Prolactin release in children treated with risperidone: impact and role of CYP2D6 metabolism.
OBJECTIVE
Little is known about the role of CYP2D6 polymorphism in risperidone-induced prolactin release in children.


METHODS
Twenty-five children (aged 5-15 years) with pervasive developmental disorders were genotyped for CYP2D6 polymorphisms. Serum prolactin, risperidone, and 9-hydroxyrisperidone were assessed at baseline and after 8 weeks of risperidone treatment (mean dosage, 0.06 +/- 0.03 mg/kg/d). After 24 weeks of treatment, prolactin was measured in a subsample of 15 children. Adverse effects were evaluated using a clinician-rated survey.


RESULTS
Mean +/- SD prolactin levels increased from 7.8 +/- 8.0 ng/mL at baseline to 33.2 +/- 12.8 ng/mL at week 8 (P < 0.001), with a slight decrease to 28.8 +/- 13.6 ng/mL at week 24. At week 8, serum prolactin level was positively correlated with dose per kilogram (r = 0.648, P < 0.001), number of functional CYP2D6 genes (J = 2.117, P = 0.034), and serum 9-hydroxyrisperidone concentration (r = 0.664, P = 0.001) and was negatively correlated with the risperidone/9-hydroxyrisperidone ratio (r = -0.571, P = 0.004) but not with risperidone concentration (r = -0.243, P = 0.264) nor age (r = 0.072, P = 0.733). Prolactin elevation was not associated with adverse effects.


CONCLUSIONS
Low-to-intermediate doses of risperidone induced a 4-fold prolactin increase in children without a clear development of tolerance up to 6 months. CYP2D6 ultrarapid metabolism may be a risk factor for more pronounced prolactin elevation.
Troost
Pieter W
PW
Department of Psychiatry, University Medical Center Groningen, University of Groningen, The Netherlands. p.troost@accare.nl
Lahuis
Bertine E
BE
Hermans
Mirjam H
MH
Buitelaar
Jan K
JK
van Engeland
Herman
H
Scahill
Lawrence
L
Minderaa
Ruud B
RB
Hoekstra
Pieter J
PJ
D000293:Adolescent; D000367:Age Factors; D014150:Antipsychotic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D002648:Child; D002659:Child Development Disorders, Pervasive / Q000097:blood* / Q000188:drug therapy / Q000235:genetics; D002675:Child, Preschool; D019389:Cytochrome P-450 CYP2D6 / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007555:Isoxazoles / Q000097:blood; D008297:Male; D000068882:Paliperidone Palmitate; D011388:Prolactin / Q000097:blood*; D011446:Prospective Studies; D011743:Pyrimidines / Q000097:blood; D018967:Risperidone / Q000008:administration & dosage / Q000494:pharmacology*
D014150:Antipsychotic Agents; D007555:Isoxazoles; D011743:Pyrimidines; D011388:Prolactin; D019389:Cytochrome P-450 CYP2D6; D018967:Risperidone; D000068882:Paliperidone Palmitate