Dikea Roussos-Ross, MD

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The above table lists options for medication management of perinatal depression. When trying to determine which antidepressants should be initiated, several factors should be considered.

In women who have a history of depression that was successfully treated with a specific antidepressant, consideration should be given to restarting that same medication, instead of automatically initiating an SSRI. This is especially important in women who have a history of significant depression or anxiety that failed to respond to multiple medications. Although much of the data available are related to SSRI use in pregnancy, there is sufficient research on other classes of antidepressants such as serotonin-norepinephrine reuptake inhibitors and atypical antidepressants to show adequate safety data.

 Again, the goal is to help the woman achieve remission as quickly and effectively as possible.

Of SSRIs, fluoxetine and sertraline have been extensively studied and escitalopram and citalopram have also been well studied, all of which are believed to be safe in pregnancy.

 Paroxetine, also an SSRI, has been shown in some studies to possibly increase risk of cardiac malformations, however, in further study, the risk has been shown to be negligible.

 Despite this, unless necessary, other SSRIs should be initiated instead of paroxetine.

In women who are naÃ¯ve to antidepressants, initiation of sertraline should be considered as first line because of the lack of active metabolites and 24-hour half-life. Medications should be titrated serially to achieve remission of symptoms. All antidepressants take 4 to 6 weeks to show effect, thus it is important to recognize symptoms and diagnose the mood disorder so that treatment can be initiated as early as possible. Importantly, before prescribing an antidepressant, women should always be screened for bipolar disorder because using these drugs alone in such patients could precipitate a manic episode.

It bears mentioning that women with a history of depression who are on psychiatric medications at the time of pregnancy confirmation should not stop medications without speaking first to their psychiatrist or obstetrician. 

Finally, care should be given to adolescent and young adult women when beginning antidepressants due to the black box warning showing possible increased risk of suicidality in this age group with initiation of SSRIs.

 It is imperative that all women- especially younger women-be seen within 1 to 2 weeks of medication initiation for follow-up. In addition, they should all be counselled to notify the clinician about any adverse effects associated with initiation of pharmacologic therapy.

Yaris F, Kadioglu M, Kesim M, Ulku C, Yaris E, Kalyoncu NI, et al. Newer antidepressants in pregnancy: prospective outcome of a case series. Reprod Toxicol 2004;19:235–8.

Kesim M, Yaris F, Kadioglu M, Yaris E, Kalyoncu NI, Ulku C. Mirtazapine use in two pregnant women: is it safe? Teratology. 2002;66:204.

Chun–Fai–Chan B, Koren G, Fayez I, Kalra S, Voyer–Lavigne S, Boshier A, et al. Pregnancy outcome of women exposed to bupropion during pregnancy: a prospective comparative study. Am J Obstet Gynecol. 2005;192:932-936. 

Use of psychiatric medications during pregnancy and lactation. ACOG Practice Bulletin No. 92. American College of Obstetricians and Gynecologists. Obstet Gynecol. 2008;111:1001-1020.

Benvenuti A, Rucci P, Miniati M, et al. Treatment-emergent mania/hypomania in unipolar patients. Bipolar Disord. 2008;10(6):726-732. 

Stone M, Laughren T, Jones M, et al. Risk of suicidality in clinical trials of antidepressants in adults: analysis of proprietary data submitted to US Food and Drug Administration. BMJ. 2009;339 

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When trying to determine which antidepressants should be initiated for perinatal depression, several factors should be considered.

Options for pharmacologic management of perinatal depression

Up to 20% of all pregnant and postpartum women will suffer from depression during the perinatal period, including the period up to 1 year postpartum. Although perinatal depression is more common than hypertensive disorders in pregnancy (2%-8%) and gestational diabetes (7%), many women with it go untreated for lack of diagnosis and/or intervention.

 There are several reasons that perinatal depression may not be identified and subsequently treated, but the two most common are non-disclosure from patients and inadequate screening of pregnant and postpartum women. Given the far-reaching effects of perinatal depression on mothers and their offspring, appropriate and timely diagnosis and treatment are imperative. 


	A diagnosis of perinatal and/or postpartum depression is made when symptoms of depression last longer than 14 days.

 Symptoms include changes in sleep and appetite, which may be considered “normal” for pregnancy and thus overlooked by both the patient and the clinician. In addition, patients may report decreased energy, concentration, and interest, as well as feelings of guilt. These symptoms interfere with a woman’s ability to perform normal activities of daily living and cause significant impairment. Patients who describe symptoms of depression should always be screened for thoughts of self-harm/suicide. If thoughts of self-harm are accompanied by a plan, intervention becomes acutely necessary. In addition, women should be screened for signs and symptoms of psychosis as this may be associated with the rare diagnosis of postpartum psychosis, which is considered a psychiatric emergency because it puts women at risk of suicide and infanticide.

Patients who suffer from perinatal depression may have concomitant anxiety disorders, such as generalized anxiety disorder, which affects approximately 10% of pregnant and postpartum women.

 Diagnosis may be delayed or overlooked due to the overlap of anxiety and depression symptoms. Symptoms of generalized anxiety disorder (GAD) include excessive worry, inability to focus/concentrate, irritability, restlessness, fatigue and muscle tension.

 Another associated anxiety disorder seen in perinatal women is obsessive-compulsive disorder (OCD). Perinatal and postpartum OCD is believed to affect approximately 3% of pregnant and postpartum women. Approximately 50% of women with perinatal OCD also have a diagnosis of perinatal depression. Symptoms include obsessions related to fears of harm or death of the infant, contamination fears, and, compulsions such as frequent checking and cleaning behaviors.


	Women are at risk of developing perinatal depression when they have been diagnosed with a depressive disorder previously, have a history of postpartum depression in a prior pregnancy, or have a family member with a diagnosis of depression or anxiety. In addition, women who are young, of lower socioeconomic status, and who have limited resources and limited social support are at higher risk.

 Interestingly, women who have a history of premenstrual dysphoric disorder are also at risk for perinatal depression. Research shows that hormone fluctuations, and not specific levels of estrogen and progesterone, may be related to onset or exacerbation of symptoms.

 In fact, women are at increased risk of depression during specific times in their lives, including onset of menses, pregnancy, and the perimenopausal period, all times in which there is noted fluctuation in hormone levels.


	Screening women for depression during pregnancy and in the postpartum period is recommended.

 Several self-report screening tools have been validated for use in the perinatal period. Two commonly used screening tools for use in pregnant and postpartum women are the PHQ-9 and the Edinburgh Postnatal Depression Scale (EPDS). The EPDS is available in 50 languages including Spanish. The PHQ-9 is available in English and Spanish. Patients who have a positive screening result (a 12 or greater for EPDS, a 10 or greater for PHQ9) should be further evaluated to determine whether they require intervention.

It is important to remember that when a self-report questionnaire is given to a patient for completion, the findings should be reviewed. The screening tools previously mentioned both include a question related to self-harm. Thus, it is imperative that the clinician review the responses before the patient leaves the office. Some patients may not feel comfortable speaking the words “I have thoughts of hurting myself” but they will indicate this feeling by circling a response. 


	Therapy and pharmacologic management are mainstays of treatment for perinatal depression. For patients who have mild-to-moderate symptoms, therapy should be considered first line. Typically interpersonal therapy is preferred for depression, but cognitive behavioral therapy (CBT) is also beneficial and is preferred for coexisting anxiety disorders.

 For moderate-to-severe symptoms, pharmacologic management can be initiated, and selective serotonin reuptake inhibitors (SSRIs) typically are considered first line.

 A combination of therapy and medications is preferable for patients who have moderate to severe symptoms. In patients with severe symptoms or suicidal/homicidal thoughts, hospitalization in a psychiatric facility should be considered.

Initiating psychiatric medications in pregnancy may cause anxiety for both patient and physician, thus it is important to understand the indications, risks, benefits, and alternatives for treatment in pregnancy. First, there are well-
	documented risks to the fetus if a woman with moderate to severe depression in pregnancy is left untreated. These risks include limited prenatal care, preterm labor, low infant birth weight, hypertensive disorders of pregnancy, and risk of exposure to illicit substances and alcohol.

 After delivery, if the mother continues to be moderately to severely depressed or develops postpartum depression, additional risks come into play. Risks to the newborn include attachment disorders between mother and infant, inability of the mother to identify and respond to newborn cues, and poor bonding.

 Later in childhood, affected children are at increased risk of behavioral and psychiatric disorders and their total IQ points may be affected.

 Based on this information, there are adequate data to illustrate the importance of intervention and initiation of treatment of depression in pregnancy.


	When reviewing risks of SSRIs for treatment of perinatal depression, the following perinatal risks should be reviewed with the patient: congenital malformations, persistent pulmonary hypertension of the neonate (PPHN), neonatal adaptation syndrome and cognitive/behavioral issues.

In the general population, 2% to 4% of neonates unexposed to prenatal antidepressants will be born with a congenital malformation versus 3% to 5% with such drug exposure. Thus, exposure to antidepressants does not significantly increase the risk of congenital malformation.

Risk of PPHN has been investigated in several studies. Chambers et al demonstrated the risk of PPHN in the general population, for neonates not exposed to antidepressants in pregnancy to be approximately 1 to 2/1000 and the risk in exposed neonates to be approximately 6 to 12/1000.

 A more recent study by Kallen shows the risk of exposed neonates to be approximately 1 to 6/1000.

 Again, this is very similar to the risk in unexposed neonates, thus there is less than 1% risk of PPPN in SSRI-exposed neonates.

Neonatal adaptation syndrome has been well studied and researchers have documented up to a 30% risk of development in the neonate who is exposed to antidepressants in the third trimester.

 Symptoms include poor feeding, poor tone, and irritability.

 The important thing to note is that these symptoms are self-limited and resolve by day 3 to 4 of life. Previously, recommendations were made to discontinue antidepressants in the third trimester to decrease risk of neonatal adaptation syndrome, however, women were found to have relapses in their mood and thus this is no longer recommended.

With regards to cognitive and behavioral issues in children exposed to antidepressants in pregnancy, data show no increased risk of behavioral issues such as attention deficit hyperactivity disorder, oppositional defiant disorder, or mood disorders. There also is no increased risk of cognitive disorders in children exposed to antidepressants in pregnancy.

 Researchers have investigated relationships between antidepressant use in pregnancy and autism and have found no evidence of an association.


	Table 1 lists options for medication management of perinatal depression. When trying to determine which antidepressants should be initiated, several factors should be considered.

 Despite this, unless necessary, other SSRIs should be initiated instead of paroxetine.

 It is imperative that all women- especially younger women-be seen within 1 to 2 weeks of medication initiation for follow-up. In addition, they should all be counselled to notify the clinician about any adverse effects associated with initiation of pharmacologic therapy.


	For pregnant women who are severely depressed or at danger of self-harm through neglect or active thoughts of self-harm, more rapid treatment may be required. Electroconvulsive therapy (ECT) is a well-studied intervention that has been shown to quickly improve symptomatology and advance women towards remission.

 Ideally, ECT is performed in the second trimester, but it can be done in all trimesters if needed. ECT should not significantly increase risk of preterm delivery or cause non-reassuring fetal heart rate tracings. Typically, ECT is performed three times weekly; patients typically receive four to 12 treatments with the option of maintenance treatment on a once-weekly or once-monthly basis. 


	Identification and treatment of perinatal depression can positively affect a woman’s pregnancy and the health of her offspring. Women should be screened for perinatal depression at least once in pregnancy and again in the postpartum period. Screening tools such as the EPDS and PHQ-9 can detect at-risk patients and aid with expedition of treatment. Resources for patient referral are valuable in the physician’s armamentarium, but may be limited due to lack of availability of providers, transportation-related issues, and cost. Educating ob/gyns about proper diagnosis and management of perinatal depression is key to ensuring that they feel confident and comfortable about initiating treatment for this condition.

The author reports no potential conflicts of interest with regard to this article.

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Kesim M, Yaris F, Kadioglu M, Yaris E, Kalyoncu NI, Ulku C. Mirtazapine use in two pregnant women: is it safe? 

Chun–Fai–Chan B, Koren G, Fayez I, Kalra S, Voyer–Lavigne S, Boshier A, et al. Pregnancy outcome of women exposed to bupropion during pregnancy: a prospective comparative study. 

Benvenuti A, Rucci P, Miniati M, et al. Treatment-emergent mania/hypomania in unipolar patients. 

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Left untreated, depression in the perinatal period can have serious repercussions for both mother and offspring.

Author | Dikea Roussos-Ross, MD

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