Skip to main content
SpringerLink
Log in

Beyond Clinical Remission in First Episode Psychosis: Thoughts on Antipsychotic Maintenance vs. Guided Discontinuation in the Functional Recovery Era

  • Current Opinion
  • Published:
CNS Drugs Aims and scope Submit manuscript

Abstract

Treatment guidelines for first episode psychosis (FEP) recommend at least 1 year of antipsychotic treatment following remission; however, in light of some recent research and the preference of some individuals to discontinue their medication sooner, this recommendation can be questioned. The aim of this article is to appraise the current discontinuation studies given our views on how this field should progress. We conducted a review of randomized controlled trials investigating dose-reduction/medication discontinuation compared with treatment maintenance in clinically remitted FEP patients. Seven trials were identified, and these reported a higher rate of relapse in the dose reduction or discontinuation groups. Relapse rates were higher when a lower threshold for relapse was utilized. However, only three studies specified that concurrent psychosocial interventions were also provided, despite an evidence base for these interventions in reducing symptom severity and relapse. Length of follow-up may also be important, as the study with the longest follow-up (7 years), albeit with some methodological shortcomings, found greater functional recovery in the dose-reduction group and that relapse rates between the two groups (dose-reduction vs. maintenance) were equal after 3 years. Finally, in addition to discontinuation or dose reduction, a diagnosis of schizophrenia, a longer duration of illness, and poor premorbid functioning were associated with a greater risk of relapse. Further trials are needed in this area to establish the long-term risk-benefit ratio of antipsychotic medication in FEP. Meanwhile, young people with FEP who do not fulfil criteria for a diagnosis of a schizophrenia disorder, achieve clinical remission for at least 3 months, attain early functional recovery, and have good social support may be possible candidates for discontinuation of antipsychotic medication bolstered by effective psychosocial interventions provided in the context of a specialized FEP service.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Boter H, Peuskens J, Libiger J, Fleischhacker WW, Davidson M, Galderisi S, et al. Effectiveness of antipsychotics in first-episode schizophrenia and schizophreniform disorder on response and remission: an open randomized clinical trial (EUFEST). Schizophr Res. 2009;115(2–3):97–103.

    Article  PubMed  Google Scholar 

  2. Emsley R, Rabinowitz J, Medori R. Remission in early psychosis: Rates, predictors, and clinical and functional outcome correlates. Schizophr Res. 2007;89(1–3):129–39.

    Article  PubMed  Google Scholar 

  3. Early Psychosis Guidelines Working Group. Australian clinical guidelines for early psychosis. Melbourne: Orygen Youth Health; 2010.

    Google Scholar 

  4. International Early Psychosis Association Writing Group. International clinical practice guidelines for early psychosis. Br J Psychiatry. 2005;187(48):s120–4.

    Article  Google Scholar 

  5. Thompson A, Singh S, Birchwood M. Views of early psychosis clinicians on discontinuation of antipsychotic medication following symptom remission in first episode psychosis. Epub: Early Interv Psychiatry; 2015.

    Google Scholar 

  6. Coldham EL, Addington J, Addington D. Medication adherence of individuals with a first episode of psychosis. Acta Psychiatr Scand. 2002;106(4):286–90.

    Article  CAS  PubMed  Google Scholar 

  7. Sendt KV, Tracy DK, Bhattacharyya S. A systematic review of factors influencing adherence to antipsychotic medication in schizophrenia-spectrum disorders. Psychiatry Res. 2015;225(1–2):14–30.

    Article  PubMed  Google Scholar 

  8. Wiersma D, Nienhuis FJ, Slooff CJ, Giel R. Natural course of schizophrenic disorders: a 15-year followup of a Dutch incidence cohort. Schizophr Bull. 1998;24(1):75–85.

    Article  CAS  PubMed  Google Scholar 

  9. Emsley R, Nuamah I, Hough D, Gopal S. Treatment response after relapse in a placebo-controlled maintenance trial in schizophrenia. Schizophr Res. 2012;138(1):29–34.

    Article  PubMed  Google Scholar 

  10. Alvarez-Jimenez M, Gonzalez-Blanch C, Crespo-Facorro B, Hetrick S, Rodriguez-Sanchez JM, Perez-Iglesias R, et al. Antipsychotic-induced weight gain in chronic and first-episode psychotic disorders: a systematic critical reappraisal. CNS Drugs. 2008;22(7):547–62.

    Article  CAS  PubMed  Google Scholar 

  11. Foley DL, Morley KI. Systematic review of early cardiometabolic outcomes of the first treated episode of psychosis. Arch Gen Psychiatry. 2011;68(6):609–16.

    Article  PubMed  Google Scholar 

  12. Fusar-Poli P, Smieskova R, Kempton MJ, Ho BC, Andreasen NC, Borgwardt S. Progressive brain changes in schizophrenia related to antipsychotic treatment? A meta-analysis of longitudinal MRI studies. Neurosci Biobehav Rev. 2013;37(8):1680–91.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Radua J, Borgwardt S, Crescini A, Mataix-Cols D, Meyer-Lindenberg A, McGuire PK, et al. Multimodal meta-analysis of structural and functional brain changes in first episode psychosis and the effects of antipsychotic medication. Neurosci Biobehav Rev. 2012;36(10):2325–33.

    Article  CAS  PubMed  Google Scholar 

  14. Navari S, Dazzan P. Do antipsychotic drugs affect brain structure? A systematic and critical review of MRI findings. Psychol Med. 2009;39(11):1763–77.

    Article  CAS  PubMed  Google Scholar 

  15. van Haren NEM, Hulshoff Pol HE, Schnack HG, Cahn W, Mandl RCW, Collins DL, et al. Focal gray matter changes in schizophrenia across the course of the illness: a 5-year follow-up study. Neuropsychopharmacology. 2007;32(10):2057–66.

    Article  PubMed  Google Scholar 

  16. Mathalon DH, Sullivan EV, Lim KO, Pfefferbaum A. Progressive brain volume changes and the clinical course of schizophrenia in men: a longitudinal magnetic resonance imaging study. Arch Gen Psychiatry. 2001;58(2):148–57.

    Article  CAS  PubMed  Google Scholar 

  17. Lieberman J, Chakos M, Wu H, Alvir J, Hoffman E, Robinson D, et al. Longitudinal study of brain morphology in first episode schizophrenia. Biol Psychiatry. 2001;49(6):487–99.

    Article  CAS  PubMed  Google Scholar 

  18. Law H, Morrison AP. Recovery in psychosis: a Delphi study with experts by experience. Schizophr Bull. 2014;40(6):1347–55.

    Article  PubMed  PubMed Central  Google Scholar 

  19. Iyer SN, Mangala R, Anitha J, Thara R, Malla AK. An examination of patient-identified goals for treatment in a first-episode programme in Chennai, India. Early Interv Psychiatry. 2011;5(4):360–5.

    Article  PubMed  PubMed Central  Google Scholar 

  20. Chen EY, Hui CL, Lam MM, Chiu CP, Law CW, Chung DW, et al. Maintenance treatment with quetiapine versus discontinuation after one year of treatment in patients with remitted first episode psychosis: randomised controlled trial. BMJ. 2010;341:c4024.

    Article  PubMed  PubMed Central  Google Scholar 

  21. Wunderink L, Nienhuis FJ, Sytema S, Slooff CJ, Knegtering R, Wiersma D. Guided discontinuation versus maintenance treatment in remitted first-episode psychosis: relapse rates and functional outcome. J Clin Psychiatry. 2007;68(5):654–61.

    Article  PubMed  Google Scholar 

  22. Gaebel W, Riesbeck M, Wolwer W, Klimke A, Eickhoff M, von Wilmsdorff M, et al. Relapse prevention in first-episode schizophrenia: maintenance vs intermittent drug treatment with prodrome-based early intervention: results of a randomized controlled trial within the German Research Network on Schizophrenia. J Clin Psychiatry. 2011;72(2):205–18.

    Article  PubMed  Google Scholar 

  23. Boonstra G, Burger H, Grobbee DE, Kahn RS. Antipsychotic prophylaxis is needed after remission from a first psychotic episode in schizophrenia patients: results from an aborted randomised trial. Int J Psychiatry Clin Pract. 2011;15(2):128–34.

    Article  PubMed  Google Scholar 

  24. Gleeson JF, Alvarez-Jimenez M, Cotton SM, Parker AG, Hetrick S. A systematic review of relapse measurement in randomized controlled trials of relapse prevention in first-episode psychosis. Schizophr Res. 2010;119(1–3):79–88.

    Article  PubMed  Google Scholar 

  25. Bird V, Premkumar P, Kendall T, Whittington C, Mitchell J, Kuipers E. Early intervention services, cognitive-behavioural therapy and family intervention in early psychosis: systematic review. Br J Psychiatry. 2010;197(5):350–6.

    Article  PubMed  PubMed Central  Google Scholar 

  26. Morrison AP, Turkington D, Pyle M, Spencer H, Brabban A, Dunn G, et al. Cognitive therapy for people with schizophrenia spectrum disorders not taking antipsychotic drugs: a single-blind randomised controlled trial. Lancet. 2014;383(9926):1395–403.

    Article  PubMed  Google Scholar 

  27. Wunderink L, Nieboer RM, Wiersma D, Sytema S, Nienhuis FJ. Recovery in remitted first-episode psychosis at 7 years of follow-up of an early dose reduction/discontinuation or maintenance treatment strategy: long-term follow-up of a 2-year randomized clinical trial. JAMA Psychiatry. 2013;70(9):913–20.

    Article  PubMed  Google Scholar 

  28. Crow TJ, MacMillan JF, Johnson AL, Johnstone EC. A randomised controlled trial of prophylactic neuroleptic treatment. Br J Psychiatry. 1986;148:120–7.

    Article  CAS  PubMed  Google Scholar 

  29. Kane JM, Rifkin A, Quitkin F, Nayak D, Ramos-Lorenzi J. FLuphenazine vs placebo in patients with remitted, acute first-episode schizophrenia. Arch Gen Psychiatry. 1982;39(1):70–3.

    Article  CAS  PubMed  Google Scholar 

  30. McGorry PD, Edwards J, Mihalopoulos C, Harrigan SM, Jackson HJ. EPPIC: an evolving system of early detection and optimal management. Schizophr Bull. 1996;22(2):305–26.

    Article  CAS  PubMed  Google Scholar 

  31. McGorry PD, Killackey E, Yung A. Early intervention in psychosis: concepts, evidence and future directions. World Psychiatry. 2008;7(3):148–56.

    Article  PubMed  PubMed Central  Google Scholar 

  32. Craig TK, Garety P, Power P, Rahaman N, Colbert S, Fornells Ambrojo M, et al. The Lambeth Early Onset (LEO) Team: randomised controlled trial of the effectiveness of specialised care for early psychosis. BMJ. 2004;329(7474):1067.

    Article  PubMed  PubMed Central  Google Scholar 

  33. Alvarez-Jimenez M, Parker AG, Hetrick SE, McGorry PD, Gleeson JF. Preventing the second episode: a systematic review and meta-analysis of psychosocial and pharmacological trials in first-episode psychosis. Schizophr Bull. 2011;37(3):619–30.

    Article  PubMed  PubMed Central  Google Scholar 

  34. Petersen L, Jeppesen P, Thorup A, Abel MB, Ohlenschlaeger J, Christensen TO, et al. A randomised multicentre trial of integrated versus standard treatment for patients with a first episode of psychotic illness. BMJ. 2005;331(7517):602.

    Article  PubMed  PubMed Central  Google Scholar 

  35. Melle I, Larsen TK, Haahr U, Friis S, Johannessen JO, Opjordsmoen S, et al. Reducing the duration of untreated first-episode psychosis: effects on clinical presentation. Arch Gen Psychiatry. 2004;61(2):143–50.

    Article  PubMed  Google Scholar 

  36. Penn DL, Waldheter EJ, Perkins DO, Mueser KT, Lieberman JA. Psychosocial treatment for first-episode psychosis: a research update. Am J Psychiatry. 2005;162(12):2220–32.

    Article  PubMed  Google Scholar 

  37. Kapur S. A new framework for investigating antipsychotic action in humans: lessons from PET imaging. Mol Psychiatry. 1998;3(2):135–40.

    Article  CAS  PubMed  Google Scholar 

  38. McGorry P, Alvarez-Jimenez M, Killackey E. Antipsychotic medication during the critical period following remission from first-episode psychosis: less is more. JAMA Psychiatry. 2013;70(9):898–900.

    Article  PubMed  Google Scholar 

  39. Artaloytia JF, Arango C, Lahti A, Sanz J, Pascual A, Cubero P, et al. Negative signs and symptoms secondary to antipsychotics: a double-blind, randomized trial of a single dose of placebo, haloperidol, and risperidone in healthy volunteers. Am J Psychiatry. 2006;163(3):488–93.

    Article  PubMed  Google Scholar 

  40. Kim JH, Son YD, Kim HK, Lee SY, Cho SE, Kim YB, et al. Antipsychotic-associated mental side effects and their relationship to dopamine D2 receptor occupancy in striatal subdivisions: a high-resolution PET study with [11C]raclopride. J Clin Psychopharmacol. 2011;31(4):507–11.

    Article  PubMed  Google Scholar 

  41. Gleeson JF, Cotton SM, Alvarez-Jimenez M, Wade D, Gee D, Crisp K, et al. A randomized controlled trial of relapse prevention therapy for first-episode psychosis patients. J Clin Psychiatry. 2009;70(4):477–86.

    Article  PubMed  Google Scholar 

  42. Gleeson JF, Cotton SM, Alvarez-Jimenez M, Wade D, Gee D, Crisp K, et al. A randomized controlled trial of relapse prevention therapy for first-episode psychosis patients: outcome at 30-month follow-up. Schizophr Bull. 2013;39(2):436–48.

    Article  PubMed  PubMed Central  Google Scholar 

  43. Killackey E, Jackson HJ, McGorry PD. Vocational intervention in first-episode psychosis: individual placement and support v. treatment as usual. Br J Psychiatry. 2008;193(2):114–20.

    Article  PubMed  Google Scholar 

  44. Jackson HM, McGorry PD. The recognition and management of early psychosis: a preventive approach, 2nd ed. Cambridge: Cambridge University Press; 2009.

  45. Schimmelmann BG, Huber CG, Lambert M, Cotton S, McGorry PD, Conus P. Impact of duration of untreated psychosis on pre-treatment, baseline, and outcome characteristics in an epidemiological first-episode psychosis cohort. J Psychiatr Res. 2008;42(12):982–90.

    Article  PubMed  Google Scholar 

  46. Melle I, Haahr U, Friis S, Hustoft K, Johannessen JO, Larsen TK, et al. Reducing the duration of untreated first-episode psychosis—effects on baseline social functioning and quality of life. Acta Psychiatr Scand. 2005;112(6):469–73.

    Article  CAS  PubMed  Google Scholar 

  47. 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 NZ J Psychiat. 2006;40(8):616–22.

    Article  Google Scholar 

  48. Marshall M, Lewis S, Lockwood A, Drake R, Jones P, Croudace T. Association between duration of untreated psychosis and outcome in cohorts of first-episode patients: a systematic review. Arch Gen Psychiatry. 2005;62(9):975–83.

    Article  PubMed  Google Scholar 

  49. Sansonnet-Hayden H, Haley G, Marriage K, Fine S. Sexual abuse and psychopathology in hospitalised adolescents. J Am Acad Child Adolesc Psychiatry. 1987;26:753–7.

    Article  CAS  PubMed  Google Scholar 

  50. Andreasen NC, Carpenter WT Jr, Kane JM, Lasser RA, Marder SR, Weinberger DR. Remission in schizophrenia: proposed criteria and rationale for consensus. Am J Psychiatry. 2005;162(3):441–9.

    Article  PubMed  Google Scholar 

  51. Cassidy CM, Norman R, Manchanda R, Schmitz N, Malla A. Testing definitions of symptom remission in first-episode psychosis for prediction of functional outcome at 2 years. Schizophr Bull. 2010;36(5):1001–8.

    Article  PubMed  PubMed Central  Google Scholar 

  52. Day JC, Bentall RP, Roberts C, Randall F, Rogers A, Cattell D, et al. Attitudes toward antipsychotic medication: the impact of clinical variables and relationships with health professionals. Arch Gen Psychiatry. 2005;62(7):717–24.

    Article  PubMed  Google Scholar 

  53. Morrison AP, Hutton P, Shiers D, Turkington D. Antipsychotics: is it time to introduce patient choice? Br J Psychiatry. 2012;201:83–4.

    Article  PubMed  Google Scholar 

  54. Alvarez-Jimenez M, Bendall S, Lederman R, Wadley G, Chinnery G, Vargas S, et al. On the HORYZON: moderated online social therapy for long-term recovery in first episode psychosis. Schizophr Res. 2013;143(1):143–9.

    Article  CAS  PubMed  Google Scholar 

  55. McCreadie RG, Wiles D, Grant S, Crockett GT, Mahmood Z, Livingston MG, et al. The Scottish first episode schizophrenia study. Acta Psychiatr Scand. 1989;80(6):597–602.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Author notes

    Authors and Affiliations

    1. Orygen, The National Centre of Excellence in Youth Mental Health, 35 Poplar Rd, Parkville, Melbourne, VIC, 3052, Australia

      M. Alvarez-Jimenez, B. O’Donoghue, S. Bendall, E. Killackey & P. D. McGorry

    2. Centre for Youth Mental Health, The University of Melbourne, Melbourne, VIC, Australia

      M. Alvarez-Jimenez, B. O’Donoghue, S. Bendall, E. Killackey & P. D. McGorry

    3. Division of Mental Health and Wellbeing, University of Warwick, Warwick, UK

      A. Thompson

    4. School of Psychology, Australian Catholic University, Melbourne, VIC, Australia

      J. F. Gleeson

    5. Mental Health Centre, University Hospital ‘Marques de Valdecilla’, Santander, Spain

      C. Gonzalez-Blanch

    6. Education and Research, Friesland Mental Health Services, Leeuwarden and University Medical Center Groningen, Sixmastraat 2, 8932 PA, Leeuwarden, The Netherlands

      L. Wunderink

    Authors
    1. M. Alvarez-Jimenez
      View author publications

      You can also search for this author in PubMed Google Scholar

    2. B. O’Donoghue
      View author publications

      You can also search for this author in PubMed Google Scholar

    3. A. Thompson
      View author publications

      You can also search for this author in PubMed Google Scholar

    4. J. F. Gleeson
      View author publications

      You can also search for this author in PubMed Google Scholar

    5. S. Bendall
      View author publications

      You can also search for this author in PubMed Google Scholar

    6. C. Gonzalez-Blanch
      View author publications

      You can also search for this author in PubMed Google Scholar

    7. E. Killackey
      View author publications

      You can also search for this author in PubMed Google Scholar

    8. L. Wunderink
      View author publications

      You can also search for this author in PubMed Google Scholar

    9. P. D. McGorry
      View author publications

      You can also search for this author in PubMed Google Scholar

    Corresponding authors

    Correspondence to M. Alvarez-Jimenez or B. O’Donoghue.

    Ethics declarations

    Conflict of interest

    M Alvarez-Jimenez, B O’Donoghue, A Thompson, JF Gleeson, S Bendall, C Gonzalez-Blanch, E Killackey, L Wunderink, and PD McGorry have no conflicts of interest.

    Funding

    Dr M Alvarez-Jimenez is supported by the CR Roper Fellowship, Faculty of Medicine, Dentistry, and Health Science, the University of Melbourne, Australia, and a Career Development Fellowship from the National Health and Medical Research Council of Australia. Professor PD McGorry is supported by a Research Fellowship from the National Health and Medical Research Council of Australia. Assistant Professor E Killackey is supported by a Career Development Fellowship from the National Health and Medical Research Council of Australia. Dr. S Bendall is supported by an Early Career Research Fellowship from the National Health and Medical Research Council of Australia. In addition, support was provided by the Australian Government and the Colonial Foundation to Orygen, The National Centre of Excellence in Youth Mental Health. The sponsors did not participate in the design or conduct of this review; in the collection, management, analysis, or interpretation of data; in the writing of the manuscript; or in the preparation, review, approval, or decision to submit this manuscript for publication.

    Additional information

    M. Alvarez-Jimenez and B. O’Donoghue contributed to this work equally.

    Electronic supplementary material

    Below is the link to the electronic supplementary material.

    Supplementary material 1 (DOCX 15 kb)

    Rights and permissions

    Reprints and permissions

    About this article

    Check for updates. Verify currency and authenticity via CrossMark

    Cite this article

    Alvarez-Jimenez, M., O’Donoghue, B., Thompson, A. et al. Beyond Clinical Remission in First Episode Psychosis: Thoughts on Antipsychotic Maintenance vs. Guided Discontinuation in the Functional Recovery Era. CNS Drugs 30, 357–368 (2016). https://doi.org/10.1007/s40263-016-0331-x

    Download citation

    • Published:

    • Issue Date:

    • DOI: https://doi.org/10.1007/s40263-016-0331-x

    Keywords

    Search

    Navigation