Managing Mental Illness in Pregnancy: What to Know

For women with, or at a risk for, depression, anxiety, bipolar disorder, or other psychiatric conditions, managing mental health during pregnancy and postpartum presents unique challenges. For physicians, understanding the latest research and clinical guidance is essential for managing these patients effectively.

What does the latest evidence reveal, and what key factors should guide decisions about psychotropic prescribing, nondrug interventions, and emerging treatments decisions during pregnancy and postpartum?

The latest research suggests that the risks for relapse, suicidal behavior, and adverse obstetric outcomes from untreated maternal depression often outweigh the relatively low teratogenic risks for most antidepressants.

“We have very clear data that tells us that if a pregnant or postpartum individual doesn’t get the treatment that they need, if they’re experiencing a mood or anxiety disorder, that can have a negative impact on themselves and on their babies,” Nancy Byatt, DO, perinatal psychiatrist with the Women’s Mental Health at UMass Memorial Medical Center, professor of psychiatry, ob/gyn, and population and quantitative health sciences, UMass Chan Medical School, Worcester, Massachusetts, noted in an interview with Medscape Medical News.

Yet a recent national US cohort study showed that nearly half the women who were taking antidepressants stopped their medication once they became pregnant.

A separate study revealed that women who discontinued antidepressants during pregnancy had a fivefold increase in the relapse risk for major depression compared with those who stayed on treatment. In addition, a recent meta-analysis revealed a twofold increased risk for relapse after antidepressant discontinuation.

Antidepressants: What’s the Risk?

A common clinical challenge in pregnancy is the use of antidepressants, particularly selective serotonin reuptake inhibitors (SSRIs). Historically, concerns have centered on the potential risk for congenital malformations, especially cardiac defects. However, large observational studies and systematic reviews over the past decade have largely demonstrated that SSRIs pose a low absolute risk for major teratogenic effects.

Another potential concern with in utero SSRI exposure is neonatal adaptation syndrome (NAS). Common symptoms include jitteriness, restlessness, increased muscle tone, and rapid breathing, which are typically transient and resolve without medical intervention. However, more severe manifestations, such as respiratory distress, pulmonary hypertension, seizures, or brain injury, can also occur.

A recent study from University of California San Francisco found that SSRI use in late pregnancy (after 20 weeks) was associated with an overall doubling of the risk for delayed NAS. However, after adjusting for potential confounders, including the presence and severity of maternal depression and anxiety, there was no association with more severe NAS symptoms.

Studies on the long-term effects of in utero SSRI exposure on autism spectrum disorder and attention-deficit/hyperactivity disorder have yielded conflicting results. While some suggest a modestly increased risk for these disorders, others after controlling for maternal mental illness severity and genetic predisposition showed no such association.

As for the serotonin-norepinephrine reuptake inhibitors such as venlafaxine and duloxetine, evidence suggests a risk profile broadly similar to that of SSRIs.

Older tricyclic antidepressants, such as nortriptyline and amitriptyline, have historically been associated with sedation and anticholinergic side effects. The teratogenic risk appears relatively low, but they are often second-line choices due to tolerability issues. Less is known about bupropion and mirtazapine — two atypical antidepressants.

Bupropion has been used for smoking cessation in pregnant women, with limited but generally reassuring data on fetal effects. Mirtazapine is less studied but has not been strongly linked to congenital anomalies; sedation and weight gain remain practical concerns.

Antidepressants are “the most commonly used medication in pregnancy, and we have studies on many people taking these medications, and overall, they are not major teratogens,” said Byatt.

“If someone’s on an antidepressant medication and they’ve had severe illness or they needed medication, then I’m often more concerned about the risk of stopping that medication than continuing during pregnancy,” she added.

Lithium and Other Mood Stabilizers

A recent systematic review and meta-analysis showed that the risk any congenital anomaly or cardiac malformation with in utero exposure to the mood stabilizer lithium any time during pregnancy is low overall, but higher for first-trimester or higher-dosage exposure.

“Ideally, pregnancy should be planned during remission from bipolar disorder and lithium prescribed within the lowest therapeutic range throughout pregnancy, particularly during the first trimester and the days immediately preceding delivery, balancing the safety and efficacy profile for the individual patient,” the authors concluded.

Guidance from the American College of Obstetricians and Gynecologists (ACOG) states that lithium can be continued if a woman’s bipolar disorder is severe and well-controlled on the drug but requires close therapeutic monitoring (eg, monitoring lithium levels every 2-4 weeks, then weekly near term).

In contrast, valproic acid has been consistently shown to have one of the highest teratogenic potentials among mood stabilizers, associated with neural tube defects and adverse neurodevelopmental outcomes. Multiple guidelines recommend avoiding valproate in pregnancy if at all possible.

Valproate “should not be used for women of childbirth age in general, unless they’re on a reliable form of contraception,” Byatt noted.

With antipsychotic use in pregnancy, observational data from pregnancy registries have generally been reassuring, indicating no significant increase in the risk for major congenital malformations.

Evidence from a separate large cohort study suggested that the use of antipsychotics early in pregnancy generally does not meaningfully increase the risk for congenital malformations overall or cardiac malformations in particular. However, a slight increase in the risk for malformations was observed with risperidone, the authors reported.

In addition, findings from a large multinational cohort study suggested little to no increased risk for child neurodevelopmental disorders or learning difficulties after prenatal exposure to antipsychotics.

Benzodiazepines, which include lorazepam, clonazepam, alprazolam, are often prescribed for anxiety and insomnia, both of which may worsen during pregnancy.

A large Korean cohort study showed that first-trimester benzodiazepine exposure was associated with a small increased risk for overall malformations and heart defects, particularly at the higher daily dose. The absolute risks and population attributable fractions were modest.

“The benefits of benzodiazepines for their major indications must be considered despite the potential risks; if their use is necessary, the lowest effective dosage should be prescribed to minimize the risk,” the investigators concluded.

Byatt said benzodiazepines “wouldn’t be my first choice in pregnancy. However, if people need them, it doesn’t mean they can’t take them because they are pregnant.”

Psychedelics and Other Therapies

Interest in psychedelic-assisted therapies for treatment-resistant depression and posttraumatic stress disorder have led to questions about their use in pregnant women.

However, currently, there are no robust, large-scale studies on the use of psilocybin, lysergic acid diethylamide, 3,4-methylenedioxymethamphetamine or ketamine in pregnancy.

Medications aside, cognitive-behavioral therapy, interpersonal therapy, and mindfulness-based therapy have shown efficacy for mild to moderate depression and anxiety.

For example, a recent systematic review showed that structured psychotherapy can significantly improve mood and reduce relapse during pregnancy, particularly when combined with consistent prenatal care.

Advantages of nondrug approaches include no teratogenic risk; therapy can be continued into the postpartum period and may strengthen coping skills for parenting. However, access to these services and insurance coverage may be challenging, and effectiveness for severe psychiatric conditions may be limited unless combined with medication.

What About Electroconvulsive therapy (ECT) and Transcranial magnetic stimulation (TMS)?

ECT has decades of use in treating severe depression and psychosis, even during pregnancy.

Current literature and clinical practice guidelines largely regard ECT as relatively safe for both mother and fetus, especially if indicated for life-threatening depression or catatonia, with adverse effects in pregnancy similar to the risks for ECT in any individual.

TMS is a newer, noninvasive brain stimulation technique used for treatment-resistant depression.

A University of Pennsylvania study of TMS and pregnancy showed that among 10 pregnant women treated with TMS, 70% responded well within just 20 sessions, with no adverse effects on pregnancy or fetal outcomes.

A separate study looking at 26 children aged 1-5 years whose mothers had received TMS treatment during pregnancy revealed no differences between the children born to women who had TMS during pregnancy and those born to women who did not undergo TMS.

Resources for Clinicians

In addition to ACOG, the following organizations provide guidance on treating psychiatric disorders during pregnancy.

• The American Psychiatric Association provides a fact sheet and resources to help mental health providers guide pregnant and postpartum women.
• The UK National Institute for Health and Care Excellence provides comprehensive guidelines on antenatal and postnatal mental health, covering the clinical management and service guidance for mental health problems during pregnancy and the postpartum period.
• The Massachusetts General Hospital Center for Women’s Mental Health offers clinical guidance and conducts research on the management of psychiatric disorders during pregnancy and postpartum.
• The Society of Obstetricians and Gynaecologists of Canada also provides guidance on use of psychiatric medications during pregnancy.
• Perinatal Psychiatry Access Programs, which aim to increase access to perinatal mental healthcare. Modeled after the Massachusetts Child Psychiatry Access Program for Moms (MCPAP for Moms), these programs build the capacity of frontline providers to support frontline providers (obstetricians, family physicians, general psychiatrists, etc.) to address perinatal mental health and substance use disorders.

Byatt reported no relevant disclosures.