Therapeutic spectrum of nemonapride and its relationship with plasma concentrations of the drug and prolactin

The therapeutic spectrum of nemonapride, a new substituted benzamide, and i ts relationship with plasma concentrations of the drug and prolactin were i nvestigated by a fixed-dose study (18 mg/day for 3 weeks) in 31 patients wi th acutely exacerbated schizophrenia. Of 31 patients, 25 (80.6%) were respo nders who showed a reduction in symptoms (percentage of improvement) of 50% or more after 3 weeks. The mean values of percentage of improvement in sco res on the total Brief Psychiatric Rating Scale (BPRS) and the five subscal e symptoms were 71.5% for total, 73.2% for Positive, 86.0% for Excitement, 53.9% for Negative, 84.2% for Cognitive, and 67.5% for Anxiety-Depression. Responders had higher percentage of improvement in positive (84.6 +/- 17.0( dagger) 9/0 vs. 25.9 +/- 15.7%; p < 0.001) and anxiety-depression (76.9 +/- 18.8% vs. 28.5 +/- 39.9%; p < 0.005) symptoms than did nonresponders after 3 weeks. The percentage of improvement in total BPRS after 2 weeks was wel l correlated with that after 3 weeks (Spearman rank correlation coefficient : r(s) = 0.711; p < 0.01). There was an inverted U-shaped relationship betw een plasma drug concentrations (nemonapride plus desmethylnemonapride) and percentage of improvement in total BPRS symptoms after a 3-week treatment ( y = 46.9 + 73.9x - 44.2x(2); p < 0.001). These findings suggest that nemona pride has a broad therapeutic spectrum in the treatment of acute schizophre nia. The improvements in scores for the Positive and Anxiety-Depression sub scale symptoms are regarded as determinant factors for total response to ne monapride. An assessment of clinical status after 2 weeks and plasma drug m onitoring may be useful for the prediction of the final outcome for patient s.