Psychiatric Disorders and Pregnancy

35 1

6. Freeman EW, Rickels K, Sondheimer SJ, Polansky M: Ineffectiveness of progesterone suppository treatment for premenstrual syndrome. JAMA 264:349-353, 1990. 7. Freeman EW, Rickels K, Sondheimer SJ, et al: Nefazadone in the treatment of premenstrual syndrome: A preliminary study. J Clin Psychopharmacol 14:180-1 86, 1994. 8. Halbreich U, Rojanksy N, Palter S: Elimination of ovulation and menstrual cyclicity (with danazol) improves dysphoric premenstrual syndromes. Fertil SterilS6:10661069, 199I. 9. Moden-Vrtovec H, Vujc D: Bromocriptine in the management of premenstrual syndrome. Clin Exp Obstet Gynecol 19:242-248, 1992. 10. Menkes DB, Taghavi E, Mason PA, Howard RC: Flnoxetines spectrum of action in premenstrual syndrome. Int Clin Psychophmacol8:95-102, 1993. 11. Schmidt PJ, Nieman LK, Grover GN, et al: Lack of effect of induced menses on symptoms in women with premenstrual syndrome. New Engl J Med 324: 1174, 1991 . 12. Steiner M, Wilkins BA: Diagnosis and assessment of premenstrual dysphoria. Psychiatric Ann 25(9):571575, 1996. 13. Steiner M, Korzekwa M, Lamont J, et al: Intermittent fluoxetine dosing in the treatment of women with premenstrual dysphoria. Psychopharmacol Bull 33(4):771-774, 1997. 14. Thys-Jacobs S, Starkey P, Bernstein D, Tian J: Calcium carbonate and the premenstrual syndrome: Effects of premenstrual and menstrual symptoms. Premenstrual Syndrome Study Group. Am J Obstet Gynecol 179:444452, 1998. 15. Yonkers KA, Gullion C, Williams A, et al: Paroxetine as a treatment for premenstrual dysphoric disorder. J Clin Psychopharmacol 16:3-8, 1994. 16. Young SA, Hurt PH, Benedek DM, Howard RS: Treatment of premenstrual dysphoric disorder with sertraline during the luteal phase: A randomized, double-blind, placebo-controlled crossover trial. J Clin Psychiatry 59:76-80, 1998.

63. PSYCHIATRIC DISORDERS AND PREGNANCY

Doris C. GurtderseM, M.D

1. How common are eating disorders in pregnant women? Few reports of anorexia nervosa associated with pregnancy are found in the literature. To some extent, the two conditions are mutually exclusive. The endocrine abnormalities associated with anorexia nervosa substantially diminish fertility. The paucity of published information on bulimia in pregnancy may reflect the failure of physicians to identify the problem, despite an incidence of up to 13% in women of childbearing age.

2. How are pregnant women with eating disorders diagnosed and managed?
T h e possibility of an eating disorder should b e considered in any woman whose pregravid weight is subnormal or who fails to gain weight as pregnancy progresses. Any patient who casually mentions that she has an eating problem should be carefully questioned. An eating disorder should be suspected in patients who are excessively preoccupied with weight gain and body image during pregnancy. A history of persistent vomiting before o r during pregnancy should be investigated. A psychosocial history may reveal comorbidity with other psychiatric conditions, such as depression or chemical dependency in bulimic women. Hospitalization is recommended for the eating-disordered pregnant patient with excessive weight loss, severe metabolic disarray, or prominent symptoms of depression. Psychotherapy and nutritional counseling should complement prenatal care. Enlisting the support of families to monitor weight gain and nutrition is helpful. Ideally, eating disorders should be identified before conception. The afflicted woman should be advised to delay pregnancy until the eating disorder is truly in remission.

352

Psychiatric Disorders and Pregnancy

3. How might issues specific to pregnancy affect the eating-disordered patient and, thus, the fetus?
Psychological conflicts thought to be important in the development of eating disorders concern adult sexuality, body image, autonomy, dependency, and relationships with parents. Because such issues become highlighted during pregnancy, exacerbations of eating disorders are likely. Women with active eating disorders at the time of conception typically experience many difficulties during pregnancy. They gain less weight and have smaller babies with lower Apgar scores. Serious complications of bulimia include acid-base disturbances, electrolyte imbalances, and disruption of normal intestinal motility. Anorexic women with reduced weight gain during pregnancy have associated intrauterine growth retardation. In one Danish study of 50 pregnant women treated for anorexia nervosa, 7 perinatal deaths were reported, with 6 attributed to prematurity.

4. What risks do illicit substances, tobacco, and alcohol pose to the child exposed in utero? The incidence of substance abuse in women of childbearing age is high. The risk for developmental abnormalities in the fetus of a drug abusing mother is significant. Cocaine-abusingwomen have a significantly higher rate of spontaneous abortion, abruptio placentae, and stillbriths. Infants of opiate-dependentmothers face greater perinatal morbidity and mortality. In the first trimester, a common complication is spontaneous abortion. A 30-50% increased risk for growth retardation is observed. Heavy tobacco use doubles the rate of spontaneous abortion. Smoking is linked to intrauterine growth retardation, premature labor, and low birth weight. Cannabis abuse also is associated with negative effects on fetal growth. Alcohol and its metabolite acetaldehyde have direct toxic effects on cellular growth and metabolism.
Summary of Mujor Risks of Drug Use During Pregnancy
Cocaine Maternal depression, cerebrovascular accident Fetal cerebral hemorrhage Spontaneous abortion Low birth weight Increased rate of sudden infant death syndrome Neurobehavioral problems in neonates Increased perinatal morbidity and mortality Spontaneous abortion Fetal growth retardation Premature labor Neonatal septicemia, liver damage, cerebrovascular accidents Neonatal addiction and withdrawal Slowed fetal growth Fetal hypoxia Spontaneous abortion Slowed fetal growth Low birth weight Premature labor Fetal alcohol syndrome includes Mental retardation Cardiac defects Growth retardation Facial and limb deformities

Opiates

Cannabis Tobacco

Alcohol

Psychiatric Disorders and Pregnancy

353

5. What specific effects does cocaine use have on the fetus?

Peripherally, cocaine causes a marked rise in maternal catecholamines with concomitant increases in blood pressure and heart rate. Acute myocardial infarction or cardiac arrhythmias may result. Maternal brain hemorrhage has been reported. Prolonged administration of cocaine results in depletion of presynaptic intraneuronal neurotransmitters, which is associated with profound depression. Increased levels of circulating catecholamines also lead to increased uterine vascular resistance and decreased uterine blood flow. Fetal hypoxia is produced by the diminished placental perfusion. Cocaine freely crosses the placenta. Fetal hypertension and tachycardia are direct effects of the cocaine. The cocaine-exposed fetus risks hemorrhagic cerebral lesions. Intrauterine growth retardation is common. Neonates of cocaine-abusing mothers demonstrate low birth weight and low Apgar scores. They have a higher than expected rate of genitourinary tract malformations and cardiac anomalies. An increased frequency of sudden infant death syndrome (SIDS) is reported. Neonates with in utero exposure to cocaine exhibit transient neurobehavioral symptoms, including tremulousness, hyperreflexia, and hypertonicity. They are irritable and less consolable and have abnormal sleep patterns. They are at high risk for abuse and neglect. Cocaine appears in significant quantities in breast milk. Longterm administration of cocaine may result i n irreversible decreases in dopamine, persistent mood dysfunction, and an inability to experience pleasure.

6. How do opiates harm pregnancy?

The majority of drug-dependent pregnant women must rely on the street supply of narcotics. Because of the irregularity of with which they receive opiates, intermittent withdrawal may occur, leading to uterine imtability. The incidence of premature labor is increased. Meconium aspiration is a common complication. Infants born to drug-addicted mothers often suffer from septicemia, hyperbilirubinemia, intracranial hemorrhage, and hypoglycemia. They demonstrate a withdrawal syndrome, characterized by irritability, poor feeding, respiratory difficulties, and tremulousness. Such infants are difficult to console and, like cocaine-exposed babies, are at high risk for abuse and neglect.

7. Give an example of the evidence for negative effects of tobacco on unborn children. One study assessed over 700 children of mothers who smoked during pregnancy. At the age of 3 years, the children demonstrated decreased height and weight compared with unexposed 3-year-old controls. Statistically significant cognitive impairment in the tobacco-exposed children persisted, even after controlling for environmental variables.

8. How does cannabis cause risks?

Delta-9-tetrahydrocannabinol elevates carbon monoxide levels in the mother, resulting in poorer oxygenation in the fetus. Elevations in maternal heart rate and blood pressure reduce placental blood flow to the fetus. Finally, delta-9-tetrahydrocannabinol freely crosses the placenta and is exceptionally fat-soluble, requiring up to 30 days for the fetus to excrete.

9. How much alcohol is safe for a pregnant woman to consume? Five to six drinks of hard liquor per day are associated with the most serious teratogenicity, called fetal alcohol syndrome. Abnormalities include mental retardation, cardiac defects, growth retardation, and facial and limb deformities. Irritability in infancy and attention deficit symptoms during childhood are characteristic findings. The severity of the syndrome depends on the amount of alcohol exposure, the gestational age of exposure, and the genetic constitution of the infant. No safe level of alcohol consumption has been determined.

10. How can substance abuse be detected and managed in the pregnant woman? Clinical management of substance-abusing women during pregnancy can be challenging. Drugabusing women commonly neglect health care in general. Up to 75% fail to seek prenatal care. Drug abuse should be suspected in women who present late for prenatal care or have poor weight gain or other signs of compromised health. The patient also should be screened for other psychiatric conditions that predispose to substance abuse, such as anxiety and depression. Most pregnant women will

354

Psychiatric Disorders and Pregnancy

disclose a history of drug or alcohol abuse if questioned in a nonjudgmental, straightforward manner. Authoritarian moralizing leads to an avoidance of prenatal care altogether. Providing an opportunity for treatment is the most effective strategy. The first intervention should be to educate the patient about the hazards of drug use during pregnancy. Some will discontinue use on their own in response to the counseling. They should be offered prenatal care in conjunction with treatment for substance abuse. Outpatient care is usually indicated, but hospitalization may be needed for more severe cases, such as mothers addicted to tranquilizers or barbiturates in addition to opiates. In some cases it is necessary to pursue involuntary commitment to protect the fetus.

11. What sort of issues should be addressed in treatment?

Treatment goals should include developing a strong support system to allow the woman to break ties with the drug culture. Social stressors such as poor housing and inadequate income must be remedied. Emotional problems, including depression, low self-esteem, and poor coping skills, should be addressed in individual as well as group therapy. Urine toxicology screening detects relapse.

12. Describe the pharmacotherapyfor a pregnant substance abuser. Pharmacotherapy during pregnancy may be used to prevent or lessen withdrawal symptoms, to diminish cocaine craving, and/or to treat comorbid psychiatric disorders. The benefits of using a particular drug must be carefully weighed against the risks posed to the fetus. If possible, avoid medication in the first trimester. Administer it in the lowest effective doses for the briefest periods possible. Dopamine agonists decrease acute cocaine craving. Bromocriptine has been used in pregnancy to treat hyperprolactinemia and pituitary adenomas. Multiple studies show no increase in pregnancy complications or untoward effects in the fetus. For severe cocaine craving, bromocriptine, 2.5 to 10 mg/day, may be a reasonable short-term intervention to facilitate abstinence after acute withdrawal. The tricyclic antidepressant desipramine also reduces cocaine craving and appears to be effective in facilitating longer-term abstinence. It should be avoided in the first trimester and during the few weeks before delivery. Detoxification from opiates during pregnancy is possible but extremely difficult and fraught with possible hazards of abortion in the first trimester and fetal distress in the third. If detoxification is requested, it should be attempted from the 14th to 28th weeks of gestation and should not exceed a taper of more than 5 mg/week. The absolute safety of methadone during pregnancy is uncertain. Infants have a lower birth weight, shorter length, and smaller head circumference. They suffer from a greater incidence of SIDS. However, methadone likely poses less risk to the fetus than do severe withdrawal, infectious diseases contracted by the mother from contaminated needles, and absence of prenatal care. Research suggests that the results for patients receiving methadone maintenance along with good prenatal care and counseling are comparable to those for nonaddicted mothers. A vulnerable period for relapse is the postpartum period. Treatment and supportive measures should continue. Note that the pediatrician must consider relapse in the mother of any infant exhibiting signs of neglect andor abuse. Child protective services should be notified. 13. Which psychotropic agent should be considered most carefully before deciding on use in pregnancy? In most industrialized nations, about 0.1% of the population receives maintenance lithium therapy for bipolar illness; 50% are women, many in the fertile age range. Of all the psychotropic agents, lithium warrants the most caution during pregnancy. It should be avoided altogether, if possible, because of the potential risks to the developing fetus and neonate. However, note that lithium is the safest mood-stabilizing agent currently available.
14. Describe the potential hazards of in-utero exposure to lithium. Lithium is a known teratogen in the first trimester. An increased rate of cardiovascular abnormalities is observed. The most recent epidemiologic data suggest a relative risk of 1:lOOO for

Psychiatric Disorders and Pregnancy

355

Ebsteins anomaly-ten times lower than previously estimated. The risk for any congenital abnormality in lithium-exposed infants is estimated to be between 4 and 12%, a rate 2-3 times greater than that in untreated comparison groups. Stillbirth and Downs syndrome are associated with lithium exposure during the first 12 weeks of pregnancy. In the last trimester, lithium inhibits hormone release from the thyroid gland of the developing fetus, thereby stimulating increased TSH production and resulting in goiter. Lithium exerts an insulin-like effect on carbohydrate metabolism, leading to macrosomia. Premature delivery and increased perinatal mortality are potential complications. Neonates exhibit decreased renal clearance. The half-life of lithium is generally prolonged, increasing the risk for toxicity. Lithium toxicity in the newborn is characterized by hypothermia, bradycardia, shallow respiration, and cyanosis. Hypotonia and feeding difficulties are not uncommon. Such effects are presumed to be reversible, but conclusive studies are lacking. Animal studies suggest that behavioral teratogenicity may result from in-utero exposure to lithium. In one study, rats with in-utero exposure demonstrated significant impairment in performance on T-mazes. A large Scandinavian study of lithium-exposed children who were born without physical malformations and reached the age of 5 years or older revealed no significant neurobehavioral differences compared with unexposed but genetically similar siblings. The study does not rule out the possibility of behavioral teratogenicity in humans but suggests that, if present, the changes are subtle. This data is encouraging for pregnant women who require maintenance lithium treatment. Finally, it is not clear whether in-utero exposure to lithium increases the risk for behavioral or affective abnormalities later in life.

15. What are the risks of other mood stabilizers? Carbamazepine is associated with craniofacial abnormalities (1 1 %), developmental delay (20%),and digital hypoplasia (26%).First-trimester exposure to carbamazepine has been associated with spina bifida, with a 0.5-1% risk. The risk of spina bifida with valproic acid is 1 4 % . The use of these anticonvulsants during pregnancy is not justified except perhaps in the clinical setting of nonresponse to other treatment modalities and severe, life-threatening illness. If they are used during pregnancy, the mother should receive folate supplementation. Clonazepam, a benzodiazepine with anticonvulsant and antimanic properties, has proved to be the least teratogenic of six anticonvulsant agents in mice. Whether this holds true for humans is yet to be determined. Lee Cohen, et al. (unpublished data, 1995) found no evidence of neonatal malformations in infants born to 25 mothers prescribed clonazepam during pregnancy. Some of the data regarding neurobehavioral effects of in-utero exposure to these anticonvulsants are difficult to interpret due to a failure to control for variables such as parental IQ, seizures occurring during pregnancy and psychological and/or social factors. However, a recent study comparing children with and without prenatal exposure to carbamazepine failed to demonstrate any adverse neurobehavioral effects (i.e., lowered IQ) in the exposed children.
16. What is known about the safety of tricyclic antidepressants (TCAs) in pregnant women? TCAs are the most studied class of antidepressants. During pregnancy, they are considered relatively safe. However, because they readily cross the placenta, the developing fetus is vulnerable to anticholinergic side effects, including tachymhythmias. Thus the less anticholinergic compounds nortriptyline and desipramine are recommended for pregnant women needing somatic treatment for depression. After delivery, the neonate no longer has the support of maternal circulation to metabolize drugs. Toxicity may result, characterized by respiratory distress, cyanosis, hypertonia, irritability, and even seizures. In addition, a tricyclic withdrawal syndrome has been described, consisting of colic, irritability, difficulty with feeding, and tachypnea. The medication may be gradually withdrawn several weeks before the estimated date of delivery to provide a washout period for the fetus and to lessen the risk for anticholinergic complications. If necessary, the antidepressants may be reinstated immediately after delivery.

356

Psychiatric Disorders and Pregnancy

The effect of TCAs on the developing central nervous system of humans is not known. Neurobehavioral sequelae have been demonstrated in animals. Studies have revealed decreased exploratory responses, delayed reflex development, and changes in hypothalamic dopamine levels in rats exposed to imipramine. The changes in behavioral response persist into adulthood. Although no human studies have conclusively clarified this issue, pooled analysis of 414 children with known first-trimester exposure to TCAs failed to reveal a significant association between fetal exposure and high rates of congenital malformations. Furthermore, normal motor and behavioral development was found in children (followed from birth to the age of 3 years) exposed to TCAs in utero.

17. What is known about the safety of selective serotonin reuptake inhibitors (SSRIs) in pregnant women? Data on the safety of SSRIs during pregnancy is promising. In humans, the safety of fluoxetine in pregnancy has been evaluated in several prospective and retrospective studies and surveys consisting of over 2000 women. The incidence of major malformations in infants exposed in-utero does not appear to exceed the rate (2-7%) observed in the general population. The tendency for spontaneous abortion in fluoxetine-treated pregnant women was similar to that observed for TCAs (13.5%) and not greater than the rate of spontaneous abortion found in historical controls (1 5%). The outcomes of all prospectively identified, spontaneously reported pregnancies with confirmed fluoxetine exposure during the third semester suggest that fluoxetine use during pregnancy is unlikely to result in significant postnatal complications. Finally, one prospective study conducted by Nulman and colleagues demonstrated normal cognitive, language, and behavioral development in children exposed in-utero to fluoxetine. Similar data exists for sertraline. In one study of 267 pregnant women, 147 were exposed to sertraline. No difference was found in the exposed women compared to controls with respect to rates of miscarriage, congenital malformations, stillbirth, prematurity, weight, or gestational age. Preliminary data for paroxetine points to a similar safety profile. Less is known about the newer antidepressant agents, including citalopram, venlafaxine, and nefazodone. Data is also lacking for trazadone and buproprion. Until a more substantial database is established for these medications, supporting their safety in pregnancy, they should be avoided.
18. What is known about the safety of monoamine oxidase inhibitors (MAOIs) in pregnancy? MAOIs are known teratogens in animals. Preclinical studies suggest that this teratogenicity may also apply to humans. Given the risk of an MAOI-precipitated hypertensive crisis and the availability of safer alternatives, MAOIs are contraindicated in pregnancy.
19. What is known about the safety of antipsychotic agents during pregnancy? Reviews of the literature, including several prospective studies of tens of thousands of women exposed to high-potency neuroleptics in the first trimester, do not support an increased rate of malformations. Low-potency neuroleptics are associated with a 2.4% risk of congenital malformations. Neuroleptics, like TCAs, readily cross the placenta. Toxicity is similar to that seen in adults. Extrapyramidal symptoms, including hypertonicity, restlessness, and tremor, are observed in neonates of mothers taking antipsychotic agents at the time of delivery. Tachycardia, urinary retention, and functional bowel obstruction are seen in infants of mothers taking low-potency (and therefore strongly anticholinergic) antipsychotic drugs. Maintaining pregnant on high-potency neuroleptics such as Haldol, with gradual discontinuation 5-1 0 days before delivery, minimizes complications in the newborn. Postnatal behavioral changes, including poor performance in maze learning and shock avoidance, have been demonstrated in animals, whether or not exposure occurred before or after the completion of organogenesis. Rats exposed to Haldol have decreased dopamine receptor activity. Data about long-term behavioral consequences in humans are lacking. One study of 14 children exposed to antipsychotics i n utero failed to reveal memory or learning deficits by age 4 years. Another study of 52 children exposed prenatally to thorazine failed to identify behavioral abnormalities or changes in IQ scores compared with controls. A cohort of 3,056 infants exposed to phenothiazines at various times during gestation showed no statistically significant differences in IQ scores

Psychiatric Disorders and Pregnancy

357

by age 4 years. More prolonged prospective follow-up studies are needed to establish the possible relationship between such drugs and subtle long-term behavioral or cognitive abnormalities. Little is known about the safety of atypical antipsychotic drugs such as clozapine, risperidone, and other newer agents. They should be avoided during pregnancy until adequate data is available to support their safe use.

20. Is prophylaxis against extrapyramidal symptoms of antipsychotic therapy a good idea? Prophylaxis against extrapyramidal symptoms (dystonias, tremor, akathisia) is not recommended. Anticholinergic agents used to treat the side effects of antipsychotic drugs are best prescribed on an as-needed basis and withdrawn at the earliest possible time to avoid complications in the neonate. In one study, a possible association between the use of these drugs and malformations was found. Risk for malformations has not been associated with diphenhydramine. Amantadine exposure in-utero has been linked to congenital nialfomiations and should be avoided during pregnancy.

21. What is known about the effects of benzodiazepineson the developing fetus? Pregnant women should be advised that pooled data analysis of several small studies points to a positive association between first-trimester exposure to benzodiazepines and oral cleft anomalies. Estimating the strength of that association is difficult secondary to the heterogeneity of the study subjects, different benzodiazepine drug use, and variations in reports of malformations. As with all drugs, benzodiazepines should be withheld in the first trimester of pregnancy or at least until the tenth week of gestation when palate closure is complete. In addition to cleft palate abnormalities, a syndrome reminiscent of fetal alcohol syndrome has been reported in infants with in-utero exposure to benzodiazepines. However, the most recent prospective data are contradictory. The literature suggests that use of benzodiazepines in the second and third trimesters is probably safe. However, with prolonged administration, cord plasma concentrations in the fetus may become greater than in the maternal circulation. Transient neurologic deficits, hypotonia, and respiratory depression have been reported in neonates born to mothers medicated in the later stages of pregnancy. In addition, neonates are at risk for withdrawal symptoms within a few days to 3 weeks after birth. Gradual discontinuation several weeks before delivery is recommended. Abnormalities of motor and arousal processes in rodents exposed to diazepam in utero have been demonstrated. The significance of these findings in humans is not known. Some studies suggest that in-utero exposure to benzodiazepines is associated with developmental delay. 22. What legal considerations must be kept in mind when prescribing medication for a pregnant woman with psychiatric illness? Remember that you are treating two patients: the psychiatrically impaired pregnant woman and her unborn child. The literature about psychotropic drug use in pregnant women is primarily retrospective and to some extent anecdotal. Thus the decision to prescribe such medications during pregnancy must be made based on a thoughtful risk-benefit analysis. Be sure to document the specific benefits that justify the risk. In documenting consent, indicate the patients competence to understand the specific risks, benefits, and alternative treatments, including no treatment. Ideally, a course of action should be agreed upon before conception and when the woman is psychiatrically stable. It should be documented clearly in treatment records. If the woman deteriorates during the course of pregnancy and becomes incompetent to participate in treatment decisions, temporary guardianship must be pursued so that appropriate psychiatric care can proceed.

23. Describe the management of the bipolar patient who desires pregnancy. Bipolar disorder (manic-depressive illness) has a mean age of onset in the early twenties, coinciding with childbearing years. Bipolar women need prenatal counseling to be advised of the risk of fetal anomalies associated with psychotropic medication. The prospective mother also must be made aware of her risk for manic decompensation when somatic therapy is withdrawn. Ideally, psychotropic medications should be discontinued several weeks before conception. For the woman who has had a single episode of mania with complete recovery and a long period of

358

Psychiatric Disorders and Pregnancy

stability, slowly tapering medication before attempting to conceive is a reasonable course of action. When a woman taking lithium conceives unknowingly, the drug should be gradually discontinued because abrupt withdrawal is associated with manic relapse. Close observation should follow. With early and mild relapse, hospitalization with structure, reduced environmental stimulation, and elimination of exacerbating stressors may avert worsening of symptoms. If conservative measures fail, low-dose antipsychotics should be instituted to ameliorate the most severe symptoms, for example, insomnia. An adjuvant benzodiazepine such as clonazepam may reduce the total required dose of either medication used alone. If such measures fail to stabilize the patient, lithium may be reinstated-ideally in the second trimester after organ formation is complete. Bipolar patients are 4-5 times more likely to develop mania in the postpartum period than at any other time. Clinicians should follow such women closely. Extending the postpartum hospital stay for longer observation is warranted. Provisions for continued monitoring and support by family or professional agencies should be arranged before discharge.

24. Is management different for bipolar patients with brittle illness? A more difficult decision must be made for women with brittle illness, which is characterized by high relapse risk in the absence of mood-stabilizing medication. The potential morbidity associated with the drugs must be weighed against the likelihood of severe psychiatric symptoms and the associated danger to the mother and her developing child. The decision to continue psychotropic medication through pregnancy must be made jointly by the physician and the carefully informed couple wishing to conceive. The consent process, which outlines risks, benefits, and alternative treatments as well as the planned course of action, should be documented carefully in the patients records. 25. Describe some specifics of lithium therapy for the pregnant, bipolar woman. For women maintained on lithium in the first trimester, fetal ultrasound should be obtained at 18 weeks to rule out cardiac malformations. Women need to understand the prognosis of Ebsteins anomaly. The literature suggerts that up to 50% of affected infants die in the first week of life. If lithium is used during pregnancy, it must be administered in several small doses to decrease the risk of toxicity associated with peak serum levels. Lithium levels should be monitored frequently. In the second trimester, higher doses may be necessary because of the increased glomerular filtration rate in the mother. Minimal effective serum levels should be maintained. The dosage should be reduced by at least 50% at the onset of labor to avoid toxicity due to abrupt falls in renal filtration rates and pronounced fluid shifting.

26. Is depression a problem in pregnant women? Several recent prospective studies have demonstrated an incidence of depression during pregnancy as high as 20%. Symptoms are generally of less severity than those observed with postpartum mood disorders. Risk factors for developing depression during pregnancy include prior history of depression, family history of mood disorders, negative feelings about the pregnancy, and unrelated bereavement. Impoverished social supports and negative life events are also risk factors.
27. Describe the management of women who experience depression during pregnancy. Despite the the relatively high number of women who experience depression during pregnancy, not all require pharmacotherapy. Many women develop minor depressive symptoms in the first trimester of pregnancy that are more consistent with an adjustment disorder. They usually respond to support, reassurance, and efforts to minimize psychosocial sources of distress. Pharmacotherapy is generally reserved for the most severe depressions characterized by neurovegetative dysfunction, including poor appetite and sleep disturbance. As with all psychotropic medications, the risks associated with pharmacotherapy must be weighed against the risks of withholding treatment. TCAs and SSRIs can be given to pregnant women requiring pharmacologic intervention. Nonbiological interventions including cognitive-behavioral therapy and interpersonal therapy have proven efficacy and may provide adequate support to delay initiation of medication. Serum TCA

Psychiatric Disorders and Pregnancy

359

levels should be monitored frequently as the pregnancy progresses and maternal fluid shifts occur. The medication may need to be tapered before or at the onset of labor to avoid adverse effects in the newborn. A severely depressed woman expressing suicidal intent andlor showing signs of nutritional or physical deterioration represents a psychiatric emergency. Electroconvulsive therapy is the treatment of choice in such patients, who require rapid response.

28. Describe the management of women with psychotic illnesses during pregnancy. Women with schizophrenia are at high risk of exacerbation during pregnancy and poor fetal outcome. For each month medication is withheld, approximately 10% of schizophrenics will relapse. It is estimated that 65% of unmedicated schizophrenics and 26% of those maintained on psychotropics will relapse during pregnancy. Schizophrenia is the most difficult psychiatric disorder to deal with both during pregnancy and in the postpartum period. Psychotic women often have exaggerated and distorted responses to the somatic changes associated with pregnancy. Not infrequently, psychotic denial of the pregnancy prevents participation in prenatal care. Health professionals caring for them may develop intense and conflicting feelings toward the patient, ranging from anger to sadness. When pregnancy is confirmed, if the patient is stable, a trial of no medication in the first trimester, with a plan to reinstitute treatment at the first sign of psychosis is recommended. A woman who first becomes psychotic during pregnancy should be thoroughly evaluated to identify reversible organic causes. Hospitalization or intense care management is desirable to ensure compliance with prenatal care and perhaps to reduce the total amount of medication required for adequate stabilization. High-potency neuroleptics, such as perphenazine or haloperidol, should be given at the minimal effective dose for controlling the most disabling symptoms. As with other psychiatric disorders, complete amelioration of symptoms is not the goal in managing a pregnant woman with schizophrenia. Maintenance of self-care and moderately good functioning are more realistic achievements. Antiparkinson agents, such as Cogentin or Artane, should be given in the smallest effective dose on an as-needed basis. A close obstetric-psychiatric liaison must be established and maintained throughout the pregnancy and postpartum period. When the patient is transferred to the obstetrics department for labor and delivery, she should be accompanied by psychiatrically trained nursing staff.

29. What issues are concerning postpartum in the schizophrenicmother?

During the postpartum period, schizophrenic mothers often demonstrate limited ability to attend to the infant or to recognize its needs. This should be anticipated by making provisions for supervised feedings and visits with the infant. The decision must be made about the appropriateness of a referral to child protective services for ongoing evaluation and monitoring of the mothers ability to care for her infant. If the mother shows gross inability or severely impaired reality testing, it may be necessary for the infant to be temporarily placed in foster care. Schizophrenic patients have an increased risk of postpartum psychotic decompensation. Extended hospitalization should be planned. Many schizophrenic mothers are unmarried and have impoverished support systems. Before discharge, arrangements for a visiting nurse and involvement of social agencies should be made. Note that contraception should be strongly encouraged to prevent a close succession of pregnancies in vulnerable women. Noncompliance with oral contraceptives and barrier methods is common. The patient should be informed of the availability of long-acting injectable preparations such as Depo-Provera and Norplant. The option of tuba1 ligation should be discussed.

30. How is the patient with anxiety disorder managed during pregnancy? Anxiety disorders are common in women and tend to aggregate in those of childbearing age. Historically, it was believed that pregnancy was a time of quiescence for women with pregravid histories of anxiety. More recent literature suggests that although pregnancy may ameliorate symptoms of panic disorder in some women, such conditions tend to worsen during pregnancy, especially in

360

Psychiatric Disorders and Pregnancy

the last trimester and postpartum period. For example, several studies have associated the onset of obsessive-compulsive disorder (OCD) with pregnancy and childbirth. Pre-existing disease typically is exacerbated by pregnancy. Women with moderate to severe symptoms of anxiety during pregnancy and delivery experience more complications. Preterm labor, preeclampsia, placental abruption, stillbirths, and fetal hypoxia have been reported. Such complications may be related to increases in catecholamine secretion, which result in transient elevations in blood pressure and vasoconstriction of the fetoplacental unit. The goal of managing anxiety-disordered women during pregnancy is to minimize risk to the mother and infant, not to achieve complete control of symptoms. Before instituting pharmacologic treatment, behavioral techniques such as progressive relaxation or biofeedback should be attempted. Such measures, in addition to supportive psychotherapy, may prevent the need for medication or at least minimize the required amount. If psychotropic medication is required, fluoxetine, sertraline, and paroxetine are options. The TCA nortriptyline is also an option. Benzodiazepines should be avoided, if possible. If employed, the smallest effective dose for the shortest period of time is the goal. A reduction of benzodiazepine and TCA doses may be required before the estimated date of confinement to avoid toxicity and/or withdrawal in the neonate.

31. Is electroconvulsive therapy safe for pregnant women? Electroconvulsive therapy (ECT) is an underutilized treatment modality in pregnant as well as nonpregnant patients. It is an excellent therapeutic alternative when psychotropic medications have failed or are contraindicated. ECT is considered the first-line treatment in pregnant women requiring a rapid therapeutic response. Studies suggest that ECT is safe for women in any stage of pregnancy. Mortality associated with ECT is less than that observed for inadequately treated depression during pregnancy. The ECT complication rate of 5-6% is less than that for untreated pregnant psychotic women and pregnant women without psychiatric illness. Finally, the rate of miscarriage in the general population is considerably higher than that observed in pregnant women undergoing ECT, suggesting that ECT does not increase the likelihood of miscarriage.

32. Describe the management of the pregnant patient undergoing ECT. The following steps decrease potential risk to the mother and fetus:
Pelvic examination to rule out vaginal bleeding or cervical dilation is performed before a course of ECT. The prolonged gastric emptying time in pregnant women increases the risk of aspiration. Nonessential anticholinergic medications are discontinued to avoid further slowing of gastric transit. A nonparticulate antacid, such as sodium citrate, is administered to raise gastric pH, and thus to minimize the risk of aspiration pneumonitis. After the first trimester, some anesthesiologists recommend intubation. Fetal circulation may be compromised if the gravid uterus is large and heavy enough to compress the inferior vena cava when the patient is in a supine position. Elevating the patients right hip to displace the uterus to the left can prevent this complication. Pretreatment intravenous hydration is also recommended. Excessive hyperventilation, usually done to lower the seizure threshold, is not recommended. Respiratory alkalosis in the mother hinders oxygen unloading from maternal to fetal hemoglobin. Fetal hypoxia is a real risk. Transient hypertension during a seizure may increase the risk for placental abruption. Intravenous Labetalol is recommended to control blood pressure. Self-limited fetal cardiac arrhythmias may occur during the seizure. External fetal cardiac monitoring is performed through the procedure and recovery period. An anticholinergic agent is administered before ECT to prevent excessive vagal bradycardia and to decrease oropharyngeal and tracheal secretions. Atropine, which quickly crosses the placental barrier, may produce fetal tachycardia. Glycopyrrolate has a more limited rate of transfer across the

Psychiatric Disorders and Pregnancy

36 1

placenta and thus reduces risk to the fetus; it is the preferred anticholinergic drug for pregnant patients undergoing ECT. Adequate relaxation in the mother is essential to prevent injury to the fetus. Fortunately, succinylcholine in ordinary doses does not cross the placenta.

33. How do psychotropic medications affect breastfeeding? The benefits of breastfeeding are well documented. Human milk possesses antimicrobial and unique trophic properties that benefit the infant. Breastfeeding enhances the process of maternal bonding. Unfortunately, the literature contains little information about psychotropic drug excretion in breast milk. However, all major classes of psychotropic drugs have been isolated in breast milk. Concentrations vary depending on the properties of the individual compound. Drugs that have protein binding tend to remain in the mothers plasma. Low-molecular-weight compounds and compounds with high lipid solubility diffuse into breast milk. Weak bases undergo ion trapping in the relatively acidic milk.
34. Discuss the effects of specific psychotropic agents on breast milk. Lithium concentration in breast milk is about 30-50% of that in the mothers serum. Because an infants regulatory and excretory mechanisms are not fully developed, toxicity is a real risk. Breastfeeding is contraindicated for women requiring maintenance lithium treatment. Carbamazepine and valproic acid are listed with the American Academy of Pediatrics as drugs considered compatible with breastfeeding. Valproic acid should be used with caution due to an associated risk of hepatotoxicity in infants. In general, benzodiazepinesshould not be given to breastfeeding mothers because of the risk of prolonging physiologic jaundice in the infant and because withdrawal syndromes have been observed in nursing infants exposed to benzodiazepines. However, intermittent, judicious use of benzodiazepines by highly anxious women is less likely to lead to accumulation and adverse effects in the nursing infant. Short-acting compounds lacking active metabolites (i.e., lorazepam) are preferred. Antidepressants should be used with caution in the nursing mother. Imipramine, nortriptyline, and desipramine are not excreted in breast milk in appreciable quantities. If a mother taking these medications insists on nursing her infant, care should be taken to minimize the infants exposure. This can be accomplished by having the mother take the medication immediately after the breastfeeding that precedes the infants longest period of sleep. The infant should be observed for signs of drug effect, such as sedation or inexplicable irritability. Fluoxetine is likely compatible with breastfeeding. While one case study revealed a lactating mothers infant developed watery stools, crying, and sleep disturbance, there is evidence that the infants hepatic metabolism was immature. The serum levels of fluoxetine and norfluoxetine in the infant were much higher than expected for the amount ingested by the mother. A case series of 11 nursing infants exposed to fluoxetine revealed no adverse effects. A similar case series for sertraline revealed no adverse effects in the infants exposed to the drug via breastmilk. If a mother requires antipsychoticmedication, she is best advised to bottle-feed her infant.
BIBLIOGRAPHY 1 . Altushuler LL, Cohen L, Szuba MP, et al: Pharmacologic management of psychiatric illness during pregnancy: Dilemmas and guidelines. Am J Psychiatry 1996;153(5):592-606. 2. Appleby L, Warner R, Whitton A, Faragher B: A controlled study of fluoxetine and cognitive behavioral counseling in the treatment of postnatal depression. BMJ 1997;314(7085):932-936. 3. Brunel P, Vial T, Roche I, et al: Follow-up on 151 pregnancies exposed to an antidepressant treatment (excluding MAOIs) during organogenesis. Therapy 1994;49:117-122. 4 . Burch KJ, Wells BG: Fluoxetinehorfluoxetine concentrations in human milk. Experienced Reason 1992; 676677. 5. Chambers CD, Johnson KA, Dick LM, et al: Birth outcomes in pregnant women taking fluoxetine. N Engl J Med 1996;335:1010-1015. 6. Chasnoff IJ, Bums WJ, Schnoli SH, Kayreen AB: Cocaine use in pregnancy. N Engl J Med 313:666-669, 19x5.

362

Psychiatric Disorders and Pregnancy

7. Chelmow D, Halfin VP: Pregnancy complicated by obsessive-compulsive disorder. J Maternal-Fetal Med 1997;6(1):31-34, 8. Cohen LS: The use of psychotropic drugs during pregnancy and the puerperium. Curr Affect Illness 11.9, 1992. 9. Cohen LS, Friedman JM, Jefferson JW, et al: A reevaluation of risk of in utero exposure to lithium. JAMA I994;27l(2):146-1 50. 10. Cohen LS, Rosenbaum JF: Birth outcomes in pregnant women taking fluoxetine (letter). N Engl J Med 1997;336(12):872. 11. Cooper PJ, Murray L, Stein A: Psychosocial factors associated with the early termination of breast-feeding. J Psychosom Res 1993;37(2):171-176. 12. Duffull SB, Begg EJ, Ilett KF: Fluoxetine distribution in human milk (letter). J Clin Pharmacol 1996;36(1I ) : 1078-1079. 13. Feingold M, Lyons, Kaminer Y,et al: Bulimia nervosa in pregnancy. Obstet Gynecol 71:1025-1027, 1988. 14. Flaherty B, Krenzelok EP: Neonatal lithium toxicity as a result of maternal toxicity. Vet Hum Toxicol 1997; 39(2):92-93. 15. Goldstein DJ: Effects of third-trimester fluoxetine exposure on the newborn. J Clin Psychopharmacol 1995; 15:417420. 16. Goldstein DJ, Corbin LA, Sundell KL: Effects of first-trimester fluoxetine exposure on the newborn. Obstet Gynecol 1997;89(5 Pt 1):713-718. 17. Goldstein DJ, Marvel DE: Psychotropic medications during pregnancy: Risk to the fetus. JAMA 1993;270 (18):2177. 18. Haynes JS: An update on psychotropic drugs in breastfeeding. Psychiatr Times June 1994. 19. Isenberg KE: Excretion of fluoxetine in human breast milk. J Clin Psychiatry 1990:51(4):169. 20. James M E Cocaine abuse during pregnancy: Psychiatric considerations. Oral presentation, 1990. 21. Kulin NA, Pastuszak A, Sage SR, et al: Pregnancy outcome following maternal use of the new selective serotonin reuptake inhibitors. JAMA 1998;279:609410. 22. Lester BM, Cucca J, Andreozzi BA, et al: Possible association between fluoxetine hydrochloride and colic in an infant. J Am Acad Child Adolesc Psychiatry 1993;32(6):1253-1255. 23. McCance-Katz EF: The consequences of maternal substance abuse for the child exposed in utero. Psychosomatics 32:268-274, 199I . 24. McIntosh R, Memtt KK, Richards MR, et al: The incidence of congenital malformations: A study of 5964 pregnancies. Pediatrics 1954;14:505-521. 25. McDonald AD: Maternal health and congenital defect. N Engl J Med 1958;258:767-774. 26. MeElhatton PR, Garbis HM, Elefant E, et al: The outcome of pregnancy in 689 women exposed to therapeutic doses of antidepressants. The collaborative study of the European network of the teratology information services (ENTIS). Reprod Toxicol 1996;10:285-294. 27. Miller LJ: Clinical strategies for the use of psychotropics during pregnancy. Psychiatr Med 2:275-298, 1991. 28. Milner G, OLeary MM: Anorexia nervosa occurring in pregnancy. Acta Psychiatr Scand 77:491492, 1988. 29. Miller LJ: Use of electroconvulsive therapy during pregnancy. Hosp Community Psychiatry 45:444450, 1994. 30. Misri S, Sivertz K: Tricyclic drugs in pregnancy and lactation: A preliminary report. Int J Psychiatry Med 1991;21(2):157-171. 31. Muqtadir S, Hamann MW: Management of psychotic pregnant patients in a medical-psychiatric unit. Psychosomatics 1986;27(1):31-33. 32. Murray L, Stein A: The effects of postnatal depression on the infant. Baillieres Clin Obstet Gynecol 1989; 3(4):921-933. 33. Nulman I, Rovet J, Stewart DE, et al: Neurodevelopment of children exposed in utero to antidepressant drugs. N Engl J Med 1997;336:258-262. 34. Numberg HG: An overview of somatic treatment of psychosis during pregnancy and postpartum. Gen Hosp Psvchiatrv 1989:l 1(5):328-338. 35. Number HG, Prudic J: Guidelines for treatment of psychosis during pregnancy. Hosp Community Psychiatry 35:67-71, 1984. 36. Oates MR: The treatment of psychiatric disorders in pregnancy and the puerperium. Clin Obstet Gynecol 13: 385-395, 1984. 37. OHara M W Social support, life events, and depression during pregnancy and the puerperium. Arch Gen Psychiatry 43569-573, 1986. 38. OHara MW, Schlechte JA, Lewis DA, Varner MW: Controlled prospective study of postpartum mood disorders: Psychological, environmental, and hormonal variables. J Abnorm Psycho1 1991;loo(1):63-73. 39. Pastuszak A, et al: Pregnancy outcome following first trimester exposure to fluoxetine. JAMA 269:22462248, 1993. 40. Rattan DA, Friedman T Antidepressants in pregnancy and breastfeeding. Br J Psychiatry 1995;167(6):824. 41. Repke JT, Berger NG: Electroconvulsive therapy in pregnancy. Obstet Gynceol 63:3941, 1984.

Postpartum Psychiatric Disorders

363

42. Riccardi VM: The genetic approach to human disease. New York, NY, Oxford University Press, 1977, pp 34. 43. Robert E: Treating depression in pregnancy. N Engl J Med 1996;335;1056-1058. 44. Roberts RJ, Blumer J, Gorman R, et al: Transfer of drugs and other chemicals into human milk. Pediatrics 84:924-936, 1989. 45. Robinson GE: The rational use of psychotropic drugs in pregnancy and postpartum. Can J Psychiatry 3 1 : 183-1 90, 1986. 46. Robinson L: Cognitive-behavioral treatment of panic disorder during pregnancy and lactation. Can J Psychiatry 37523-626, 1992. 47. Schou M: Lithium treatment during pregnancy, delivery and lactation: An update. J Clin Psychiatry 51:410412, 1990. 48. Sitland-Marken PA, Rickman L, Wells B, et al: Pharmacologic management of acute mania in pregnancy. J Clin Psychopharrn 9:78-87, 1989. 49. Spencer MJ: Fluoxetine hydrochloride (Prozac) toxicity in a neonate. Pediatrics 1993;92:721-722. so. Stewart DE, Raskin J, Garfinkel P, et al: Anorexia nervosa, bulimia and pregnancy. Am J Obstet Gynecol 157:1194-1198, 1987. 51. Susman VL, Katz JL: Weaning and depression: Another postpartum complication. Am J Psychiatry 145: 498-501, 1988. 52. Williams KE, Koran LM: Obsessive-compulsive disorder in pregnancy, the puerperium, and the premenstruum. J Clin Psychiatry 1997;58:33&334. 53. Willis DC, Rand CS: Pregnancy in bulimic women. Obstet Gynceol 71 :708-7 10, 1988. 54. Wisner KL, Perel JM: Serum levels of valproate and carbamazepine in breastfeeding mother-infant pairs. J Clin Psychopharmacol 1998;18:167-169. 55. Wisner KL, Perel JM, Blumer J: Serum sertraline and N-desmethylsertraline levels in breast-feeding motherinfant pairs. Am J Psychiatry 1998;155(5):690-692. 56. Wisner KL, Perel JM, Wheeler SB: Tricyclic dose requirements across pregnancy. Am J Psychiatry 1993;150(10):1541-1542.

64. POSTPARTUM PSYCHIATRIC DISORDERS

Doris C . Gundersm, M.D.

1. What psychiatric disorders are seen in the postpartum period? Maternity blues, postpartum psychosis, and postpartum depression are the psychiatric diagnoses most often made after delivery. 2. Define maternity blues. Maternity blues, or baby blues, is a term used to describe a self-limiting, relatively mild mood syndrome experienced by 30-80% of all postpartum women. Symptoms include lability of mood, anxiety, sadness, crying spells, insomnia, and fatigue. The onset of maternity blues is usually 3-10 days after parturition. The symptoms typically remit within 2 weeks.

3. Which risk factors predispose women to maternity blues? Many regard maternity blues as a normal postpartum phenomenon because of its frequency and
spontaneous remission. However, some women appear to be at higher risk. Major predictive factors include primiparous pregnancy, history of late luteal phase dysphoria (PMS), personal history of depression, or first-degree relative with depression.
4. What causes maternity blues? The precise cause of maternity blues is unknown. Because the condition is common in all cultures and races and appears to occur independently of psychosocial factors, a biologic cause is likely. Studies have demonstrated that estrogen and progesterone influence the sensitivity of neurotransmitter-binding sites much like chronic administration of antidepressant drugs. With the delivery of the