Bipolar Network News just published a set of articles on pregnancy and depression which are a useful update of the research in this important area. Other recent articles on moodsurfing about pregnancy include one by Nancy on apps for depression in pregnancy, an article summarizing a controversial study suggesting a link between antidepressants in pregnancy and autism, an article on the subject of pregnancy and mental health which we wrote a couple of years ago and an article reminding us that depression in pregnancy affects the child.
Depression and Pregnancy
Lauren Osbourne, Assistant Director of the Women’s Mood Disorders Clinic at Johns Hopkins Hospital summarized the literature in this area in a presentation in November 2017 at the Maryland Psychiatric Research Society’s continuing medical education conference.
According to Dr. Osbourne, two thirds of pregnant women with unipolar depression who stop taking antidepressants have an episode of depression during pregnancy. Women with bipolar disorder who stop taking mood stabilizers have higher rates of recurrence. She suggests that 85% will experience a mood episode, while about a third of those who stay on their medications relapse. This high risk might have to do with the fact that the studies that have been done include a larger number of more severely ill women with bipolar 1 than is found in the general population, since they are done in tertiary care academic centers.
Depression and the Fetus
Dr. Osbourne reminds us that depression in pregnancy carries its own risks for the fetus. These include preterm delivery, low birth weight, poor muscle tone, hypoactivity, increased cortisol, poor reflexes, and increased incidence of attention deficit hyperactivity disorder (ADHD) and other behavioral disorders.
Why this is the case could have to do with the effect of depression on the body’s response to an enzyme 11-BHSD2 that lowers the stress hormone cortisol in the baby. This enzyme appears to less active in women who are depressed, and, as a result, the fetus is exposed to higher levels of cortisol during the pregnancy.
Risks of Antidepressants
Dr. Osbourne suggests that most antidepressants are now considered safe during pregnancy. As we wrote about, there was a recent study suggesting a link between antidepressants in pregnancy and autism but this study did not adequately control for the fact that women with more severe depression are more likely to require antidepressants. When severity of depression is controlled for by using matched controls, the risks of treatment with antidepressants are no longer significant.
In a 2017 article in the Journal of Clinical Psychiatry, researcher Chittaranjan Andrade reexamined the data from several studies that suggested an increased risk of adverse outcomes in children whose mother’s took antidepressants during pregnancy. Andrade found that while there is a small link between antidepressant use in pregnancy and autism in the offspring, it is most likely the mother’s depressive illness rather than the medications that is responsible for this link.Andrade found that antidepressant exposure was linked to an increased risk of autism spectrum disorders in the offspring even when the antidepressant use occurred only before conception occurred, when it could not possibly have affected the future fetus’ physiology. This implies that it is the mother’s illness rather than the antidepressant treatment that is a determinant of autism risk.
There does appear to be an increased risk of Neonatal Adaption Syndrome (NAS) in the first weeks of life in babies who are exposed to selective serotonin reuptake inhibitor (SSRI) antidepressants in the third trimester. This syndrome results from antidepressant withdrawal, and may be associated with respiratory distress, temperature changes, decreased feeding, jitteriness/irritability, floppiness or rigidity, hypoglycemia, and jaundice. We recommend tapering the dose of SSRI’s in the last few weeks of pregnancy, where possible.
In her practice, Dr. Osbourne prefers to prescribe sertraline, which has the best safety data in pregnancy. Sertraline is also OK for breastfeeding because of relatively low levels of the medication found in breast milk. There is less data on bupropion, but it also appears to be safe during pregnancy. Endocrine and enzyme changes in pregnancy typically cause a 40% to 50% decrease in concentrations of antidepressants, so doses of antidepressants typically must be increased in order to maintain their effectiveness.
Mood Stabilizers and Pregnancy
Dr. Osbourne ranked mood stabilizers for bipolar disorder, from safest to most worrisome.
Lamotrigine is safest. In June 2017, researcher Gali Pariente and colleagues published a systematic review and meta-analysis in the journal CNS Drugs in which they reported that, across 21 studies, lamotrigine use during pregnancy was not linked to an increase in birth defects. Consistent with this conclusion, a small study published in the British Journal of Clinical Pharmacology in November 2017 by Merav Cohen-Israel and colleagues found that, in 83 women who received lamotrigine during their first trimester of pregnancy, there was no increased risk of congenital malformations, neurodevelopmental disorders, or withdrawal symptoms in the offspring.
Lithium is next safest. There are cardiac risks for one in 1,200 patients, but these can be monitored.
Carbamazepine is third safest. One percent of babies exposed to carbamazepine will develop spina bifida or craniofacial abnormalities.
Valproate is least safe during pregnancy. Seven to ten percent of babies exposed to valproate will develop neural tube defects, other malformations, or developmental delay, with a mean decrease of 9 IQ points.
Folate and Mood Stabilizers
A 2017 study form Norway suggests that the offspring of women taking anti-epileptic drugs during pregnancy are less likely to develop autism if the women also take folic acid supplements. The study by Marte Bjørk and colleagues in the journal JAMA Neurology used data from 104,936 children aged 18 to 36 months. Those whose mothers took anti-epileptic drugs during pregnancy had elevated autism rates, but only if their mothers did not use folic acid supplements. The mothers’ folate levels in weeks 17 to 19 of their pregnancies were inversely related to the degree of autistic traits in their offspring.
There is less data on the atypical antipsychotics, but they all appear safe so far. As an example, a 2017 systematic review in the Journal of Affective Disorders by Alessandro Cuomo and colleagues, found that the atypical antipsychotic medication aripiprazole (Abilify) was relatively safe for use during pregnancy and lactation.
Non-medication approaches to depression during pregnancy include: psychotherapy (including cognitive behavioral therapy and interpersonal therapy), mindfulness, exercise, yoga, acupuncture, high intensity light, and repeated transcranial magnetic stimulation (rTMS). Nutritional supplements including folic acid, vitamin D3, and omega-3-fatty acids can also be helpful.