Obstetrics and Gynecology

Depression

Dysthymia, Major Depression, Minor Depression

1. What every clinician should know

Clinical features and incidence

Depression during pregnancy affects more than 12% of women. Depression in pregnancy, as at other times, is characterized by persistent low mood, lack of interest or pleasure in activities, changes in appetite and weight (increase or decrease), changes in sleep (including insomnia or hypersomnia), feeling of physical agitation or motor slowing, feelings of worthlessness or guilt, poor concentration or inability to make decisions, low energy, feelings of hopelessness and thoughts of death and/or suicide.

Some patients with depression may feel sad and tearful; others may describe feeling anxious or numb. Depressed women often describe having difficulty functioning at work and/or at home, and may be increasingly socially isolated. Some depressed pregnant women may seem or report difficulty "bonding" with the baby to be.

Postpartum depression affects between 10–15% of women. Symptoms of postpartum depression are similar to those of depression at other times, including those during pregnancy (see above). However, anxiety is very often comorbid and is very often the presenting complaint. A woman with postpartum depression may describe not feeling bonded to her baby, difficulty caring for herself and the baby, and poor sleep even when the baby is sleeping. Often there is excessive worrying about the baby, the baby's safety and well–being (for example a woman may awake several times during the night to check that the baby is breathing, preventing her own sleep).

In some cases, women may have intrusive thoughts or images about harm coming to the baby, or even about her harming the baby. In most cases, these thoughts or images are very distressing to the woman and do not put her at high risk of harming of the baby. However, it is important to distinguish these thoughts from any psychotic symptoms and/or intent to hurt the baby.

Risk factors

Risk factors for developing depression during pregnancy include: a prior history of psychiatric illness (including with depression, bipolar disorder, and/or an anxiety disorder), low social support, partner conflict, poor overall health, use of substances, domestic violence, unwanted pregnancy, unemployment and low education. There also is emerging data that prior trauma is a risk factor for perinatal depression.

2. Diagnosis and differential diagnosis

A. Establishing the diagnosis

Formal diagnosis of a major depressive episode during pregnancy depends on the presence of either persistent depressed mood and/or lack of interest or pleasure nearly every day for most of the day for over 2 weeks and at least four of the following symptoms: low energy, changes in appetite, changes in sleep, feelings of worthlessness or guilt, poor concentration, psychomotor agitation or retardation, or thoughts of death or suicide.

However, this diagnosis can be more complicated in pregnancy due to the overlap of normal somatic symptoms of pregnancy with these symptoms. In addition, many women may report some symptoms of depression without meeting full criteria for a major depressive episode. These women are likely at high risk of developing major depression during or after pregnancy and in most cases should be considered for mental health referral, or at least be followed closely for worsening of their symptoms.

Some useful depression screening tools that have been validated in pregnancy and the postpartum period are the Physician's Health Questionnaire -9 (PHQ-9) and the Edinburgh Postnatal Depression Scale (EPDS). These tools are available in multiple languages.

B. Differential diagnosis

It is important to evaluate patients for medical issues that may mimic some signs of depression, including thyroid abnormalities, renal impairment and liver abnormalities. Women with depression also are at significantly higher risk for substance use and abuse during pregnancy and should be screened for use of alcohol, tobacco and other drugs.

Other psychiatric diagnoses with overlapping symptoms include bipolar disorder, anxiety disorders, adjustment disorders, and rarely schizophrenia or other psychotic disorders. For example, patients with an adjustment disorder may present with sad mood and/or anxiety for up to 6 months following an adverse life event (such as stillbirth, miscarriage, prolonged infertility, loss of close friends or relatives) and may benefit most from targeted psychotherapy rather than antidepressant treatment.

As antidepressant treatment may actually exacerbate some of these disorders, it is important to ask patients about a history of mania, psychosis or reactions to prior mental health treatments before prescribing an antidepressant. One useful screening tool for bipolar disorder is the mood disorders questionairre (MDQ).

Up to 85% of women experience some mood changes in the first 2 weeks after delivery. This is known as the "baby blues" and is characterized by crying, irritability, fatigue, anxiety and emotional ups and downs. Symptoms are generally mild and self-limited and do not involve total loss of interest, persistent low mood or suicidal ideation. These symptoms resolve within 2 weeks after delivery and do not require intervention other than emotional support.

On the other extreme, postpartum psychosis is a psychiatric emergency requiring immediate intervention. It is characterized by the rapid onset of severe mood swings, disorientation, delusions, hallucinations, disorganized behaviors and a relatively high incidence of suicidal ideation or homicidal ideation to the infant. These symptoms may wax and wane, complicating evaluation. Patients suspected of postpartum psychosis should be seen emergently by a mental health practitioner in a safe setting such as an emergency room.

If a patient with any of the above symptoms reports suicidal ideation or psychotic symptoms (loss of touch with reality such as paranoia, delusions or hallucinations), an urgent referral to a mental health practitioner is indicated.

3. Management

Antepartum

When possible, for patients with mild to moderate symptoms, the initial indicated treatment is referral for psychotherapy. Psychotherapeutic modalities include interpersonal psychotherapy (IPT), a time-limited treatment that has shown efficacy in the treatment of depression in pregnant women, as well as cognitive behavioral therapy (CBT) and other supportive treatments.

If the patient has severe symptoms, a history or current symptoms of bipolar disorder, psychosis or suicidal ideation, the obstetric provider should refer the patient to a mental health professional for evaluation and treatment.

According to ACOG guidelines, for uncomplicated patients with mild to moderate symptoms who have no evidence of a history of bipolar illness, current manic symptoms, psychosis, suicidality, and who previously have not responded to psychotherapy alone or for whom this is not available, obstetric providers may consider prescribing an antidepressant. The prescribing obstetrician should discuss with the patient the known risks and benefits of both the medication and of untreated depression to both mother and fetus (see "Complications" below). In addition, the patient should be followed closely for treatment response, side effects and compliance.

Choices of antidepressants include the selective serotonin reuptake inhibitors (SSRI), serotonin-norepinephrine reuptake inhibitors (SNRI) and tricyclic antidepressants (TCA), as well as bupropion and mirtazepine. The choice of which antidepressant to prescribe depends on the patient's prior history of response to antidepressants (i.e. if a patient has previously responded to fluoxetine, this should be strongly considered for treatment in order to most efficiently treat the current episode as well as avoiding the possibility of needing to switch agents and thus exposing the fetus to more than one drug).

The patient should be placed on the lowest effective dose for that patient; as this varies from patient to patient, this requires ongoing clinical assessment. In addition, the metabolic changes in pregnancy and increased blood volume may decrease the effective blood levels of antidepressants in the second and third trimesters, so some patients may have breakthrough symptoms that require an increase in dose. Some women may choose to taper off their antidepressant prior to delivery to lower the risk for neonatal adaptation syndrome (see below). However, as the abrupt hormonal change and psychosocial adjustments of delivery and motherhood may put vulnerable women at higher risk for postpartum depression (particularly women who have had depressive symptoms during the pregnancy), the risk of postpartum depression must be factored in to any decision to taper at this time.

Bright light therapy (which consists of patients sitting under a broad-spectrum high-intensity white light for a specified period of time each day), has been shown to be effective for treatment of depression in pregnancy in some patients. Other alternative treatments in pregnancy with some evidence of effectiveness and low risk include acupuncture, Omega-3 fatty acids and massage. Most herbal treatments have limited to no data on safety or effectiveness in pregnancy.

In severe or treatment-resistant cases, electroconvulsive therapy (ECT) has proven effective and safe in most cases with appropriate monitoring. There is emerging data about a new form of somatic treatment for depression called transcranial magnetic stimulation (TMS).

Postpartum

As in treatment of depression during pregnancy, the standard of care for initial treatment of mild-to-moderate postnatal depression is psychotherapy and other psychosocial modalities, including individual therapy, support groups and group therapy, as well as peer support.

For patients with severe symptoms or who have not responded to psychotherapy or other supportive interventions, antidepressant treatment has been shown to be effective. Most antidepressants do pass into breast milk in small amounts, so breastfeeding status does impact treatment decisions (see below under "Complications"). As with treatment during pregnancy, however, prior history of response to a particular agent should strongly influence medication choice in the postpartum, as it is important to alleviate symptoms as rapidly as possible.

4. Complications

A. Risk of untreated depression during pregnancy and postpartum

In some studies, untreated antenatal depression has been associated with adverse birth outcomes such as lower birth weight or small for gestational age, and preterm delivery; however, the data are contradictory. There are stronger data from animal and human studies suggesting that psychosocial stress is associated with earlier birth; depression and stress are highly associated. There is an emerging literature suggesting that significant psychiatric symptoms (i.e. depression, anxiety, significant stress) may "program" fetal neurobehavioral development, via variation in maternal stress-linked biology (i.e. cortisol levels), with implications for increasing children's risk for behavioral symptoms in the future.

Depressed women are at significantly higher risk for substance use/abuse (including alcohol, tobacco, and prescription and non-prescription drugs), poor nutrition and lower rates of compliance with prenatal care. In severe cases, women may develop suicidal or self-injurious thoughts and behaviors. Depression during pregnancy is a leading risk factor for postpartum depression.

Untreated postpartum depression can have adverse effects on the health of the mother, the child and the family system. According to the World Health Organization, maternal suicide is the second leading cause of maternal mortality in resource-rich countries. Depression during the postpartum period can greatly exacerbate the already fragmented sleep patterns typical of the newborn period, which in turn can magnify the depressive illness, anxiety and diminished level of functioning. Depressed mothers have lower rates of initiating and sustaining breastfeeding.

Poor nutrition related to depression may further compromise the mother's health and her ability to provide adequate nutrition via breast milk. Some, but not all, depressed mothers have difficulty bonding with the baby. Maternal-child bonding is an important factor for the child's future neurobehavioral development. Postpartum depression is associated with decrements in children's cognitive development and behavioral regulation. Children of depressed mothers have higher rates of psychiatric disorders; the children of women whose depression remits, however, have fewer psychiatric diagnoses at follow-up.

B. Risks vs. benefits of medications during pregnancy

Full discussion of all the known and possible risks of psychiatric medications in pregnancy is beyond the scope of this article (see references below for more detailed information). Virtually all the data about risks of antidepressant medications in pregnancy is based on epidemiologic research and pregnancy registries, thus raising important questions about possible confounding factors. For example, it is often difficult to control for the role of the underlying depressive illness and its biologic and behavioral correlates (i.e. elevated cortisol, higher rates of alcohol and tobacco use among the cohort on antidepressants, etc.) from the effects of the medications used to treat it.

Unfortunately, precise risk stratification of pharmacologically treated vs. untreated depression is not possible with the data available at this time. Below is a summary of the current knowledge base regarding antidepressant exposure in pregnancy. Because SSRIs are the most commonly prescribed antidepressants and a significant number of women are exposed to these medications during pregnancy, most of the data below is based on studies looking at SSRI exposure.

Miscarriage: Some but not all studies have found higher rates of early pregnancy loss in women taking SSRIs. Data is still inconclusive at this point.

Congenital malformations: Most studies have not found that SSRIs as a class are associated with higher rates of birth defects overall. However, there are some epidemiologic data linking exposure to some SSRIs in the first trimester to certain malformations. Specific defects found by some groups include ventricular outflow defects, craniosynostosis, and omphalocele; however these risks are extremely small and not consistently replicated between studies.

Delivery outcomes: Several studies have found an association between SSRI exposure in pregnancy and lower birth weight and earlier delivery with a trend toward preterm birth.

Neonatal adaptation syndrome: SSRI exposure in late pregnancy has been associated with a neonatal syndrome consisting of CNS, motor, respiratory and gastrointestinal signs. Symptoms most commonly consist of crying, jitteriness, tremor, feeding problems, reflux, sneezing and sleep dysregulation. The syndrome may be identified in up to 30% of babies exposed to SSRIs in the third trimester, but the symptoms are generally mild and resolve with supportive care within 48 hours to 2 weeks of age.

Persistent pulmonary hypertension of the newborn (PPHN): Several studies have linked exposure to SSRI medication, particularly in the second half of gestation (after 20 weeks) to an increased risk for PPHN. The baseline risk for PPHN in the general population is 0.5-2 per thousand live births. According to the case control studies that identified this potential association, the risk increases to 3-6 per thousand with exposure after 20 weeks. However, a number of epidemiologic studies have not confirmed this increased risk. The FDA recently updated its warning about this potential risk, stating that there is currently insufficient evidence to definitively link SSRI exposure to elevated risk for PPHN in the neonate. More studies about this risk are forthcoming.

Neurodevelopmental outcomes: Most studies that have looked at neurodevelopmental outcomes of children longitudinally after in utero exposure to SSRI or other antidepressants have not found an association with adverse cognitive or behavioral outcomes. However, the data are limited at this time. There is evidence that there may be an association with SSRI exposure and mild motor delays, although data indicate that these delays are still within the normal range and that the differences normalize over the course of development (i.e. by 18-24 months).

Although there is one retrospective case-control study suggesting a possible link between SSRI exposure in utero with increased risk for a diagnosis of autism spectrum disorders, it is a single study with multiple methodological limitations; other previous studies have associated untreated depression in mothers with higher risk of autism as well. The data on this issue are not strong enough to alter clinical practice at this time. Similarly, there are animal studies that have suggested altered brain and behavioral outcomes in animals exposed to SSRIs at critical periods of development, but the relevance for human illness and treatment are not clear at this time.

5. Prognosis and outcome

In one significant study, women with a history of major depressive disorder who were on antidepressant medication prior to pregnancy and who elected to stop medications during pregnancy were at significantly higher risk of relapse to depression during the pregnancy than women who continued their antidepressant treatment (68% vs. 24%). Depression during pregnancy is a risk factor for postpartum depression.

There is good evidence that both pharmacologic and psychosocial treatments for depression during pregnancy and postpartum are as effective as at other times in the life cycle; in general, most depressive episodes remit. While some women, particularly those with a history of prior recurrent depression, remain at risk for future depression, many women will remain well over time.

6. What is the evidence for specific management and treatment recommendations

Charil, A, Laplante, DP, Vaillancourt, C, King, S. "Prenatal stress and brain development". Brain Res Rev. vol. 65. 2010. pp. 56-79.

(Excellent review article of human and animal data suggesting "programming" of the fetus and future neurobehavioral development in relation to maternal distress during pregnancy.)

Fitelson, E, Kim, S, Baker, AS, Leight, K. "Treatment of postpartum depression: clinical, psychological and pharmacological options". Int J Womens Health. vol. 3. 2010. pp. 1-14.

(Up-to-date review of symptoms and treatment of PPD.)

Gentile, S, Galbally, M. "Prenatal exposure to antidepressant medications and neurodevelopmental outcomes: a systematic review". J Affect Disord. vol. 128. 2011. pp. 1-9.

(Summarizes literature on neurobehavioral effects of prenatal exposure to psychiatric medications.)

Monk, C, Fitelson, EM, Werner, E. "Mood disorders and their pharmacological treatment during pregnancy: is the future child affected?". Pediatr Res. vol. 69. 2011. pp. 3R-10R.

(Review article of data covering developmental effects of exposure to pharmacologically treated and untreated prenatal depression.)

Stewart, DE. "Clinical practice.Depression during pregnancy". N Engl J Med. vol. 365. 2011. pp. 1605-11.

(Clinical perspective on the care of depressed pregnant women.)

Yonkers, KA, Wisner, KL, Stewart, DE, Oberlander, TF, Dell, DL. "(2009). The management of depression during pregnancy: a report from the American Psychiatric Association and the American College of Obstetricians and Gynecologists". Obstet Gynecol. vol. 114. 2009. pp. 703-13.

(Review article co-authored by psychiatric and OBGYN researchers on the management of mood disorders during pregnancy. Provides decision trees for management questions.)
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