Biology of Schizophrenia: Is Treatment Refractoriness Synonymous with Severity of Illness [A.K.A. Is This a Drug Efficacy Problem or an Expression of Severe Illness?]

Wewould like to start this chapter by describing three severe cases of schizophrenia where treatment resistance developed at different time points of the evolution or natural history of disorder. Case report 1—AB is a man of 34 years who developed his first psychotic symptoms at the age of 17 years. He has a history of neurodevelopmental abnormalities such as birth complications and motor and language retardation as well as use of cannabis which triggered his psychotic with concomitant mood swings. Due to this he was considered to have bipolar disorder and was admitted for the first time and treated according to such diagnosis, i.e., with antipsychotics and mood stabilizers but was discharged with no improvement. He was then subsequently admitted five more times due to the presence of clear persecutory delusions, auditory hallucinations, thought disorganization, and agitation without mood features. In one of the episodes he hit his mother in the chest and menaced his father with a knife. Patient was diagnosed as having paranoid schizophrenia due to the characteristics of the psychotic episodes and absence of concomitant mood symptoms. He has been treated with six different antipsychotics during this period (haloperidol, trifluoperazine, olanzapine, risperidone, quetiapine, and aripiprazol) without satisfactory response with persistence of persecutory delusions and auditory hallucinations. The patient was again admitted and then defined as having treatment for resistant schizophrenia, and clozapine monotherapy was introduced with progressive doses, reaching 500 mg/day. The patient was discharged and after some weeks responded to treatment, achieving full remission at 6 months. He presently