Clinical correlates of early onset antipsychotic treatment resistance

Author:

Fonseca de Freitas Daniela12ORCID,Agbedjro Deborah1,Kadra-Scalzo Giouliana1ORCID,Francis Emma13,Ridler Isobel1ORCID,Pritchard Megan145,Shetty Hitesh4,Segev Aviv167,Casetta Cecilia18,Smart Sophie E.19ORCID,Morris Anna1,Downs Johnny14,Christensen Søren Rahn10,Bak Nikolaj10,Kinon Bruce J.1112,Stahl Daniel1,Hayes Richard D.1ORCID,MacCabe James H.14ORCID

Affiliation:

1. Institute of Psychiatry, Psychology and Neuroscience, King’s College London, London, UK

2. Department of Psychiatry, University of Oxford, Oxford, UK

3. Division of Psychology and Language Sciences, University College London, London, UK

4. South London and Maudsley NHS Foundation Trust, London, UK

5. Norwich Medical School, University of East Anglia, Norwich, UK

6. Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel

7. Shalvata Mental Health Center, Hod Hasharon, Israel

8. Department of Health Sciences, Università degli Studi di Milano, Milan, Italy

9. MRC Centre for Neuropsychiatric Genetics and Genomics, Cardiff University, Cardiff, UK

10. H. Lundbeck A/S, Copenhagen, Denmark

11. Lundbeck Pharmaceuticals LLC, Deerfield, IL, USA

12. Cyclerion Therapeutics, Cambridge, MA, USA

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.

Funder

Medical Research Council

H. Lundbeck A/S

National Institute for Health Research

Publisher

SAGE Publications

Subject

Pharmacology (medical),Psychiatry and Mental health,Pharmacology

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