INITIAL IMPROVEMENT AS A CRITERION FOR DRUG CHOICE IN ACUTE SCHIZOPHRENIA

Several investigators have found that the initial improvement of acute schizophrenia after some days of neuroleptic treatment is correlated in a statistically significant way to the outcome after four weeks. In all these studies the question arises as to whether the correlation between early response and subsequent outcome is due to a specific response to a certain neuroleptic, or whether patients who respond early simply have a better prognosis. In order to isolate the specific drug effect from prognostic influenccs we performed a controlled double-blind study in 50 newly admitted schizophrenic inpatients. All patients were treated over three days with 15 mg haloperidol i. v., following which they were classified as 'early responders (ER)' (markedly improved or improved) or as 'early nonresponders (EN)' and then randomly assigned to group 1 (3 x 5 mg haloperidol p.o./d) or to group 2 (3 x 100 mg perazin p.o./d). If there was a specific drug effect on the correlation between early response and subsequent outcome a therapeutic superiority of perazin in EN and no superiority in ER was expected. Independently of the treatment condition the mean BPRS score had decreased from 61.2 (Sx = 12. 1) to 38.1 (Sx = 13.9) at the end of the study. ER and EN were evenly distributed in the haloperidol and perazin group. The analysis of variance revealed no significant interactions of the factors 'treatment condition' x 'duration' x 'early response' (p = 0.27) and 'treatment condition' x 'early response' (p = 0.88) on the outcome (BPRS, CGI). This means that the initial hypothesis of this study has to be rejected. Possible reasons for this result (e.g., drug choice and dosage, duration of pretreatment, relatively low number of patients in each group) and the clinical value of the so called 'test dosage model' are discussed below.