Document Detail


Teratogenesis associated with antibipolar agents.
MedLine Citation:
PMID:  19330496     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
OBJECTIVE: To review the teratogenic effects associated with the use of Food and Drug Administration-approved agents for bipolar disorder. METHODS: A PubMed search of all English language articles published from January 1966 to December 2008 was conducted. The key search terms included all major bipolar agents, cross-referenced with: teratogenicity, teratogen, safety, pregnancy, fetus, bipolar disorder, and malformation. The search was augmented with manual reviews of relevant article reference lists as well as http://clinicaltrials.gov and http://www.fda.gov (both last accessed in April 2008). Several pregnancy registries were also reviewed to determine malformation rates as well as teratogenesis attributable to each agent. Articles selected for review were based on author consensus, adequacy of sample size, the use of standardized experimental procedures, validated assessment measures, and overall manuscript quality. RESULTS: Valproate is associated with the highest rate of major congenital malformations (6.2%-16%). The relative risk of neural tube defects with valproate and carbamazepine is reported as approximately 1%-5% and 0.5%-1%, respectively. Preliminary evidence suggests that the relative risk for oral clefts (cleft lip or palate) is increased with lamotrigine relative to other antiepileptic drugs (AED) (ie, approximately 0.4%). The rate of major congenital malformations is higher in fetuses exposed to AED polytherapy (ie, >or=2 drugs) in comparison with AED monotherapy. Adverse neurobehavioral effects are insufficiently reported for most agents. In-utero exposure to valproate is associated with a greater risk of developmental difficulty requiring special education interventions as well as decreased verbal IQ scores. The risk of Ebstein's anomaly associated with lithium use is increased relative to the general population. The major congenital malformation rate with chlorpromazine and atypical antipsychotics is not established as being higher than a non-exposed group; the teratogenic risks associated with the olanzapine-fluoxetine combination are unknown. CONCLUSIONS: Well-characterized risks are associated with valproate, carbamazepine, lamotrigine, and lithium. The risks associated with psychotropic drug use need to be understood in the context of significant rates of relapse and associated morbidity when discontinuing bipolar treatment during pregnancy.
Authors:
Ha T T Nguyen; Verinder Sharma; Roger S McIntyre
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Publication Detail:
Type:  Journal Article; Review     Date:  2009-03-28
Journal Detail:
Title:  Advances in therapy     Volume:  26     ISSN:  1865-8652     ISO Abbreviation:  Adv Ther     Publication Date:  2009 Mar 
Date Detail:
Created Date:  2009-04-14     Completed Date:  2010-02-18     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8611864     Medline TA:  Adv Ther     Country:  United States    
Other Details:
Languages:  eng     Pagination:  281-94     Citation Subset:  T    
Affiliation:
Department of Psychiatry, Mood Disorders Psychopharmacology Unit, University Health Network, Toronto, Ontario, Canada.
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MeSH Terms
Descriptor/Qualifier:
Abnormalities, Drug-Induced / epidemiology,  etiology*
Anticonvulsants / therapeutic use,  toxicity*
Antipsychotic Agents / therapeutic use,  toxicity*
Bipolar Disorder / drug therapy*
Female
Humans
Incidence
Pregnancy
Pregnancy Complications / drug therapy*
Registries
Chemical
Reg. No./Substance:
0/Anticonvulsants; 0/Antipsychotic Agents

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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