Are lithium and mood-stabilizing antipsychotics safe in pregnancy?
  From Psychiatry Drug Alerts Volume XXXIII / July 2019 

Lithium, Mood Stabilizers and Placental Complications

Results of a cohort study suggest that women taking lithium or mood-stabilizing anticonvulsants during the first half of pregnancy are at increased risk of preterm delivery and other placenta-mediated complications. However, risk appears to be associated with the underlying illness.
Methods: The study was based on nearly 1.5 million Medicaid-covered deliveries between 2000 and 2010. Exposed women were those who filled a prescription for lithium or an anticonvulsant (carbamazepine, lamotrigine, oxcarbazepine, topiramate, or valproate) in the first 20 weeks of pregnancy. The study outcomes were complications likely related to placental insufficiency: small for gestational age births, placental abruption, and a composite outcome that included these and also low birth weight at term and preterm delivery. The analysis was extensively adjusted using a propensity score that included indications for the prescription and other variables.
Results: During the first 20 weeks of pregnancy, 10,575 women (0.7%) were exposed to a single mood stabilizer, and 917 women (0.1%) were exposed to polytherapy. The indications for monotherapy were bipolar disorder (39%), migraine (32%), epilepsy (25%), and neuropathic pain (7%). Pregnancies with exposure had increased risk of ischemic placental disease: relative risk (RR),* 1.34 for monotherapy and 1.56 for polytherapy. However, after adjustment for treatment indication, risk was no longer elevated (adjusted RR, 0.97 for monotherapy and 1.16 for polytherapy). Risk was not elevated for any individual medication or for most individual complications. Only polytherapy was associated with risk of preeclampsia and possibly placental abruption, but confidence intervals for these estimates were wide. Women who continued filling prescriptions during the second half of pregnancy were at lower risk of complications than those who stopped taking the medications.
Sensitivity analysis stratified by indication for treatment found mood stabilizer monotherapy in women with bipolar disorder was not associated with increased risk of preeclampsia or small for gestational age births. However, risk for placental abruption was increased in these women.
Discussion: Previous studies linking anticonvulsant mood stabilizers and lithium with placenta-related complications may not have adequately accounted for the effects of underlying indications. The authors hypothesize that smoking, diabetes, other medication use, and lifestyle-associated factors may account for increased risk of placenta-mediated complications in exposed women. Conversely, women who continued taking medications throughout pregnancy may have been at lower risk due to behavioral factors associated with compliance with their medications. The authors caution that other evidence of these agents' possible teratogenicity, which was not assessed in the study, should be considered when making treatment decisions.

Cohen J, Huybrechts K, Patorno E, Desai R, et al: Anticonvulsant mood stabilizer and lithium use and risk of adverse pregnancy outcomes. Journal of Clinical Psychiatry 2019; doi 10.4088/JCP.18m12572. From Harvard TH Chan School of Public Health, Boston, MA; and other institutions. Funded by the NIMH. Six of 7 authors disclosed potentially relevant financial relationships; the remaining author declared no competing interests.

Common Drug Trade Names: carbamazepine—Tegretol;   lamotrigine—Lamictal;   oxcarbazepine—Trileptal;   topiramate—Topamax;   valproate—Depakene, Depakote

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