Depressive symptoms and plasma monoamine levels as predictors of response to clozapine treatment in adolescents with schizophrenia

Objectives: The purpose of this study was to assess the relationships between neuroleptic medication, biogenic amines and symptomatology in a sample of adolescents with schizophrenia (ICD-IO critria). Method: Psychopathological symptoms were rated weekly by means of standard rating scales (BPRS, SANS, SAPS), parallel to weekly blood samplings for measurement of biogenic amines and serum levels of clozapine. These measures were obtained for the 6 weeks of conventional neuroleptic treatment and the subsequent 6-week open-label clozapine trial. Results: Serum levels of serotonin and plasma norepinephrine were significantly higher during treatment with clozapine than during preteatment with typical neuroleptics. A comparison of the plasma norepinephrine levels in responders (n = 7) and non-responders (n = 8) to those of clozapine revealed that response to clozapine can be predicted on the basis of the epinephrine levels prior to initiation of clozapine treatment. Additionally, plasma concentrations of methoxyhydroxyphenylglycol (MHPG) and epinephrine were both increased in clozapine responders in comparison to the levels measured during pretreatment with typical neuroleptics. Finally, our results demonstrate that depressive symptomatology prior to initiation of clozapine treatment is also predictive of response to this atypical neuroleptic. schizophrenia.