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Predicting first-episode psychosis patients who will never relapse over 10 years

  • Christy LM Hui (a1), William G Honer (a2), Edwin HM Lee (a1), WC Chang (a1) (a3), Sherry KW Chan (a1) (a3), Emily SM Chen (a1), Edwin PF Pang (a4), Simon SY Lui (a5), Dicky WS Chung (a6), WS Yeung (a7), Roger MK Ng (a8), William TL Lo (a9), Peter B Jones (a10), Pak Sham (a1) (a3) (a11) and Eric YH Chen (a1) (a3)...



Although relapse in psychosis is common, a small proportion of patients will not relapse in the long term. We examined the proportion and predictors of patients who never relapsed in the 10 years following complete resolution of positive symptoms from their first psychotic episode.


Patients who previously enrolled in a 12-month randomized controlled trial on medication discontinuation and relapse following first-episode psychosis (FEP) were followed up after 10 years. Relapse of positive symptoms was operationalized as a change from a Clinical Global Impression scale positive score of <3 for at least 3 consecutive months to a score of ⩾3 (mild or more severe). Baseline predictors included basic demographics, premorbid functioning, symptoms, functioning, and neurocognitive functioning.


Out of 178 first-episode patients, 37 (21%) never relapsed during the 10-year period. Univariate predictors (p ⩽ 0.1) of patients who never relapsed included a duration of untreated psychosis (DUP) ⩽30 days, diagnosed with non-schizophrenia spectrum disorders, having less severe negative symptoms, and performing better in logical memory immediate recall and verbal fluency tests. A multivariate logistic regression analysis further suggested that the absence of any relapsing episodes was significantly related to better short-term verbal memory, shorter DUP, and non-schizophrenia spectrum disorders.


Treatment delay and neurocognitive function are potentially modifiable predictors of good long-term prognosis in FEP. These predictors are informative as they can be incorporated into an optimum risk prediction model in the future, which would help with clinical decision making regarding maintenance treatment in FEP.


Corresponding author

Author for correspondence: Christy LM Hui, E-mail:


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Addington, D, Addington, J, Maticka-Tyndale, E and Joyce, J (1992) Reliability and validity of a depression rating scale for schizophrenics. Schizophrenia Research 6, 201208.
Alverez-Jimenez, M, Gleeson, JF, Henry, LP, Harrigan, SM, Harris, MG, Amminger, GP, Killackey, E, Yung, AR, Herrman, H, Jackson, HJ and McGorry, PD (2011) Prediction of a single psychotic episode: a 7.5-year, prospective study in first-episode psychosis. Schizophrenia Research 125, 236246.
Amador, XF, Flaum, M, Andreasen, NC, Strauss, DH, Yale, SA, Clark, SC and Gorman, JM (1994) Awareness of illness in schizophrenia and schizoaffective and mood disorders. Archives of General Psychiatry 51, 826836.
American Psychiatric Association (1994) Diagnostic and Statistical Manual of Mental Disorders, 4th Edn., revised. Washington, DC: American Psychiatric Association.
Andreasen, NC (1983) The Scale for the Assessment of Negative Symptoms (SANS). Iowa City: University of Iowa.
Andreasen, NC (1984) The Scale for the Assessment of Positive Symptoms (SAPS). Iowa City: University of Iowa.
Barnes, TR (1989) A rating scale for drug-induced akathisia. British Journal of Psychiatry 154, 672676.
Bottlender, R, Sato, T, Jager, M, Wegener, U, Wittmann, J, Strauss, A and Moller, HJ (2003) The impact of the duration of untreated psychosis prior to first psychiatric admission on the 15-year outcome in schizophrenia. Schizophrenia Research 62, 3744.
Cannon-Spoor, HE, Potkin, SG and Wyatt, RJ (1982) Measurement of premorbid adjustment in chronic schizophrenia. Schizophrenia Bulletin 8, 470484.
Chan, SKW, So, HC, Hui, CLM, Chang, WC, Lee, EHM, Chung, DWS, Tso, S, Hung, SF, Yip, KC, Dunn, E and Chen, EYH (2015) 10-year outcome study of an early intervention program for psychosis compared with standard care service. Psychological Medicine 45, 11811193.
Chen, E (2004) Developing an early intervention service in Hong Kong. In Ehmann, T, MacEwan, GW and Honer, WG (eds), Best Care in Early Psychosis Intervention. London: Taylor & Francis, pp. 125130.
Chen, EYH, Dunn, EL, Miao, MY, Yeung, WS, Wong, CK, Chan, WF, Chen, RY, Chung, KF and Tang, WN (2005 a) The impact of family experience on the duration of untreated psychosis (DUP) in Hong Kong. Social Psychiatry and Psychiatric Epidemiology 405, 350356.
Chen, EYH, Hui, CLM, Dunn, EL, Miao, MY, Yeung, WS, Wong, CK, Chan, WF and Tang, WN (2005 b) A prospective 3-year longitudinal study of cognitive predictors of relapse in first-episode schizophrenic patients. Schizophrenia Research 77, 99104.
Chen, EYH, Hui, CLM, Lam, MML, Chiu, CPY, Law, CW, Chung, DWS, Tso, S, Pang, EPF, Chan, KT, Wong, YC, Mo, FYM, Chan, KPM, 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. British Medical Journal 341, c4024.
Crow, TJ, MacMillan, JF, Johnson, AL and Johnstone, EC (1986) The Northwick Park Study of first episodes of schizophrenia II. A randomized controlled trial of prophylactic neuroleptic treatment. British Journal of Psychiatry 148, 120127.
Gaebel, W, Riesbeck, M, Wolwer, W, Klimke, A, Eickhoff, M, von Wilmsdorff, M, de Millas, W, Maier, W, Ruhrmann, S, Falkai, P, Sauer, H, Schmitt, A, Riedel, M, Klingberh, S and Moller, HJ (2016) Predictors for symptom re-exacerbation after targeted stepwise drug discontinuation in first-episode schizophrenia: results of the first-episode study within the German research network on schizophrenia. Schizophrenia Research 170, 168176.
Goldman, HH, Skodol, AE and Lave, TR (1992) Revising axis V for DSM-IV: a review of measures of social functioning. American Journal of Psychiatry 149, 11481156.
Guy, W (1976 a) Abnormal involuntary movements scale (AIMS). In Guy, W (ed.), The ECDEU Assessment Manual for Psychopharmacology, revised. Rockville, MD: Dept of Health, Education and Welfare, National Institute of Mental Health, pp. 534537.
Guy, W (1976 b) Clinical global impression scale (CGI). In Guy, W (ed.), ECDEU Assessment Manual for Psychopharmacology, Revised. Rockville, MD: Dept of Health, Education and Welfare, National Institute of Mental Health, pp. 217222.
Hafner, H, Riecher-Rossler, A, Hambrecht, M, Maurer, K, Meissner, S, Schmidtke, A, Fatkenheuer, B, Loffler, W and van der Heiden, W (1992) IRAOS: an instrument for the assessment of onset and early course of schizophrenia. Schizophrenia Research 6, 209223.
Haro, JM, Kamath, SA, Ochoa, S, Novick, D, Rele, K, Fargas, A, Rodriguez, MJ, Rele, R, Orta, J, Kharbeng, A, Araya, S, Gervin, M, Alonso, J, Mavreas, V, Lavrentzou, E, Liontos, N, Gregor, K and Jones, PB, SOHO Study Group (2003) The Clinical Global Impression-Schizophrenia scale: a simple instrument to measure the diversity of symptoms present in schizophrenia. Acta Psychiatrica Scandinavica Supplementum 416, 1623.
Haro, JM, Novick, D, Bertsch, J, Karagianis, J, Dossenbach, M and Jones, PB (2011) Cross-national clinical and functional remission rates: Worldwide Schizophrenia Outpatient Health Outcomes (W-SOHO) study. British Journal of Psychiatry 199, 194201.
Hui, CLM, Wong, GHY, Tang, JYM, Chang, WC, Chan, SKW, Lee, EHM, Lam, MML, Chiu, CPY, Law, CW, Chung, DWS, Tso, S, Pang, EPF, Chan, KT, Wong, YC, Mo, FYM, Chan, KPM, Hung, SF, Honer, WG and Chen, EYH (2013) Predicting 1-year risk for relapse in patients who have discontinued or continued quetiapine after remission from first-episode psychosis. Schizophrenia Research 150, 297302.
Hui, CLM, Li, YK, Li, AWY, Lee, EHM, Chang, WC, Chan, SKW, Lam, SY, Thornton, AE, Sham, P, Honer, WG and Chen, EYH (2016) Visual working memory deterioration preceding relapse in psychosis. Psychological Medicine 46, 24352444.
Hui, CLM, Honer, W, Lee, EHM, Chang, WC, Chan, SKW, Chen, ESM, Pang, EPF, Lui, SSY, Chung, DWS, Yeung, WS, Ng, RMK, Lo, WTL, Jones, PB, Sham, P and Chen, EYH (2018) Long-term effects of discontinuation from antipsychotic maintenance following first episode schizophrenia and related disorders. The Lancet. Psychiatry 5, 432442.
Kay, SR, Fiszbein, A and Opler, LA (1987) Positive and Negative Symptom Scale (PANSS) for schizophrenia. Schizophrenia Bulletin 13, 2176.
Larsen, TK, Moe, LC, Vibe-Hansen, L and Johannessen, JO (2000) Premorbid functioning versus duration of untreated psychosis in 1 year outcome in first-episode psychosis. Schizophrenia Research 45, 19.
Lenior, ME, Dingemans, PMAJ, Schene, AH and Linszen, DH (2005) Predictors of the early 5-year course of schizophrenia: a path analysis. Schizophrenia Bulletin 31, 781791.
Lingjaerde, O, Ahlfors, UG, Bech, P, Dencker, SJ and Elgen, K (1987) The UKU side effect rating scale. A new comprehensive rating scale for psychotropic drugs and a cross-sectional study of side effects in neuroleptic-treated patients. Acta Psychiatrica Scandinavica Supplementum 334, 1100.
Linszen, D, Dingemans, P and Lenior, M (2001) Early intervention and a five year follow up in young adults with a short duration of untreated psychosis: ethical implications. Schizophrenia Research 51, 5561.
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, 241247.
Rund, BR, Melle, I, Friis, S, Johannessen, JO, Larsen, TK, Midbøe, LJ, Opjordsmoen, S, Simonsen, E, Vaglum, P and McGlashan, T (2007) The course of neurocognitive functioning in first-episode psychosis and its relation to premorbid adjustment, duration of untreated psychosis, and relapse. Schizophrenia Research 91, 132140.
Rund, BR, Barder, HE, Evensen, J, Haahr, U, Hegelstad, WV, Joa, I, Johannessen, JO, Langeveld, J, Larsen, TK, Melle, I, Opyjordsmoen, S, Rossberg, JI, Simonsen, E, Sundet, K, Vaglum, P, McGlashan, T and Friis, S (2016) Neurocognition and duration of psychosis: a 10-year follow-up of first-episode patients. Schizophrenia Bulletin 42, 8795.
Shepherd, M, Watt, D, Falloon, I and Smeeton, N (1989) The natural history of schizophrenia: a five-year follow-up study of outcome and prediction in a representative sample of schizophrenics. Psychological Medicine Monograph Supplementary 15, 146.
Simpson, GM and Angus, JW (1970) A rating scale for extrapyramidal side effects. Acta Psychiatrica Scandinavica Supplementum 212, 1119.
So, E, Kam, I, Leung, CM, Chung, D, Liu, Z and Fong, S (2003) The Chinese-bilingual SCID-I/P project: stage 1 - reliability for mood disorders and schizophrenia. Hong Kong Journal of Psychiatry 13, 718.
Strauss, JS and Carpenter, WT Jr (1972) The prediction of outcome in schizophrenia: i. Characteristics of outcome. Archives of General Psychiatry 27, 739746.
Tang, JYM, Chang, WC, Hui, CLM, Wong, GHY, Chan, SKW, Lee, EHM, Yeung, WS, Wong, CK, Tang, WN, Chan, WF, Pang, EPF, Tso, S, Ng, RMK, Hung, SF, Dunn, ELW, Sham, PC and Chen, EYH (2014) Prospective relationship between duration of untreated psychosis and 13-year clinical outcome: a first-episode psychosis study. Schizophrenia Research 153, 18.
Thara, R and Eaton, WW (1996) Outcome of schizophrenia: the Madras longitudinal study. Australian and New Zealand Journal of Psychiatry 30, 516522.
Verdoux, H, Lengronne, J, Liraud, F, Gonzales, B, Assens, F, Abalan, F and van Os, J (2000) Medication adherence in psychosis: predictors and impact on outcome. A 2-year follow-up of first-admitted subjects. Acta Psychiatrica Scandinavica 102, 203210.
White, C, Stirling, J, Hopkins, R, Morris, J, Montague, L, Tantam, D and Lewis, S (2009) Predictors of 10-year outcome of first-episode psychosis. Psychological Medicine 39, 14471456.
Wölwer, W, Brinkmeyer, J, Riesbeck, M, Freimüller, L, Klimke, A, Wagner, M, Möller, HJ, Klingberg, S and Gaebel, W, German Study Group on First Episode Schizophrenia (2008) Neuropsychological impairments predict the clinical course in schizophrenia. European Archives of Psychiatry and Clinical Neuroscience 258, 2834.
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. Journal of Clinical Psychiatry 68, 654661.
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, 913920.
Zipursky, RB, Menezes, NM and Streiner, DL (2014) Risk of symptom recurrence with medication discontinuation in first-episode psychosis: a systematic review. Schizophrenia Research 152, 408414.



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