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Effect of discontinuation v. maintenance of antipsychotic medication on relapse rates in patients with remitted/stable first-episode psychosis: a meta-analysis

Published online by Cambridge University Press:  18 June 2018

Taro Kishi ,
Toshikazu Ikuta ,
Yuki Matsui ,
Ken Inada ,
Yuki Matsuda ,
Kazuo Mishima  and
Nakao Iwata
Taro Kishi*
Affiliation:
Department of Psychiatry, Fujita Health University School of Medicine, Toyoake, Aichi 470-1192, Japan
Toshikazu Ikuta
Affiliation:
Department of Communication Sciences and Disorders, School of Applied Sciences, University of Mississippi, University, MS 38677, USA
Yuki Matsui
Affiliation:
Department of Psychiatry, Fujita Health University School of Medicine, Toyoake, Aichi 470-1192, Japan
Ken Inada
Affiliation:
Department of Psychiatry, Tokyo Women's Medical University, Shinjuku-ku, Tokyo 162-8666, Japan
Yuki Matsuda
Affiliation:
Department of Psychiatry, Jikei University School of Medicine, Minato-ku, Tokyo 105-8461, Japan
Kazuo Mishima
Affiliation:
Department of Sleep-Wake Disorders, National Institute of Mental Health, National Center of Neurology and Psychiatry, Kodaira, Tokyo 187-8551, Japan
Nakao Iwata
Affiliation:
Department of Psychiatry, Fujita Health University School of Medicine, Toyoake, Aichi 470-1192, Japan
*
Author for correspondence: Taro Kishi, E-mail: tarok@fujita-hu.ac.jp
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Abstract

Background

Discontinuation of antipsychotics predisposes patients with remitted/stable first-episode psychosis (FEP) to a higher risk of relapse, but it remains unclear how long discontinuation increases the relapse rate in these patients compared with maintenance.

Methods

This meta-analysis of randomized controlled trials (RCTs) compared relapse rates in FEP patients between antipsychotic treatment discontinuation and maintenance groups at 1, 2, 3, 6, 9, 12 (primary), and 18–24 months. The risk ratio (RR) and numbers needed to treat/harm (NNT/NNH) were calculated using a random-effects model.

Results

Ten RCTs were identified (n = 776; mean study duration, 18.6 ± 6.0 months). The antipsychotics were discontinued abruptly in four RCTs (which reported data only at 12 months) and after tapering off gradually over several months (mean length, 3 months) in six RCTs. Compared with the discontinuation group, the maintenance group experienced significantly fewer relapses at all time points except 1 month [RR (NNT): 2 months, 0.49 (13); 3 months, 0.46 (9); 6 months, 0.55 (6); 9 months, 0.48 (3); 12 months, 0.47 (3); and 18–24 months, 0.57 (4)]. The maintenance group was associated with higher discontinuation due to adverse events (RR, 2.61; NNH, not significant).

Conclusions

Maintaining antipsychotic treatment prevented relapse for up to 24 months in FEP patients. Discontinuation of antipsychotics for ⩾2 months significantly increased the risk of relapse. However, 45.7% of patients who discontinued antipsychotics for 12 months (39.4% after 18–24 months) did not experience a relapse.

Keywords

Antipsychotics discontinuationantipsychotics maintenancefirst-episode psychosismeta-analysisrelapse ratesystematic review
Type
Original Articles
Information
Psychological Medicine , Volume 49 , Issue 5 , April 2019 , pp. 772 - 779
Copyright
Copyright © Cambridge University Press 2018 

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References

Alvarez-Jimenez, M, O'Donoghue, B, Thompson, A, Gleeson, JF, Bendall, S, Gonzalez-Blanch, C, Killackey, E, Wunderink, L and McGorry, PD (2016) Beyond clinical remission in first episode psychosis: thoughts on antipsychotic maintenance vs. guided discontinuation in the functional recovery era. CNS Drugs 30, 357–368.Google Scholar
Boonstra, G, Burger, H, Grobbee, DE and Kahn, RS (2011) Antipsychotic prophylaxis is needed after remission from a first psychotic episode in schizophrenia patients: results from an aborted randomised trial. International Journal of Psychiatry in Clinical Practice 15, 128–134.Google Scholar
Buchanan, RW, Kreyenbuhl, J, Kelly, DL, Noel, JM, Boggs, DL, Fischer, BA, Himelhoch, S, Fang, B, Peterson, E, Aquino, PR, Keller, W and Schizophrenia Patient Outcomes Research Team (2010) The 2009 schizophrenia PORT psychopharmacological treatment recommendations and summary statements. Schizophrenia Bulletin 36, 71–93.Google Scholar
Byerly, MJ, Nakonezny, PA and Lescouflair, E (2007) Antipsychotic medication adherence in schizophrenia. Psychiatric Clinics of North America 30, 437–452.Google Scholar
Chen, EY, Hui, CL, Lam, MM, Chiu, CP, Law, CW, Chung, DW, Tso, S, Pang, EP, Chan, KT, Wong, YC, Mo, FY, Chan, KP, Yao, TJ, Hung, SF and Honer, WG (2010) Maintenance treatment with quetiapine versus discontinuation after one year of treatment in patients with remitted first episode psychosis: randomised controlled trial. BMJ 341, c4024.Google Scholar
Crow, TJ, MacMillan, JF, Johnson, AL and Johnstone, EC (1986) A randomised controlled trial of prophylactic neuroleptic treatment. The British Journal of Psychiatry 148, 120–127.Google Scholar
Day, JC, Wood, G, Dewey, M and Bentall, RP (1995) A self-rating scale for measuring neuroleptic side-effects. Validation in a group of schizophrenic patients. The British Journal of Psychiatry 166, 650–653.Google Scholar
De Hert, M, Sermon, J, Geerts, P, Vansteelandt, K, Peuskens, J and Detraux, J (2015) The use of continuous treatment versus placebo or intermittent treatment strategies in stabilized patients with schizophrenia: a systematic review and meta-analysis of randomized controlled trials with first- and second-generation antipsychotics. CNS Drugs 29, 637–658.Google Scholar
DerSimonian, R and Laird, N (1986) Meta-analysis in clinical trials. Controlled Clinical Trials 7, 177–188.Google Scholar
Emsley, R, Chiliza, B and Asmal, L (2013) The evidence for illness progression after relapse in schizophrenia. Schizophrenia Research 148, 117–121.Google Scholar
Gaebel, W, Janner, M, Frommann, N, Pietzcker, A, Kopcke, W, Linden, M, Muller, P, Muller-Spahn, F and Tegeler, J (2002) First vs multiple episode schizophrenia: two-year outcome of intermittent and maintenance medication strategies. Schizophrenia Research 53, 145–159.Google Scholar
Gaebel, W, Riesbeck, M, Wolwer, W, Klimke, A, Eickhoff, M, von Wilmsdorff, M, Lemke, M, Heuser, I, Maier, W, Huff, W, Schmitt, A, Sauer, H, Riedel, M, Klingberg, S, Kopcke, W, Ohmann, C, Moller, HJ and German Study Group on First-Episode Schizophrenia (2011) 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. The Journal of Clinical Psychiatry 72, 205–218.Google Scholar
Goff, DC, Falkai, P, Fleischhacker, WW, Girgis, RR, Kahn, RM, Uchida, H, Zhao, J and Lieberman, JA (2017) The long-term effects of antipsychotic medication on clinical course in schizophrenia. The American Journal of Psychiatry 174, 840–849.Google Scholar
Hasan, A, Falkai, P, Wobrock, T, Lieberman, J, Glenthoj, B, Gattaz, WF, Thibaut, F, Moller, HJ and World Federation of Societies of Biological Psychiatry Task Force on Treatment Guidelines for Schizophrenia (2012) 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. The World Journal of Biological Psychiatry 13, 318–378.Google Scholar
Higgins, J and Green, S (2011) Cochrane Handbook for Systematic Reviews of Interventions. Version 5.1.0. The Cochrane Collaboration. Available at https://www.cochrane-handbook.org.Google Scholar
Higgins, JP, Thompson, SG, Deeks, JJ and Altman, DG (2003) Measuring inconsistency in meta-analyses. BMJ 327, 557–560.Google Scholar
Hogarty, GE and Goldberg, SC (1973) Drug and sociotherapy in the aftercare of schizophrenic patients. One-year relapse rates. Archives of General Psychiatry 28, 54–64.Google Scholar
Kane, JM, Rifkin, A, Quitkin, F, Nayak, D and Ramos-Lorenzi, J (1982) Fluphenazine vs placebo in patients with remitted, acute first-episode schizophrenia. Archives of General Psychiatry 39, 70–73.Google Scholar
Kay, SR, Fiszbein, A and Opler, LA (1987) The positive and negative syndrome scale (PANSS) for schizophrenia. Schizophrenia Bulletin 13, 261–276.Google Scholar
Leucht, S, Tardy, M, Komossa, K, Heres, S, Kissling, W, Salanti, G and Davis, JM (2012) Antipsychotic drugs versus placebo for relapse prevention in schizophrenia: a systematic review and meta-analysis. Lancet 379(9831), 2063–2071.Google Scholar
McCreadie, RG, Wiles, D, Grant, S, Crockett, GT, Mahmood, Z, Livingston, MG, Watt, JA, Greene, JG, Kershaw, PW and Todd, NA (1989) The Scottish first episode schizophrenia study. VII. Two-year follow-up. Scottish Schizophrenia Research Group. Acta Psychiatrica Scandinavica 80, 597–602.Google Scholar
Merlo, MC, Hofer, H, Gekle, W, Berger, G, Ventura, J, Panhuber, I, Latour, G and Marder, SR (2002) Risperidone, 2 mg/day vs. 4 mg/day, in first-episode, acutely psychotic patients: treatment efficacy and effects on fine motor functioning. The Journal of Clinical Psychiatry 63, 885–891.Google Scholar
Messias, EL, Chen, CY and Eaton, WW (2007) Epidemiology of schizophrenia: review of findings and myths. Psychiatric Clinics of North America 30, 323–338.Google Scholar
Moher, D, Liberati, A, Tetzlaff, J, Altman, DG and PRISMA Group (2009) Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. BMJ 339, b2535.Google Scholar
Murray, RM, Quattrone, D, Natesan, S, van Os, J, Nordentoft, M, Howes, O, Di Forti, M and Taylor, D (2016) Should psychiatrists be more cautious about the long-term prophylactic use of antipsychotics? The British Journal of Psychiatry 209, 361–365.Google Scholar
NICE (National Institute for Health and Care Excellence) (2014) Psychosis and Schizophrenia in Adults: Treatment and Management: Updated Edition 2014: (NICE Clinical Guidance 136): Available at: https://www.nice.org.uk/guidance/cg178/evidence/full-guideline-490503565Google Scholar
Oliver, JP, Huxley, PJ, Priebe, S and Kaiser, W (1997) Measuring the quality of life of severely mentally ill people using the Lancashire Quality of Life Profile. Social Psychiatry and Psychiatric Epidemiology 32, 76–83.Google Scholar
Oosthuizen, P, Emsley, R, Jadri Turner, H and Keyter, N (2004) A randomized, controlled comparison of the efficacy and tolerability of low and high doses of haloperidol in the treatment of first-episode psychosis. The International Journal of Neuropsychopharmacology 7, 125–131.Google Scholar
Owen, MJ, Sawa, A and Mortensen, PB (2016) Schizophrenia. Lancet 388, 86–97.Google Scholar
Rifkin, A, Quitkin, F, Kane, J, Klein, DF and Ross, D (1979) The effect of fluphenazine upon social and vocational functioning in remitted schizophrenics. Biological Psychiatry 14, 499–508.Google Scholar
Robinson, D, Woerner, MG, Alvir, JM, Bilder, R, Goldman, R, Geisler, S, Koreen, A, Sheitman, B, Chakos, M, Mayerhoff, D and Lieberman, JA (1999) Predictors of relapse following response from a first episode of schizophrenia or schizoaffective disorder. Archives of General Psychiatry 56, 241–247.Google Scholar
Robinson, DG, Woerner, MG, Delman, HM and Kane, JM (2005) Pharmacological treatments for first-episode schizophrenia. Schizophrenia Bulletin 31, 705–722.Google Scholar
Sham, PC, MacLean, CJ and Kendler, KS (1994) A typological model of schizophrenia based on age at onset, sex and familial morbidity. Acta Psychiatrica Scandinavica 89, 135–141.Google Scholar
Simpson, GM and Angus, JW (1970) A rating scale for extrapyramidal side effects. Acta Psychiatrica Scandinavica. Supplementum 212, 11–19.Google Scholar
van Os, J and Kapur, S (2009) Schizophrenia. Lancet 374, 635–645.Google Scholar
Whiteford, HA, Degenhardt, L, Rehm, J, Baxter, AJ, Ferrari, AJ, Erskine, HE, Charlson, FJ, Norman, RE, Flaxman, AD, Johns, N, Burstein, R, Murray, CJ and Vos, T (2013) Global burden of disease attributable to mental and substance use disorders: findings from the Global Burden of Disease Study 2010. Lancet 382, 1575–1586.Google Scholar
Wunderink, L, Nieboer, RM, Wiersma, D, Sytema, S and Nienhuis, FJ (2013) 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 70, 913–920.Google Scholar
Wunderink, L, Nienhuis, FJ, Sytema, S, Slooff, CJ, Knegtering, R and Wiersma, D (2007) Guided discontinuation versus maintenance treatment in remitted first-episode psychosis: relapse rates and functional outcome. The Journal of Clinical Psychiatry 68, 654–661.Google Scholar
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