Issues in Treating Anxiety Disorders in Pregnancy

Anxiety disorders are a frequent occurrence in pregnancy. While some worries and anxiety are experienced by more than 50% of pregnant women, a full-blown anxiety disorder involves risk to both mother and fetus and increases the risk of postpartum depression.^1,2 The prevalence of antenatal generalized anxiety disorder (GAD) is highest (8.5% to 10.5%), followed by panic disorder (1.4% to 5.2%), obsessive-compulsive disorder (OCD; 1.2% to 5.2%), and PTSD (3%).^3-7 The majority of these estimates are either higher than or comparable to rates seen in the general population.⁸

Antenatal vulnerability to anxiety

Although sex hormones are poised to have an anxiolytic effect (progesterone via γ-aminobutyric acid enhancement and attenuation of the noradrenergic response to stress, and estrogen via direct effect on the serotonergic system), anxiety symptoms may be exacerbated or precipitated by pregnancy.^9-11 In addition to genetic susceptibility and increased vulnerability to hormonal flux in some women, role transitions and social expectations are key factors in the development of antenatal anxiety. They may awaken painful memories, even in women without a history of anxiety.^12,13

Effects of maternal anxiety on the developing fetus

Untreated, significant, and ongoing antenatal anxiety exposes the fetus to excess glucocorticoids, which may influence the fetus’s susceptibility to enduring neuroendocrine changes.¹⁴ This fetal programming is believed to be mediated by cortisol binding to promoter regions of genes, which influences their expression.^14,15 The effects on stress-related behavior, emotions, and cognitive abilities in adult life have been established by independent prospective studies.¹⁶ Other associated risks include preterm labor, low birth weight, and lower Apgar scores.^17-19

Screening and treatment for antenatal anxiety can reduce these risks. The anxiety subscale of the Edinburgh Postnatal Depression Scale can be used for this purpose.

Presentation of anxiety disorders in pregnancy

Panic disorder. Normal pregnancy-related changes, such as increased heart rate, shortness of breath, heartburn, dizziness, and sweating, can easily be misinterpreted as harmful. Many women report onset of panic symptoms as these changes become more prominent between the 6th and 28th week of gestation.⁵ The combination of physical symptoms, cognitive factors (eg, catastrophic misappraisal), and maladaptive behavioral responses (eg, avoidance) can result in escalating physical symptoms of anxiety and panic.

CASE VIGNETTE

Panic attacks developed when Jennifer was 7 months’ pregnant with her first child. Although she felt they were not triggered by a specific event, close examination revealed that they were usually precipitated by mild breathlessness when walking, climbing stairs, or performing household chores [physical]. This would trigger the thought: “What is happening to me? I might pass out” [cognitive].

Jennifer’s anxiety would rise, her heart would race, and her hands would tremble [physical]. She would ask her husband to come home from work [behavioral]. While waiting for him to arrive, she would scan her body for any further sensations [behavioral] and worry: “What if something is wrong with the baby?” [cognitive]. She would become dizzy and warm [physical], clutching the telephone in case of an emergency [behavioral], convinced that something was terribly wrong [cognitive].

What is already known about anxiety during pregnancy?

• Clinicians have long known that anxiety is common during pregnancy, although only recently has research begun to better elucidate its etiology, prevalence, and treatment. The 2 most effective, evidence-based treatments for antenatal anxiety are cognitive-behavioral therapy (CBT) and psychopharmacology.

What new information does this article provide?

• This article discusses the specific risks of anxiety and its treatment during pregnancy and illustrates common presentations of the anxiety disorders in pregnant women. Key considerations for both CBT and psychopharmacological treatment are outlined, with specific recommendations for practitioners.

What are the implications for psychiatric practice?

• The unique presentation of common anxiety disorders in pregnancy and their potential risks to both mother and fetus as well as confusing information about the safety of psychotropics in pregnant women pose a challenge to the treating physician. This article provides the most up-to-date information about the risks associated with anxiety, the use of common psychotropics, and general guidelines for treatment of anxiety during pregnancy.

Generalized anxiety disorder. In GAD, symptom expression is influenced by an intolerance of uncertainty and inaccurate beliefs about the utility of worry. Together, these result in the hallmark of GAD: worry about the future.

CASE VIGNETTE

Millie was 6 months’ pregnant and consumed with worries about the impending arrival of her baby. “What if the baby isn’t healthy? What if I’m not a good mother? What if I can’t handle the pain? What if my marriage doesn’t survive?” Millie lay awake at night, her mind racing, and planned how she would deal with each of these imagined scenarios.

She spent much of her time poring over Internet discussion boards and parenting books. Although it never made her feel better, she believed that her worrying somehow prepared her for disappointment and prevented bad things from happening. When her husband tried to be reassuring, Millie became irritable and insisted that worrying is “what responsible mothers do.”

Obsessive-compulsive disorder. Pregnancy increases vulnerability to obsessive thoughts about the overwhelming responsibility for the baby’s well-being and safety.²⁰ Obsessions tend to focus on possible harm to the baby, and compulsions often include washing and cleaning rituals and compulsive checking on and/or avoidance of the baby. While intrusive thoughts are common and normal among new mothers, avoidance, ritualizing, and attempts to control or suppress these thoughts reinforce and escalate anxiety.

CASE VIGNETTE

Jillian had a history of subclinical OCD. Soon after she learned that she was pregnant, she experienced distressing intrusive thoughts and vivid images about abnormal fetal development and of having a miscarriage. The more she tried not to think about it, the more frequent and intense her thoughts became. She avoided contact with household chemicals and made everyone around her wash their hands thoroughly. She meticulously planned her diet, avoided many foods, and compulsively logged her daily intake of fruits, proteins, and vegetables. She only bought organic food, refused to eat out, and became socially isolated. She eventually stopped using the microwave and going to work because she feared the radiation from the computers there would harm her baby. Being told by the doctor that her baby was developing appropriately only reinforced her belief that her strategies were effective.

Childbirth-related specific phobia. Most women report some fear of delivery, but for a subset it can reach phobic proportions. Fear is learned through previous traumatic deliveries, negative information, or witnessing others’ fearful behavior. Extreme fear of childbirth can be associated with prolonged labor, increased perception of pain, and avoidance of labor in favor of cesarean birth.^21-23

CASE VIGNETTE

Since Carol learned she was pregnant, she has been very anxious about the delivery. She becomes distressed when pregnancy is discussed and pictures herself in excruciating pain during labor. At times, she seems to forget that she is pregnant and engages in unhealthy and unsafe behaviors. She often misses her prenatal care appointments and refuses to discuss or plan for delivery. She has admitted to wishing she were not pregnant and wants to be “knocked out” for the entire delivery.

PTSD. Aside from stress resulting from premature delivery, preeclampsia, pregnancy loss, or lack of emotional or social support, non–pregnancy-related traumatic events can negatively influence pregnancy and precipitate PTSD.^24-28 A history of rape, childhood sexual abuse, and domestic violence are commonly endorsed by pregnant women with PTSD.²⁹ These women often avoid health care providers and exhibit extreme sensitivity to bodily exposure as well as dissociation, flashbacks, or excessive need to control situations.

CASE VIGNETTE

After therapy, Laurie thought that her childhood sexual abuse was behind her. She was initially overjoyed at the prospect of becoming a parent, but as the pregnancy progressed, her growing baby led to physical discomfort that triggered memories of her previous abuse. Laurie had nightmares about her abuser and became hypervigilant of her surroundings, fearing for the safety of herself and her baby. After a flashback during a prenatal examination, she stopped going to her obstetrician and avoided all discussion of the baby.

Psychotherapy

Cognitive-behavioral therapy (CBT) has been found to be effective in the treatment of anxiety disorders. However, few data are available on the treatment of anxiety during pregnancy.^30,31 Strategies such as stress reduction, exercise, sleep, and social support may improve well-being and reduce anxiety during pregnancy.

Short-term CBT is focused on concrete strategies to manage symptoms. During pregnancy, the aim is to correct distorted or catastrophic thinking, misinterpretations of physical symptoms, and maladaptive behavioral patterns that may maintain or escalate anxiety (eg, avoidance or ritualizing).³²

Psychoeducation to assist in correctly identifying benign physical symptoms serves to counter fearful misappraisals. This, coupled with anxiety management strategies that include diaphragmatic breathing modified for use in pregnancy, can de-escalate panic symptoms and allow women to return to avoided situations.³²

Identifying and challenging distorted beliefs about the protective function of worry and learning to better tolerate uncertainty are primary goals in treatment. The gradual reduction of reassurance or safety behaviors (such as excessive information-gathering or phone calls to the obstetrician) and focusing on the present moment using mindfulness techniques may also be effective in reducing anxiety.³³

Recognizing obsessions as thoughts that are universal and do not require analysis or action is vital to reducing anxiety. The nature of feared consequences makes a gradual approach to testing out beliefs and approaching avoided thoughts or situations particularly important for antenatal OCD.

Correcting negative appraisals and addressing fears of childbirth early in the pregnancy may minimize vulnerability to postnatal PTSD symptoms.³⁴ In addition to psychotherapy, women who have childbirth-related phobias and PTSD may benefit from preventive strategies. Developing a birth plan with the patient’s active involvement in decision making whenever feasible may increase perceptions of control and improve the experience of pregnancy and childbirth.³⁵

Psychopharmacology

Pregnant women with moderate to severe prenatal anxiety may require psychopharmacological treatment. However, information of mixed quality in lay media, stigma, and fear may lead women to decline effective pharmacological treatment; take less than the recommended dose; or stop treatment prematurely, which may lead to discontinuation symptoms, relapse of underlying anxiety, and even suicidal ideation.^36,37

Clinicians may also be ambivalent about prescribing antidepressants and benzodiazepines for pregnant women because of personal attitudes and stigma and confusing information about the efficacy and safety of these agents in pregnancy.

Antidepressants. All antidepressants cross the placenta, and their transfer averages 70% to 86% of the maternal dose.³⁸ Data on their effects in pregnancy are largely limited to case-control or retrospective studies because randomized, double-blind, placebo-controlled trials in pregnant women are not available.³⁹

In prospective controlled studies or meta-analyses, no association has been found between antidepressant exposure and congenital anomalies as a result of antidepressant treatment in the first trimester.^40-42 Retrospective studies show mixed results. However, in animal studies, paroxetine has been clearly identified as teratogenic, and it has been associated with cardiac malformations in several clinical studies.^43-45 A statistically significant risk of miscarriage has been demonstrated in SSRI users; 3 of 10 prospective controlled studies support this finding.⁴⁶

Preterm labor has been associated not only with venlafaxine, mirtazapine, and continuous exposure to SSRIs in the last trimester but also, to a lesser extent, with untreated anxiety.^17,47-49 Other risks of preterm labor include gestational hypertension and smaller birth weight.⁵⁰

Self-limited adverse effects as a consequence of medication withdrawal or hepatic immaturity develop in up to 30% of neonates.⁵¹ The risk of these adverse effects may be related to the length of antenatal antidepressant exposure rather than to the timing (early versus late pregnancy). A small yet significant increase in the risk of primary pulmonary hypertension in the newborn has been associated with SSRI exposure in late pregnancy.^52,53 However, a recent case-control study found this rare condition (0.17% incidence) to be associated with early cesarean birth-before the onset of labor-not with SSRI use.⁵⁴

Special considerations for antidepressant use in pregnancy include:

• Typical adverse effects of antidepressants may be particularly challenging during pregnancy (Table 1)

• Some women may need dose increases as pregnancy progresses because of pharmacokinetic and pharmacodynamic changes⁵⁵

• A partial dose taper may be considered toward the end of pregnancy in women with relatively low relapse risk

• The best-studied antidepressants in pregnancy are fluoxetine and sertraline⁵⁶

• If breast-feeding is planned, sertraline is the treatment of choice because the average breast milk sertraline level is low (an estimated 0.5% of the maternal weight-adjusted dose)⁵⁷

• Paroxetine should be avoided in the first trimester

Benzodiazepines. All benzodiazepines cross the placenta, but data on their adverse effects in pregnancy are largely based on methodologically flawed studies.⁵⁸ Risks that have been implicated by these studies are, therefore, controversial and include oral cleft, which was not borne out; preterm birth; and low birth weight.^59,60 Neonatal withdrawal has been associated with maternal use of benzodiazepines in late pregnancy and neonatal toxicity, with predelivery exposure.^61,62

Special considerations for benzodiazepine use in pregnancy are as follows:

• Caution is warranted in the first trimester, because data about teratogenicity are lacking and controversial

• A gradual taper may be considered toward the end of pregnancy

• Lorazepam does not accumulate in fetal tissue and may therefore decrease the risks associated with antenatal benzodiazepine use

Nutritional and herbal supplements. Use of vitamins, minerals, amino acids, and herbs are often perceived as safe, and patients may continue to use them during pregnancy. Although some agents have shown promise in the treatment of anxiety, they are not regulated by the FDA nor are they well studied, which raises concern about their purity, strength, and safety in pregnancy and their concomitant use with prescription medication. Caution is warranted in the use of such remedies in women who are pregnant or plan to become pregnant.

Summary

Anxiety disorders are common in pregnancy and have been associated with short- and long-term risks to both mother and fetus. As such, they should be identified and treated. Evidence-based, effective treatments for anxiety include CBT and pharmacological interventions. The risks of antenatal antidepressant treatment are minimal; data about risks associated with benzodiazepine use in the first trimester are lacking. Other potential risks can be minimized by following a few simple guidelines (Table 2). A multidisciplinary team approach that includes obstetricians, primary care physicians, and mental health professionals (as well as neonatologists and pediatricians when postnatal risks are anticipated) is recommended.

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