Prolactin elevation of the antipsychotic risperidone is predominantly related to its 9-hydroxy metabolite.
OBJECTIVE
Treatment with the antipsychotic risperidone is frequently associated with hyperprolactinemia. The aim of this study was to evaluate the role of the main compound risperidone and its active 9-hydroxy metabolite on elevating prolactin levels.


METHODS
Twenty patients with psychotic disorders, on therapy with risperidone, were studied. All patients had been receiving risperidone for at least 2.5 months, and the median daily dose of risperidone was 3 mg (range 1-10). Morning serum samples for prolactin were analyzed and investigated in relation to the serum concentrations of risperidone and 9-hydroxyrisperidone.


RESULTS
Elevated prolactin levels were found in 17 (85%) of the patients. Levels of prolactin were positively correlated to the 9-hydroxyrisperidone serum concentration (r(s) = 0.48, p = 0.03) and to the daily dose of risperidone (r(s) = 0.51, p = 0.03), but did not correlate to the risperidone serum concentration.


CONCLUSIONS
The present results suggest that 9-hydroxyrisperidone and not risperidone is the main contributor to the increased serum levels of prolactin observed in many risperidone-treated patients.
Melkersson
Kristina I
KI
Department of Molecular Medicine and Surgery, Karolinska Institute, Stockholm, Sweden. Kristina.Melkersson@ki.se
D000328:Adult; D014150:Antipsychotic Agents / Q000009:adverse effects* / Q000493:pharmacokinetics*; D001711:Biotransformation; D005260:Female; D006801:Humans; D007555:Isoxazoles / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D000068882:Paliperidone Palmitate; D011388:Prolactin / Q000097:blood*; D011569:Psychiatric Status Rating Scales; D011618:Psychotic Disorders / Q000097:blood / Q000188:drug therapy; D011743:Pyrimidines / Q000009:adverse effects*; D018967:Risperidone / Q000009:adverse effects* / Q000493:pharmacokinetics*; D012559:Schizophrenia / Q000097:blood / Q000188:drug therapy
D014150:Antipsychotic Agents; D007555:Isoxazoles; D011743:Pyrimidines; D011388:Prolactin; D018967:Risperidone; D000068882:Paliperidone Palmitate