Peripartum depression: Early recognition improves outcomes

CLINICAL MANAGEMENT

Many women prefer nondrug therapy

The gold standard treatment for moderate to severe major depressive disorder is psychotherapy plus pharmacotherapy. Yet many peripartum women voice concerns about exposure to pharmacologic treatment, and studies have shown that many women prefer nonpharmacologic intervention.⁴⁷

Evidence-based psychotherapies that have demonstrated efficacy in peripartum women include cognitive behavioral therapy⁴⁸ and interpersonal psychotherapy when administered by a psychotherapist trained in these treatments. Pregnant and breastfeeding women often express preference for psychotherapy and complementary and alternative treatments as a means of avoiding fetal and infant exposure to antidepressants.⁴⁷

For mild to moderate depression, complementary therapies such as exercise, yoga, bright light therapy, and acupuncture have shown efficacy and can be used alone or adjunctively.⁴⁹ Because a poor marital relationship is consistently associated with peripartum depression,²⁵ primary care physicians who routinely address social support and screen for family conflict are well positioned to detect this significant correlate and to recommend marital or family therapy as a primary or adjunctive treatment.

When to consider drug therapy

The decision to recommend drug therapy must be individualized and based on the severity of symptoms, functional impairment, number and frequency of depressive episodes, history of response to medications, and the preferences of the patient, with the recognition that no decision is risk-free and that antidepressants enter the amniotic fluid, so fetal exposure is unavoidable.

Table 2 lists common antidepressants. The antidepressants most commonly prescribed, especially in the primary care setting, are selective serotonin reuptake inhibitors (SSRIs), which are favored because of their effectiveness, low side-effect profile, and lack of overdose toxicity.

Serotonin syndrome is no more likely to occur in pregnant than in nonpregnant women. Close monitoring for this condition is warranted only when patients are taking very  high doses of SSRIs or SSRIs in combination with other serotonergic agonists.

Prescribing antidepressants for pregnant or breastfeeding women requires thoughtful consideration of the patient’s preferences, as well as weighing the risks and benefits of fetal and infant exposure to maternal depression vs exposure to medications. Additional considerations include monotherapy, avoiding medication changes, choosing drugs that have been effective in the past, and avoiding drugs with known drug-drug interactions or teratogenic effects.⁵⁰

There is increasing consensus that the short- and long-term consequences of undertreatment or nontreatment of maternal depression outweigh the risk of fetal exposure to SSRIs.^3,51,52 Cohen et al⁵³ have recommended that if a woman is on an antidepressant and learns she is pregnant, she should not discontinue it because of the likelihood of relapse; they found a 68% relapse rate in women who discontinued their antidepressant in the first trimester of pregnancy.⁵³

In a comprehensive review of studies published between 1996 and 2012 that examined antidepressant use during pregnancy, Byatt et al⁵⁴ found little or no evidence of increased teratogenic risk with antidepressants with the exception of paroxetine, which is associated with a small but significant increased risk of cardiac malformation during first-trimester exposure.⁵⁴

These conclusions were underscored in a large cohort study in the United Kingdom.⁵⁵ In addition, a joint task force of the American Psychiatric Association and ACOG reviewed studies looking at the association between depression, antidepressants, and birth outcomes including miscarriage, preterm birth, cardiac abnormalities (resulting from first trimester exposure), persistent pulmonary hypertension (related to second- and third-trimester exposure), and neonatal adaptation syndrome (associated with third-trimester exposure).⁸ They concluded that the available data neither support nor refute a link between the use of antidepressants and several of the above outcomes. No increase in risk of congenital malformations (including cardiac abnormalities) was found. An increased risk of persistent pulmonary hypertension was noted, although the absolute risk of this disorder remained low, at 3 to 6 per 1,000 infants exposed to SSRIs in utero.^8,56

Neonatal adaptation syndrome

Neonatal adaptation syndrome is characterized by jitteriness, irritability, decreased muscle tone, and feeding difficulty in the neonate. It can occur in 15% to 30% of infants exposed to SSRIs antenatally.^57,58 These symptoms, however, are transient and typically resolve within 7 to 10 days after birth. A more recent study suggested that neurobehavioral symptoms for some infants extend beyond 2 weeks and that concomitant exposure to benzodiazepines results in even higher rates of this syndrome.⁵⁹ There is no evidence that tapering or discontinuing antidepressants near term is necessary, safe, or effective in preventing transient neonatal complications. However, this approach would increase the risk of relapse for the mother.

Autism spectrum disorders

The possible association between antidepressants and autism spectrum disorders in pregnancy has captured much attention in recent years. One study based on healthcare claims⁶⁰ and one registry-based study⁶¹ associated in utero exposure to antidepressants with autism liability in children. However, a large-scale Danish registry-based study did not replicate this association.⁶² In addition, 2 recent cohort studies, identifying children with autism spectrum disorder or attention-deficit hyperactivity disorder from electronic health records, found that neither disorder was significantly associated with prenatal antidepressant exposure in crude or adjusted models. However, both studies found a significant association with the use of antidepressants before pregnancy, indicating that the risk of autism observed with prenatal antidepressant exposure is likely confounded by the severity of maternal illness.^63,64

Concerns about drug therapy during breastfeeding

For infants of breastfeeding women, exposure to antidepressants through breast milk is minimal. Amounts in breast milk depend on the timing of the antidepressant dose, timing of feeding, and genetically influenced metabolic activity in mother and infant. The current literature supports antidepressant use for breastfeeding mothers of healthy full-term infants.⁶⁵

The 2 most widely studied antidepressants in breastfed infants are paroxetine and sertraline. It has been shown that very little can be detected in the infant’s serum, with relative infant doses ranging from 0.4% to 2.8%.⁶⁵ While clinicians are cautioned against prescribing paroxetine for pregnant women, the drug remains a suitable alternative for breastfeeding women.

If an antidepressant is started postpartum, the recommendation is to start with a low dose and then slowly titrate upward while monitoring the infant for adverse effects.^65,66 Possible adverse effects in breastfeeding infants include irritability, sedation, poor weight gain, and a change in feeding patterns.⁶⁷ Adverse events are most likely to occur in newborns up to 8 weeks of age, and infants born prematurely or with medical problems may be particularly at risk.^65,68

Helping patients weigh risks and benefits of drug therapy

Women may hear about the risks of medications to the fetus and during breastfeeding and so may be reluctant to seek or accept intervention. Often, the information is not from a reliable, scientifically based source. Primary care physicians are well positioned to guide peripartum women in risk-benefit analysis of proper treatment of their depression vs no treatment or undertreatment. In addition, establishing referral sources—ideally with a peripartum mental health specialist—is advisable. Online resources that clinicians can refer patients to for help in managing peripartum depression include the following:

• www.postpartum.net
• www.womensmentalhealth.org
• www.mothertobaby.org (for pharmacologic guidance).

INCREASED AWARENESS IS KEY

Primary care physicians must remain alert to the high prevalence of depression in women of childbearing age and embrace routine screening for depression. (See the sidebar, “The primary care management of peripartum depression.”) Since half of pregnancies are unintended, awareness of the risks of undetected and untreated peripartum depression to the mother, developing fetus, and infant is essential. Untreated antepartum depression has been linked to poor pregnancy outcomes, nutritional deficits, and substance abuse. Untreated postpartum depression negatively affects mother-infant attachment, infant, and child development and maternal self care.

Not treating depression is hazardous

Drug treatment during pregnancy and breastfeeding poses challenges for the patient and physician due to the inevitability of fetal and infant exposure, but lack of treatment can be hazardous.

To date, the evidence on the use of antidepressants in pregnant and lactating women is reassuring. Specialized peripartum psychiatric partial hospital programs⁶⁹ and inpatient programs⁷⁰ exist for women who need a higher level of care. There is also substantial evidence that psychotherapy, especially cognitive behavioral therapy and interpersonal therapy, is highly effective, and emerging data on complementary and alternative treatments are promising. Coordinated care between primary care and behavioral healthcare providers with expertise in treating peripartum depression is most likely to yield optimal outcomes.