Skip to main content Accessibility help
×
Home
Hostname: page-component-684899dbb8-x64cq Total loading time: 0.73 Render date: 2022-05-18T01:20:43.233Z Has data issue: true Feature Flags: { "shouldUseShareProductTool": true, "shouldUseHypothesis": true, "isUnsiloEnabled": true, "useRatesEcommerce": false, "useNewApi": true }

Duration of untreated psychosis: What are we talking about?

Published online by Cambridge University Press:  24 June 2014

Andrea Polari
Affiliation:
Treatment and early Intervention in Psychosis Program (TIPP), Département de Psychiatrie CHUV, Université de Lausanne, Clinique de Cery, 1008 Prilly, Switzerland
Michael Berk
Affiliation:
Orygen Youth Health Research Centre, Department of Psychiatry, University of Melbourne, 35 Poplar Road, Parkville Victoria 3052, Melbourne, Australia Department of Clinical and Biomedical Sciences: Barwon Health, University of Melbourne, Geelong, Australia Mental Health Research Institute, Parkville, Australia
Craig Macneil
Affiliation:
Orygen Youth Health Research Centre, Department of Psychiatry, University of Melbourne, 35 Poplar Road, Parkville Victoria 3052, Melbourne, Australia
Philippe Conus
Affiliation:
Treatment and early Intervention in Psychosis Program (TIPP), Département de Psychiatrie CHUV, Université de Lausanne, Clinique de Cery, 1008 Prilly, Switzerland Orygen Youth Health Research Centre, Department of Psychiatry, University of Melbourne, 35 Poplar Road, Parkville Victoria 3052, Melbourne, Australia
Rights & Permissions[Opens in a new window]

Abstract

Type
Editorial
Copyright
Copyright © 2009 Blackwell Munksgaard

Duration of untreated psychosis (DUP) broadly refers to the time elapsing between onset of psychosis and treatment initiation. Its relationship with outcome has been intensely studied in the framework of the development of early intervention strategies for psychosis. Results of such research are however still a matter of controversy, some studies showing a negative impact of long DUP on outcome (Reference Clarke, Whitty and Browne1Reference Schimmelmann, Huber, Lambert, Cotton, McGorry and Conus4) while others do not (Reference Craig, Bromet, Fennig, Tanenberg-Karant, Lavelle and Galambos5Reference Malla, Schimtz and Norman8). In a systematic literature review, Marshall Reference Marshall, Lewis, Lockwood, Drake, Jones and Croudace(9) nevertheless concluded that there is a significant, albeit small to moderate, negative association between DUP and outcome, and most early intervention programmes rank reduction of DUP as a primary priority.

From a clinical point of view, reduction of DUP emerges as a logical target when witnessing the collateral damage suffered by patients who experience long delays prior to onset of care Reference McGorry(10). Additionally, recent imaging data have shown that the prodrome and the early phase of psychotic disorders are periods of active and progressive structural changes in key brain areas such as the hippocampus Reference Pantelis, Velakoulis and McGorry(11). If one assumes that there is an active process of neuroprogression underlying these changes, then the longer the DUP, the greater the time available for this potentially neurotoxic process to unfold Reference Berk(12). The nature of the pathogenic process remains to be fully elucidated; however, it probably includes reduction in neurotrophins, oxidative stress and inflammatory cytokines. Given the evidence that appropriate treatment is potentially neuroprotective Reference Lieberman, Tollefson and Charles(13), reduction in DUP could therefore be associated with reduction in potentially cumulative brain insult, and hence improvement in symptomatic and functional outcomes.

In the last few years, assessment of psychosis onset has been the object of a considerable attention, and this interest has led to both a degree of consensus about its definition and the development of scales specifically designed to determine the date of its initial occurrence Reference Singh, Cooper and Fischer(14,Reference Yung, Yuen and McGorry15). A closer look at this literature reveals on the other hand that criteria applied to define the endpoint of DUP, in other words the time of treatment initiation, is much less consistent and vary greatly between studies.

According to international guidelines, an adequate treatment of first episode psychosis should combine adapted medication (generally utilising low-dose strategy) and psychosocial intervention delivered in the context of easily accessible and specialised treatment teams (1618). However, despite the availability of such guidelines, the concept of ‘treatment initiation’ usually refers to the commencement of very incomplete and often ill-defined interventions (Table 1). These include ‘initiation of medication’, ‘commencement of any form of treatment', ‘initiation of adequate treatment', ‘time of first effective treatment', as well as ‘hospitalisation’ or ‘entry to a specialised programme’. In addition, adherence to treatment is in the vast majority of cases not assessed when in fact clinical experience reveals that enrollment in a specialised service or prescription of medication does not necessarily equate with the person being fully engaged with the service, receiving sufficient psychosocial support, or taking medication as prescribed.

Table 1 Definitions of treatment initiation in the literature

In the studies mentioned above, it is therefore highly likely that many patients for whom DUP was defined as having concluded actually remained untreated or partially treated. Only two studies defined treatment initiation on the basis of adherence to or observed response to medication treatment Reference Singh, Cooper and Fischer(14,Reference Malla, Norman and Manchanda30). However, by focusing on this aspect of treatment, they neglect the importance of psychosocial intervention in the recovery process Reference Malla and Norman(31), while recent randomised controlled trials have now clearly proven that integrated early intervention programmes that include specialised psychosocial treatment lead first episode psychosis patients to a better outcome than generic mental health programmes Reference Garety, Craig and Dunn(32,Reference Petersen, Jeppesen and Thoru33).

This lack of consistency in definition is concerning, considering that an absence of consensus on what ‘treatment initiation’ actually comprises could very well be one of the critical factors that so far limited the conclusiveness of studies exploring potential consequences of DUP. While research exploring DUP impact on outcome should not interfere with common sense arguments justifying the necessity of mental health services reforms aimed at facilitating treatment access for patients with psychosis Reference McGorry(10), conclusive research on DUP, based on valid data, would only provide more momentum to such a reform process.

It seems therefore timely to establish a clearer definition of what should be considered as the end of the DUP period. First, given that medication is a key element in treatment of the vast majority of first episode psychosis patients, antipsychotic treatment initiation should belong to the definition. However, adherence to treatment ought to be assessed as well and the medication criterion considered fulfilled only if patients have taken their treatment for at least 75% of the time during at least 4 weeks. Second, based on the above data supporting the efficacy of specialised treatment, end of DUP should be considered only when patients are well engaged in an early intervention programme. It is clear that psychosocial treatments remain inconsistently available, and subject to the vagaries of service, economic, training and resource variables, but this is precisely what research on the impact of DUP is all about: to show that adequate treatment provided early has a positive impact on outcome of psychosis. Once this point established, the argument to justify the need for a reform of mental health programmes and for an earlier access to adequate psychosocial and medication treatment in early psychosis would only be stronger. However, in order to supply evidence-based arguments to this debate, the definition of DUP needs to be applied with more precision.

Acknowledgements

Financial and material support: Dr Philippe Conus is supported by the Leenaards Foundation, Switzerland, and by a Visiting Scholar Award from Melbourne University, Australia.

References

Clarke, M, Whitty, P, Browne, Set al. Untreated illness and outcome of psychosis. Br J Psychiatry 2006;189: 235240. CrossRefGoogle Scholar
Melle, I, Larsen, TK, Haahr, Uet al. Reducing the duration of untreated first-episode psychosis: Effects on clinical presentation. Arch Gen Psychiatry 2004;61: 143150. CrossRefGoogle ScholarPubMed
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: 17851804. CrossRefGoogle ScholarPubMed
Schimmelmann, B, Huber, C, Lambert, M, Cotton, S, McGorry, P, 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: 982990. CrossRefGoogle Scholar
Craig, TJ, Bromet, EJ, Fennig, S, Tanenberg-Karant, M, Lavelle, J, Galambos, N.Is there an association between duration of untreated psychosis and 24-month clinical outcome in a first-admission series? Am J Psychiatry 2000;157: 6066. CrossRefGoogle Scholar
Goldberg, TE, Burdick, KE, McCormack, Jet al. Lack of an inverse relationship between duration of untreated psychosis and cognitive function in first episode schizophrenia. Schizophr Res 2009;107: 262266. CrossRefGoogle ScholarPubMed
Ho, B, Andreasen, N.Long delays in seeking treatment for schizophrenia. Lancet 2001;357: 898899. CrossRefGoogle Scholar
Malla, A, Schimtz, N, Norman, Ret al. A multisite Canadian study of outcome of first-episode psychosis treated in publicly funded early intervention services. Can J Psychiatry 2007;52: 563571. CrossRefGoogle ScholarPubMed
Marshall, M, Lewis, S, Lockwood, A, Drake, R, Jones, P, Croudace, T.Association between duration of untreatedpsychosis andoutcome in cohorts of first-episode patients: A Systematic Review. Arch Gen Psychiatry 2005;62: 975983. CrossRefGoogle ScholarPubMed
McGorry, PD.Evaluating the importance of reducing the duration of untreated psychosis. Aust N ZJ Psychiatry 2000;34: 145149. CrossRefGoogle ScholarPubMed
Pantelis, C, Velakoulis, D, McGorry, PDet al. Neuroanatomical abnormalities before and after onset of psychosis: a cross-sectional and longitudinal MRI comparison. The Lancet 2003;361: 281288. CrossRefGoogle ScholarPubMed
Berk, M.Neuroprogression: pathways to progressive brain changes in bipolar disorder. Int J Neuropsychopharmacol 2009;12: 441445. CrossRefGoogle ScholarPubMed
Lieberman, JA, Tollefson, GD, Charles, Cet al. for the HGDH Study Group. Antipsychotic drug effects on brain morphology in first-episode psychosis. Arch Gen Psychiatry 2005;62: 361370. CrossRefGoogle ScholarPubMed
Singh, SP, Cooper, J, Fischer, Het al. Determining the chronology and components of psychosis onset: the Nottingham Onset Schedule (NOS). Schizophr Res 2005;80: 117130. CrossRefGoogle Scholar
Yung, AR, Yuen, HP, McGorry, PDet al. Mapping the onset of psychosis: The comprehensive assessment of at-risk mental states. Aust N Z J Psychiatry 2005;39: 964971. CrossRefGoogle ScholarPubMed
International Early Psychosis Association Writing Group. International clinical practice guidelines for early psychosis. Br J Psychiatry 2005;187: s120s124. CrossRefGoogle Scholar
Lambert, M, Conus, P, Lambert, T, McGorry, PD.Pharmacotherapy of first-episode psychosis. Expert Opinion on Pharmacotherapy 2003;4: 717750. CrossRefGoogle ScholarPubMed
The National Early Psychosis Project (NEPP). Australian Guidelines for Early Psychosis. Melbourne: University of Melbourne, 1998. Google ScholarPubMed
Barnes, T, Hutton, S, Chapman, M, Mutsatsa, S, Puri, B, Joyce, E.West London first-episode study of schizophrenia: Clinical correlates of duration of untreated psychosis. Brit J Psychiatry 2000;177: 207211. CrossRefGoogle ScholarPubMed
Browne, S, Clarke, M, Gervin, M, Waddington, J, Larkin, C, O’callaghan, E.Determinants of quality of life at first presentation with schizophrenia. Brit J Psychiatry 2000; 176: 173176. CrossRefGoogle ScholarPubMed
Haas, GL, Garratt, LS, Sweeney, JA.Delay to first antipsychotic medication in schizophrenia: impact on symptomatology and clinical course of illness. J Psychiatr Res 1998;32: 151159. CrossRefGoogle ScholarPubMed
Szymanski, SR, Cannon, TD, Gallacher, F, Erwin, RJ, Gur, RE.Course of treatment response in first-episode and chronic schizophrenia. Am J Psychiatry 1996;153: 519525. Google ScholarPubMed
Tirupati, NS, Rangaswamy, T, Raman, P.Duration of untreated psychosis and treatment outcome in schizophrenia patients untreated for many years. Aust N Z J Psychiatry 2004;38: 339343. CrossRefGoogle ScholarPubMed
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: 7585. CrossRefGoogle ScholarPubMed
Larsen, TK, McGlashan, TH, Moe, LC.First-episode Schizophrenia: I. Early Course Parameters. Schizophr Bull 1996;22: 241256. CrossRefGoogle ScholarPubMed
Addington, J, Van Mastrigt, S, Addington, D.Duration of untreated psychosis: Impact on 2-year outcome. Psychol Med 2004;34: 277284. CrossRefGoogle ScholarPubMed
Hafner, H, Maurer, K, Loffler, W, Riecher-Rossler, A.The influence of age and sex on the onset and early course of schizophrenia. Brit J Psychiatry 1993;162: 8086. CrossRefGoogle ScholarPubMed
Kalla, O, Aaltonen, J, Wahl-ström, J, Lethinen, V, Garcia Cabeza, I, Gonzales de Chavez, M.Duration of untreated psychosis and its correlates in first-episode psychosis in Finland and Spain. Acta Psychiatr Scand 2002;106: 265275. CrossRefGoogle ScholarPubMed
Carbone, S, Harrigan, S, McGorry, PD, Curry, C.Duration of untreated psychosis and 12-month outcome in first-episode psychosis: the impact of treatment approach. Acta Psychiatr Scand 1999;100: 96104. CrossRefGoogle ScholarPubMed
Malla, AK, Norman, RMG, Manchanda, Ret al. One year outcome in first episode psychosis: influence of DUP and other predictors. Schizophr Res 2002;54: 231242. CrossRefGoogle ScholarPubMed
Malla, AK, Norman, RMG.Treating psychosis: Is there more to early intervention than intervening early? Can J Psychiatry 2001;46: 645648. CrossRefGoogle ScholarPubMed
Garety, P, Craig, T, Dunn, Get al. Specialised care for early psychosis: symptoms, social functioning and patient satisfaction: Randomised controlled trial. Brit J Psychiatry 2006;188: 3745. CrossRefGoogle ScholarPubMed
Petersen, L, Jeppesen, P, Thoru, Aet al. A randomized multicentre trial of integrated versus standard treatment for patients with a first episode of psychotic illness. BMJ 2005;331: 602. CrossRefGoogle ScholarPubMed
Figure 0

Table 1 Definitions of treatment initiation in the literature

You have Access
3
Cited by

Save article to Kindle

To save this article to your Kindle, first ensure coreplatform@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 saving to your Kindle.

Note you can select to save to either the @free.kindle.com or @kindle.com variations. ‘@free.kindle.com’ emails are free but can only be saved 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: What are we talking about?
Available formats
×

Save article to Dropbox

To save 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 used this feature, you will be asked to authorise Cambridge Core to connect with your Dropbox account. Find out more about saving content to Dropbox.

Duration of untreated psychosis: What are we talking about?
Available formats
×

Save article to Google Drive

To save 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 used this feature, you will be asked to authorise Cambridge Core to connect with your Google Drive account. Find out more about saving content to Google Drive.

Duration of untreated psychosis: What are we talking about?
Available formats
×
×

Reply to: Submit a response

Please enter your response.

Your details

Please enter a valid email address.

Conflicting interests

Do you have any conflicting interests? *