The Influence of Therapeutic Drug Monitoring (TDM) and Objective Symptom Rating for Prediction of Antipsychotic Response to Second-Generation Antipsychotic Drugs

Prediction of response to antipsychotic drug therapy in schizophrenic patients is at present the subject of few study groups and not well investigated in real life patients. Here we report that objective symptom ratings using the Brief Psychiatric Rating Scale (BPRS) and drug concentration measurement (TDM) on week two after start of the antipsychotic medication are useful for prediction of later drug response in the early phase of treatment.

We recruited 100 acutely ill schizophrenic inpatients who were treated with atypical antipsychotics and assessed clinical changes by measuring BPRS and Clinical Global Impressions (CGI) scores and drug concentrations. Clinical response was defined as ≥25% BPRS reduction on week 4. Statistical evaluations included receiver operating characteristics and logistic regression analysis.

Reduction of BPRS by at least 16.2% on week 2 and therapeutically recommended concentrations of the atypical antipsychotic drugs were significant predictors for later response. Specificity and sensitivity were 90% and 67%, respectively. Odds ratio for the cut-off 16.2% were 24.7 and 5.2 for therapeutic drug concentrations. In patients whose drug concentrations were not within the therapeutic range on week 2, the improvement according to BPRS was significantly worse than in patients with optimal drug concentrations. Of these patients 81% were treated with a fixed drug regime without changes in medication. Contrary, patients within the range had more BPRS reduction and had frequently more changes in their drug regime.

It is concluded that objective symptom ratings and therapeutic drug monitoring at week 2 should be implemented into the treatment of schizophrenic patients to guide the antipsychotic drug therapy.