Investigating treatment- resistance (TRS)
About one third of patients with schizophrenia are treatment resistant (TRS), i.e. they do not respond adequately to treatment with antipsychotic medication other than clozapine, and up to half of these show clozapine resistance, i.e. they do not improve at all on any medication. To date, the atypical antipsychotic drug clozapine is the only evidence-based treatment for TRS (Essali et al., 2009; Mortimer et al., 2010), and in addition, is also superior for negative and cognitive symptoms, as well as reducing suicidality (the InterSept study) and all-cause mortality, but only if two trials of the ususal antipsychotics fail (Picchioni and Murray, 1997),
However this process might take many years (Taylor et al., 2003) and it at present not possible to predict which patients will require clozapine. To improve the treatment outcomes in schizophrenia, research efforts are urgently needed that elucidate biomarkers of the illness and of treatment response, both with respect to therapeutic (clinical response to treatment) and adverse drug reactions (ADRs).