Drake, Richard J., Husain, Nusrat, Marshall, Max, Lewis, Shôn W, Tomenson, Barbara, Chaudhry, Imran B., Everard, Linda, Singh, Swaran P., Freemantle, Nick, Fowler, David, Jones, Peter B, Amos, Tim, Sharma, Vimal, Green, Chloe D, Fisher, Helen, Murray, Robin M, Wykes, Til, Buchan, Iain and Birchwood, Max (2020) Effect of delaying treatment of first-episode psychosis on symptoms and social outcomes : a longitudinal analysis and modelling study. The Lancet Psychiatry, 7 (7). pp. 602-610. doi:10.1016/S2215-0366(20)30147-4 ISSN 2215-0366.

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Abstract

Background
Delayed treatment for first episodes of psychosis predicts worse outcomes. We hypothesised that delaying treatment makes all symptoms more refractory, with harm worsening first quickly, then more slowly. We also hypothesised that although delay impairs treatment response, worse symptoms hasten treatment, which at presentation mitigates the detrimental effect of treatment delay on symptoms.
Methods
In this longitudinal analysis and modelling study, we included two longitudinal cohorts of patients with first-episode psychosis presenting to English early intervention services from defined catchments: NEDEN (recruiting 1003 patients aged 14–35 years from 14 services between Aug 1, 2005, and April 1, 2009) and Outlook (recruiting 399 patients aged 16–35 years from 11 services between April 1, 2006, and Feb 28, 2009). Patients were assessed at baseline, 6 months, and 12 months with the Positive and Negative Symptom Scale (PANSS), Calgary Depression Scale for Schizophrenia, Mania Rating Scale, Insight Scale, and Social and Occupational Functioning Assessment Scale. Regression was used to compare different models of the relationship between duration of untreated psychosis (DUP) and total symptoms at 6 months. Growth curve models of symptom subscales tested predictions arising from our hypotheses.
Findings
We included 948 patients from the NEDEN study and 332 patients from the Outlook study who completed baseline assessments and were prescribed dopamine antagonist antipsychotics. For both cohorts, the best-fitting models were logarithmic, describing a curvilinear relationship of DUP to symptom severity: longer DUP predicted reduced treatment response, but response worsened more slowly as DUP lengthened. Increasing DUP by ten times predicted reduced improvement in total symptoms (ie, PANSS total) by 7·339 (95% CI 5·762 to 8·916; p<0·0001) in NEDEN data and 3·846 (1·689 to 6·003; p=0·0005) in Outlook data. This was true of treatment response for all symptom types. Nevertheless, longer DUP was not associated with worse presentation for any symptoms except depression in NEDEN (coefficients 0·099 [95% CI 0·033 to 0·164]; p=0·0028 in NEDEN and 0·007 [−0·081 to 0·095]; p=0·88 in Outlook).
Interpretation
Long DUP was associated with reduced treatment response across subscales, consistent with a harmful process upstream of individual symptoms' mechanisms; response appeared to worsen quickly at first, then more slowly. These associations underscore the importance of rapid access to a comprehensive range of treatments, especially in the first weeks after psychosis onset.

Item Type:	Journal Article
Subjects:	R Medicine > RC Internal medicine
Divisions:	Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School > Health Sciences Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School > Health Sciences > Mental Health and Wellbeing Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School
Library of Congress Subject Headings (LCSH):	Psychoses, Psychoses -- Diagnosis -- Treatment, Psychoses -- Patients -- Treatment
Journal or Publication Title:	The Lancet Psychiatry
Publisher:	Elsevier Ltd.
ISSN:	2215-0366
Official Date:	1 July 2020
Dates:	Date Event 1 July 2020 Published 2 April 2020 Accepted
Volume:	7
Number:	7
Page Range:	pp. 602-610
DOI:	10.1016/S2215-0366(20)30147-4
Status:	Peer Reviewed
Publication Status:	Published
Access rights to Published version:	Open Access (Creative Commons)
Date of first compliant deposit:	30 June 2020
Date of first compliant Open Access:	30 June 2020
RIOXX Funder/Project Grant:	Project/Grant ID RIOXX Funder Name Funder ID UNSPECIFIED Medical Research Council http://dx.doi.org/10.13039/501100000265 UNSPECIFIED [NIHR] National Institute for Health Research http://dx.doi.org/10.13039/501100000272 UNSPECIFIED Department of Health Care Services http://dx.doi.org/10.13039/100005001

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