Evaluating the postmarketing experience of risperidone use during pregnancy: pregnancy and neonatal outcomes.
BACKGROUND
A significant number of women of childbearing age have schizophrenia or other psychoses. This means that there is a considerable risk of in utero exposure to risperidone due to maternal use.


OBJECTIVE
To determine whether in utero exposure to the atypical antipsychotic risperidone is associated with poor pregnancy and fetal/neonatal outcomes.


METHODS
A search of the Benefit Risk Management Worldwide Safety database, using a selection of preferred terms from the Medical Dictionary of Regulatory Activities, was performed to identify all cases of pregnancy or fetal/neonatal outcomes reported in association with risperidone treatment from its first market launch (international birth date, 1 June 1993) to 31 December 2004. The main measures were the patterns and reporting rates of pregnancy (stillbirth and spontaneous and induced abortion) and fetal/neonatal outcomes (congenital abnormalities, perinatal syndromes and withdrawal symptoms) for women administered risperidone during pregnancy.


RESULTS
Overall, 713 pregnancies were identified in women who were receiving risperidone. Data were considered prospective in 516 of these, and retrospective in the remaining 197 cases. The majority of the known adverse pregnancy and fetal/neonatal outcomes were retrospectively reported. Of the 68 prospectively reported pregnancies with a known outcome, organ malformations and spontaneous abortions occurred 3.8% and 16.9% (when the 15 induced abortions were excluded from the denominator, as they were predominantly undertaken for nonmedical reasons), respectively, a finding consistent with background rates of the general population. There were 12 retrospectively reported pregnancies involving major organ malformations, the most frequently reported of which affected the heart, brain, lip and/or palate. There were 37 retrospectively reported pregnancies involving perinatal syndromes, of which 21 cases involved behavioural or motor disorders. In particular, there was a cluster of cases reporting tremor, jitteriness, irritability, feeding problems and somnolence, which may represent a withdrawal-emergent syndrome.


CONCLUSIONS
This comprehensive review of the Benefit Risk Management Worldwide Safety database for case reports of risperidone exposure during pregnancy represents the largest ever published dataset documenting pregnancy outcomes for women taking the atypical antipsychotic risperidone. It indicates that in utero exposure to risperidone does not appear to increase the risk of spontaneous abortions, structural malformations and fetal teratogenic risk above that of the general population. Self-limited extrapyramidal effects in neonates were observed after maternal exposure to risperidone during the third trimester of pregnancy. Risperidone should only be used during pregnancy if the benefits outweigh the potential risks.
Coppola
Danielle
D
Benefit Risk Management, a division of Johnson & Johnson Pharmaceutical Research & Development, LLC, Titusville, New Jersey 08560, USA. Dcoppol2@BRMUS.JNJ.com
Russo
Leo J
LJ
Kwarta
Robert F
RF
Varughese
Ruana
R
Schmider
Juergen
J
D000014:Abnormalities, Drug-Induced / Q000453:epidemiology; D000028:Abortion, Induced; D000022:Abortion, Spontaneous / Q000139:chemically induced*; D000328:Adult; D014150:Antipsychotic Agents / Q000009:adverse effects*; D016208:Databases, Factual; D005260:Female; D006801:Humans; D007231:Infant, Newborn; D018811:Maternal Exposure / Q000009:adverse effects; D001523:Mental Disorders / Q000188:drug therapy*; D008875:Middle Aged; D011247:Pregnancy; D011256:Pregnancy Outcome / Q000453:epidemiology*; D011264:Pregnancy Trimesters / Q000187:drug effects; D012189:Retrospective Studies; D018570:Risk Assessment; D012308:Risk Management; D018967:Risperidone / Q000009:adverse effects*; D013375:Substance Withdrawal Syndrome
D014150:Antipsychotic Agents; D018967:Risperidone