Treatment-resistant schizophrenia (TRS) is defined in several different guidelines in different ways, but can broadly be described as schizophrenia that has no significant improvement in target symptoms after treatment with at least two different antipsychotics (at an adequate dose and duration).[Hasan et al., 2012; Lehman et al., 2010]
That many patients with schizophrenia fail to respond to antipsychotic drugs – known to bind to dopamine receptors in the brain – poses a challenge to the dominance of the dopamine hypothesis.[Gillespie et al., 2017] This has led some to consider whether treatment-resistant schizophrenia (TRS) is a separate pathophysiological entity to what is classically termed schizophrenia.[Gillespie et al., 2017]
There are some indications that TRS may be characterised by a dysregulated glutamate system, however much more research is needed.[Gillespie et al., 2017] One of the problems that plagues researchers in this field is the lack of a universal definition of ‘treatment resistance’.[Gillespie et al., 2017] A consensus definition, were it to be adopted, would allow for easier comparison of different studies and pooling of samples.[Gillespie et al., 2017]
References:
Gillespie AL, Samanaite R, Mill J, et al. Is treatment-resistant schizophrenia categorically distinct from treatment-responsive schizophrenia? A systematic review. BMC Psychiatry 2017; 17 (1): 12.
Hasan A, Falkai P, Wobrock T, et al. World Federation of Societies of Biological Psychiatry (WFSBP) guidelines for biological treatment of schizophrenia, part 1: update 2012 on the acute treatment of schizophrenia and the management of treatment resistance. World J Biol Psychiatry 2012; 13 (5): 318–378.
Lehman AF, Lieberman JA, Dixon LB, et al. APA. Practice guideline for the treatment of patients with schizophrenia. 2nd ed. 2010; 1–184.
Anderson VM, Goldstein ME, Kydd RR, Russell BR. Extensive gray matter volume reduction in treatment-resistant schizophrenia. Int J Neuropsychopharmacol 2015; 18 (7): pyv016.
Roberts RC, Roche JK, Conley RR, Lahti AC. Dopaminergic synapses in the caudate of subjects with schizophrenia: relationship to treatment response. Synapse 2009; 63 (6): 520–530.
White TP, Wigton R, Joyce DW, et al. Dysfunctional striatal systems in treatment-resistant schizophrenia. Neuropsychopharmacology 2016; 41 (5): 1274–1285.