Relationship between plasma risperidone and 9-hydroxyrisperidone concentrations and clinical response in patients with schizophrenia.
BACKGROUND
Evaluation of relationships between serum antipsychotic drug concentrations and clinical response may provide valuable information for rational dosage adjustments. For risperidone, this relationship has been little investigated to date.


OBJECTIVE
To assess the relationship between plasma concentrations of risperidone and its active 9-hydroxy-metabolite (9-OH-risperidone) and clinical response in schizophrenic patients who experienced an acute exacerbation of the disorder.


METHODS
Forty-two patients (30 males, 12 females, age 24-60 years) were given risperidone at dosages ranging from 4 to 9 mg/day for 6 weeks. The design of the study was open and risperidone dosage could be adjusted individually according to clinical response. Steady-state plasma concentrations of risperidone and its 9-hydroxymetabolite were measured after 4 and 6 weeks using a specific HPLC assay. Psychopathological state was assessed at baseline and at weeks 2, 4, and 6 by means of the positive and negative syndrome scale (PANSS), and patients were considered responders if they showed a greater than 20% reduction in total PANSS score at final evaluation compared with baseline.


RESULTS
Mean plasma concentrations of risperidone, 9-OH-risperidone, and active moiety (sum of risperidone and 9-OH-risperidone concentrations) did not differ between responders (n = 28) and non-responders (n = 14). No correlation between plasma levels and percent decrease in total PANSS score was found for risperidone (rs = -0.187, NS), 9-OH-risperidone (rs = 0.246, NS), and active moiety (rs = 0.249, NS). Active moiety concentrations in plasma were higher (P < 0.001) in patients developing clinically significant parkinsonian symptoms (n = 7) than in those with minimal (n = 7) or no drug-induced parkinsonism (n = 28).


CONCLUSIONS
In chronic schizophrenic patients experiencing an acute exacerbation of the disorder, plasma levels of risperidone and its active metabolite correlate with the occurrence of parkinsonian side effects, whereas no significant correlation appears to exist with the degree of clinical improvement.
Spina
E
E
Institute of Pharmacology, University of Messina, Policlinico Universitario, Italy. espina@www.unime.it
Avenoso
A
A
Facciolà
G
G
Salemi
M
M
Scordo
M G
MG
Ancione
M
M
Madia
A G
AG
Perucca
E
E
D000293:Adolescent; D000328:Adult; D000368:Aged; D014150:Antipsychotic Agents / Q000009:adverse effects / Q000097:blood* / Q000627:therapeutic use*; D001480:Basal Ganglia Diseases / Q000139:chemically induced / Q000523:psychology; D002851:Chromatography, High Pressure Liquid; D002908:Chronic Disease; D005260:Female; D006801:Humans; D007555:Isoxazoles / Q000097:blood*; D008297:Male; D008875:Middle Aged; D000068882:Paliperidone Palmitate; D011569:Psychiatric Status Rating Scales; D011743:Pyrimidines / Q000097:blood*; D018967:Risperidone / Q000009:adverse effects / Q000097:blood* / Q000627:therapeutic use*; D012559:Schizophrenia / Q000188:drug therapy*; D012565:Schizophrenic Psychology
D014150:Antipsychotic Agents; D007555:Isoxazoles; D011743:Pyrimidines; D018967:Risperidone; D000068882:Paliperidone Palmitate