Treatment-Resistant Schizophrenia : Pathophysiology and Treatment

Euitae Kim

doi:10.4306/jknpa.2018.57.3.230

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Kim: Treatment-Resistant Schizophrenia : Pathophysiology and Treatment

Special Article

Current Knowledge and Treatment Strategies of Ultra-High Risk for Psychosis and Schizophrenia

Journal of Korean Neuropsychiatric Association 2018; 57(3): 230-234.

Published online: 29 August 2018

DOI: https://doi.org/10.4306/jknpa.2018.57.3.230

Treatment-Resistant Schizophrenia : Pathophysiology and Treatment

Euitae Kim, MD, PhD

Department of Psychiatry, College of Medicine, Seoul National University, Seoul, Korea.

Department of Neuropsychiatry, Seoul National University Bundang Hospital, Seongnam, Korea.

Address for correspondence: Euitae Kim, MD, PhD. Department of Psychiatry, College of Medicine, Seoul National University, Department of Neuropsychiatry, Seoul National University Bundang Hospital, 82 Gumi-ro 173beon-gil, Bundang-gu, Seongnam 13620, Korea. Tel +82-31-787-7435, Fax +82-31-787-4058, euitae.kim@snu.ac.kr

Received 19 July 2018 Revised 31 July 2018 Accepted 16 August 2018

Korean Neuropsychiatric Association

Abstract

A large proportion of patients with schizophrenia show a poor response to first-line antipsychotic drugs, which is termed treatment-resistant schizophrenia. Previous studies found that a different neurobiology might underlie treatment-resistant schizophrenia, which necessitates the development of different therapeutic approaches for treating treatment-resistant schizophrenia. This study reviewed previous studies on the pathophysiology of treatment-resistant schizophrenia and the pharmacological intervention, and forthcoming investigations of treatment-resistant schizophrenia are suggested.

Keywords: Treatment-resistant, Schizophrenia, Neurobiology, Strategy

Notes

^{Conflicts of Interest} The authors have no financial conflicts of interest.

References

1. Howes OD, Murray RM. Schizophrenia: an integrated sociodevelopmental-cognitive model. Lancet. 2014; 383:1677–1687.

2. López-Muñoz F, Alamo C, Cuenca E, Shen WW, Clervoy P, Rubio G. History of the discovery and clinical introduction of chlorpromazine. Ann Clin Psychiatry. 2005; 17:113–135.

3. Rössler W, Salize HJ, van Os J, Riecher-Rössler A. Size of burden of schizophrenia and psychotic disorders. Eur Neuropsychopharmacol. 2005; 15:399–409.

4. Claghorn J, Honigfeld G, Abuzzahab FS Sr, Wang R, Steinbook R, Tuason V, et al. The risks and benefits of clozapine versus chlorpromazine. J Clin Psychopharmacol. 1987; 7:377–384.

5. Lehman AF, Lieberman JA, Dixon LB, McGlashan TH, Miller AL, Perkins DO, et al. Practice guideline for the treatment of patients with schizophrenia, second edition. Am J Psychiatry. 2004; 161:2 Suppl. 1–56.

6. Hasan A, Falkai P, Wobrock T, Lieberman J, Glenthoj B, Gattaz WF, et al. World Federation of Societies of Biological Psychiatry (WFSBP) Guidelines for Biological Treatment of Schizophrenia, part 1: update 2012 on the acute treatment of schizophrenia and the management of treatment resistance. World J Biol Psychiatry. 2012; 13:318–378.

7. Howes OD, McCutcheon R, Agid O, de Bartolomeis A, van Beveren NJ, Birnbaum ML, et al. Treatment-resistant schizophrenia: treatment response and resistance in psychosis (TRRIP) working group consensus guidelines on diagnosis and terminology. Am J Psychiatry. 2017; 174:216–229.

8. Royal Australian and New Zealand College of Psychiatrists Clinical Practice Guidelines Team for the Treatment of Schizophrenia and Related Disorders. Royal Australian and New Zealand College of Psychiatrists clinical practice guidelines for the treatment of schizophrenia and related disorders. Aust N Z J Psychiatry. 2005; 39:1–30.

9. Barnes TR. Schizophrenia Consensus Group of British Association for Psychopharmacology. Evidence-based guidelines for the pharmacological treatment of schizophrenia: recommendations from the British Association for Psychopharmacology. J Psychopharmacol. 2011; 25:567–620.

10. Verma S, Chan LL, Chee KS, Chen H, Chin SA, Chong SA, et al. Ministry of Health clinical practice guidelines: schizophrenia. Singapore Med J. 2011; 52:521–525. quiz 526.

11. McCutcheon R, Beck K, Bloomfield MA, Marques TR, Rogdaki M, Howes OD. Treatment resistant or resistant to treatment? Antipsychotic plasma levels in patients with poorly controlled psychotic symptoms. J Psychopharmacol. 2015; 29:892–897.

12. Kane JM, Kishimoto T, Correll CU. Non-adherence to medication in patients with psychotic disorders: epidemiology, contributing factors and management strategies. World Psychiatry. 2013; 12:216–226.

13. Velligan DI, Wang M, Diamond P, Glahn DC, Castillo D, Bendle S, et al. Relationships among subjective and objective measures of adherence to oral antipsychotic medications. Psychiatr Serv. 2007; 58:1187–1192.

14. Jónsdóttir H, Opjordsmoen S, Birkenaes AB, Engh JA, Ringen PA, Vaskinn A, et al. Medication adherence in outpatients with severe mental disorders: relation between self-reports and serum level. J Clin Psychopharmacol. 2010; 30:169–175.

15. Byerly M, Fisher R, Whatley K, Holland R, Varghese F, Carmody T, et al. A comparison of electronic monitoring vs. clinician rating of antipsychotic adherence in outpatients with schizophrenia. Psychiatry Res. 2005; 133:129–133.

16. Seeman P, Lee T. Antipsychotic drugs: direct correlation between clinical potency and presynaptic action on dopamine neurons. Science. 1975; 188:1217–1219.

17. Madras BK. History of the discovery of the antipsychotic dopamine D2 receptor: a basis for the dopamine hypothesis of schizophrenia. J Hist Neurosci. 2013; 22:62–78.

18. Kapur S, Seeman P. Does fast dissociation from the dopamine d(2) receptor explain the action of atypical antipsychotics?: a new hypothesis. Am J Psychiatry. 2001; 158:360–369.

19. Cross AJ, Crow TJ, Owen F. 3H-flupenthixol binding in post-mortem brains of schizophrenics: evidence for a selective increase in dopamine D2 receptors. Psychopharmacology (Berl). 1981; 74:122–124.

20. Howes OD, Kambeitz J, Kim E, Stahl D, Slifstein M, Abi-Dargham A, et al. The nature of dopamine dysfunction in schizophrenia and what this means for treatment. Arch Gen Psychiatry. 2012; 69:776–786.

21. Howes OD, Bose SK, Turkheimer F, Valli I, Egerton A, Valmaggia LR, et al. Dopamine synthesis capacity before onset of psychosis: a prospective [¹⁸F]-DOPA PET imaging study. Am J Psychiatry. 2011; 168:1311–1317.

22. Demjaha A, Murray RM, McGuire PK, Kapur S, Howes OD. Dopamine synthesis capacity in patients with treatment-resistant schizophrenia. Am J Psychiatry. 2012; 169:1203–1210.

23. Kim E, Howes OD, Veronese M, Beck K, Seo S, Park JW, et al. Presynaptic dopamine capacity in patients with treatment-resistant schizophrenia taking clozapine: an [¹⁸F]DOPA PET study. Neuropsychopharmacology. 2017; 42:941–950.

24. Mouchlianitis E, Bloomfield MA, Law V, Beck K, Selvaraj S, Rasquinha N, et al. Treatment-resistant schizophrenia patients show elevated anterior cingulate cortex glutamate compared to treatment-responsive. Schizophr Bull. 2016; 42:744–752.

25. Duncan GE, Moy SS, Knapp DJ, Mueller RA, Breese GR. Metabolic mapping of the rat brain after subanesthetic doses of ketamine: potential relevance to schizophrenia. Brain Res. 1998; 787:181–190.

26. Veerman SR, Schulte PF, de Haan L. The glutamate hypothesis: a pathogenic pathway from which pharmacological interventions have emerged. Pharmacopsychiatry. 2014; 47:121–130.

27. Agid O, Remington G, Kapur S, Arenovich T, Zipursky RB. Early use of clozapine for poorly responding first-episode psychosis. J Clin Psychopharmacol. 2007; 27:369–373.

28. Stansley BJ, Conn PJ. The therapeutic potential of metabotropic glutamate receptor modulation for schizophrenia. Curr Opin Pharmacol. 2018; 38:31–36.

29. Shim SS, Hammonds MD, Kee BS. Potentiation of the NMDA receptor in the treatment of schizophrenia: focused on the glycine site. Eur Arch Psychiatry Clin Neurosci. 2008; 258:16–27.

30. Asenjo Lobos C, Komossa K, Rummel-Kluge C, Hunger H, Schmid F, Schwarz S, et al. Clozapine versus other atypical antipsychotics for schizophrenia. Cochrane Database Syst Rev. 2010; 11:CD006633.

31. Nielsen J, Damkier P, Lublin H, Taylor D. Optimizing clozapine treatment. Acta Psychiatr Scand. 2011; 123:411–422.

32. Kapur S, Seeman P. Antipsychotic agents differ in how fast they come off the dopamine D2 receptors. Implications for atypical antipsychotic action. J Psychiatry Neurosci. 2000; 25:161–166.

33. Burki HR. Effects of fluperlapine on dopaminergic systems in rat brain. Psychopharmacology (Berl). 1986; 89:77–84.

34. Saller CF, Salama AI. Seroquel: biochemical profile of a potential atypical antipsychotic. Psychopharmacology (Berl). 1993; 112:285–292.

35. Barbui C, Accordini S, Nosè M, Stroup S, Purgato M, Girlanda F, et al. Aripiprazole versus haloperidol in combination with clozapine for treatment-resistant schizophrenia in routine clinical care: a randomized, controlled trial. J Clin Psychopharmacol. 2011; 31:266–273.

36. Taylor DM, Smith L, Gee SH, Nielsen J. Augmentation of clozapine with a second antipsychotic - a meta-analysis. Acta Psychiatr Scand. 2012; 125:15–24.

37. Barnes TRE, Leeson V, Paton C, Marston L, Osborn DP, Kumar R, et al. Amisulpride augmentation of clozapine for treatment-refractory schizophrenia: a double-blind, placebo-controlled trial. Ther Adv Psychopharmacol. 2018; 8:185–197.

38. Wang J, Omori IM, Fenton M, Soares B. Sulpiride augmentation for schizophrenia. Cochrane Database Syst Rev. 2010; 1:CD008125.

39. Fleischhacker WW, Heikkinen ME, Olié JP, Landsberg W, Dewaele P, McQuade RD, et al. Effects of adjunctive treatment with aripiprazole on body weight and clinical efficacy in schizophrenia patients treated with clozapine: a randomized, double-blind, placebo-controlled trial. Int J Neuropsychopharmacol. 2010; 13:1115–1125.

40. Parsons CG, Gilling K. Memantine as an example of a fast, voltage-dependent, open channel N-methyl-D-aspartate receptor blocker. Methods Mol Biol. 2007; 403:15–36.

41. Areosa SA, Sherriff F, McShane R. Memantine for dementia. Cochrane Database Syst Rev. 2005; 20:CD003154.

42. Veerman SR, Schulte PF, Smith JD, de Haan L. Memantine augmentation in clozapine-refractory schizophrenia: a randomized, doubleblind, placebo-controlled crossover study. Psychol Med. 2016; 46:1909–1921.

43. Veerman SR, Schulte PF, Deijen JB, de Haan L. Adjunctive memantine in clozapine-treated refractory schizophrenia: an open-label 1-year extension study. Psychol Med. 2017; 47:363–375.

44. Tiihonen J, Wahlbeck K, Kiviniemi V. The efficacy of lamotrigine in clozapine-resistant schizophrenia: a systematic review and meta-analysis. Schizophr Res. 2009; 109:10–14.

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