Skip to main content
×
×
Home

Duration of untreated psychosis as predictor of long-term outcome in schizophrenia: systematic review and meta-analysis

  • Matti Penttilä, Erika Jääskeläinen, Noora Hirvonen, Matti Isohanni and Jouko Miettunen...
Abstract
Background

Duration of untreated psychosis (DUP) is one of the few potentially modifiable predictors of outcomes of schizophrenia. Long DUP as a predictor of poor short-term outcome has been addressed in previous meta-analyses, but the long-term effects of DUP remain unclear.

Aims

To analyse the associations between DUP and long-term outcomes of schizophrenia.

Method

A systematic literature search was performed using seven electronic databases and manual searches. Random effects weighted meta-analysis with correlation coefficients was used to pool the results.

Results

We identified 3493 unique publications, from which 33 samples met our predefined selection criteria. Long DUP correlated statistically significantly with poor general symptomatic outcome, more severe positive and negative symptoms, lesser likelihood of remission and poor social functioning and global outcome (correlations 0.13–0.18). Long DUP was not associated with employment, quality of life or hospital treatment.

Conclusions

The small but mostly consistent correlation between long DUP and poor outcome indicates that early intervention in psychosis may have at least subtle positive effects on the long-term course of illness.

    • Send article to Kindle

      To send this article to your Kindle, first ensure no-reply@cambridge.org is added to your Approved Personal Document E-mail List under your Personal Document Settings on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part of your Kindle email address below. Find out more about sending to your Kindle. Find out more about sending to your Kindle.

      Note you can select to send to either the @free.kindle.com or @kindle.com variations. ‘@free.kindle.com’ emails are free but can only be sent to your device when it is connected to wi-fi. ‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.

      Find out more about the Kindle Personal Document Service.

      Duration of untreated psychosis as predictor of long-term outcome in schizophrenia: systematic review and meta-analysis
      Available formats
      ×
      Send article to Dropbox

      To send this article to your Dropbox account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your <service> account. Find out more about sending content to Dropbox.

      Duration of untreated psychosis as predictor of long-term outcome in schizophrenia: systematic review and meta-analysis
      Available formats
      ×
      Send article to Google Drive

      To send this article to your Google Drive account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your <service> account. Find out more about sending content to Google Drive.

      Duration of untreated psychosis as predictor of long-term outcome in schizophrenia: systematic review and meta-analysis
      Available formats
      ×
Copyright
Corresponding author
Matti Penttilä, University of Oulu, PO Box 5000, Oulu 90014, Finland. Email: matti.penttila@oulu.fi
Footnotes
Hide All

Preliminary results of this meta-analysis were presented at the 21st European Congress of Psychiatry, Nice, France, 2013, and the 4th European Conference on Schizophrenia Research, Berlin, Germany, 2013.

This work was supported by Oulu University Hospital, University of Oulu, the Academy of Finland; the Sigrid Jusélius Foundation; National Alliance for Research in Schizophrenia and Affective Disorders (NARSAD): The Brain and Behavior Research Fund (Dr Mortimer D. Sackler Developmental Psychobiology Research Program); the Oulu University Pharmacy Foundation; H. Lundbeck; the Northern Finland Health Care Support Foundation; and the Jalmari and Rauha Ahokas Foundation.

Declaration of interest

None.

Footnotes
References
Hide All
1 Jääskeläinen, E, Juola, P, Hirvonen, N, McGrath, JJ, Saha, S, Isohanni, M, et al. A systematic review and meta-analysis of recovery in schizophrenia. Schizophr Bull 2013; 39: 1296–306.
2 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: 975–83.
3 Perkins, DO, Gu, H, Boteva, K, Lieberman, JA. Relationship between duration of untreated psychosis and outcome in first-episode schizophrenia: a critical review and meta-analysis. Am J Psychiatry 2005; 162: 1785–804.
4 Bertelsen, M, Jeppesen, P, Petersen, L, Thorup, A, Øhlenschlaeger, J, le Quach, P, et al. Five-year follow-up of a randomized multicenter trial of intensive early intervention vs standard treatment for patients with a first episode of psychotic illness: the OPUS trial. Arch Gen Psychiatry 2008; 65: 762–71.
5 Gafoor, R, Nitsch, D, McCrone, P, Craig, TKJ, Garety, PA, Power, P, et al. Effect of early intervention on 5-year outcome in non-affective psychosis. Br J Psychiatry 2010; 196: 372–6.
6 Hegelstad, WT, Larsen, TK, Auestad, B, Evensen, J, Haahr, U, Joa, I, et al. Long-term follow-up of the TIPS early detection in psychosis study: effects on 10-year outcome. Am J Psychiatry 2012; 169: 374–80.
7 Penttilä, M, Miettunen, J, Koponen, H, Kyllönen, M, Veijola, J, Isohanni, M, et al. Association between the duration of untreated psychosis and short- and long-term outcome in schizophrenia within the Northern Finland 1966 Birth Cohort. Schizophr Res 2013; 143: 310.
8 Norman, RMG, Townsend, L, Malla, AK. Duration of untreated psychosis and cognitive functioning in first-episode patients. Br J Psychiatry 2001; 179: 340–5.
9 Dassa, D, Boyer, L, Benoit, M, Bourcet, S, Raymondet, P, Bottai, T. Factors associated with medication non-adherence in patients suffering from schizophrenia: a cross-sectional study in a universal coverage health-care system. Aust N Z J Psychiatry 2010; 44: 921–8.
10 Stroup, DF, Berlin, JA, Morton, SC, Olkin, I, Williamson, GD, Rennie, D, et al. Meta-analysis of observational studies in epidemiology: a proposal for reporting. Meta-analysis Of Observational Studies in Epidemiology (MOOSE) group. JAMA 2000; 283: 2008–12.
11 McGrath, J, Saha, S, Welham, J, El Saadi, O, MacCauley, C, Chant, D. A systematic review of the incidence of schizophrenia: the distribution of rates and the influence of sex, urbanicity, migrant status and methodology. BMC Med 2004; 28: 213.
12 Menezes, NM, Arenovich, T, Zipursky, RB. A systematic review of longitudinal outcome studies of first-episode psychosis. Psychol Med 2006; 36: 1349–62.
13 Shrivastava, A, Johnston, M, Shah, N, Bureau, Y. Redefining outcome measures in schizophrenia: integrating social and clinical parameters. Curr Opin Psychiatry 2010; 23: 120–6.
14 Parellada, M, Boada, L, Fraguas, D, Reig, S, Castro-Fornieles, J, Moreno, D, et al. Trait and state attributes of insight in first episodes of early-onset schizophrenia and other psychoses: a 2-year longitudinal study. Schizophr Bull 2011; 37: 3851.
15 Nielssen, OB, Malhi, GS, McGorry, PD, Large, MM. Overview of violence to self and others during the first episode of psychosis. J Clin Psychiatry 2012; 73: e5807.
16 Andreasen, NC, Carpenter, WT, Kane, JM, Lasser, RA, Marder, SR, Weinberger, DR. Remission in schizophrenia: proposed criteria and rationale for consensus. Am J Psychiatry 2005; 162: 441–9.
17 Faerden, A, Nesvåg, R, Marder, SR. Definitions of the term ‘recovered’ in schizophrenia and other disorders. Psychopathology 2008; 41: 271–8.
18 Rosenthal, R. Parametric measures of effect size. In The Handbook of Research Synthesis (eds Cooper, H, Hedges, LV). Sage, 1994.
19 Rosenthal, R, Rosnow, RL, Rubin, DB. Contrasts and Effect Sizes in Behavioral Research: A Correlational Approach: 212. Cambridge University Press, 2000.
20 Cohen, J. A power primer. Psychol Bull 1992; 112: 155–9.
21 Stata Corporation. Stata User's Guide, Release 11. Stata Press; 2009.
22 Higgins, JP, Thompson, SG, Deeks, JJ, Altman, DG. Measuring inconsistency in meta-analyses. BMJ 2003; 327: 557–60.
23 Sterne, J. Meta-Analysis in Stata: An Updated Collection from the Stata Journal. Stata Press, 2009.
24 Röpcke, B, Eggers, C. Early-onset schizophrenia: a 15-year follow-up. Eur Child Adolesc Psychiatry 2005; 14: 341–50.
25 Górna, K, Jaracz, K, Rybakowski, F, Rybakowski, J. Determinants of objective and subjective quality of life in first-time-admission schizophrenic patients in Poland: a longitudinal study. Qual Life Res 2008; 17: 237–47.
26 White, C, Stirling, J, Hopkins, R, Morris, J, Montague, L, Tantam, D, et al. Predictors of 10-year outcome of first-episode psychosis. Psychol Med 2009; 39: 1447–56.
27 Hill, M, Crumlish, N, Clarke, M, Whitty, P, Owens, E, Renwick, L, et al. Prospective relationship of duration of untreated psychosis to psychopathology and functional outcome over 12 years. Schizophr Res 2012; 141: 215–21.
28 Boonstra, N, Klaassen, R, Sytema, S, Marshall, M, De Haan, L, Wunderink, L, et al. Duration of untreated psychosis and negative symptoms – a systematic review and meta-analysis of individual patient data. Schizophr Res 2012; 142: 12–9.
29 McGlashan, TH. Premorbid adjustment, onset types, and prognostic scaling: still informative? Schizophr Bull 2008; 34: 801–5.
30 Compton, MT, Chien, VH, Leiner, AS, Goulding, SM, Weiss, PS. Mode of onset of psychosis and family involvement in help-seeking as determinants of duration of untreated psychosis. Soc Psychiatry Psychiatr Epidemiol 2008; 43: 975–82.
31 Compton, MT, Gordon, TL, Weiss, PS, Walker, EF. The ‘doses’ of initial, untreated hallucinations and delusions: a proof-of-concept study of enhanced predictors of first-episode symptomatology and functioning relative to duration of untreated psychosis. J Clin Psychiatry 2011; 72: 1487–93.
32 Tandon, R. Antipsychotics in the treatment of schizophrenia: an overview. J Clin Psychiatry 2011; 72 (supp 1): 48.
33 Chiliza, B, Asmal, L, Emsley, R. Early intervention in schizophrenia in developing countries: focus on duration of untreated psychosis and remission as a treatment goal. Int Rev Psychiatry 2012; 24: 483–8.
34 Moncrieff, J. Questioning the ‘neuroprotective’ hypothesis: does drug treatment prevent brain damage in early psychosis or schizophrenia? Br J Psychiatry 2011; 198: 85–7.
35 Ichinose, H, Nakane, Y, Nakane, H, Kinoshita, H, Ohta, Y, Honda, S. Nagasaki Schizophrenia Study: relationship between ultralong-term outcome (after 28 years) and duration of untreated psychosis. Acta Med Nagasaki 2010; 54: 5966.
36 Bottlender, R, Sato, T, Jager, M, Wegener, U, Wittmann, J, Strauss, A, et al. The impact of the duration of untreated psychosis prior to first psychiatric admission on the 15-year outcome in schizophrenia. Schizophr Res 2003; 62: 3744.
37 Chang, WC, Tang, JY, Hui, CL, Lam, MM, Wong, GH, Chan, SK, et al. Duration of untreated psychosis: relationship with baseline characteristics and three-year outcome in first-episode psychosis. Psychiatry Res 2012; 198: 360–5.
38 Norman, RM, Manchanda, R, Windell, D, Harricharan, R, Northcott, S, Hassall, L. The role of treatment delay in predicting 5-year outcomes in an early intervention program. Psychol Med 2012; 42: 223–33.
39 Selten, JP, Veen, ND, Hoek, HW, Laan, W, Schols, D, van der Tweel, I, et al. Early course of schizophrenia in a representative Dutch incidence cohort. Schizophr Res 2007; 97: 7987.
40 Rupp, C, Fletcher, E. A five to ten year follow-up study of 641 schizophrenic cases. Am J Psychiatry 1940; 96: 877–88.
41 Achte, K. On prognosis and rehabilitation in schizophrenic and paranoid psychoses: a comparative follow-up study of two series of patients first admitted to hospital in 1950 and 1960 respectively. Acta Psychiatr Scand 1967; 43: 9217.
42 Scully, PJ, Coakley, G, Kinsella, A, Waddington, JL. Psychopathology, executive (frontal) and general cognitive impairment in relation to duration of initially untreated versus subsequently treated psychosis in chronic schizophrenia. Psychol Med 1997; 27: 1303–10.
43 Jeppesen, P, Petersen, L, Thorup, A, Abel, MB, Øhlenschlaeger, J, Christensen, , et al. The association between pre-morbid adjustment, duration of untreated psychosis and outcome in first-episode psychosis. Psychol Med 2008; 38: 1157–66.
44 Petersen, L, Thorup, A, Øqhlenschlaeger, J, Christensen, , Jeppesen, P, Krarup, G, et al. Predictors of remission and recovery in a first-episode schizophrenia spectrum disorder sample: 2-year follow-up of the OPUS trial. Can J Psychiatry 2008; 53: 660–70.
45 Tomotake, M. Quality of life and its predictors in people with schizophrenia. J Med Invest 2011; 58: 167–74.
46 Thorup, A, Petersen, L, Jeppesen, P, Nordentoft, M. The quality of life among first-episode psychotic patients in the OPUS trial. Schizophr Res 2010; 116: 2734.
Recommend this journal

Email your librarian or administrator to recommend adding this journal to your organisation's collection.

The British Journal of Psychiatry
  • ISSN: 0007-1250
  • EISSN: 1472-1465
  • URL: /core/journals/the-british-journal-of-psychiatry
Please enter your name
Please enter a valid email address
Who would you like to send this to? *
×
Type Description Title
PDF
Supplementary materials

Penttilä et al. supplementary material
Supplementary Tables S1-S4

 PDF (268 KB)
268 KB
PDF
Supplementary materials

Penttilä et al. supplementary material
Supplementary Figure S1-S9

 PDF (289 KB)
289 KB
PDF
Supplementary materials

Penttilä et al. supplementary material
Appendices

 PDF (176 KB)
176 KB
PDF
Supplementary materials

Penttilä et al. supplementary material
Supplementary Tables S1-S4

 PDF (268 KB)
268 KB
PDF
Supplementary materials

Penttilä et al. supplementary material
Appendices

 PDF (176 KB)
176 KB
PDF
Supplementary materials

Penttilä et al. supplementary material
Supplementary Figure S1-S9

 PDF (289 KB)
289 KB
PDF
Supplementary materials

Penttilä et al. supplementary material
Supplementary Figure S1-S9

 PDF (289 KB)
289 KB
PDF
Supplementary materials

Penttilä et al. supplementary material
Supplementary Tables S1-S4

 PDF (268 KB)
268 KB
PDF
Supplementary materials

Penttilä et al. supplementary material
Appendices

 PDF (176 KB)
176 KB

Metrics

Altmetric attention score

Full text views

Total number of HTML views: 0
Total number of PDF views: 100 *
Loading metrics...

Abstract views

Total abstract views: 264 *
Loading metrics...

* Views captured on Cambridge Core between 2nd January 2018 - 21st April 2018. This data will be updated every 24 hours.

Duration of untreated psychosis as predictor of long-term outcome in schizophrenia: systematic review and meta-analysis

  • Matti Penttilä, Erika Jääskeläinen, Noora Hirvonen, Matti Isohanni and Jouko Miettunen...
Submit a response

eLetters

Are we reinforcing the anti-medical model?

Dr Dorothea C Bindman, Core Trainee
09 September 2014

We read with interest the meta-analysis by Penttila et al. (http://bjp.rcpsych.org/content/205/2/88.full) in this month's issue.The results of this meta-analysis emphasised the importance of the duration untreated psychosis (DUP) in the long term recovery from schizophreniform illness. Timely initiation of effective treatment has been demonstrated to improve outcome but the modality of treatment is currently under much debate. Robust evidence exists for the efficacy of antipsychotic medication (1) but recent studies have proposed psychological interventions, specifically cognitive behavioural therapy, as an alternative first-line treatment.

In a recent randomised controlled trial (2), CBT was used as the single intervention instead of conventional antipsychotic treatment. To our complete surprise, one of the exclusion criteria was treatment with antipsychotic drugs. We wonder how ethical approval was granted, despite Tiihonen's robust demonstration of reduced mortality (3) over a considerable follow up period for patients receiving antipsychotic medication. We feel that this will set a dangerous precedent of offering psychological treatment as an alternative to evidence-based treatment. In a clinical setting, compliance with drug treatment is already a significant issue and there is potential to reinforce the idea that antipsychotic medication is harmful and unnecessary. We feel that this would further disadvantage an already vulnerable group of patients.

This issue has recently received a fair degree of coverage in the media (http://www.theguardian.com/science/sifting-the-evidence/2014/apr/02/has-cognitive-behavioural-therapy-for-psychosis-been-oversold), with articles such as Freeman and Freeman's piece in The Guardian (http://www.theguardian.com/science/blog/2014/mar/07/treat-schizophrenia-antipsychotics-drugs-cognitive-therapy) fuelling long-held popular beliefs that antipsychotics are ineffective and in fact damaging to health. Given the well-documented draw backs of antipsychotic drugs, itis understandable that patients and professionals will invest hope in non-drug based alternatives. However, Jauhar et al's large meta-analysis (4) with over 3,000 participants shows at best a small effect size for CBT. Inreference to Penttila's paper, we would be interested to read subgroup analysis of specific first line treatments and wonder if outcomes would differ between modalities.

While we would endorse any treatment, drug or non-drug based, that isproven to reduce the duration of untreated psychosis, it is vital that we do not lose sight of the fact that antipsychotics are the only evidence-based first line therapy in psychotic illness.

1. Leucht S, Arbter D, Engel RR, Kissling W and Davis JM (2009a)How effective are second-generation antipsychotic drugs? A metaanalysisof placebo-controlled trials. Molecular Psychiatry 14:429-447.

2. Morrison AP, Hutton P, Wardle M, Spencer H, Barratt S, Brabban A, et al. Cognitive therapy for people with a schizophrenia spectrum diagnosis not taking antipsychotic medication: an exploratory trial. Psychol Med 2012; 42: 1049-56.

3.Tiihonen J1, Lannqvist J, Wahlbeck K, Klaukka T, Niskanen L, Tanskanen A, Haukka J). 11-year follow-up of mortality in patients with schizophrenia: a population-based cohort study (FIN11 study). Lancet. 2009Aug 22;374(9690):620-7.

4. Jauhar S, McKenna PJ, Radua J, Fung E, Salvador R, Laws KR. Cognitive-behavioural therapy for the symptoms of schizophrenia: systematic review and meta-analysis with examination of potential bias. BrJ Psychiatry. 2014 Jan;204(1):20-9.

... More

Conflict of interest: None declared

Write a reply

×

Reply to: Submit a response


Your details


Conflicting interests

Do you have any conflicting interests? *