Early Lexapro exposure (right) influences adult serotonin signaling and anxiety differently than genetic reduction in serotonin transporters (left).
Many women are prescribed medications during pregnancy to treat anxiety and depression, but little is known about the effect these drugs have on their children. It is an important question; 5 percent of all babies born in the U.S. — more than 200,000 a year — are exposed to antidepressants in utero.
A UCLA team studying early developmental exposure to two common antidepressants, Prozac and Lexapro, has found that although the two drugs were thought to work the same way — both are serotonin-selective reuptake inhibitors, or SSRIs — they have markedly different long-term effects on developing fetuses. The scientists studied the drugs’ effects in a mouse model that mimicked exposure to the medications during the third trimester of human pregnancy.
The mice exposed to Lexapro (escitalopram) had permanent changes in serotonin neurotransmission and were less anxious as adults than the mice exposed to Prozac (fluoxetine), says Anne M. Andrews, PhD, Richard Metzner Endowed Chair in Clinical Pharmacology at the Jane and Terry Semel Institute for Neuroscience and Human Behavior at UCLA. “This was quite surprising, since these medications belong to the same drug class and are believed to work by the same mechanism,” she says. “The implications of these findings suggest it may be possible to identify specific antidepressants that are safer for pregnant women.”
SSRIs like Prozac and Lexapro block the actions of a type of protein called a serotonin transporter, which removes the neurotransmitter serotonin from the signaling space between neurons. Dr. Andrews and her team also studied mice that had been genetically engineered to have a reduction or absence of serotonin transporters in the brain, so they were able to compare the effects of early exposure to antidepressants with the effects of the mice’s permanent reductions in serotonin transporter function.
In humans, genetic reductions in serotonin transporters are thought to be a risk factor for developing anxiety and mood disorders, particularly when combined with stressful life experiences. In fact, in Dr. Andrews’ study, the genetically engineered mice showed more anxiety as adults. “It might be possible that when mothers are treated for depression or anxiety during pregnancy, certain SSRIs taken by the mother may prevent the children from developing the disorders later in their lives,” Dr. Andrews says.
Based on the findings, Dr. Andrews and her team suspect that early exposure to Lexapro might alter the way serotonin neurons innervate brain regions involved in mood and anxiety behavior — a concept they plan to investigate in the future. They also plan to evaluate other SSRIs such as Paxil and Zoloft. “Current antidepressant therapies are ineffective in treating anxiety and depression in large numbers of patients, and advances in predicting individual responses are hindered by difficulties associated with characterizing complex influences of genetic and environmental factors on serotonergic transmission in humans,” the study states. “Highly controlled animal models, such as those studied here, represent avenues by which to identify factors potentially influencing behavioral domains associated with emotion-related disorders.”
“Perinatal vs. Genetic Programming of Serotonin States Associated with Anxiety,” Neuropsychopharmacology, December 2014