Depression During Pregnancy
You say that I’m depressed
I wonder if you understand
You’ve never lived, I think
In this God-forsaken land
I always fight to function
I’m fighting to survive
I’m trying desperately to remember
What it’s like to feel alive
You say I’m carrying life inside
How can that really be?
How could life possibly survive
In a non-existent me?
This poem is the heartbreaking account of a pregnant woman who was suffering from depression. Women are at greatest risk for depression between ages 25 and 44; up to 13% have full blown depression while they are pregnant. Pregnancy could be a stressor that might be linked with higher rates of depression and more severe episodes.
Depression during pregnancy is a widespread problem that often is undiagnosed and untreated. In a study of more than 3000 pregnant women who were asked questions about their mood while they were at their obstetricians’ office, 20% scored with high levels of depression symptoms. Of these women, only 13.8% were receiving treatment for depression.
The fourth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) defines a major depressive episode as two weeks of either persistent depressed mood or loss of interest or pleasure in daily activities (or both). Therefore, it is possible to have major depression without having the symptom of depression. To make the diagnosis, four additional symptoms also must be present (or three if both depression and decreased interest co-exist): appetite disturbance or significant weight change, sleep loss or excess, feelings of being agitated or slowed down, tiredness or energy loss, feelings of worthlessness or guilt, poor concentration, and thoughts of death or actual thoughts to take one’s life.
Risk-benefit decision-making. Dr. Wisner and her colleagues created a model to structure risk-benefit decision-making during pregnancy. The responsibility of the physician is to provide an accurate diagnosis and information about therapies that are tailored to the individual woman’s clinical history. Treatment decisions must be a delicate balance between maximizing maternal wellness while minimizing toxicity for the mother-fetal pair. The patient must decide on her personal values regarding treatment choices and let her physician know about her position on treatments.
Risks of Untreated Depression. In animals, maternal stress is associated with low birth weight babies, small size, and miscarriage. In the rat, maternal stress (without exposure to chemical agents) can cause behavioral changes in their offspring. In humans, severe stress may cause congenital malformations. Ample research supports that parenting is not optimal in the presence of depression, with negative effects on children’s cognitive and psychological development. Anxiety in the third trimester of pregnancy is linked with increased uterine artery resistance that could cause problems with fetal growth and development. Thus, aggressive treatment of psychological distress in the pregnant woman is crucial.
Risks of pharmacotherapy. Five major investigations have provided information about the effects of antidepressant treatment during pregnancy for the following drugs: fluoxetine, combined newer serotonin-selective reuptake inhibitors (SSRI; sertraline, paroxetine and fluvoxamine), combined tricyclic antidepressants (TCA), and venlafaxine. Outcomes after exposure to these agents were compared with those of control subjects, who were exposed to agents believed to be non-teratogenic (such as acetaminophen).
Intrauterine Death. Women who take antidepressants have an increased rate of miscarriage compared to controls, which may be due to depression or factors associated with the disorder. There is no evidence that the rate of stillbirths is increased during antidepressant treatment.
Physical Malformations. There is no evidence to implicate fluoxetine, newer SSRI, TCA or venlafaxine as causes of major birth defects in humans or animals. An increased risk for three or more minor malformations was found in one study for exposure to fluoxetine. By definition, minor malformations have no functional or cosmetic significance.
Growth Impairment. Prenatal growth and birth weights of infants exposed to TCA, newer SSRI, and venlafaxine during the first trimester were comparable to those of infants exposed to drugs identified as nonteratogens. Tina Chambers and her colleagues found that fetuses exposed to fluoxetine after 25 weeks gestation had significantly lower birth weights which were related to lower maternal weight gain. These researchers also reported an increased risk for premature birth (14.3%) in infants whose mothers took fluoxetine in the third trimester compared to infants whose mothers discontinued fluoxetine before the third trimester (4.1%). However, it is possible that mothers who continued fluoxetine until delivery were more likely to be depressed, which also could have affected the birth weights.
Behavioral Teratogenicity. This term refers to long-term postnatal effects on behavior due to prenatal exposure to agents which affect the central nervous system. In two published studies, cognitive function, temperament and general behavior were similar in children who were exposed prenatally to tricyclics or fluoxetine compared to controls. No data are available for newer drugs.
Neonatal Toxicity. Both withdrawal symptoms and direct pharmacologic effects can occur after prenatal exposure to any antidepressant. Poor neonatal adaptation (hypotonia, difficulty feeding, low oxygen levels with feeding) has been reported in infants whose mothers received fluoxetine in the third trimester (31.5%) compared to infants whose mothers discontinued fluoxetine before the third trimester (8.9%). Laine and colleagues reported that the newborns of mothers who took either citalopram or fluoxetine during pregnancy had similar birth weights but a fourfold higher risk for central nervous system effects such as tremor, restlessness, and rigid muscle tone compared to matched controls. These effects were temporary; after two weeks, there was no difference between the symptoms of newborns exposed to SSRIs and those of the control group.
Antidepressant dosage during pregnancy. There has been only one publication about the management of antidepressant (TCA) dosage across pregnancy that includes serum drug levels.1 Doses of SSRI might need to be increased to maintain the efficacy of the drug during pregnancy. A strategy to determine the minimum effective dose of any antidepressant across pregnancy has been described. The mothers selected a target symptom that was most disturbing (typically insomnia or irritability toward other children). The dose was increased until the target symptom improved considerably. Women were asked to contact the physician each time the symptom emerged, and an incremental dose was added. The dosages increased during the second half of pregnancy and rapidly accelerated during the third trimester. The final dose achieved during gestation was an average of 1.6 times the non-pregnant dose.
Non-drug treatments. When feasible, treatment of maternal depression without pharmacologic intervention is preferable because fetal exposure is averted. Several promising non-drug therapies have been employed to treat depression in pregnant women.
Interpersonal psychotherapy (IPT). This form of psychotherapy is used to address interpersonal problems. IPT is administered though a course of 12 to 16 weekly sessions that focuses on grief, interpersonal role disputes, role transitions, or interpersonal deficits. Other focused short-term therapies, such as cognitive behavioral therapy, are reasonable strategies for depression during childbearing.2
Bright light therapy. Exposure to a bright light box has been identified as an effective treatment modality for depression. Improvement from light therapy depends on the intensity of the light source, duration of the treatment, and the distance from the box. In controlled trials, bright light therapy has proven successful in the treatment of seasonal affective disorder as well as non-seasonal depression. The response of depressed pregnant women to bright light therapy has been explored in two studies. A trial of 16 women demonstrated a response comparable to antidepressant pharmacotherapy across five weeks. In a small randomized clinical trial of 10 women, significant improvement of depressive symptoms was demonstrated.
Acupuncture. A traditional Chinese medicine technique, acupuncture entails the insertion of fine needles into the skin. It exerts therapeutic effects by stimulating specific points in the body involved in the mechanisms that result in disease or pain. The acupuncturist targets treatment to the specific physical or psychological condition. Manber and colleagues found the group who received acupuncture treatment specifically for depression had a significantly higher rate of response compared to two groups (69% vs. 47% and 32%, respectively). A follow-up trial of acupuncture for depression in pregnancy is underway.
Omega-3 fatty acids. Omega-3 fatty acids (O-3 FAs) that are recognized increasingly as critical for health. O-3 FA intake by pregnant women in the United States is inadequate, and an inverse relationship between O-3 FA consumption and depressive symptoms has been described. O-3 FAs play a critical role in fetal development. Increased maternal intake of O-3 FAs during pregnancy may confer multiple benefits to the developing fetus. Confirming the efficacy of O-3 FAs as safe and effective agents for the treatment of depression during pregnancy will require a large placebo-controlled study.
Exercise. Physical exercise has long been thought to benefit mental health and is an attractive, low-risk and low-cost approach to the management of depression during pregnancy. DaCosta et al3 conducted a prospective study of pregnant women. Subjects responded to questions about mood, anxiety, stress, and leisure-time physical activity during each trimester of pregnancy. In the first and second trimesters, exercisers reported less depressed mood than non-exercisers, but a significant difference between the two groups was not seen during the third trimester. To our knowledge, the efficacy of exercise for major depression in pregnant women has not been performed.
Many depressed pregnant women are reluctant to initiate or continue treatment with antidepressant medication and/or psychotherapy, even when their physicians have strongly recommended treatment, due to concerns about potential fetal risks. In the interest of both maternal and fetal health, finding a treatment option that is acceptable to the depressed pregnant patient is optimal. If a patient is unwilling to undergo treatment for depression, her mood can be closely monitored so that a significant decline in mental health can be addressed.
Depression in childbearing women is a major public health problem. We must invest in the mothers and infants who are our next generation of Americans. The poet who introduced this article makes this point poignantly.
(Endnotes) 1 Wisner KL, Perel JM, Wheeler SB: Tricyclic dose requirements across pregnancy. Am J Psych 1993;150:1541-1542.
2 Appleby L, Warner R, Whitton A, Faragher B. A controlled study of fluoxetine and cognitive-behavioural counselling in the treatment of postnatal depression. BMJ. 1997 Mar 29; 314(7085):932-6.
3 Da Costa D, Rippen N, Dritsa M, Ring A. Self-reported leisure-time physical activity during pregnancy and relationship to psychological well-being. J Psychosom Obstet Gynaecol. 2003 Jun;24(2):111-9.