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. 2022 Nov;36(11):1226-1233.
doi: 10.1177/02698811221132537. Epub 2022 Oct 21.

Clinical correlates of early onset antipsychotic treatment resistance

Daniela Fonseca de Freitas  1   2 , Deborah Agbedjro  1 , Giouliana Kadra-Scalzo  1 , Emma Francis  1   3 , Isobel Ridler  1 , Megan Pritchard  1   4   5 , Hitesh Shetty  4 , Aviv Segev  1   6   7 , Cecilia Casetta  1   8 , Sophie E Smart  1   9 , Anna Morris  1 , Johnny Downs  1   4 , Søren Rahn Christensen  10 , Nikolaj Bak  10 , Bruce J Kinon  11   12 , Daniel Stahl  1 , Richard D Hayes  1 , James H MacCabe  1   4
Affiliations

Clinical correlates of early onset antipsychotic treatment resistance

Daniela Fonseca de Freitas et al. J Psychopharmacol. 2022 Nov.

Abstract

Background: There is evidence of heterogeneity within treatment-resistant schizophrenia (TRS), with some people not responding to antipsychotic treatment from illness onset and others becoming treatment-resistant after an initial response period. These groups may have different aetiologies.

Aim: This study investigates sociodemographic and clinical correlates of early onset of TRS.

Method: Employing a retrospective cohort design, we do a secondary analysis of data from a cohort of people with TRS attending the South London and Maudsley. Regression analyses were conducted to identify the correlates of the length of treatment to TRS. Predictors included the following: gender, age, ethnicity, problems with positive symptoms, problems with activities of daily living, psychiatric comorbidities, involuntary hospitalisation and treatment with long-acting injectable antipsychotics.

Results: In a cohort of 164 people with TRS (60% were men), the median length of treatment to TRS was 3 years and 8 months. We observed no cut-off on the length of treatment until TRS presentation differentiating between early and late TRS (i.e. no bimodal distribution). Having mild to very severe problems with hallucinations and delusions at the treatment start was associated with earlier TRS (~19 months earlier). In sensitivity analyses, including only complete cases (subject to selection bias), treatment with a long-acting injectable antipsychotic was additionally associated with later TRS (~15 months later).

Conclusion: Our findings do not support a clear separation between early and late TRS but rather a continuum of the length of treatment before TRS onset. Having mild to very severe problems with positive symptoms at treatment start predicts earlier onset of TRS.

Keywords: Psychotic disorders; antipsychotic agents; clozapine; schizophrenia; treatment refractory.

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Conflict of interest statement

The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: DFdF, GKS, EF and IR have received research funding from Janssen and H. Lundbeck A/S. RDH and HS have received research funding from Roche, Pfizer, Janssen and Lundbeck. SES is employed on a grant held by Cardiff University from Takeda Pharmaceutical Company Ltd. for work unrelated to the analysis reported here. SRC, NB and BK were employees of Lundbeck at the time of the study. JHM received research funding for this study from H. Lundbeck A/S.

Figures

Figure 1.
Figure 1.
Selection of study cohort.
Figure 2.
Figure 2.
Distribution of length of treatment until TRS onset. TRS: treatment-resistant schizophrenia.
See this image and copyright information in PMC

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