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Reducing long-term antipsychotic use: A therapeutic dead end?

Published online by Cambridge University Press:  02 January 2018

Stanley V. Catts
Affiliation:
School of Medicine, University of Queensland. Email: s.catts@uq.edu.au
Brian I. O'Toole
Affiliation:
Brain and Mind Centre, University of Sydney
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Abstract

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Columns
Copyright
Copyright © Royal College of Psychiatrists, 2017 

Murray and colleagues' confident advice Reference Murray, Quattrone, Natesan, van Os, Nordentoft and Howes1 to psychiatrists, encouraging them to leave fewer patients with schizophrenia on long-term medication, is based on one of several possible interpretations of a selected literature, and little clinical evidence. We consider that at times Murray and colleagues misrepresented the literature in their descriptions of what some papers report; sometimes these descriptions are misleading (e.g. their references to Mace et al (2015), Vita et al (2015) and Boonstra et al (2011)) or incorrect (Saha et al (2007)). If the evidence so strongly supports the authors' recommendations, why have they relied so heavily on single case reports and personal communications, and on qualifying words such as ‘doubts’, ‘possibilities’, ‘suggest’, ‘appear’, ‘raise the possibilities’, ‘several Japanese groups have suggested’? Why have they given prominence to a study (Harrow et al (2014)) that they admit has a ‘major confounder’, and another (Wunderink et al (2013)) that they describe as ‘a study less open to bias’, which others consider grossly flawed (reviewed by Catts & O'Toole Reference Catts and O'Toole2 )? And why do they consistently refer to use of low or no doses, without ever describing the conditions that discriminate these indications?

Murray and colleagues assert that continuous antipsychotic medication loses its effectiveness over time, but do not present any clinical evidence for this, and that this putative treatment resistance is due to antipsychotic-induced dopamine receptor supersensitivity that has been found in animal studies. Indeed, the authors rely heavily on animal studies generally to make their case for a range of issues, without highlighting the fact that the relevant animal studies were all carried out on healthy animals. The authors seem overly confident that the results of these animal studies can be applied directly to the clinical situation, although no psychiatrist uses antipsychotic medication in healthy humans. The authors fail to see the complete disconnect between healthy animal research and clinical research on patients with schizophrenia. It seems to us that the reliance on animal studies by Murray and colleagues has resulted in their treatment recommendations being almost the opposite of others based on clinical literature. Reference Catts and O'Toole2

We suggest that Murray and colleagues are proposing a therapeutic dead end. With current practice, most patients stop their medication anyway (mainly owing to non-adherence to oral medication) – 60% of patients with first-episode psychosis do so within 60 days of hospital discharge: Reference Tiihonen, Haukka, Taylor, Haddad, Patel and Korhonen3 so how will taking more patients off their antipsychotic medication improve the current overall recovery rates in schizophrenia of 13.5%, Reference Jaaskelainen, Juola, Hirvonen, McGrath, Saha and Isohanni4 and the death rates that all agree are unacceptably high? Murray and colleagues' answer is more psychosocial intervention, but they present no evidence for the effectiveness of such intervention in unmedicated patients. The clinical evidence for antipsychotic medication reducing the mortality rate at all stages of the illness is of high quality and very consistent (summarised by Tiihonen Reference Tiihonen5 ); the simple truth is that taking more patients off maintenance medication will result in more patients dying unnecessarily – the ultimate therapeutic dead end.

Footnotes

Declaration of interest

S.V.C. has received funding for acting in the role of an advisory board member, as a sponsored educational speaker, and for research projects from the following pharmaceutical companies: Janssen-Cilag Pty Ltd, Eli Lilly Australia Pty Ltd, Lundbeck Australia Pty Ltd, Novartis Pharmaceuticals Australia Pty Ltd, Pfizer Australia Pty Ltd, Bristol-Myers Squibb Pty Ltd, Sanofi-Aventis Australia Pty Ltd, Hospira Australia Pty Ltd, and AstraZeneca Pty Ltd. He is also a Trustee for the Psychosis Australia Trust and the Queensland Schizophrenia Research Foundation, and a board member of Clearthinking Queensland Ltd.

References

1 Murray, RM, Quattrone, D, Natesan, S, van Os, J, Nordentoft, M, Howes, O, et al. Should psychiatrists be more cautious about the long-term prophylactic use of antipsychotics? Br J Psychiatry 2016: 209: 361–5.CrossRefGoogle ScholarPubMed
2 Catts, SV, O'Toole, BI. The treatment of schizophrenia: can we raise the standard of care? Aust NZ J Psychiatry 2016; 50: 1128–38.CrossRefGoogle ScholarPubMed
3 Tiihonen, J, Haukka, J, Taylor, M, Haddad, PM, Patel, MX, Korhonen, P. A nationwide cohort study of oral and depot antipsychotics after first hospitalization for schizophrenia. Am J Psychiatry 2011; 168: 603–9.CrossRefGoogle Scholar
4 Jaaskelainen, 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.CrossRefGoogle Scholar
5 Tiihonen, J. Editorial: real-world effectiveness of antipsychotics. Acta Psychiatr Scand 2016; 134: 371–3.CrossRefGoogle ScholarPubMed
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