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 its relationship with plasma concentrations of the drug and prolactin were investigated by a fixed-dose study (18 mg/day for 3 weeks) in 31 patients with acutely exacerbated schizophrenia. Of 31 patients, 25 (80.6%) were responders who showed a reduction in symptoms (percentage of improvement) of 50% or more after 3 weeks. The mean values of percentage of improvement in scores on the total Brief Psychiatric Rating Scale (BPRS) and the five subscale 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% 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 well correlated with that after 3 weeks (Spearman rank correlation coefficient: r(s) = 0.711; p < 0.01). There was an inverted U-shaped relationship between plasma drug concentrations (nemonapride plus desmethylnemonapride) and percentage of improvement in total BPRS symptoms after a 3-week treatment (y = 46.9 + 73.9x - 44.2x2; p < 0.001). These findings suggest that nemonapride has a broad therapeutic spectrum in the treatment of acute schizophrenia. The improvements in scores for the Positive and Anxiety-Depression subscale symptoms are regarded as determinant factors for total response to nemonapride. An assessment of clinical status after 2 weeks and plasma drug monitoring may be useful for the prediction of the final outcome for patients.
Kondo
T
T
Department of Neuropsychiatry, Hirosaki University School of Medicine, Japan.
Mihara
K
K
Yasui
N
N
Nagashima
U
U
Ono
S
S
Kaneko
S
S
Ohkubo
T
T
Osanai
T
T
Sugawara
K
K
Otani
K
K
D000293:Adolescent; D000328:Adult; D014150:Antipsychotic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D001549:Benzamides / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D001711:Biotransformation; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011388:Prolactin / Q000097:blood*; D011569:Psychiatric Status Rating Scales; D012559:Schizophrenia / Q000188:drug therapy*; D013997:Time Factors
D014150:Antipsychotic Agents; D001549:Benzamides; D011388:Prolactin; C030265:nemonapride