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Review
. 2017 Jan 13;17(1):12.
doi: 10.1186/s12888-016-1177-y.

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

Amy L Gillespie  1 , Ruta Samanaite  2 , Jonathan Mill  3   4 , Alice Egerton  2 , James H MacCabe  2
Affiliations
Free PMC article
Review

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

Amy L Gillespie et al. BMC Psychiatry. .
Free PMC article

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.

Keywords: Classification; Clozapine; Schizophrenia; Treatment refractory; Treatment resistance; Treatment response.

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Fig. 1
Flowchart of identified, included and excluded studies
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References

    1. Elkis H. Treatment-resistant schizophrenia. Psychiatr Clin North Am. 2007;30:511–33. doi: 10.1016/j.psc.2007.04.001. - DOI - PubMed
    1. Farooq S, Agid O, Foussias G, Remington G. Using treatment response to subtype schizophrenia: proposal for a new paradigm in classification. Schizophr Bull. 2013;39:1169–72. doi: 10.1093/schbul/sbt137. - DOI - PMC - PubMed
    1. Agid O, Arenovich T, Sajeev G, Zipursky RB, Kapur S, Foussias G, Remington G. An algorithm-based approach to first-episode schizophrenia: response rates over 3 prospective antipsychotic trials with a retrospective data analysis. J Clin Psychiatry. 2011;72:1439–44. doi: 10.4088/JCP.09m05785yel. - DOI - PubMed
    1. Kolakowska T, Williams AO, Ardern M, Reveley MA, Jambor K, Gelder MG, Mandelbrote BM. Schizophrenia with good and poor outcome, I: early clinical features, response to neuroleptics and signs of organic dysfunction. Br J Psychiatry. 1985;146:229–39. doi: 10.1192/bjp.146.3.229. - DOI - PubMed
    1. May PRA, van Putten T, Yale C. Predicting outcome of antipsychotic drug treatment from early response. Am J Psychiatry. 1980;137:1088–9. doi: 10.1176/ajp.137.9.1088. - DOI - PubMed