Anxious for Two: Assessing and Treating Antenatal Anxiety Disorders

                                                      Part I- Screening and Diagnosis

She just paged you again. It is “urgent”, just like the last 5 times. You sigh deeply: no matter how many times you tell her that her labs are normal, explain that some shortness of breath is expected in the last trimester, or reassure her that her heartburn is not a first sign of a heart attack (yes, you checked) – it simply won’t stick.

She tells you that she knows better but can’t help it, or that this time something really is wrong with her baby - she just knows it. The fact that her last ultrasound, (merely 2 days ago), was completely normal is irrelevant. She is consumed with worry, can’t sleep at night and feels “totally exhausted.” You can share the sentiment.

How common are anxiety disorders during pregnancy?

Quite. About 10% of pregnant women suffer form Generalized Anxiety Disorder (GAD), up to 5 %  suffer from a panic disorder, a similar percentage meets criteria for Obsessive Compulsive Disorder and about 3% of expecting mothers exhibit signs and symptoms of Post Traumatic Stress Disorder. ^(1,2)  Overall, the prevalence of these disorders is equal or higher in pregnant women than the prevalence among the general population. Since one third of women will suffer from an anxiety disorder at some point in their lives, chances are you are no stranger to these challenging, yet highly treatable disorders:

GAD: “the worrier”: This patient tends to worry excessively and uncontrollably about a variety of everyday issues (health, relationships, money etc.) leading to intense anxiety, insomnia, muscle tension and other physical symptoms. This disorder is chronic, lasting at least 6 months and often as long as the patient remembers. DSM-IV TR diagnostic criteria

Panic Disorder: Recurrent episodes of intense anxiety that develop unpredictably and almost instantaneously, subside within 30 minutes or so, and include at least 4 of 13 physical symptoms (e.g. shortness of breath, palpitations, perspiration). These episodes lead to anticipatory anxiety for at least a month, and avoidance of feared triggers. In its most severe form, patients avoid all triggers by staying at home, leaving only when absolutely necessary and with a companion (=agoraphobia). The diagnosis of a panic disorder is made only after relevant medical and drug induced conditions have been ruled out.  DSM-IV TR diagnostic features

OCD: A combination of intrusive, irrational, anxiety provoking thoughts and images (=obsessions) that are counteracted by repetitive behaviors (compulsions) that may become very time consuming. Unlike psychotic disorders, patients with OCD are fully aware of their “crazy” thoughts and “silly” rituals and are embarrassed by them but feel compelled to carry them on, in order to reduce their anxiety.  DSM-IV TR diagnostic criteria

PTSD:  chronic re-experiencing (via visual flashbacks and/and dreams), hyper vigilance and avoidance of triggers that remind a patient of a highly distressing event in her past. The trauma involves a perceived threat to the psychological or physical well being of the patient herself or to someone else.  DSM-IV TR diagnostic criteria

Unlike milder worries and concerns, antenatal anxiety disorders involve intense, very distressing symptoms, and carry risks of preterm labor ⁽³⁾, low birth weight ⁽⁴⁾, lower Apgar scores ⁽⁵⁾, enduring emotional and cognitive changes ⁽⁶⁾, indirect risks associated with maternal behavior (substances used for self treatment, missing appointments, avoiding important tests or undergoing risky, unnecessary ones, etc.) and post partum depression⁽⁷⁾. Correct diagnosis and appropriate treatment can minimize these risks. However, most ob/gyns are more accurate in identifying depression than anxiety, and only one-fifth routinely screen pregnant patients for anxiety ⁽⁸⁾.

Specific tools (e.g. GAD-7, ⁽⁹⁾) identify specific anxiety disorder. However, a good first step toward screening is using a more general tool like The anxiety subscale of the Edinburgh Postnatal Depression Scale (EPDS ,⁽¹⁰⁾), that has been validated for anxiety symptoms in pregnancy.

Part II – Presentation of Anxiety Disorders in Pregnancy

References:

1.  Sutter-Dallay AL, Giaconne-Marcesche V, Glatigney-Dallay E, Verdoux H.  Women with anxiety disorders during pregnancy are at increased risk of intensie postnatal depressive symptoms: A prospective study of the MATQUID cohort.  European Psychiatry, 2004; 19:459-463.
2.  Adewuya AO, Ola BA, Aloba OO, Mapayi BM.  Anxiety disorders among Nigerian women in late pregnancy: A controlled study. Arch Womens Ment Health. 2006; 9: 325-328
3.  Dayan J, Creveuil C, Herlicoviez M, et al. Role of anxiety and depression in the onset of spontaneous preterm labor. Am J Epidemiol. 2002;155(4):293-301.
4.  Warren SL, Racu C, Gregg V, Simmens SJ. Maternal panic disorder: Infant prematurity and low birth weight. J Anxiety Disord. 2006;20(3):342-352.
5.  Berle J, Mykletun A, Daltveit AK, et al. Neonatal outcomes in offspring of women with anxiety and depression during pregnancy. A linkage study from The Nord-Trndelag Health Study (HUNT) and Medical Birth Registry of Norway. Arch Womens Ment Health 2005;8(3):181-189.
6.  Van den Bergh BR, Mulder EJ, Mennes M, Glover V. Antenatal maternal anxiety and stress and the neurobehavioural development of the fetus and child: links and possible mechanisms. A review.  Neuroscience & Biobehavioral Reviews. 2005;29(2):237-258.
7.  Coelho HF, Murray L, Royal-Lawson M, Cooper PJ. Antenatal anxiety disorder as a predictor of postnatal depression: a longitudinal study. J Affect Disord. 2011;129(1-3):348-53.
8.  Leddy MA, Lawrence H, Schulkin J. Obstetrician-Gynecologists and Women's Mental Health: Findings of the Collaborative Ambulatory Research Network 2005-2009. Obstet Gynecol Surv. 2011 May;66(5):316-23.
9.  Spitzer RL, Kroenke K, Williams JB, Lwe B. A brief measure for assessing generalized anxiety disorder: the GAD-7.Arch Intern Med. 2006;22;166(10):1092-1097.
10.  Swalm D, Brooks J, Doherty D, et al. Using the Edinburgh postnatal depression scale to screen for perinatal anxiety.  Arch Womens Ment Health 2010;13(6):515-522.
 

Anxious for Two: Assessing and Treating Antenatal Anxiety DisordersPart II – Presentation of Anxiety Disorders in Pregnancy

Pregnant women are more vulnerable to anxiety due to the physiological, emotional and social changes that are associated with pregnancy. The risk is higher in women with psychiatric history and those who discontinue their psychiatric medications during pregnancy, (especially if they do so abruptly ⁽¹⁾).

Pregnant women’s anxieties are influenced by their cognitive style and coping skills and may be fueled by the abundance of confusing (and often inaccurate) information in the media, by social role transition and by personal and social expectations. They are more likely to feel guilty about various behaviors and interventions and to have difficulty discarding negative information, whether true or not ⁽²⁾ (“I should stop eating potatoes. I heard it can cause heart defects”). In an anxious patient these can take catastrophic proportions and induce relentless worries (“did that salad have potatoes in it?”), sleepless nights, frantic phone calls (“I think my baby is dead. I haven’t’ felt her move in 10 minutes!”), or avoidance (“what if they find something wrong with the baby? This is too much for me. I’m cancelling my ultrasound”).

Therefore, in addition to the typical challenge of correctly diagnosing anxiety disorders It is important (and helpful) to be aware of the specific presentations of anxiety disorders during pregnancy:

GAD: The patient who suffers from GAD is unable to tolerate uncertainty and believes that her worry protects her from the worst case scenarios she imagines. She might interpret normal, meaningless findings as ominous, get second, third and fourth opinions, make elaborate plans far in advance and exhaust herself worrying about various issues: from her baby’s health to not being able to get to the hospital in time to deliver. She might be reassured but only temporarily, and is, therefore, likely to seek feedback over and over again – to no avail.

Panic Disorder: The overlap between the symptoms of panic attacks and those of normal pregnancy is quite significant: both may involve shortness of breath, light headedness, nausea, vomiting and palpitations. Therefore, misinterpretation of normal physical symptoms may escalate the patient’s anxiety and induce a bona fide panic attack. In patients who suffer from panic disorder, anticipatory anxiety may lead to avoidance of feared situations (e.g. physical activity) that can, in turn, worsen the patient’s physical and mental well being.

OCD:  Carrying a pregnancy inside her body gives a pregnant woman a unique responsibility for her baby’s well being. Obsessive thoughts about its safety are, therefore, not uncommon. In OCD patients these thoughts are intrusive and intense and are accompanied by compulsions that serve to decrease the overwhelming anxiety the patient is experiencing. Because the feared harm does not occur (“my baby doesn’t have heart defects”), the compulsive behavior is reinforced (“I was right. I should continue to check everything I eat and make sure my food is potato-free”) -however irrational, “silly” or time consuming those may be.

PTSD:  Pregnancy may precipitate or exacerbate PTSD symptoms in women with history of complicated pregnancies, deliveries, abuse or sexual assault. Symptoms may be expressed as extreme anxiety, sensitivity and discomfort when bodily parts are exposed, dissociation, difficulty undergoing invasive exams and avoidance of necessary follow up appointments and procedures.

A history of traumatic delivery or being exposed to another woman’s traumatic experience may lead to phobic response to delivery with associated with an increased perception of pain ⁽³⁾, prolonged labor ⁽⁴⁾ and refusal to deliver vaginally ⁽⁵⁾.

Being aware of these presentations and addressing their underlying anxiety may not only offer relief to suffering patients, but also help their providers plan and manage their care more effectively and efficiently.

Part III - Treatment of Antenatal Anxiety Disorders

References

1.  Einarson, A, Selby, P, Gideon, Korean. Abrupt discontinuation of psychotropic drugs during pregnancy: fear of teratogenic risk and impact of counseling. J Psychiatry Neurosci 2001;26(1):44-8.
2.  Bonari L, Koren G, Einarson TR, Jasper JD, Taddio A, Einarson A. Use of antidepressants by pregnant women: Evaluation of perception of risk, efficacy of evidence based counseling and determinants of decision making. Arch Women Ment Health 2005;8:214-220.
3.  Saisto T, Kaaja R, Ylikorkala O, Halmesmaki E.  Reduced pain tolerance during and after pregnancy in women suffering from fear of labor.  Pain. 2001; 93: 123-127.
4.  Alehagen S, Wijma K, Wijma B. Fear during labor.  Acta Obstetricia et Gynecologica Scandinavica.  2001; 80: 315-320.
5.  Ryding EL.  Investigation of 33 women who demanded a cesarean section for personal reasons.  Acta Obstetricia et Gynecologica Scandinavica. 1993; 72: 28-285.
 

Anxious for Two: Assessing and Treating Antenatal Anxiety DisordersPart 3 - Treatment of Antenatal Anxiety Disorders

Mild to moderate symptoms of anxiety are highly treatable using CBT (Cognitive Behavioral Therapy), an evidence based ⁽¹⁾ short term and focused treatment, in which patients learn to identify their distorted thinking, increase awareness of triggers and modify maladaptive behaviors.

Acupuncture and biofeedback (where patients learn to use their own bodily responses to monitor and control their anxiety) show promise but are not conclusively effective.

Stress reduction techniques such as meditation, deep breathing (modified for pregnant women ⁽²⁾) and exercising (when medical condition allows) may serve as adjuncts to other forms of treatment. In contrast, food supplements and herbs are not recommended for use in pregnancy, as they are not devoid of side effects, may interact with prescription medications, are not FDA regulated and are typically not well studied.

Moderate to severe cases of anxiety may require medical intervention. However, the information about psychotropic’s use in pregnancy is complicated and confusing and many feel apprehensive about it.

Your pregnant patient's anxiety is so bad she is unable to function. All of the psychiatrists you know are out of town and their pagers are off.

What do you do with this hot potato? First, take your own pulse ⁽³⁾. Now keep reading.

Here are the six most important things you need to know:

1.  Anxiety disorders are not benign. They carry risks of preterm labor ⁽⁴⁾, low birth weight ⁽⁵⁾ and other medical problems in addition to intense symptoms and impaired ability to function. These need to be weighed against the potential risks of antenatal psychotropic use in each patient, individually.

2.  Discontinuation of ongoing psychotropic treatment, especially if abrupt, may be dangerous. In addition to relapse of the underlying anxiety disorder and psychological decompensation, benzodiazepine withdrawal may induce life threatening seizures ⁽⁶⁾ and anti-depressant discontinuation syndrome may include gastro-intestinal symptoms, tremors, insomnia and suicidal thoughts ⁽⁷⁾.

3.  Randomized double-blind, placebo-controlled trials in pregnant women are not available. The data on anti-depressants and benzodiazepine effects in pregnancy are largely based on case control or retrospective studies (with their inherent methodological flaws) ⁽⁸⁾.

4.  Anti-depressants:

• Potential risks of antidepressant exposure include: cardiac malformations (Paroxetine ⁽⁹⁾; No association has been found between other antidepressant exposure and congenital anomalies in prospective, controlled studies or meta-analyses ⁽¹⁰⁾), miscarriage (according to 3 out of 10 prospective controlled studies),  preterm labor (venlafaxine, mirtazapine, continuous exposure to SSRI ^(11-13)) but also anxiety itself ⁽⁴⁾, gestational hypertension ⁽¹⁴⁾ and reduced growth ⁽¹⁵⁾. Self-limiting withdrawal in up to 30% of newborns ⁽¹⁶⁾ and a very small risk of PPHN (Primary Pulmonary Hypertension of the Newborn), if any ^(17,18) may be minimized by a partial taper in the last 4 weeks of gestation in patient's with low relapse risk ⁽¹⁹⁾. The recent concern about possible autism ⁽²⁰⁾ is controversial, as the study included (yet did not address) confounding factors and was based on a very small number of exposures to SSRI.

• The best studied, recommended antidepressants in pregnancy are Fluoxetine (in general) and Sertraline (in women who plan to breastfeed). Other considerations include potential side effects in the context of pregnancy (e.g weight issues, over sedation) and previous response to specific antidepressants.

• Pregnant women may need progressively higher doses of anti-depressants due to pregnancy related physiological changes.

 5.  Benzodiazepines:

• Potential risks of benzodiazepine exposure include oral cleft ⁽²¹⁾ (controversial), preterm birth and low birth weight ⁽²²⁾. Use in late pregnancy may lead to neonatal withdrawal (prevented by a timely taper). Pre-delivery exposure may cause neonatal toxicity ⁽²³⁾, which may be minimized by a gradual taper toward the end of gestation ⁽²⁴⁾.

• Lorazepam is the preferred benzodiazepine as it doesn’t accumulate in fetal tissue ⁽²⁴⁾.

6. Ideally, both parents should take part in the discussion and make their informed decision about antenatal psychotropic treatment together.

Overall, when used judiciously and after a thorough risk/benefit analysis, psychopharmacologic treatment can be a reasonably safe option for pregnant women, when clinically warranted. Consulting a women’s mental health specialist is recommended whenever in doubt.

References

1 Butler AC, Chapman JE, Forman EM, Beck, AT. The empirical status of cognitive-behavioral therapy: A review of meta-analyses. Clinical Psychology Review, 2006; 26: 17-31.
2.    Wiegartz PS, Gyoerkoe KL.  The pregnancy and postpartum anxiety workbook: Practical skills to help you overcome anxiety, worry panic attacks, obsessions and compulsions.  Oakland, CA: New Harbinger; 2009.
3.    Shem S. The house of god.  Dell Publishing,1978.
4.    Dayan J, Creveuil C, Herlicoviez M, et al. Role of anxiety and depression in the onset of spontaneous preterm labor. Am J Epidemiol. 2002;155(4):293-301.
5.    Warren SL, Racu C, Gregg V, Simmens SJ. Maternal panic disorder: Infant prematurity and low birth weight. J Anxiety Disord. 2006;20(3):342-352.
6.    Hu X. Benzodiazepine withdrawal seizures and management. J Okla State Med Assoc. 2011;104(2):62-65.
7.    Einarson, A, Selby, P, Gideon, Korean. Abrupt discontinuation of psychotropic drugs during pregnancy: fear of teratogenic risk and impact of counseling. J Psychiatry Neurosci 2001;26(1):44-48.
8.    Einarson A. Studying the safety of drugs in pregnancy: and the gold standard is…. J Clinical Pharmacol and Pharmacoepidemiol. 2008;1:3-8
9.    Bar-Oz B, Einarson T, Einarson A, et al. Paroxetine and congenital malformations: meta-Analysis and consideration of potential confounding factors. Clin Ther. 2007;29(5):918-926.
10.    Rahimi R, Nikfar S, Abdollahi M. Pregnancy outcomes following exposure to serotonin reuptake inhibitors: a meta-analysis of clinical trials. Reprod Toxicol. 2006;22(4):571-575.
11.    Lennestl R, Klln B. Delivery outcome in relation to maternal use of some recently introduced antidepressants. J Clin Psychopharmacol. 2007;27(6):607-613.
12.     Djulus J, Koren G, Einarson TR, et al. Exposure to mirtazapine during pregnancy: a prospective, comparative study of birth outcomes. J Clin Psychiatr. 2006;67(8):1280-1284.
13.    Wisner KL, Sit DK, Hanusa BH, et al. Major depression and antidepressant treatment: impact on pregnancy and neonatal outcomes. Am J Psychiatry. 2009;166(5):557-566.
14.    Toh S, Mitchell AA, Louik C, et al. Selective serotonin reuptake inhibitor use and risk of gestational hypertension. Am J Psychiatry. 2009;166(3):320-328.
15.    Davidson S, Prokonov D, Taler M, et al.  Effect of exposure to selective serotonin reuptake inhibitors in utero on fetal growth: potential role for the IGF-I and HPA axes. Pediatr Res. 2009;65(2):236-241.
16.    Levinson-Castiel R, Merlob P, Linder N, et al. Neonatal abstinence syndrome after in utero exposure to selective serotonin reuptake inhibitors in term infants. Arch Pediatr Adolesc Med. 2006;160(2):173-176.
17.     Reis M, Klln B. Delivery outcome after maternal use of antidepressant drugs in pregnancy: an update using Swedish data. Psychol Med. 2010;40(10):1723-1733.
18.    Wilson KL, Zelig CM, Harvey JP, et al.  Persistent pulmonary hypertension of the newborn is associated with mode of delivery and not with maternal use of selective serotonin reuptake inhibitors. Am J Perinatol. 2011;28(1):19-24.
19.    Miller LJ, Bishop JR, Fischer JH, et al. Balancing risks: dosing strategies for antidepressants near the end of pregnancy. J Clin Psychiatry 2008;69(2):323-324.
20.    Croen LA, Grether JK, Yoshida CK, Odouli R, Hendrick V. Antidepressant Use During Pregnancy and Childhood Autism Spectrum Disorders. Arch Gen Psychiatry. 2011 Jul 4. [Epub ahead of print]
21.      Acs N, Bnhidy F, Horvth-Puh E, Czeizel AE. Maternal panic disorder and congenital abnormalities: a population-based case-control study. Birth Defects Res A Clin Mol Teratol. 2006;76(4):253-261.
22.      Calderon-Margalit R, Qiu C, Ornoy A, et al. Risk of preterm delivery and other adverse perinatal outcomes in relation to maternal use of psychotropic medications during pregnancy. Am J Obstet Gynecol. 2009; 201(6):579.e1-8.
23.    Schulz MS, Cowan CP, Cowan PA. Promoting healthy beginnings: a randomized controlled trial of a preventive intervention to preserve marital quality during the transition to parenthood. J Consult Clin Psychol. 2006;74:20-31.
24.    Whitelaw AG, Cummings AJ, McFadyen IR. Effect of maternal lorazepam on the neonate. Br Med J (Clin Res Ed). 1981;282(6270):1106-1108.