Benefits and Risks of Psychiatric

Medications During Pregnancy

Psychiatric symptoms and pregnancyPsychiatric symptoms and pregnancy

• their effect on the mother's emotional state

• functional status

• ability to obtain proper prenatal care

• potential to engage in dangerous behavior • effect on the infant's development and well-

being.

Difficulties in pregnancyDifficulties in pregnancy• Fear of teratogenesis

• Concern about subtle effects on infant’s neurodevelopment

• Altered pharmacokinetics across the three trimesters • Need to safeguard the smooth progress of labor and

delivery • Need to prevent withdrawal effects in the neonate

Individualizing Treatment DecisionsIndividualizing Treatment Decisions

• a history of previous psychiatric hospitalization (generally considered evidence of significant dysfunction)

• suicidality or similar self-destructive thoughts or behaviors

• an assessment of the patient's ability to meet home, educational, and occupational responsibilities.

• The natural history of symptoms and dysfunction during previous pregnancies and deliveries

Risks of Psychiatric MedicationsRisks of Psychiatric Medications

• Structural teratogenesis

• Behavioral Teratogenesis

• Perinatal syndromes

Perinatal Syndromes Reported with Perinatal Syndromes Reported with Classes of Psychiatric MedicationsClasses of Psychiatric Medications

• Tricyclic antidepressants: Jitteriness, irritability, seizures, tachypnea, tachycardia ,sweating, functional bowel obstruction, urinary retention

• SSRIs: Agitation, tachycardia

• Lithium: Hypotonicity, cyanosis • Benzodiazepines: Impaired temperature regulation, apnea, low

Apgar scores, hypotonicity; feeding difficulties

• Antipsychotics :Motor restlessness, tremor, feeding difficulties, hypertonicity, dystonic movements, parkinsonian movements

Depressive disordersDepressive disorders

• 10 to 16 percent of pregnant women meet diagnostic criteria for depression

• up to 70 percent of pregnant women have symptoms of depression.

• relapse rate of 68 percent in women who discontinue antidepressant therapy during pregnancy.

• Untreated maternal depression is associated with increased rates of adverse outcomes (e.g., premature birth, low birth weight, fetal growth restriction, postnatal complications), especially when depression occurs in the late second to early third trimesters

Low risk of relapse (postpartum)Low risk of relapse (postpartum)

• Without history of psychiatric illness

• Postpartum blues

• History of subsyndromal (minor) depression

• Past history of MDD, currently euthymic without medication

• History of a single episode of MDD, euthymic on medication after nine months or more of adequate treatment

• Emergence of first episode of MDD in a woman anticipating pregnancy within the next year

Moderate risk of relapse (postpartum)Moderate risk of relapse (postpartum)

• History of postpartum depression without recurrent nonpuerperal depression

• History of cyclothymia

• History of severe, recurrent MDD, euthymic following medication discontinuation

High risk of relapse (postpartum)High risk of relapse (postpartum)

• History of postpartum depression with recurrent MDD

• History of severe, recurrent MDD, euthymic on medication during pregnancy

• Emergence of depression during pregnancy

• History of bipolar disorder (I or II)

• History of puerperal psychosis

AntidepressantsAntidepressants

• Neither the TCAs nor fluoxetine has been associated with major teratogenic effects.

• a well-designed follow-up study revealed no evidence of behavioral teratogenicity with these agents after up to seven years of follow-up.

• There have been case reports of perinatal syndromes relating to all of these agents, but the effects appear to be mild, transient, and of questionable causation

• Paroxetine (Paxil) should be avoided by pregnant women and women who plan to become pregnant

• fewer data are available about novel agents such as venlafaxine (Effexor), nefazodone (Serzone), or bupropion (Wellbutrin).

• Limited data on the use of monoamine oxidase inhibitors are not reassuring, and use of these agents is not recommended during pregnancy.

Antidepressants and lactationAntidepressants and lactation • The combination of breastfeeding and SSRI use has not

been studied extensively; however, medication exposure from breastfeeding is less than the exposure that occurs transplacentally.

• transient apnea after being exposed to citalopram.

• no long-term neurobehavioral studies have been done in infants exposed to SSRIs through breast milk.

• Most tricyclic antidepressants seem to be safe during lactation except for doxepin , which reportedly led to an incident of infant respiratory depression.

Bipolar disorderBipolar disorder

• Rates of postpartum relapse in women with bipolar disorder range from 32 to 67 percent.

• Perinatal episodes of the disorder tend to be depressive and are more likely to recur in subsequent pregnancies.

• The risk of postpartum psychosis is increased by as much as 46 percent in women with this disorder.

Lithium TherapyLithium Therapy

• The use of lithium during pregnancy has been associated with congenital cardiac malformations, fetal and neonatal cardiac arrhythmias, hypoglycemia, premature delivery, and other adverse outcomes.

• neurobehavioral sequelae were not found

• The physiologic changes of pregnancy may affect the absorption, distribution, metabolism, and elimination of lithium, and close monitoring of lithium levels during pregnancy and the postpartum period is recommended.

Lithium Therapy guidelinesLithium Therapy guidelines

• Lithium therapy should be gradually tapered before conception in women who have mild, infrequent episodes.

•Lithium therapy should be tapered before conception, but gradually restarted after organogenesis in women who have more severe episodes and are at moderate risk of short-term relapse.

•Lithium therapy should be continued throughout the pregnancy in women who have severe, frequent episodes, and these patients should be counseled about the reproductive risks associated with therapy.

•Fetal echocardiography should be considered in women exposed to lithium in the first trimester.

lithium during breastfeedinglithium during breastfeeding

• lethargy, hypotonia, hypothermia, cyanosis, and electrocardiography changes

• No long-term studies have examined the neurobehavioral consequences of lithium therapy during breastfeeding.

Antiepileptic Therapy for Bipolar Antiepileptic Therapy for Bipolar DisorderDisorder

• Exposure to valproic acid during pregnancy is associated with an increased risk of neural tube defects, craniofacial and cardiovascular anomalies, fetal growth restriction, and cognitive impairment.

• Carbamazepine exposure during pregnancy is associated with

facial dysmorphism and fingernail hypoplasia.. • Although these drugs are superior to lithium in the treatment of

patients with mixed episodes or rapid cycling, they should be avoided during pregnancy.

• The use of lamotrigine during pregnancy has not been associated with any major fetal anomalies and is an option for maintenance therapy in women with bipolar disorder.

Antiepileptic Therapy and lactationAntiepileptic Therapy and lactation

• The American Academy of Pediatrics and the World Health Organization consider valproic acid safe in breastfeeding women.

• Carbamazepine is ruled “probably safe”; rare side effects include transient cholestatic hepatitis and hyperbilirubinemia

Anxiety DisordersAnxiety Disorders

• Anxiety disorders are the most common psychiatric disorders, and some are twice as likely to be diagnosed in women than in men.

• Pregnancy does not have a clear impact on the natural history of

anxiety disorders, although there is an apparent risk of susceptibility in the postpartum period.

• 24 Patients on maintenance pharmacotherapy for these disorders show high rates of relapse with medication discontinuation .

• Anxiety and stress during pregnancy are associated with spontaneous abortion, preterm delivery, and delivery complications, although a direct causal relationship has not been established.

BenzodiazepinesBenzodiazepines

• The use of benzodiazepines in women with anxiety disorders does not carry a significant teratogenic risk.

• Prenatal exposure to diazepam increases the risk of oral cleft, but the absolute

risk increases by only 0.01 percent (from six to seven in 10,000 infants).

• Maternal use of benzodiazepines shortly before delivery is associated with floppy infant syndrome (i.e., hypothermia, lethargy, poor respiratory effort, and feeding difficulties), and withdrawal syndromes may persist for several months after delivery in infants whose mothers took alprazolam, chlordiazepoxide, or diazepam.

• There is little data on behavioral teratogenesis, with a few reports suggesting developmental delay

• There are almost no data on the nonbenzodiazepine anxiolytic buspirone during pregnancy.

.

BenzodiazepinesBenzodiazepines

• If benzodiazepines are used during pregnancy, they should be avoided in the first trimester because of possible teratogenicity and before delivery because of an apparent perinatal syndrome.

• In women receiving chronic daily benzodiazepine

therapy who wish to conceive, medication should be weaned gradually (approximately 10 percent per week) and consideration given to cognitive behavior therapy or antidepressant therapy.

• The best-studied agents for use during pregnancy are alprazolam, clonazepam, and diazepam

BenzodiazepinesBenzodiazepines

• use of benzodiazepines during breastfeeding affects the infant only if he or she has an impaired ability to metabolize the drug.

In this situation, the infant may demonstrate sedation and poor feeding.

SchizophreniaSchizophrenia

• Chronic schizophrenia has an extremely high rate of relapse when medications are withdrawn.

• Adverse outcomes have been reported in women with schizophrenia, including preterm delivery, low birth weight, placental abnormalities, increased rates of congenital malformation, and a higher incidence of postnatal death.

• Pharmacologic treatment is guided by the woman's

psychiatric history, with continued maintenance treatment usually being the safest overall strategy

SchizophreniaSchizophrenia

• New-onset psychosis during pregnancy is a psychiatric and obstetric emergency.

• Careful diagnostic assessment to evaluate for psychiatric and organic disorders is necessary.

• Decisions regarding regular dosing or as-needed use of antipsychotics are guided by the patient's symptoms and the likely primary diagnosis.

Antipsychotic agentsAntipsychotic agents

• The reproductive safety data on atypical antipsychotics are limited, but the use of olanzapine, risperidone, quetiapine, and clozapine has been associated with increased rates of low birth weight and therapeutic abortion.

• No long-term studies of children exposed to atypical antipsychotics during gestation have been conducted.

Therefore, the routine use of these drugs during pregnancy and lactation is not recommended.

Antipsychotic agentsAntipsychotic agents

• Typical antipsychotics have a larger reproductive safety profile; no significant teratogenic effect has been documented with chlorpromazine, haloperidol, or perphenazine .

• Doses of typical antipsychotics should be minimized during the peripartum period to limit the necessity of using additional medications to manage extrapyramidal side effects.

Antipsychotic agentsAntipsychotic agents

• Data on antipsychotic use in breastfeeding women are limited.

• A small study of chlorpromazine use during breastfeeding showed no developmental deficits in children up to five years of age; however, a study of both chlorpromazine and haloperidol revealed developmental deficits in children 12 to 18 months of age.

GuidelinesGuidelines

• The patient's psychiatric history is the best predictor of future functioning. The patient's diagnosis, severity of previous episodes, necessity for medication, and responsiveness to medication are strong predictors of the need for medication to maintain remission.

• Patients with schizophrenia, bipolar disorder, severe chronic depression, and panic disorder with agoraphobia are generally at risk for a high degree of dysfunction and morbidity with relapse.

• Patients with disorders such as dysthymia, generalized anxiety disorder, or panic disorder without agoraphobia may experience less of an impact on their functional status.

GuidelinesGuidelines

• Nonpharmacologic therapies may eliminate or reduce the need for medications in some disorders.

• Cognitive behavior therapy for anxiety disorders and interpersonal psychotherapy and cognitive behavior therapy for depressive disorders have proved efficacious.

GuidelinesGuidelines

• When medications are used, those that are most appropriate for the patient's condition should be chosen. The SSRIs are usually the agents of choice in the treatment of depressive and anxiety disorders.

• When there is a choice, medications should be selected on the basis of existing data

GuidelinesGuidelines

• Collaboration and consultation with mental health professionals is an important aspect of treatment planning. Diagnosis, risk assessment, symptom monitoring, and optimal medication management can require special expertise and can be time intensive. Patients with chronic severe depressive and anxiety disorders, psychotic disorders, and bipolar disorders are particularly in need of specialty consultation and management.

GuidelinesGuidelines

• Psychotherapy, in addition to being an appropriate primary symptomatic treatment for some depressive and anxiety disorders, should be considered as a means of helping patients deal with issues related to their psychiatric disorder, pregnancy, and other life stresses

GuidelinesGuidelines

• The patient should be educated about the known benefits, risks, and uncertainties of pharmacotherapy, and informed consent should be documented in the medical record.

• Contacting regional or university-based

teratogenicity centers for up-to-date information on medications and as an additional source of risk counseling is another consideration.