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Psychotropic Pregnancy and Childhood
When a pregnant woman takes psychotropic medications during pregnancy, how does the
medication reach the fetus?
All psychotropic drugs presumably cross the placenta and are present in the amniotic fluid.
Exposure to psychopharmacotherapy during pregnancy can lead to what complications?

Embryonic and fetal exposure to maternal pharmacotherapy can cause:
• Miscarriage
• Major and minor structural malformations
• Fetal growth restriction and low birth weight
• Preterm delivery
• Neonatal toxicity and withdrawal
• Postnatal developmental effects upon behavior, cognition, and emotional regulation
Describe FDA Labeling for Medication during Pregnancy

Pregnancy category A -Adequate research has been done with the conclusion that drugs in this
category are not likely to cause any harm to the fetus in the first trimester as well as later in
pregnancy.
Pregnancy Category B - Studies carried out on animals have shown no adverse effects on the
fetus; however, there is a lack of controlled studies on human pregnancy.
Pregnancy category C -Animal studies have shown evidence of harmful effects on the
fetus;however, no controlled study has been done on a human pregnancy. The medicines may
beprescribed in cases where the potential benefits outweigh the possible adverse effects.
Pregnancy category D -Studies done on human pregnancy have shown positive risks to the
fetus. However, doctors might prescribe them in certain cases where the potential benefits
outweigh the risks.
Pregnancy category X - Both human and animal studies have shown positive risks to the
fetus,with the adverse effects extending to serious birth defects, miscarriage and fetal death.
Thepossible risks of using these medicines outweigh any potential benefits.
What are the risks for medication exposure in utero?

Teratogenicity (organmalformation) -> 1st trimester is mostvulnerable time
Neonataltoxicity/withdrawalsyndromes -> 3rd trimester most critical (short-term)
Behavioral teratogenicity(sequelae) -> Long-term
What are the pregnancy development makers for teratogenicity?

Baseline rate is 2-4%
Exposure during 1st 2 weeks: no defect, no placental connection
Formation of:
- Neural tube closure ≤ 4.5 weeks
- Heart/great vessels 3-8 weeks
- Lip/palate 6-9 weeks
Most women learn they are pregnant at 5-6 weeks.
MUST discuss pregnancy risks with every woman of childbearing age.
What are the risk of untreated maternal mental illness?

• Poor compliance with prenatal care
• Inadequate nutrition
• Exposure to undesired drugs, medications, or herbs
• Increased alcohol, caffeine, and tobacco use
• Deficits in mother-infant bonding
• Disruptions in the family environment
What are the benefits and risks of psychotropic medication in pregnancy?

Pregnancy does not protects against mental disorders
Untreated maternal mental illness may adversely affect obstetrical outcome
Known risks of mental disorder must be weighed against largely unknown risks of medication
What are the benefits of breast feeding?

Child health
- Reduced rates of infectious diseases
- Reduced infant mortality
- Reduced rates of diabetes,lymphoma, leukemia, Hodgkin disease,
obesity,hypercholesterolemia, asthma
Maternal health
- Decreased risk of breast and ovarian cancers
What should you know about psychotropic medications and breast feeding?
The post-partum period is a high-risk time for onset/relapse/recurrence ofmental disorders.
All psychotropics are excreted into breast milk to some degree.
Hepatic capacity of newborns - ⅕ adult capacity during first 2 weeks of life
Babies can be genetically slow (or fast) metabolizers: in utero exposure toenzyme inhibitors (or
inducers) can affect metabolism
No psychotropic is FDA-approved for use during breastfeeding.
Untreated maternal illness may affect mother-infantattachment and infant development.
Generally, total dose of drug ingested via breast mild is quite small.
What are the therapeutic goals of psychotropic therapy in pregnancy?

Eliminate the child's exposure to maternal illness by achieving clinicalremission, WHILE
Minimizing the child's exposure to psychotropic medication.
Which psychotropic medications cause major congenital malformations?

The estimated risk of major congenital malformations appears to vary among psychotropic
medications; the rank order from greatest to least teratogenic risk is:
• Valproate
• Carbamazepine
• Lithium
• Lamotrigine
• Antipsychotics
• Antidepressants
What are the risk of depression in pregnancy?

Risks of Depression inPregnancy:
• Poor prenatal care, nutrition,sleep

• Substance abuse
• Suicide
• Obstetrical complications
• Postpartum irritability
Which 2 antidepressants have shown risk of spontaneous abortions?

• Paroxetine
• Venlafaxine
What dosage adjustments may be needed in pregnancy with antidepressants?

Decreased gastric motility, increased extracellular fluid space and total body water, decreased
albumin concentration, increased activity of CYP 2C19,2D6 and 3A4
All can affect drug levels
Pregnant women may need increased dosages of SSRIs or TCAs
What are the risk or taking antidepressants during pregnancy related to neonatal
toxicity/withdrawal?
SSRI discontinuation syndrome: observed in offspring of mothers who used SSRI-type
antidepressants during third trimester
• Anticholinergic side effects• Withdrawal symptoms (tachypnea, tachycardia, hypertonia,clonus,

spasm)
• Rarely, convulsions
• Occurs in 30 of exposed neonates
• Symptoms are usually mild and gone by 2 weeks of age
• A severe syndrome with seizures, dehydration, excessive weight loss, hyperpyrexia and
intubation in 1/313 cases
What are the guidelines for the use of antidepressants during pregnancy?
Medication is first line treatment only if -> Depression is severe -> The likelihood for
relapse/recurrence is high
Psychotherapy alone is recommended for milder depression
What are the risks of post partum depression to the infant?

Less positive and more negative affect
• Compromised ability to self regulate
• Lower activity levels
• Decreased engagement in social and object interactions
• Increased physiological reactivity

- Heart rate
- Cortisol levels
• Impaired cognitive development at ages 1-11yrs
Which antidepressants should you monitor during lactation?

• Nortriptyline, paroxetine, sertraline, escitalopram usually produce undetectable infant levels
• May be preferred
• Fluoxetine may accumulate due to its long half-life
• Citalopram may be less desirable because of the potentially high breast milkconcentration
What are the recommendations for antidepressants during lactation?

• Obtain a thorough baseline exam
• Use low-dose, shorter-actingmedication
• Limit total number of medications (1 is better than 2)
• Time breastfeeding to minimize exposure - prior to scheduled medication
• Consider psychotherapy if depression is mild
What are the risk for untreated bipolar disorder in pregnant women?
Untreated maternal mood disorders are serious risk factors for the fetus.
• Risks of untreated bipolar disorder in the pregnant female:
• Impulsivity and impaired judgments

• Poor self-care
• Drug and alcohol abuse
• Manic episodes
• Interpersonal life interruptions
What is the teratogenicity of mood stabilizers?
Lithium: a modest teratogen, some risk of cardiac malformations.
• Valproic acid (Depakote): highest risk of major congenital malformations
• Carbamazepine (Tegretol, Equitro): slightly teratogenic,risk of adverse fetal outcomes

increased 3%.
• Lamotrigine (Lamictal): not considered a major teratogen, slight increase risk for cleft
lip/palate.
• Topiramate (Topamax): associated with increase in major congenital malformations, including

oral clefts and penile malformations.
What supplements should pregnant women be prescribed when taking Valproic Acid during
pregnancy?
All women of childbearing potential who are prescribed VPA should receive folate
supplementation (4-5 mg/day)
Folate supplementation, from preconception through the 1st trimester,decreases the risk of
neural tube defects generally, but has not been tested in women taking antiepileptic drugs.
What are the neonatal toxicity risks for taking valproic acid in pregnancy?
• Heart rate decelerations
• Withdrawal syndrome (irritability, jitteriness, feeding difficulties, abnormal tone)
• Hepatotoxicity
• Hypoglycemia
• Reduced fibrinogen levels
Carbamazepine is associated with what fetal defects?

CBZ is associated with a fetal anticonvulsant syndrome including facial abnormalities
What supplements should pregnant women be prescribed when taking Carbamazepine during
pregnancy?
Women on CBZ during pregnancy should receive vitamin K, 20mg/day during the last month to
prevent fetal prenatal bleeding
• Vitamin K 1mg IM should be administered to the neonate
What are the neonatal toxicity risks of antipsychotics in pregnancy?

Chronic administration of antipsychotics during the third trimester may cause symptoms of
neonatal toxicity and withdrawal,including:
• Abnormal movements (dyskinesia),Abnormally increased or decreased muscle tone, Agitation,

Crying,Hyperactivity, Hyperreflexia,Irritability, Motor restlessness,Sedation, Tremor,
Hypotension,Tachycardia, Difficulty breathing,Difficulty feeding, Gastrointestinal dysfunction
(e.g., functional bowel obstruction)
Extrapyramidal symptoms (e.g., abnormal movements,restlessness, and tremor) may be more

likely to occur with first-generation antipsychotics and risperidone hanwith other
second-generation antipsychotics.
• Symptoms typically subside within hours to days, but may persist for weeks to months after
birth.
• Specific treatment is usually not necessary, but more severely affected newborns may require
longer hospital stays
Are benzodiazepines safe to use in pregnancy?

no- category D (risk of cleft lift/palate)

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Psychotropic Pregnancy and Childhood

Exposure to psychopharmacotherapy during pregnancy can lead to what complications?

Describe FDA Labeling for Medication during Pregnancy

What are the risks for medication exposure in utero?

Behavioral teratogenicity(sequelae) -> Long-term

What are the pregnancy development makers for teratogenicity?

Exposure during 1st 2 weeks: no defect, no placental connection

Most women learn they are pregnant at 5-6 weeks.

MUST discuss pregnancy risks with every woman of childbearing age.

What are the risk of untreated maternal mental illness?

What are the benefits and risks of psychotropic medication in pregnancy?

Untreated maternal mental illness may adversely affect obstetrical outcome

What are the benefits of breast feeding?

All psychotropics are excreted into breast milk to some degree.

Hepatic capacity of newborns - ⅕ adult capacity during first 2 weeks of life

No psychotropic is FDA-approved for use during breastfeeding.

Untreated maternal illness may affect mother-infantattachment and infant development.

What are the therapeutic goals of psychotropic therapy in pregnancy?

Minimizing the child's exposure to psychotropic medication.

Which psychotropic medications cause major congenital malformations?

What are the risk of depression in pregnancy?

• Poor prenatal care, nutrition,sleep

Which 2 antidepressants have shown risk of spontaneous abortions?

What dosage adjustments may be needed in pregnancy with antidepressants?

All can affect drug levels

Pregnant women may need increased dosages of SSRIs or TCAs

• Anticholinergic side effects• Withdrawal symptoms (tachypnea, tachycardia, hypertonia,clonus,

Psychotherapy alone is recommended for milder depression

What are the risks of post partum depression to the infant?

• Compromised ability to self regulate

• Lower activity levels

• Decreased engagement in social and object interactions

• Increased physiological reactivity

• Impaired cognitive development at ages 1-11yrs

Which antidepressants should you monitor during lactation?

• Fluoxetine may accumulate due to its long half-life

What are the recommendations for antidepressants during lactation?

• Risks of untreated bipolar disorder in the pregnant female:

• Impulsivity and impaired judgments

• Valproic acid (Depakote): highest risk of major congenital malformations

• Carbamazepine (Tegretol, Equitro): slightly teratogenic,risk of adverse fetal outcomes

• Topiramate (Topamax): associated with increase in major congenital malformations, including

• Withdrawal syndrome (irritability, jitteriness, feeding difficulties, abnormal tone)

• Reduced fibrinogen levels

Carbamazepine is associated with what fetal defects?

• Vitamin K 1mg IM should be administered to the neonate

What are the neonatal toxicity risks of antipsychotics in pregnancy?

• Abnormal movements (dyskinesia),Abnormally increased or decreased muscle tone, Agitation,

Extrapyramidal symptoms (e.g., abnormal movements,restlessness, and tremor) may be more

Are benzodiazepines safe to use in pregnancy?

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