Dopamine supersensitivity psychosis and delay of clozapine treatment in patients with treatment-resistant schizophrenia.

Both the underutilization of clozapine and treatment resistance of patients to clozapine are serious problems worldwide. Identifying clinical markers predicting response to clozapine would help clinicians more effectively utilize clozapine treatment. The present study retrospectively assessed dopamine supersensitivity psychosis (DSP) in addition to other measures such as age at disease onset and delay of clozapine introduction for a total of 47 treatment-resistant schizophrenia (TRS) patients. The response to clozapine was judged with CGI-C at 1 and 2 years from clozapine introduction. Results revealed that the DSP group tended to have a longer delay between designation of TRS and introduction of clozapine and continued to have slightly more severe psychopathology after treatment with clozapine, showing only slight improvement. The logistic regression analysis showed that the age at disease onset was the only significant indicator, predicting responsiveness to clozapine: patients with an onset age <20 years had a significantly better response to clozapine than patients with an onset age ≥20 years. The present study suggests that DSP might be related to a longer delay in clozapine introduction and the persistence of refractory symptoms despite clozapine treatment, whereas early age of disease onset might be related to a better response to clozapine.

The cortical silent period in schizophrenia: A systematic review and meta-analysis focusing on disease stage and antipsychotic medication.

BACKGROUND: Although numerous studies reported some changes of cortical silent period (CSP), an indicator of gamma-aminobutyric acid (GABA) function in central nervous system, in schizophrenia patients, it has been unknown how the disease stage and antipsychotic medication affect CSP values. METHODS: The present study conducted a systematic review of previous literature comparing CSP between schizophrenia patients and healthy subjects, and then performed meta-analysis on the effects of (1) the disease stage and (2) antipsychotics on CSP. RESULTS: (1) In the comparison of the disease stage comprising a total of 17 reports, there was no significant difference in CSP between patients under drug-naïve first-episode psychoses and healthy controls, or between patients with antipsychotic medication and healthy controls. (2) In the comparison of the antipsychotic class, patients treated with clozapine were longer in CSP compared to healthy controls. Patients treated with olanzapine/quetiapine or with other type of antipsychotics were not different from healthy controls. Regarding other type of antipsychotics, the iteration analysis after leaving out one literature showed that patients were shorter in CSP than healthy controls. CONCLUSION: The results showed that clozapine seems to surely prolong CSP, indicating the enhancement of GABA transmission via GABAB receptors, suggesting the possible relationship between the CSP prolongation by clozapine and its high efficacy in psychopathology. The finding of shorter CSP in patients with other type of antipsychotics was distinct from clozapine/olanzapine/quetiapine, but was difficult to interpret since this group included a variety of transcranial magnetic stimulation (TMS) methodologies and patients' background.