Does pharmacology explain dosing adjustments during antipsychotic combination therapy under naturalistic clinical conditions?

Introduction: Dopamine D2 receptor blockade by antipsychotics is thought to mediate their effects on positive symptoms of schizophrenia. Therefore, the combination of two antipsychotics with similar affinity for the D2 receptor (1) should result in additive effects on psychotic symptoms or (2) could be used to decrease the dosage of the first antipsychotic. Methods: We tested this hypothesis in a retrospective analysis of all plasma samples submitted for therapeutic drug monitoring (TDM) by the University Hospital Innsbruck from April 01 to September 30, 2008, in patients diagnosed with schizophreniform disorders (ICD 10 codes F20 to F29). Results and Discussion: The addition of a second antipsychotic (amisulpride, aripiprazole or clozapine) resulted in a decrease in the dosage and in the plasma level of the first antipsychotic (clozapine or risperidone) only in those patients whose antipsychotic plasma levels under monotherapy with the first antipsychotic were within the recommended therapeutic level, i.e., only in patients who were adequately dosed and showed sufficient compliance under monotherapy.