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BMC Psychiatry
Published in: BMC Psychiatry 1/2017

Open Access 01-12-2017 | Research article

Is treatment-resistant schizophrenia categorically distinct from treatment-responsive schizophrenia? a systematic review

Authors: Amy L. Gillespie, Ruta Samanaite, Jonathan Mill, Alice Egerton, James H. MacCabe

Published in: BMC Psychiatry | Issue 1/2017

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Abstract

Background

Schizophrenia is a highly heterogeneous disorder, and around a third of patients are treatment-resistant. The only evidence-based treatment for these patients is clozapine, an atypical antipsychotic with relatively weak dopamine antagonism. It is plausible that varying degrees of response to antipsychotics reflect categorically distinct illness subtypes, which would have significant implications for research and clinical practice. If these subtypes could be distinguished at illness onset, this could represent a first step towards personalised medicine in psychiatry. This systematic review investigates whether current evidence supports conceptualising treatment-resistant and treatment-responsive schizophrenoa as categorically distinct subtypes.

Method

A systematic literature search was conducted, using PubMed, EMBASE, PsycInfo, CINAHL and OpenGrey databases, to identify all studies which compared treatment-resistant schizophrenia (defined as either a lack of response to two antipsychotic trials or clozapine prescription) to treatment-responsive schizophrenia (defined as known response to non-clozapine antipsychotics).

Results

Nineteen studies of moderate quality met inclusion criteria. The most robust findings indicate that treatment-resistant patients show glutamatergic abnormalities, a lack of dopaminergic abnormalities, and significant decreases in grey matter compared to treatment-responsive patients. Treatment-resistant patients were also reported to have higher familial loading; however, no individual gene-association study reported their findings surviving correction for multiple comparisons.

Conclusions

Tentative evidence supports conceptualising treatment-resistant schizophrenia as a categorically different illness subtype to treatment-responsive schizophrenia. However, research is limited and confirmation will require replication and rigorously controlled studies with large sample sizes and prospective study designs.
Appendix
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Footnotes
1
Demjaha et al. (2014) used a subset of patients reported in Demjaha et al. (2012). The 2012 paper reported on dopamine synthesis capacity, and the 2014 reported on dopamine synthesis capacity and levels of glutamate. Only the 2012 dopamine findings and 2014 glutamate findings are included in this review.
 
2
Molina et al. [29] and de Bartolomeis et al. [43] also measured PANSS scores but with cross-sectional designs
 
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Metadata
Title
Is treatment-resistant schizophrenia categorically distinct from treatment-responsive schizophrenia? a systematic review
Authors
Amy L. Gillespie
Ruta Samanaite
Jonathan Mill
Alice Egerton
James H. MacCabe
Publication date
01-12-2017
Publisher
BioMed Central
Published in
BMC Psychiatry / Issue 1/2017
Electronic ISSN: 1471-244X
DOI
https://doi.org/10.1186/s12888-016-1177-y

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