Major Depressive Disorder

Box 51-1 includes diagnostic criteria for major depressive disorder. Although depression is recognized as being relatively common during pregnancy, many of its symptoms (e.g., weight gain, appetite changes, sleep disturbances, fatigue) must be differentiated from symptoms that may occur during normal pregnancy. Risk factors for depression during pregnancy include a history of depression or bipolar disorder, childhood mistreatment, being a single mother or having more than three children, marital problems, unwanted pregnancy, smoking, low income, age younger than 20 years, poor social support, and domestic violence.^7,8 The risk for major depressive illness is increased in women who have a miscarriage (i.e., spontaneous abortion); this most frequently occurs in the first month after miscarriage and is more likely to occur in women who are childless or who have a prior history of major depressive disorder.⁹ Depression during pregnancy is associated with an increased risk for poor obstetric outcomes such as miscarriage, preterm birth, and low birth weight.¹⁰

Bipolar (Manic-Depressive) Disorder

Patients with bipolar disorder (BPD) have episodes of major depression with other distinct periods of mania or hypomania. A strong familial association exists. Diagnostic criteria for mania are summarized in Box 51-2. BPD in pregnancy is particularly important because there is a strong link between discontinuation of medication and relapse of BPD and a relatively high suicide rate among patients. Treatment of BPD typically consists of mood stabilizer and antipsychotic medication, with psychotherapy as an adjunct.¹¹ Electroconvulsive therapy (ECT) is very effective for patients with BPD and severe depression.

Postpartum Depression

Postpartum depression describes a major depressive episode that occurs in the first 4 to 6 weeks after birth. Symptoms do not differ from those of depression occurring at other times. There may be accompanying psychotic features, which are thought to be more common in nulliparous women,^4,12 and there is a high risk for recurrence in subsequent pregnancies. It is important to differentiate postpartum depression from the “baby blues,” which affects up to 70% of women in the first 10 days after delivery and is transient without func­tional impairment. It is also important to differentiate postpartum depression from delirium that arises from physical causes.⁴ In a systematic review, Robertson et al.¹³ showed that the strongest predictors of postpartum depression were (1) depression, anxiety, or stressful life events occurring during pregnancy or the early puerperium; (2) low levels of social support; and (3) previous history of depression. Biologic effects such as hormonal changes and psychologic and social role changes that occur with childbirth may increase the risk for postpartum depression.¹⁴

Postpartum Psychosis

Postpartum psychosis occurs within 2 weeks of approximately 1 to 2 per 1000 live births; a relatively high risk continues for the first 3 months postpartum.¹⁵ The risk is higher in patients with a history of BPD or a history of previous postpartum psychosis,¹⁶ as well as in women with major depression and schizophrenia. Typical features include prominence of cognitive symptoms such as disorganization, confusion, impaired sensorium, disorientation, and distractibility.¹⁵ Infanticide may be associated with command hallucinations to kill the infant or delusions that the infant is possessed.¹²

Panic Disorder

Panic disorder is characterized by the occurrence of recurrent, unexpected panic attacks. Affected women experience discrete episodes of intense fear or discomfort in the absence of a true danger; these episodes are accompanied by somatic or cognitive symptoms such as palpitations, sweating, shaking, dyspnea, choking, chest pain, nausea, paresthesias, chills, and/or flushes. Typically there is a rapid onset and peak of symptoms that may be accompanied by an urge to escape.⁴ It is important to be aware of the possibility that panic attacks may occur during preparation of a patient for cesarean delivery. Panic attacks with hyperventilation may mimic systemic local anesthetic toxicity.¹⁹ A possible role of lactated Ringer’s solution as a trigger has been refuted.²⁰ Patients with panic disorder often have co-morbid major depression.¹⁷

Post-traumatic Stress Disorder

Post-traumatic stress disorder (PTSD) occurs after the experience of a traumatic event that evokes intense fear or helplessness.¹ Pregnancy and childbirth may exacerbate symptoms of PTSD. Symptoms of PTSD are more common after emergency cesarean delivery than after other modes of delivery,²¹ and PTSD has resulted from (1) awareness during general anesthesia,²² (2) inadequate regional anesthesia for cesarean delivery,²³ and (3) inadequate pain control during vaginal delivery.²³ The risk for PTSD may be increased if the pregnancy has resulted from rape or if memories of sexual trauma are triggered. It has been suggested that the childbirth experience itself can precipitate PTSD with a resulting fear of pregnancy termed tocophobia.¹ Fear of vaginal delivery may be a factor that contributes to maternal request for cesarean delivery.²¹

Obsessive-Compulsive Disorder

Obsessive-compulsive disorder (OCD) is characterized by the presence of obsessions (intrusive thoughts or images) and compulsions (repetitive or ritualistic behaviors or thought patterns).¹⁷ Pregnancy is a potential trigger of the onset of symptoms.¹ Classically, pregnant women with OCD may focus on protection of the fetus, which may manifest as cleaning and checking compulsions.¹⁸ Care should be taken to identify infanticidal ideation.¹⁷

Personality Disorders

Personality disorders have high prevalence rates of approximately 10% in the general population and up to 40% among psychiatric patients.²⁴ The DSM 5 lists 10 specific personality disorders that are grouped into three clusters based on descriptive similarities. Patients in cluster A (paranoid, schizoid, schizotypal) appear odd or eccentric; patients in cluster B (antisocial, borderline, histrionic, narcissistic) appear dramatic, emotional, or erratic; and patients in cluster C (avoidant, dependent, obsessive-compulsive) appear anxious and fearful.⁴ There is also one further category, personality disorder not otherwise specified. The DSM-5 also provides an alternative dimensional model for personality disorders based on both personality functioning and pathologic personality traits that takes the perspective that personality disorders represent maladaptive variants of personality traits that merge into normality and into one another.⁴ This accounts for the observation that patients who meet criteria for a specific personality disorder frequently also meet criteria for other personality disorders.⁴

Pseudocyesis

Pseudocyesis is a clinical syndrome in which a woman firmly believes that she is pregnant in the absence of a true gestation. Patients may develop convincing signs and symptoms suggestive of pregnancy, including abdominal enlargement and menstrual disturbance.²⁵ Diagnosis can be made using a pregnancy test and ultrasonography. Physical diagnoses should be excluded. For example, tumors such as bronchogenic carcinoma may produce hormones (e.g., human chorionic gonadotrophin [hCG]) that can cause secondary amenorrhea, which may be confused with pregnancy.²⁶

Denial of Pregnancy

In contrast to pseudocyesis, denial of pregnancy is more common, with an estimated incidence of 1 in 400 to 516 pregnancies.²⁷ It may be associated with adverse outcomes, including psychological stress, unassisted delivery, and infanticide. Patients who are identified should be referred for psychiatric assessment.²⁷

Substance Abuse

Substance abuse during pregnancy is covered in Chapter 54.

General Considerations

Treatment options for different psychiatric disorders overlap. Data are limited on pregnancy-specific efficacy, but, in general, response in pregnant patients is thought to be similar to that in nonpregnant patients.¹ There is often concern about potential harmful effects of psychotropic drugs given during pregnancy and lactation, particularly the potential for teratogenicity, perinatal syndromes, neonatal toxicity, and abnormal postnatal behavioral development.¹² Because of the difficulties of performing experimental studies in this area, inadequate data are available from randomized controlled trials, and much of the available information is based on observational studies, which provide a less-than-optimal level of evidence. Because many patients with psychiatric disorders also smoke or abuse illicit substances, it can be difficult to separate the effects of psychiatric drugs on the fetus from the effects of these other substances and other behavioral factors.⁸ Further, because women who take medication for their psychiatric disorders are likely to have more severe disease than women who do not, some of the risks associated with psychiatric drugs may be attributable to factors associated with the more severe disease (i.e., confounding by indication).⁷ These considerations are important because the risks of withholding psychiatric drugs in pregnancy must always be balanced against the risks and potential harm of exacerbation of psychiatric disorders that can result from cessation or withholding of treatment.

General recommendations for the management of women with psychiatric disorders include the following⁶: (1) a psychiatric history should be identified prenatally, and even if affected patients are well, they should be frequently monitored and supported during pregnancy and the first few weeks postpartum; (2) psychiatric services should have priority-care pathways for pregnant and postpartum women; and (3) care by multiple psychiatric teams should be avoided. Conversely, care should be taken to avoid misattribution of physical symptoms to psychological causes in patients with no psychiatric history and other concurrent disease. Consensus guidelines for the treatment of depression during pregnancy are available from the APA and the American College of Obstetricians and Gynecologists (ACOG).¹⁴ The National Institute for Health and Clinical Excellence (NICE) in the United Kingdom has also published guidelines for antenatal and postnatal mental health.²⁸ All patients with psychiatric disorders, particularly those with acute or postpartum psychosis, should be carefully screened for thoughts of harm to themselves and/or their infants.

A multidisciplinary approach is essential in the management of pregnant patients with psychiatric disorders, especially because many anesthesia providers may not be familiar with management of these patients. Patients who are noncooperative or violent may be challenging and require patience, compassion, and emotional support. Flexibility in management is important. For example, general anesthesia may sometimes be required if neuraxial anesthesia is considered not practical or unsafe. Consent and medicolegal issues are covered in Chapter 33.

Psychotherapy and Light Therapy

These nonpharmacologic options are effective particularly for treatment of anxiety disorders and depression but are underinvestigated.¹ They have the advantage of nonexposure to potentially teratogenic drugs. Psychotherapy techniques include cognitive-behavioral therapy and interpersonal psychotherapy. A randomized controlled trial demonstrated that light therapy (fluorescent white light for 1 hour per morning for 5 weeks) improved antenatal depression compared with placebo.²⁹

Psychotropic Drugs

Box 51-3 includes principles related to the use of psychiatric medications during pregnancy. The use of nonanesthetic drugs during pregnancy and lactation is discussed in Chapter 14.

Selective serotonin uptake inhibitors (SSRIs), which include sertraline (Zoloft), paroxetine (Paxil), fluoxetine (Prozac), and citalopram (Celexa) are a mainstay therapy for depression and anxiety. Some concerns have been raised about a possible association between their use in pregnancy and an increased risk for birth defects, although data are conflicting. In a large multicenter evaluation, Louik et al.³⁰ found no overall association between first-trimester maternal use of SSRIs and birth defects; however, analysis of individual drugs showed small but significant associations between the use of sertraline and omphalocele and cardiac septal defects and between the use of paroxetine and right ventricular outflow tract obstruction. Other studies have also found associations between use of SSRIs and these and other birth defects, including craniosynostosis, anencephaly, and persistent pulmonary hypertension of the newborn.⁷ Exposure to SSRIs in the third trimester has been associated with an increased risk for perinatal complications, including preterm delivery, admission to the special care nursery, poor neonatal adaptation, and lower birth weight and length.³¹ Of note, the absolute risk of exposure to SSRIs during pregnancy is considered to be small, and overall these drugs are not considered major teratogens.¹² However, the ACOG¹² has recommended that paroxetine should be avoided by pregnant women and women planning pregnancy, if possible, and fetal echocardiography should be considered for women who are exposed to paroxetine in early pregnancy. Serotonin syndrome (i.e., agitation, restlessness, hallucinations, increased body temperature, vomiting) may occur with an overdose or a combination of serotonergic drugs.³²

Serotonin-norepinephrine reuptake inhibitors (SNRIs) are a class of drugs related to SSRIs that are also considered relatively safe in pregnancy, although fewer reassuring data are available for this class of drug than for SSRIs.⁷

Tricyclic antidepressants have a long history of use and have generally been considered safe to use in pregnancy. However, a large review of data from the Swedish Medical Birth Registry reported that these drugs were associated with a greater risk for congenital malformations compared with other antidepressants.³³ Tricyclic antidepressants may have anticholinergic side effects, especially after overdose; clinical features include dilated pupils, agitation, seizures, delirium, hyperthermia, and arrhythmias. The fatality risk after overdose is greater with most tricyclic antidepressants than with SSRIs. Tricyclic antidepressants have been largely replaced by SSRIs and SNRIs as first-line therapy for depression.

Routine prescription of benzodiazepines for pregnant women is typically avoided, except for short-term treatment of extreme anxiety and agitation, because of concern for risks including oral clefts, floppy baby syndrome, and neonatal withdrawal syndrome.^12,28 The risk for oral clefts is a matter of dispute.¹² If benzodiazepine use is discontinued during pregnancy, this should not be done abruptly.¹²

Lithium is a foundation therapy for management of BPD. Early studies reported that use of lithium in early pregnancy was associated with an increased risk for congenital malformations, with particular concern for cardiac abnormalities, especially Ebstein’s anomaly. Although the risk now appears to be less than initially thought, it has been recommended that women who are exposed to lithium in the first trimester undergo fetal echocardiography. Exposure in later gestation has been associated with fetal and neonatal diabetes insipidus, polyhydramnios (thought to occur from fetal diabetes insipidus), thyroid dysfunction, cardiac arrhythmias, hypoglycemia, preterm delivery, and floppy baby syndrome.¹² Renal clearance of lithium is increased in pregnancy, and a reduced serum lithium concentration may result in a relapse of symptoms; therefore, serum levels should be closely monitored in pregnant women who are taking lithium. Discontinuation of lithium is associated with a high risk for recurrent illness, particularly in the postpartum period.

Anticonvulsant drugs are often used as mood stabilizers in patients with BPD. Valproate use in pregnancy is associated with an increased risk for many congenital anomalies (e.g., craniofacial, limb, cardiovascular abnormalities) and a variable risk for cognitive impairment.¹ A meta-analysis showed that the risk for neural tube defects in infants of mothers taking valproate was 3.8% and that the risk for major congenital malformations was dose-related, with the risk particularly high when the daily dose exceeded 1000 mg.³⁴ Fetal valproate syndrome, which includes fetal growth restriction (also known as intrauterine growth restriction), facial dysmorphology, and limb and heart defects, has been described.¹² Carbamazepine has also been associated with congenital abnormalities, although with less frequency or severity compared with valproate.¹ Fetal carbamazepine syndrome, which includes facial dysmorphism and fingernail hypoplasia, has been described.¹² Lamotrigine appears to be associated with less fetal risk than occurs with valproate and carbamazepine.^1,12 Folate supplementation is sometimes offered to patients taking anticonvulsants to reduce the risk for neural tube defects.

Typical antipsychotic drugs (e.g., haloperidol, thioridazine, fluphenazine, perphenazine, chlorpromazine, trifluoperazine) have a long history of use in pregnant patients and generally have minimal teratogenic effects.¹² The phenothiazines are also used for their antiemetic effects. Fetal and neonatal toxicity after maternal exposure can include dyskinesia, extrapyramidal side effects, neonatal jaundice, and postnatal intestinal obstruction. The neuroleptic malignant syndrome is of particular interest to anesthesia providers because of its similarity to malignant hyperthermia. Features include hyperthermia, rigidity, mental status alteration, creatine kinase elevation, sympathetic nervous system lability, tachycardia, and tachypnea.³⁵ Treatment is largely supportive and includes discontinuation of triggering agents, antipyretics, cooling, rehydration, and management of autonomic instability. Use of dantrolene, bromocriptine, and amantadine has been described.³²

Atypical antipsychotic drugs (e.g., clozapine, olanzapine, quetiapine, risperidone, ziprasidone, aripiprazole) are now commonly used for schizophrenia and also for BPD, OCD, and resistant depression. Although these drugs are well tolerated, fewer data about repro­ductive safety are available, when compared with older drugs.

Drug Interactions

A number of drug interactions involving psychiatric drugs are relevant to anesthesia providers. The most important of these involve monoamine oxidase inhibitors (MAOIs), which include older irreversible drugs (e.g., phenelzine, tranylcypromine) and newer reversible drugs (e.g., selegiline, moclobemide). Potential interactions include (1) hypertension after administration of an indirect-acting vasopressor (e.g., ephedrine, metaraminol), which results from increased norepinephrine concentration in sympathetic nerve endings, and (2) excitatory interactions associated with serotonin toxicity. The latter are characterized by clonus, hyperreflexia, hyperthermia, and agitation and may be precipitated by co-administration of an MAOI and a serotonin uptake inhibitor. Of note, phenylpiperidine opioids, especially meperidine (pethidine), but also tramadol, methadone, and dextromethor­phan, are weak serotonin uptake inhibitors and have been implicated in toxic reactions associated with MAOIs, including hyperpyrexic coma. Irreversible MAOIs should be stopped 2 weeks before administration of anesthesia to allow regeneration of MAO and restoration of normal monoamine metabolism, and reversible MAOIs should be stopped for 24 hours before administration of anesthesia.³⁶

Electroconvulsive Therapy

Electroconvulsive therapy (ECT) is considered an important treatment option in the pregnant patient with psychiatric disease, especially when balancing the risk for morbidity from psychiatric illness and the poten­tial adverse effects of psychiatric drugs. The APA has endorsed the use of ECT in all three trimesters of pregnancy.³⁷ Indications include major unipolar or bipolar depressive episodes, mania, and certain acute schizophrenia exacerbations. Acute suicide risk, poor response to medications, and patient preference may also affect the decision to use ECT.³⁸ Contraindications include anticipated intolerance of associated physiologic changes that result from autonomic activation during ECT (e.g., increased intracranial pressure). Relative contraindications include hypertensive disease and impaired uteroplacental perfusion.

There is a paucity of controlled data evaluating the use of ECT in pregnancy, with most information coming from case series. In a series of 300 published cases of ECT in pregnancy between 1942 and 1991, Miller³⁹ reported complications in 28 (9.3%) cases, which included self-limited fetal heart rate abnormalities (five cases), vaginal bleeding, uterine contractions, abdominal pain, spontaneous abortion, preterm labor, stillbirth, and neonatal death. The overall incidence of spontaneous abortion was 1.6%—a rate much lower than that in the general population—suggesting that ECT is not a significant risk factor for spontaneous abortion. There were five cases of congenital anomalies, but neither the pattern nor the number of anomalies suggested that ECT was a determining factor. The author concluded that ECT was effective and that the risks to both mother and fetus are low. However, Pinette et al.⁴⁰ reported a case of deep cerebral interhemispheric infarcts in a neonate whose mother had received ECT during pregnancy. After a review of fetal and neonatal risks, the authors recommended that ECT in pregnancy should be performed specifically according to APA guidelines and only after medical therapy has failed.

ECT for pregnant patients should be administered in a facility that can handle fetal emergencies. Anesthetic agents commonly used during ECT include barbiturates, succinylcholine, and anticholinergics (e.g., glycopyrrolate); these agents have a long history of use during pregnancy. Suggested guidelines for ECT during pregnancy are summarized in Box 51-4. These guidelines include left uterine displacement and both fetal heart rate and uterine monitoring. Pharmacologic aspira­tion prophylaxis and tracheal intubation should be considered in patients with symptoms of gastroesophageal reflux. Some anesthesia providers contend that tracheal intubation should be performed after 20 weeks’ gestation, when the enlarging uterus has arisen out of the pelvis.