Is lithium a real teratogen? What can we conclude from the prospective versus retrospective studies? A review. Isr J Psychiatry Relat Sci 45: 95-106

Department of Anatomy and Cell Biology, The Hebrew University Hadassah Medical School, Jerusalem, Israel.
The Israel journal of psychiatry and related sciences (Impact Factor: 0.79). 02/2008; 45(2):95-106.
Source: PubMed


Lithium is a drug used mainly for the treatment of Bipolar Disorder (BD). Case reports and several retrospective studies have demonstrated possible teratogenicity, but the data in the different studies was inconclusive.
We summarized all published studies in English, including case reports.
We found 24 case reports, of which six infants had congenital anomalies, five having cardiac anomalies, one of them being Ebstein's anomaly. In the retrospective studies there were, in the Lithium Baby Registry, 225 registered cases with 25 anomalies, 18 of them being cardiac, of which six had Ebstein's anomaly. An additional retrospective study on 59 cases found seven anomalies, four of them being cardiac. On the other hand, none of the prospective studies (296 liveborn infants) demonstrated any increase in the rate of congenital anomalies, although two had Ebstein's anomaly. All case control studies regarding Ebstein's anomaly were negative, and among 222 infants with Ebstein's anomaly and 44 with tricuspid atresia none of the mothers had taken lithium during pregnancy.
Considering the serious limitations of the retrospective and case control studies that are also retrospective, lithium does not seem to be a significant teratogen, and hence should be given, if indicated, in pregnancy. It is, however, advisable to perform a fetal echocardiography to exclude the possibility of cardiac anomalies. Lamotrigine seems to be a possible alternative.

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    • "Additionally, the development of heart and pulmonary vascular anomalies in fetuses exposed to Li was reported (Kozma 2005). In a systematic review of the relationship between Li use during pregnancy and its teratogenicity it was emphasized that Li does not increase the occurrence of major malformations and only slightly increases the risk of cardiovascular malformations (Yacobi and Ornoy 2008). "
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    ABSTRACT: The prevalence of bipolar disorder (BD) in males and females is almost equal. The onset of BD in females typically occurs during the reproductive years, complicating its treatment. Although it was once believed that pregnancy prevents recurrence, studies have shown that recurrence is common and severe during pregnancy. On the other hand, the effects of pharmacological treatment on obstetrical outcome are not well known and some of these agents are considered teratogenic. Thus, the decision to treat pregnant patients with psychotropic agents requires solving an ethical dilemma. Risk-benefit decisions should be made while considering both the risk of relapse of BD and its morbidity, and the risk of fetal exposure to psychotropic medications. Moreover, the risk of recurrence increases dramatically in the postpartum period. It is well known that all of the psychotropic medications studied enter the breast milk. Thus, their effects on infants should be considered while prescribing for a breastfeeding mother. The aim of this review was to discuss the safety profiles of the treatment options for pregnant and breastfeeding BD patients. Firstly, each medication's effects on organ dysgenesis, neonatal toxicity, and neurobehavioral development, and their associated adverse events during pregnancy and the postpartum period are discussed, with a focus on the emerging literature. Given this background, practical suggestions on tailoring treatment in BD patients, from preconception to breastfeeding are highlighted.
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    ABSTRACT: Lithium has long been considered as less than ideal in the management of rapid cycling and mixed states in bipolar disorder. However, these forms of bipolarity represent a generally more difficult phase of the illness to treat with any medication. Increasing knowledge about lithium's other beneficial effects, including protection against suicide and neuromodulatory effects which may protect the brain, make it a first-line treatment for any form of bipolar disorder. As newer therapies become available or receive further exploration, we should look to the past and re-embrace lithium as a core therapeutic modality for bipolarity as we move forward in the field, particularly for forms of the disorder such as rapid cycling and mixed states, historically thought to be more treatment resistant.
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