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Pregnancy health

What the research actually says about taking antidepressants during pregnancy

When you have anxiety or depression and become pregnant, should you take antidepressants or suffer with the untreated illness? Here's what you need to know.

What the research actually says about taking antidepressants during pregnancy

Photo: iStock

Kelly McDermott* was trying to focus on the road while driving with her two young kids in the car, but four-year-old Annabelle* wouldn’t stop crying and kicking her seat. McDermott felt like she was trapped in a crowded elevator that was filling with water—her senses were overloaded, her heart was racing and there was no escape. She went from zero to rage in seconds. With one hand on the steering wheel, she reached around and grabbed Annabelle’s legs. “Shut up!” she snapped. “You need to shut up!” But her daughter only screamed louder and cried harder, and McDermott completely lost it, swearing uncontrollably. For the previous few weeks, her depression and anxiety had been gaining on her, and now her anger was peaking. I need help, she thought in the midst of her tirade. I need my medication.

McDermott was in her first month of pregnancy after a successful frozen embryo transfer and had gone off her antidepressant, Effexor, a month before conceiving because she knew there was a small chance the drug could cause birth defects. The guilt she would harbour if her antidepressant harmed her baby was unfathomable. She had made it through her first two pregnancies unmedicated, but this time felt different. This time, she had a toddler and a preschooler to deal with, and was struggling to cope with the daily challenges of parenting. 

Without her medication, McDermott was irritable and quick to anger, common symptoms of depression. She felt overwhelmed by basic tasks, such as changing diapers, and had a hard time finding joy in simple things like watching her kids play at the park. She felt anxious at playgroups and judged by other moms. Sometimes all it would take was a screaming child to push her over the edge. Other times, she sat at home silently watching the chaos unfold around her and thinking, I’m not doing this right. I can’t be a mom anymore. Somebody, help me—please. 

Up to 20 percent of women experience depression or anxiety during pregnancy—some for the first time—and about eight percent of pregnant women take an anti­depressant. But about half of women who were on medication before pregnancy stop taking it when they’re trying to conceive or discover they’re expecting, largely due to concerns about adverse outcomes, such as birth defects and developmental challenges. Yet women often overestimate the risks of the drugs and gloss over the negative effects untreated mental illness can have on them and their babies. Pregnancy can increase the risk of depression, and according to research from Harvard Medical School, about 68 percent of women who discontinue their antidepressant relapse. 

For McDermott, her own mental health had been an afterthought in her decision to quit her meds. But a few days after her blow-up in the car, she had a miscarriage and immediately questioned whether sacrificing her own well-being had actually compromised her baby’s. “In that moment of loss, I blamed myself,” she says. “I blamed the rage and the angry yelling.” 

There’s no way McDermott or her doctors could confirm that stress from untreated anxiety and depression contributed to her miscarriage, but it’s possible. Studies show that both mood disorders and the use of some antidepressants may increase the risk of miscarriage—just one example of the confusing messages that come from research surrounding depression and anxiety during pregnancy. 

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Antidepressants are by far the most studied drugs when it comes to use during pregnancy, with more than 30,000 infant outcomes, including cleft palate and autism, examined in the literature. About 20 new research papers come out every year, yet the results are often conflicting. Some studies suggest antidepressants may be associated with poor outcomes such as stillbirth, heart defects, persistent pulmonary hypertension and attention deficit hyperactivity disorder (ADHD), while others exonerate the drugs from these risks. 

Complicating the situation is the fact that a mother’s mood can affect her child in utero and throughout life, and women with more severe depression are more likely to take medication, making it difficult to determine whether a particular outcome is the result of the drug, the depression or both. Indeed, many of the issues linked to antidepressants, such as preterm birth and low birth weight, have also been connected to untreated depression and anxiety. And there’s a genetic component to mental illness, which may help explain some children’s emotional, behavioural and developmental challenges. 

“We can’t say antidepressants are zero-risk medications,” says Simone Vigod, a psychiatrist and lead of the Reproductive Life Stages Program at Women’s College Hospital in Toronto. “In general, though, they are low-risk medications, and untreated depression during pregnancy is not benign.”

But with no clear answers about the risks and benefits of continuing or discontinuing medication, and a laundry list of potentially life-altering outcomes associated with both pathways, how can women make the best choices for themselves and their families? 

The real risks of antidepressant use in pregnancy 

Depression is a chronic illness that can cause persistent feelings of sadness and worthlessness, angry outbursts, loss of interest in activities and even thoughts of suicide. Anxiety, which often occurs along with depression, can lead to excessive worry, irritability and panic attacks. Life stressors can bring on these disorders, and women are twice as likely as men to experience depression, most commonly during their child-bearing years. The roller coaster of hormone levels during pregnancy and postpartum can also be a trigger. 

The most common treatments for anxiety and depression are psychotherapy, such as cognitive behavioural therapy and interpersonal therapy, and antidepressants. While psychotherapy can be effective for people who have mild or moderate depression, it typically takes 12 or more weeks for symptoms to improve. Psychotherapy alone is unlikely to help people with severe depression. Antidepressants are successful in treating depression in about 67 percent of cases, and symptoms can start to improve in one to three weeks, though people sometimes have to try multiple antidepressants before finding the one that works for them. 

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There are different types of antidepressants, but the most prescribed and studied ones are selective serotonin reuptake inhibitors and serotonin-norepinephrine reuptake inhibitors, collectively known as SRIs. These medications block the reabsorption of serotonin in the brain, making more of the so-called “happy hormone” available, which is believed to boost mood. 

SRIs are not without negative effects. They can lead to high blood pressure, which can reduce blood flow to the placenta and result in a whole host of complications. And they are believed to alter the levels of serotonin and other neurochemicals in the baby’s brain because the drugs cross the placenta and the blood-brain barrier, which may affect how a baby’s neurological system develops and functions. Some research suggests that the way a child learns, thinks and responds to stress throughout life may be altered by prenatal exposure to SRIs. 

But a woman’s stress from untreated depression and anxiety can also affect her baby. High levels of stress increase the levels of certain hormones, such as cortisol, which cross the placenta and the blood-brain barrier and may affect a baby’s growth and brain development, and have also been linked to children having mood disorders later in life. 

Concerns about in utero SRI exposure were raised soon after the drugs were introduced in the late 1980s. After birth, exposed babies exhibited “withdrawal” symptoms, such as restlessness, feeding difficulties and temperature instability. This is known as postnatal adaptation syndrome, and it occurs in about 30 percent of infants exposed to antidepressants, but it also occurs in about 10 percent of unexposed babies. Symptoms typically show up by day three of life and last for up to two weeks. The syndrome is usually mild and rarely leads to prolonged symptoms, complications or the need for treatment. 

Hundreds of studies have looked at SRI exposure and birth defects, and the only consistent pattern to emerge is an increased risk of heart defects after first-trimester use of the drugs, particularly paroxetine (sold under the brand names Paxil and Seroxat). A meta-analysis found the babies of women who take the drug during pregnancy have a one percent chance of having a heart defect, compared to 0.7 percent in the general population. But a study of more than 848,000 pregnant women from Denmark discovered the risk of heart defects is similar among women who stay on their antidepressants throughout pregnancy and those who stop taking them at least three months before conception, which suggests the underlying mood disorder may be to blame for the small increased risk.

While some studies have examined the safety of SRIs as a group, others have zeroed in on the risks associated with individual medications. For example, a study published in 2017 looked at nearly 18,500 women in Quebec who took one of 19 antidepressants (SRIs and other drugs) in their first trimester and found that only citalopram (Celexa) increased the risk for major congenital malformations. However, Vigod cautions women and physicians about making decisions based on the results of such studies, as they sometimes report conflicting results. And, she says, the information from one study shouldn’t be taken in isolation. “There is no consistent evidence to suggest that any specific medication is more ‘safe’ than the others,” she says. 

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Research on the developmental impacts of antidepressants has also been inconclusive. For instance, early studies reported an association between antidepressant use during pregnancy and autism, but larger, more recent studies found that while children of mothers with depression are at increased risk for autism, there is no evidence that antidepressants cause the condition. 

Tim Oberlander, a developmental paediatrician at BC Children’s Hospital and a researcher at BC Children’s Hospital Research Institute in Vancouver, has studied several groups of women and children, and found that mothers who took SRIs reported increased anxiety in their children at ages three and six. However, at six and 10 months old, babies of mothers treated with SRIs show earlier language perceptions than babies of depressed women. Some six-year-olds exposed to SRIs show greater resiliency in stressful situations at home than children of depressed mothers, and by age 12, some show better thinking and attention skills. Still, Oberlander stresses, it’s unclear whether these effects can be attributed to the drugs, the mother’s mood, genetics, family life or a combination of factors. 

The results of research on the effects of depression and anxiety during pregnancy are much more clear-cut and consistent. There’s strong evidence that mental health issues are associated with pre-eclampsia, preterm birth, low birth weight, developmental delays, and behavioural and emotional challenges. Two studies report that depression and anxiety triple the risk of pre-eclampsia, which can be fatal for the mother and baby if untreated. And in a study of more than 5,000 women, the risk of preterm birth increased by 40 percent when a mother suffered from depression. 

Several decades of research show that newborns of depressed mothers are less active, more irritable and more difficult to soothe. Children of women with prenatal anxiety and depression are also more likely to experience mental illness and ADHD.

Untreated anxiety and depression can negatively impact the health of a developing fetus. The mother may not be eating well, exercising or getting enough sleep. She may even avoid pre­natal care and self-medicate with drugs and alcohol, which can lead to complications. Tragically, some women take their own lives—suicide is a leading cause of death during pregnancy and is associated with a lack of treatment. Untreated depression during pregnancy is also the largest risk factor for postpartum depression, which can lead to poor mother-baby relationships and problems with child development and mental health. 

“From what we know, the risk of poorly treated or untreated depression is significantly more substantial than the risk associated with a drug itself,” says Oberlander. But that doesn’t mean that choosing to take antidepressants throughout pregnancy is an easy decision.

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Deciding on antidepressants

When McDermott and her husband were ready to start a family, she did some online research about the risks of taking antidepressants during pregnancy and decided she wanted to go off her medication. She had been on the drugs for six years and felt like she was in a better place. She was newly married, happy with her job and looking forward to being a mom; she didn’t feel like she needed Effexor. “I wanted to go into pregnancy as healthy as possible,” she says. “I thought, Why put extra stuff in my body if I’m going to grow a human?

McDermott discussed her decision with her doctor, and he was supportive, saying it’s best to reduce any risks associated with the drugs. He urged her to come in immediately if she ever had any thoughts of hurting herself, but he didn’t mention the effects untreated depression and anxiety could have on a baby. In fact, neither did her fertility doctor or her maternity doctor. Part of the problem, Vigod says, is that it would be very difficult for an OB/GYN or family doctor to stay up to date on all of the studies on the subject—searching for “antidepressants and pregnancy” in the medical research search engine PubMed returns more than 3,300 results. “It’s unmanageable, unless you are highly specialized,” she says. 

People are also more likely to see the harm in taking a medication than the harm in not taking it. Vigod researched Twitter activity and found that studies showing negative effects from antidepressant use are shared far more frequently than those offering reassurance. This may lead women and doctors to conclude that antidepressants are more dangerous than they actually are.

Plus, social pressures and stigma come into play. “Women feel so much guilt and pressure to make sure they do nothing to harm their developing baby, and that feeds into it being a very complex decision,” says Vigod, adding that there’s a perpetual myth that mental illness is not a real medical disorder and treatment is optional. 

In fact, the Society of Obstetricians and Gynaecologists of Canada says there’s no evidence suggesting antidepressants should be withheld from pregnant women. “The risks of untreated depression during pregnancy are significant and well-documented, whereas the risks associated with antidepressant exposure are less clear,” reads the organization’s position statement. 

When women come into Vigod’s office to discuss continuing antidepressant use during pregnancy, she starts by going over why they’re on medication in the first place. They explore how serious the depression was, how hard it was to treat and the likelihood of relapse. “There are all sorts of things to consider, and unfortunately, we don’t have a crystal ball and can’t make guarantees about outcomes,” she says. “The more severe the depression is, the clearer it becomes that the potential risks of antidepressants most likely don’t outweigh the benefits of staying on them.”

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For women with mild or moderate depression, Vigod may suggest they go off their medication and try psychotherapy if they begin to struggle. Women who develop mild or moderate depression during pregnancy should start with therapy, which is just as effective as antidepressants for mild cases, and introduce medication if their symptoms aren’t improving or are getting worse. Mindfulness, meditation, better sleep, exercise and reducing life stressors may also help. Antidepressants are usually necessary for women with severe depression and those who don’t respond to therapy or can’t wait several weeks for their symptoms to improve. However, antidepressants don’t work for everyone, so trying one for the first time during pregnancy could expose the baby to the risks of both the drug and the depression.

“It’s really important to remember that non-treatment is not an option,” says Oberlander. “It’s a question of risk and benefit, and we have to be very careful when we balance the two. And that’s a decision mothers need to make for themselves with their physicians. There’s no one-size-fits-all.”  

Some doctors may suggest switching medications or reducing a dose before or during pregnancy, but Vigod says that’s not recommended. Different antidepressants work for different people, and switching from an effective drug to a previously untried one, or reducing a dose, may lead to relapse. Some doctors also suggest decreasing a woman’s dose leading up to delivery to mitigate the effects of postnatal adaptation syndrome, but the condition doesn’t appear to be dose-dependent, and Vigod strongly discourages making changes to medication just before the early postpartum period because that’s when the risk of relapse is highest. Some women may actually need to increase their dose later in pregnancy if they begin experiencing symptoms again, because the liver speeds up at that stage and metabolizes drugs faster. 

Women who decide to stop taking their antidepressants should do so under the supervision of their doctor, who will work with them on a plan to wean off the medication over the course of a few weeks or even months, depending on the severity of the mood disorder, the type of drug, how long they’ve been taking it and the dose. This helps reduce the effects of withdrawal, which include flu-like symptoms, irritability, electric shock sensations and even suicidal thoughts. “It was really hard,” recalls McDermott, who experienced headaches, nausea, dizziness and an inability to focus when she slowly quit Effexor. “I was zombie-like.”

For women who have unplanned pregnancies, weaning off medication when they discover they’re expecting is possible, but quitting cold turkey is not recommended because it intensifies withdrawal symptoms, and researchers don’t know whether that may negatively affect the baby. 

Nearly three-quarters of people who have been on antidepressants for at least three years suffer withdrawal, so if you choose to go off the drugs, it’s best to have a plan in place to ensure you have the necessary support, whether that’s help with the kids or time off work. Women who are worried about in utero exposure should wait one or two menstrual cycles after fully weaning before trying to get pregnant to ensure the medication is out of their system, Vigod says. Of course, it can take a long time to get pregnant, which can be stressful and potentially lead to a relapse, she cautions. 

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Most, though not all, antidepressants are considered safe during breastfeeding, as less than 10 percent of the medication passes into breastmilk—five to 10 times less than the amount that passes through the placenta. However, some drugs lack strong evidence for safety during breastfeeding and may make babies drowsy or lead to withdrawal effects. Sertraline (Zoloft) is often recommended during breastfeeding because very little of the drug gets into breast­milk, so women who are starting antidepressants during pregnancy may want to consider trying it first. 

To help women get accurate information and make the best decisions for their circumstances, Vigod and a team of perinatal psychiatry experts in Ontario have developed an interactive online decision aid. The tool is still being studied and is not yet publicly available, but women can try it out as part of a research study. It informs women of the risks and benefits of treatment and non-treatment with antidepressants and helps them evaluate which factors are most important to them. It will also synthesize the most up-to-date evidence-based research and help women make sense of it by presenting all risks and benefits with consistent comparisons, as chances out of 1,000. “This is a way for women to get specialized care quickly and put those facts into their own context,” says Vigod.

The importance of maternal mental health

After her miscarriage, McDermott took a month off fertility treatments, as she and her husband mourned their loss. To help cope, she began taking her low-dose Effexor pills again. She started to feel better within a couple of weeks, and soon, the little things that made her fly off the handle before were non-events. 

When the couple decided to do their final frozen embryo transfer, McDermott stayed on Effexor with the support of her doctors. “I really had to weigh the pros and cons of what I knew scientifically and what was going to be the best quality of life for me and my family,” she says. “I came to the conclusion that medication allows me to be calmer and less stressed, which is better for my baby and the kids I already have. They need me, and I can’t be their mom without it.”

As McDermott took her pills daily throughout pregnancy, she wondered what effect they may be having on her baby. Still, she’s confident she made the right decision. Her son was born healthy this past November, and she knows the nine months leading up to his birth would have been much different without her medication.

One day this past summer, during her second trimester, McDermott took her kids to a family reunion, an event she would have avoided had she not been on her medication. Just the thought of packing up all their gear, driving to the lake and dealing with any meltdowns would have been too much. But instead of hunkering down at home on a beautiful day, she watched her daughter play on the beach and splashed around in the lake with her toddler, relishing the cold water on her hot, pregnant body and not worrying about anything at all.

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*Name has been changed.

Read more:
Antidepressants during pregnancy: Support, not stigma
Prenatal anxiety: Tips and treatment

This article was originally published on Dec 11, 2018

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Raina is an award-winning writer, editor, and digital journalist based in Victoria, British Columbia. She specializes in topics involving health, culture, and the environment. More of her work can be found in publications like HuffPost, The Toronto Star, and The Globe and Mail

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