In the Journals

Mood stabilizers not tied to higher risk for adverse pregnancy outcomes

Although women who used mood stabilizers were at increased risk for placenta-mediated pregnancy complications, study data showed that this increased risk was most likely not because of the treatment.

Most studies on the safety of anticonvulsant mood stabilizers during pregnancy were conducted in women with epilepsy; however, it’s important to study their safety in women with bipolar disorder and other conditions, according to Jacqueline M. Cohen, PhD, from the Harvard T.H. Chan School of Public Health, and colleagues.

“It is challenging to differentiate the effect of mood stabilizers on ischemic placental disease from the effect of epilepsy itself in these studies because some studies, though not all, have shown that epilepsy (treated or not) is associated with an increased risk of preeclampsia, preterm birth, low birth weight and [small gestational age],” they wrote in Journal of Clinical Psychiatry.

In their cohort study, researchers examined Medicaid data for pregnant women linked to live born infants enrolled from 2000 to 2010 to determine the safety of mood stabilizers regarding risk of preeclampsia, placental abruption, growth restriction and preterm birth.

Cohen and colleagues evaluated exposure to mood stabilizers — lamotrigine, valproate, topiramate, carbamazepine, oxcarbazepine and lithium — in the first 20 weeks of pregnancy and compared monotherapy and polytherapy groups with an unexposed reference group of women who did not fill a prescription for lithium or any anticonvulsant during the 3 months before pregnancy. They also compared patients who continued mood stabilizer monotherapy after 20 weeks with those who discontinued.

Of 1,472,672 pregnancies, 10,575 were exposed to anticonvulsant mood stabilizer or lithium monotherapy and 917 were exposed to polytherapy, according to the findings.

Unadjusted analyses revealed that women exposed to each specific mood stabilizer and polytherapy were at increased risk for all adverse outcomes compared with no exposure (RR range: 1.15-1.56); however, when adjusted for confounders, these estimates were not meaningfully elevated (RR range: 0.89-1.16). In addition, the investigators reported that continuing mood stabilizer therapy was not linked to a higher risk for any outcomes compared with discontinuing therapy, but was linked to a lower risk for placental abruption and growth restriction.

Sensitivity analyses also showed that mood stabilizer monotherapy was linked to an elevated risk for preeclampsia among women with epilepsy but not bipolar disorders. In contrast, mood stabilizer monotherapy and individual anticonvulsant mood stabilizers were linked to an elevated risk for placental abruption and a reduced risk for smaller gestational age among women with bipolar disorder but not epilepsy.

Cohen and colleagues concluded that these results should reassure clinicians that mood stabilizers are unlikely to be responsible for the increased risk of placenta-mediated pregnancy complications.

“While there were some modest signals, residual confounding may explain these results,” they wrote. “The previously suggested effect of mood stabilizers on placentation may have been confounded by the underlying characteristics of women with the indication.” – by Savannah Demko

Disclosures: Cohen reports salary from a grant to Harvard T.H. Chan School of Public Health from GlaxoSmithKline. Please see the study for all other authors’ relevant financial disclosures.

Although women who used mood stabilizers were at increased risk for placenta-mediated pregnancy complications, study data showed that this increased risk was most likely not because of the treatment.

Most studies on the safety of anticonvulsant mood stabilizers during pregnancy were conducted in women with epilepsy; however, it’s important to study their safety in women with bipolar disorder and other conditions, according to Jacqueline M. Cohen, PhD, from the Harvard T.H. Chan School of Public Health, and colleagues.

“It is challenging to differentiate the effect of mood stabilizers on ischemic placental disease from the effect of epilepsy itself in these studies because some studies, though not all, have shown that epilepsy (treated or not) is associated with an increased risk of preeclampsia, preterm birth, low birth weight and [small gestational age],” they wrote in Journal of Clinical Psychiatry.

In their cohort study, researchers examined Medicaid data for pregnant women linked to live born infants enrolled from 2000 to 2010 to determine the safety of mood stabilizers regarding risk of preeclampsia, placental abruption, growth restriction and preterm birth.

Cohen and colleagues evaluated exposure to mood stabilizers — lamotrigine, valproate, topiramate, carbamazepine, oxcarbazepine and lithium — in the first 20 weeks of pregnancy and compared monotherapy and polytherapy groups with an unexposed reference group of women who did not fill a prescription for lithium or any anticonvulsant during the 3 months before pregnancy. They also compared patients who continued mood stabilizer monotherapy after 20 weeks with those who discontinued.

Of 1,472,672 pregnancies, 10,575 were exposed to anticonvulsant mood stabilizer or lithium monotherapy and 917 were exposed to polytherapy, according to the findings.

Unadjusted analyses revealed that women exposed to each specific mood stabilizer and polytherapy were at increased risk for all adverse outcomes compared with no exposure (RR range: 1.15-1.56); however, when adjusted for confounders, these estimates were not meaningfully elevated (RR range: 0.89-1.16). In addition, the investigators reported that continuing mood stabilizer therapy was not linked to a higher risk for any outcomes compared with discontinuing therapy, but was linked to a lower risk for placental abruption and growth restriction.

Sensitivity analyses also showed that mood stabilizer monotherapy was linked to an elevated risk for preeclampsia among women with epilepsy but not bipolar disorders. In contrast, mood stabilizer monotherapy and individual anticonvulsant mood stabilizers were linked to an elevated risk for placental abruption and a reduced risk for smaller gestational age among women with bipolar disorder but not epilepsy.

Cohen and colleagues concluded that these results should reassure clinicians that mood stabilizers are unlikely to be responsible for the increased risk of placenta-mediated pregnancy complications.

“While there were some modest signals, residual confounding may explain these results,” they wrote. “The previously suggested effect of mood stabilizers on placentation may have been confounded by the underlying characteristics of women with the indication.” – by Savannah Demko

Disclosures: Cohen reports salary from a grant to Harvard T.H. Chan School of Public Health from GlaxoSmithKline. Please see the study for all other authors’ relevant financial disclosures.