UCLA. US: About 15 percent of U.S. women suffer from anxiety disorders and
depression during their pregnancies, and many are prescribed
antidepressants. However, little is known about how their children might
be affected by exposure to these medications in the womb. UCLA study also finds that different SSRIs may have different effects in pregnant women.
It’s a vital question because 5 percent of all babies born in the
U.S. — more than 200,000 a year — are exposed to antidepressants via
transmission from their mothers during gestation.
Now, a UCLA team studying early developmental exposure to two
different antidepressants, Prozac and Lexapro, has found that although
the two drugs were thought to work the same way, they do not produce the
same long-term changes in anxiety behavior.
The scientists studied the drugs’ effects in a mouse model that
mimicked exposure to the medications during the third trimester of human
pregnancy. Prozac and Lexapro are both serotonin-selective reuptake
inhibitors, or SSRIs.
The mice exposed to Lexapro had permanent changes in serotonin
neurotransmission and were less anxious as adults than the mice exposed
to Prozac, said Anne Andrews, the study’s senior author and a UCLA
professor of psychiatry and chemistry and biochemistry.
“This was quite surprising, since these medications belong to the
same drug class and are believed to work by the same mechanism,” said
Andrews, who also holds the Richard Metzner Endowed Chair in Clinical
Neuropharmacology at the Semel Institute for Neuroscience and Human Behavior and is a member of UCLA’s California NanoSystems Institute.
“The implications of these findings are that with additional
investigation, it may be possible to identify specific antidepressants
that are safer for pregnant women,” she said. “It’s important to
recognize that major depressive disorders and anxiety disorders are
serious medical conditions that often require therapeutic intervention.
Prescribing the medication that is safest for mother and child is
paramount.”
The results of the six-year study were published online in the peer-reviewed journal Neuropsychopharmacology.
SSRIs like Prozac and Lexapro act by blocking the actions of a type
of protein called a serotonin transporter, which removes the
neurotransmitter serotonin from the signaling space between neurons.
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
Andrews’ study, the mice that were genetically engineered studied 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,” said
Andrews, who also said it would take further research both to confirm
that idea and to understand whether certain SSRIs may be better at
promoting these effects.
Based on the findings, 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.”
The research was funded by the National Institute of Mental Health
(MH064756, MH086108), the Brain and Behavior Research Foundation, the
Shirley and Stefan Hatos Foundation, and the UCLA Weil Endowment Fund.