Schizophrenia is a mental disorder characterized by continuous or relapsing episodes of psychosis. While some individuals with schizophrenia experience treatment refractoriness from the outset, others develop refractoriness during the course of illness after having initially responded to treatment. 

About 15% of the patients diagnosed with schizophrenia have a single episode, ca. 85% has variable course and unfortunately one third – or depending on the definition 40-60% – of them do not respond to antipsychotic treatment as expected, or at all. The most frequently used definition of treatment resistant schizophrenia (TRS) is – less than 20% improvement after two adequate trials with two different antipsychotic drugs.Accumulating evidence suggests that episodes of antipsychotic discontinuation and resultant relapse episodes may be the critical factor in the evolution of emergent treatment resistance. 

Clozapine is recommended for TRS, however its use requires special attention. At times combination of non-clozapine antipsychotic drugs, electroconvulsive treatment and newer methods, such as repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS) may be considered, with lifestyle changes.