 

  70. Huber CG, Naber D, Lambert M. Incomplete remission and treatment resistance in first-episode psychosis: definition, prevalence and predictors. Expert Opin Pharmacother. 2008;9(12):2027–38.

    Article  PubMed  Google Scholar 

  71. Frank E, Prien RF, Jarrett RB, Keller MB, Kupfer DJ, Lavori PW, et al. Conceptualization and rationale for consensus definitions of terms in major depressive disorder. Remission, recovery, relapse, and recurrence. Arch Gen Psychiatry. 1991;48(9):851–5.

    Article  CAS  PubMed  Google Scholar 

  72. Rubio JM, Olfson M, Villegas L, Pérez-Fuentes G, Wang S, Blanco C. Quality of life following remission of mental disorders: findings from the National Epidemiologic Survey on Alcohol and Related Conditions. J Clin Psychiatry. 2013;74(5):e445–50.

    Article  PubMed  Google Scholar 

  73. van der Voort TY, Seldenrijk A, van Meijel B, Goossens PJ, Beekman AT, Penninx BW, et al. Functional versus syndromal recovery in patients with major depressive disorder and bipolar disorder. J Clin Psychiatry. 2015;76(6):e809–14.

    Article  PubMed  Google Scholar 

  74. Malhi GS, Byrow Y. Is treatment-resistant depression a useful concept? Evid Based Ment Health. 2016;19(1):1–3.

    Article  PubMed  Google Scholar 

  75. Hollon SD, Ponniah K. A review of empirically supported psychological therapies for mood disorders in adults. Depress Anxiety. 2010;27(10):891–932.

    Article  PubMed  PubMed Central  Google Scholar 

  76. Hunot V, Churchill R, Silva de Lima M, Teixeira V. Psychological therapies for generalised anxiety disorder. Cochrane Database Syst Rev. 2007;1:CD001848.

    Google Scholar 

  77. Marazziti D, Carlini M, Dell’Osso L. Treatment strategies of obsessive-compulsive disorder and panic disorder/agoraphobia. Curr Top Med Chem. 2012;12(4):238–53.

    Article  CAS  PubMed  Google Scholar 

  78. Fekadu A, Wooderson S, Donaldson C, Markopoulou K, Masterson B, Poon L, et al. A multidimensional tool to quantify treatment resistance in depression: the Maudsley staging method. J Clin Psychiatry. 2009;70(2):177–84.

    Article  PubMed  Google Scholar 

  79. Ruhé HG, van Rooijen G, Spijker J, Peeters FP, Schene AH. Staging methods for treatment resistant depression. A systematic review. J Affect Disord. 2012;137(1–3):35–45.

    Article  PubMed  Google Scholar 

  80. Ferguson JM, Khan A, Mangano R, Entsuah R, Tzanis E. Relapse prevention of panic disorder in adult outpatient responders to treatment with venlafaxine extended release. J Clin Psychiatry. 2007;68(1):58–68.

    Article  CAS  PubMed  Google Scholar 

  81. Mochcovitch MD, Da Rocha Freire RC, Garcia RF, Nardi AE. Can long-term pharmacotherapy prevent relapses in generalized anxiety disorder? A systematic review. Clin Drug Investig. 2017;37(8):737–43.

    Article  CAS  PubMed  Google Scholar 

  82. Rush AJ, Trivedi MH, Wisniewsky SR, Nierenberg AA, Stewart JW, Warden D, et al. Acute and longer-term outcomes in depressed outpatients requiring one or several treatment steps: a STAR*D report. Am J Psychiatry. 2006;163(11):1905–17.

    Article  PubMed  Google Scholar 

  83. Tohen M, Hennen J, Zarate CM Jr, Baldessarini RJ, Strakowski SM, Stoll AL, et al. Two-year syndromal and functional recovery in 219 cases of first-episode major affective disorder with psychotic features. Am J Psychiatry. 2000;157(2):220–8.

    Article  CAS  PubMed  Google Scholar 

  84. Tohen M, Zarate CA Jr, Hennen J, Khalsa HM, Strakowski SM, Gebre-Medhin P, et al. The McLean-Harvard First-Episode Mania Study: prediction of recovery and first recurrence. Am J Psychiatry. 2003;160(12):2099–107.

    Article  PubMed  Google Scholar 

  85. Sienaert P, Lambrichts L, Dols A, De Fruyt J. Evidence-based treatment strategies for treatment-resistant bipolar depression: a systematic review. Bipolar Disord. 2013;15(1):61–9.

    Article  CAS  PubMed  Google Scholar 

  86. Solanki RK, Singh P, Munshi D. Current perspectives in the treatment of resistant schizophrenia. Indian J Psychiatry. 2009;51(4):254–60.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  87. Ruscio AM, Hallion LS, Lim CC, Aguilar-Gaxiola S, Al-Hamzawi A, Alonso J, et al. Cross-sectional comparison of the epidemiology of DSM-5 generalized anxiety disorder across the globe. JAMA Psychiatry. 2017;74(5):465–75.

    Article  PubMed  PubMed Central  Google Scholar 

  88. Kornstein SG, Schneider RK. Clinical features of treatment-resistant depression. J Clin Psychiatry. 2001;62(Suppl 16):18–25.

    CAS  PubMed  Google Scholar 

  89. Bennabi D, Aouizerate B, El-Hage W, Doumy O, Moliere F, Courtet P, et al. Risk factors for treatment resistance in unipolar depression: a systematic review. J Affect Disord. 2015;171:137–41.

    Article  CAS  PubMed  Google Scholar 

  90. Chen MH, Tsai SJ. Treatment-resistant panic disorder: clinical significance, concept and management. Prog Neuro-Psychopharmacol Biol Psychiatry. 2016;70:219–26.

    Article  Google Scholar 

  91. Treuer T, Tohen M. Predicting the course and outcome of bipolar disorder: a review. Eur Psychiatry. 2010;25(6):328–33.

    Article  CAS  PubMed  Google Scholar 

  92. Murray RM, van Os J. Predictors of outcome in schizophrenia. J Clin Psychopharmacol. 1998;18(2 Suppl 1):2S–4S.

    Article  CAS  PubMed  Google Scholar 

  93. Brückl TM, Urh M. ABCB1 genotyping in the treatment of depression. Pharmacogenomics. 2016;17(18):2039–69.

    Article  PubMed  CAS  Google Scholar 

  94. Mrazek DA, Hornberger JC, Altar CA, Degtiar I. A review of the clinical, economic, and societal burden of treatment-resistant depression: 1996–2013. Psychiatr Serv. 2014;65(8):977–87.

    Article  PubMed  Google Scholar 

  95. Mauskopf JA, Simon GE, Kalsekar A, Nimsch C, Dunayevich E, Cameron A. Nonresponse, partial response, and failure to achieve remission: humanistic and cost burden in major depressive disorder. Depress Anxiety. 2009;26(1):83–97.

    Article  PubMed  Google Scholar 

  96. Qiao J, Qian LJ, Zhao HF, Gong GH, Geng DQ. The relationship between quality of life and clinical phenotype in patients with treatment resistant and non-treatment resistant depression. Eur Rev Med Pharmacol Sci. 2017;21(10):2432–6.

    CAS  PubMed  Google Scholar 

  97. Paykel ES. Achieving gains beyond response. Acta Psychiatr Scand Suppl. 2002;415:12–7.

    Article  Google Scholar 

  98. Greden JF. The burden of disease for treatment-resistant depression. J Clin Psychiatry. 2001;62(Suppl 16):26–31.

    PubMed  Google Scholar 

  99. Carney RM, Freedland KE. Treatment-resistant depression and mortality after acute coronary syndrome. Am J Psychiatry. 2009;166(4):410–7.

    Article  PubMed  PubMed Central  Google Scholar 

  100. Fekadu A, Rane LJ, Wooderson SC, Markopoulou K, Poon L, Cleare AJ. Prediction of longer-term outcome of treatment-resistant depression in tertiary care. Br J Psychiatry. 2012;201(5):369–75.

    Article  PubMed  Google Scholar 

  101. Berk M, Berk L, Udina M, Moylan S, Stafford L, Hallam K, et al. Palliative models of care for later stages of mental disorder: maximizing recovery, maintaining hope, and building morale. Aust N Z J Psychiatry. 2012;46(2):92–9.

    Article  PubMed  Google Scholar 

  102. Lepine BA, Moreno RA, Campos RN, Couttolenc BF. Treatment-resistant depression increases health costs and resource utilization. Rev Bras Psiquiatr. 2012;34(4):379–88.

    Article  PubMed  Google Scholar 

  103. Crown WH, Finkelstein S, Berndt ER, Ling D, Poret AW, Rush AJ, et al. The impact of treatment-resistant depression on health care utilization and costs. J Clin Psychiatry. 2002;63(11):963–71.

    Article  PubMed  Google Scholar 

  104. Ivanova JI, Birnbaum HG, Kidolezi Y, Subramanian G, Khan SA, Stensland MD. Direct and indirect costs of employees with treatment-resistant and non-treatment-resistant major depressive disorder. Curr Med Res Opin. 2010;26(10):2475–84.

    Article  PubMed  Google Scholar 

  105. Regier DA, Narrow WE, Clarke D, Kraemer HC, Kuramoto SJ, Kuhl EA, et al. DSM-5 field trials in the United States and Canada, part II: test-retest reliability of selected categorical diagnoses. Am J Psychiatry. 2013;170(1):59–70.

    Article  PubMed  Google Scholar 

  106. Insel TR, Medicine CBN. Brain disorders? Precisely Sci. 2015;348(6234):499–500.

    CAS  Google Scholar 

  107. Strawbridge R, Young AH, Cleare AJ. Biomarkers for depression: recent insights, current challenges and future prospects. Neuropsychiatr Dis Treat. 2017;13:1245–62.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  108. McGorry PD, Hickie IB, Yung AR, Pantelis C, Jackson HJ. Clinical staging of psychiatric disorders: a heuristic framework for choosing earlier, safer and more effective interventions. Aust N Z J Psychiatry. 2006;40(8):616–22.

    Article  PubMed  Google Scholar 

  109. Guo T, Xiang YT, Xiao L, Hu CQ, Chiu HF, Ungvari GS, et al. Measurement-based care versus standard care for major depression: a randomized controlled trial with blind raters. Am J Psychiatry. 2015;172:1004–13.

    Article  PubMed  Google Scholar 

  110. Lambert MJ, Whipple JL, Hawkins EJ, Vermeersch DA, Nielsen SL, Smart DW. Is it time for clinicians to routinely track patient outcome? A meta-analysis. Clin Psychol Sci Pract. 2003;10(3):288–301.

    Article  Google Scholar 

  111. Scott K, Lewis CC. Using measurement-based care to enhance any treatment. Cogn Behav Pract. 2015;22(1):49–59.

    Article  PubMed  PubMed Central  Google Scholar 

  112. Moret C. Combination/augmentation strategies for improving the treatment of depression. Neuropsychiatr Dis Treat. 2005;1(4):301–9.

    CAS  PubMed  PubMed Central  Google Scholar 

  113. Gaynes BN, Dusetzina SB, Ellis AR, Hansen RA, Farley JF, Miller WC, et al. Treating depression after initial treatment failure. Directly comparing switch and augmenting strategies in STAR*D. J Clin Psychopharmacol. 2012;32(1):114–9.

    Article  PubMed  Google Scholar 

  114. Rush AJ, Trivedi MH, Stewart JW, Nierenberg AA, Fava M, Kurian BT, et al. Combining medications to enhance depression outcomes (CO-MED): acute and long-term outcomes of a single-blind randomized study. Am J Psychiatry. 2011;168(7):689–701.

    Article  PubMed  Google Scholar 

  115. Han Y, Chen J, Zou D, Zheng P, Li Q, Wang H, et al. Efficacy of ketamine in the rapid treatment of major depressive disorder: a meta-analysis of randomized, double-blind, placebo-controlled studies. Neuropsychiatr Dis Treat. 2016;12:2859–67.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  116. Kishimoto T, Chawla JM, Hagi K, Zarate CA, Kane JM, Bauer M, et al. Single-dose infusion ketamine and non-ketamine N-methyl-D-aspartate receptor antagonist for unipolar and bipolar depression: a meta-analysis of efficacy, safety and time trajectories. Psychol Med. 2016;46(7):1459–72.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  117. Rodriguez CI, Kegeles LS, Levinson A, Feng T, Marcus SM, Vermes D, et al. Randomized controlled crossover trial of ketamine in obsessive-compulsive disorder: proof-of-concept. Neuropsychopharmacology. 2013;38(12):2475–83.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  118. Sanacora G, Frye MA, McDonald W, Mathew SJ, Turner MS, Schatzberg AF, et al. A consensus statement on the use of ketamine in the treatment of mood disorders. JAMA Psychiatry. 2017;74(4):399–405.

    Article  PubMed  Google Scholar 

  119. Sommer IE, van Westrhenen R, Begemann MJ, de Witte LD, Leucht S, Kahn RS. Efficacy of anti-inflammatory agents to improve symptoms in patients with schizophrenia: an update. Schizophr Bull. 2014;40(1):181–91.

    Article  PubMed  Google Scholar 

  120. Collins PY, Patel V, Joestl SS, March D, Insel TR, Daar AS, et al. Grand challenges in global mental health. Nature. 2011;475(7354):27–30.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  121. Ledford H. Medical research: if depression were cancer. Nature. 2014;515(7526):82–4.

    Article  Google Scholar 

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Smith-Apeldoorn, S.Y., Veraart, J.K.E., Schoevers, R.A. (2019). Definition and Epidemiology of Treatment Resistance in Psychiatry. In: Kim, YK. (eds) Treatment Resistance in Psychiatry. Springer, Singapore. https://doi.org/10.1007/978-981-10-4358-1_1

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