use of psychotropic medicines during pregnancy

1. Use of Prescribed Psychotropics during
Pregnancy
Dr Riaz.K.M, Assistant Professor
Government College of Nursing, Thrissur.

2. Introduction
• According to the World Health Organization, high-income countries
dominate global pharmaceutical consumption
• 16% percent of the world’s population living in high-income countries
accounts for over 78% of global expenditures on medicines
• Wealthy countries purchase and consume approximately 90% of total
medicines (by value).

3. Introduction
• Globally, maternal mental health problems are considered as a major
public health challenge, which requires a stronger focus on mental health
services that will benefit both mother and child.
• More preclinical and clinical research is needed in order to make well-
informed decisions, understanding the risks associated with the use of
psychotropic medications during pregnancy
• The most frequently prescribed medications are analgesics,
antihyperlipidemics and antidepressants

4. Drug Categories in Pregnancy
• Category A
• Category B
• Category C
• Category D
• Category X

5. Drug Categories in Pregnancy
• Category A
• Adequate and well-controlled studies have failed to demonstrate a risk
to the fetus in the first trimester of pregnancy (and there is no evidence
of risk in later trimesters).

6. Drug Categories in Pregnancy
• Category B
• Animal reproduction studies have failed to demonstrate a risk to the
fetus and there are no adequate and well-controlled studies in pregnant
women.

7. Drug Categories in Pregnancy
• Category C
• Animal reproduction studies have shown an adverse effect on the fetus
and there are no adequate and well-controlled studies in humans, but
potential benefits may warrant use of the drug in pregnant women
despite potential risks.

8. Drug Categories in Pregnancy
• Category D
• There is positive evidence of human fetal risk based on adverse
reaction data from investigational or marketing experience or studies
in humans, but potential benefits may warrant use of the drug in
pregnant women despite potential risks.

9. Drug Categories in Pregnancy
• Category X
• Studies in animals or humans have demonstrated fetal abnormalities
and/or there is positive evidence of human fetal risk based on adverse
reaction data from investigational or marketing experience, and the
risks involved in use of the drug in pregnant women clearly outweigh
potential benefits.

10. Prenatal exposure leads to,
• Teratogenicity,
• Neurodevelopmental effects,
• Neonatal toxicity,
• Long term neurobehavioral consequences (i.e., behavioral
teratogenicity).

11. Pharmacotherapy in pregnancy
Decisions regarding drug choice, dose, and duration is based on
• Balancing severity,
• Chronicity
• Co morbidity of the mental illness, disorder, or condition .

12. Depression Disorders
(Women have higher rates of mood disorders than men in almost every
age group)
• Major depressive disorder,
• Bipolar disorder,
• Persistent depressive disorder,
• Cyclothymia, and
• Minor depression.
highest level of depressive symptoms between 34 and 38 weeks
gestation and also that there is an improvement in mood during the
second and third trimesters

13. • During pregnancy, depression has a point prevalence of 15.5% in early
and mid-pregnancy, 11.1% in the 3rd trimester, and 8.7% in the post-
partum period
• The research does show that pregnancy does not protect or alleviate
depression symptoms, and may be, in fact, a period of high
vulnerability
• hypothalamic-pituitary-adrenal dysregulation associated with
untreated depression could have adverse effects on fetal health and the
developing child

14. Pregnancy risks and outcomes associated
with untreated maternal disorder.
• Depression (32.5 years) most
prevalent psy disorder (50%)
• Major Depression
• Persistent Depression Disorder
• Minor Depression
• Inadequate maternal weight gain
• Substance abuse
• Pre-eclampsia; preterm birth;
low birth weight
• Fetal distress
• Increased risk of cesarean birth;
increased risk of neonatal
intensive care unit( NICU)
admission

15. BIPOLAR DISORDERS 25 years)
(25-30%)
• Bipolar I and II
• Bipolar NOS
• Cyclothymia
• Low birthweight, size at birth,
preterm birth
• Increased risk of cesarean birth,
small head circumference,
hypoglycemia
• Increased risk for long-term
neurocognitive, behavioral and
social deficits
• High postpartum risk for first-onset
and recurrent bipolar episodes and
hospitalization
• Substance use, poor prenatal care,
maternal suicide

16. • ANXIETY DISORDERS
Generalized Anxiety Disorder
(GAD) (30Years) (1=3%)
• Panic Disorders (24 years)
(2.2%)
• Social Anxiety Disorder 98-
15years)(1.8%)
• Specific Phobias (7 to 11 years)
(9.2)
• Increased risk for preterm birth,
small for gestational age
• Spontaneous abortion
• pre-eclampsia, deceased head
circumference, low birth weight
• Excessive infant crying
• Long-term childhood behavioral
disorders, anxiety
• Altered maternal/foetal cortisol
levels

17. • OBSESSIVE COMPULSIVE
DISORDER (19.5 years)
(1.08%)
• Low birth weight,
• Preterm birth

18. • SLEEP DISORDERS
Insomnia (any age in childhood)
(68-90%)
• Comorbid with mood/anxiety
disorders and associated adverse
effects
• Postpartum depression
• Pre-eclampsia,
• Gestational diabetes

19. Tri- and *Tetra-cyclics (TCAs)
• Few teratogenic effects are reported, except at doses of amitriptyline
which far exceed the MRHD.
• Results of animal research on desipramime, nortriptyline, and
imipramine are described as “inconclusive.” At doses >MRHD,
increased pup mortality and low body weight were reported for
amoxapine and doxepin.
• Trimipramine exposure at 20X MRHD caused an increased risk of
major abnormalities.
Contd..

20. Tri- and *Tetra-cyclics (TCAs)
• There are no adequate and well-controlled studies in pregnant women.
• Adverse events in humans (central nervous system effects, limb
deformities, developmental delays) have been reported for amitriptyline.
• Neonatal withdrawal and anticholinergic symptoms have been observed.
The kinetics of this drug change during pregnancy, serum levels should
be monitored and the dose should be adjusted if needed.

21. Monoamine Oxidase Inhibitors (MAOIs)
• Phenelzine may increase fetal/pup mortality in rats.
• There is little information on the effects of exposure to tranylcypromine
or isocarboxazid in animals.
• Exposure to selegiline at many times the MRHD increased the risk for
major malformations (delayed ossification) and decreased fetal weight.
• There are no adequate and well controlled studies in pregnant women.

22. Serotonin Reuptake Inhibitors (SRIs) and *Serotonin-
norepinephrine reuptake inhibitors (SNRIs)
• A study of women with history of major depression who were euthymic at the
beginning of pregnancy
• showed women who discontinued AD medication during pregnancy were more
likely to experience a relapse than women who continued medication use.
• Neonates exposed late in the 3rd trimester have developed complications
requiring prolonged hospitalization, respiratory support, and tube feeding.

23. Serotonin Reuptake Inhibitors (SRIs) and *Serotonin-
norepinephrine reuptake inhibitors (SNRIs)
• Respiratory distress,
• Cyanosis,
• Apnea,
• Seizures,
• Temperature instability,
• Feeding difficulty,
• Vomiting,
• Hypoglycemia,
• Hypo-/hypertonia,
• Hyperreflexia,
• Tremor,
• Jitteriness,
• Irritability crying.
These features may be a direct toxic effect or a withdrawal syndrome.
In some cases, the clinical outcome is consistent with serotonin syndrome.

24. Sertaline and Escitalopram
• Animal studies did not suggest teratogenic effects for sertraline or
escitalopram (only at toxic doses for citalopram)
• At doses >MRHD, increased risk of skeletal abnormalities and decreased fetal
growth/survival.
• There are no adequate and well-controlled studies in pregnant women.
• First trimester fluoxetine use is associated with increased risk of
cardiovascular malformations.
• Paroxetine is linked to cardiac malformations (ventricular septal and valve
defects).
• Consideration should be given to either discontinuing paroxetine use or
switching to another antidepressant.

25. Atypical Antidepressants
• Animal studies show no clear evidence of teratogenic effects, but there
is evidence of a higher pup mortality rate, and lower birth weights, at
>MRHD.
• There are no adequate and well-controlled studies in pregnant women

26. BENZODIAZEPINES
• First trimester exposure linked to an increased risk of congenital
malformations has been suggested in several studies.
• Non-teratogenic risks
• neonatal flaccidity,
• respiratory and feeding difficulties,
• hypothermia, and
• neonatal withdrawal symptoms during the postnatal period.
• Use of these drugs is rarely a matter of urgency, so first trimester exposure
should almost always be avoided.

27. BENZODIAZEPINES
• Animal studies suggest risk for teratogenic effects; malformations (cleft
palate), have been observed
• Temazepam has caused exencephaly and fusion or asymmetry of ribs, and
is contraindicated in women who are or may become pregnant.
• Patients should be instructed to discontinue this drug prior to becoming
pregnant.

28. BETA-BLOCKERS
• In animal studies, use of propranolol at dosages at >MRHD caused
embryotoxicity and neonatal toxicity. (no adequate and well-controlled
studies in pregnant women)
• Intrauterine growth retardation, small placentas, and congenital
abnormalities have been reported in neonates whose mothers received
propranolol during pregnancy.
• Atenolol use, especially in the 2nd trimester, is associated with infants small
for gestational age. Studies with first trimester use are limited.

29. ANTIPSYCHOTICS—Typical* and
Atypical/Second Generation
• Third trimester exposure increases risk for
• neonatal extrapyramidal and/or withdrawal symptoms (EPS),
including reports of agitation,
• hyper-/hypotonia,
• tremor,
• somnolence,
• respiratory distress and
• feeding problems.
• Severity varies from self-limited symptoms to intensive care unit
support and prolonged hospitalization.

30. Atypical antipsychotics
• No teratogenic effects or foetal toxicity have been observed in animal
studies involving exposure to clozapine or lurasidone.

31. Atypical antipsychotics
At doses >MRHD:
• ziprasidone caused cardiovascular malformations,
• Quetiapine —lower foetal weights and delays in skeletal ossification;
• Aripripazole –increased fetal/pup death, lower birth weight, and skeletal
abnormalities.
• Asenapine —lower pup weights and pup mortality,
• Ziprasidone —developmental delays and neurobehavioral impairment.
• There are no adequate and well-controlled studies in pregnant women.
• Olanzapine has been associated with adverse pregnancy outcomes,
including neonatal death due to cardiovascular defect, and abortion (3
therapeutic, 1 spontaneous).

32. MOOD STABILIZERS/ ANTIEPILEPTIC
DRUGS
• There are no adequate and well-controlled studies in pregnant women.
• Lithium may cause Ebstein’s anomaly.
• Carbamazepine is associated with risk to the fetus, including
congenital malformations (spinal bifida), and developmental delays.
• Valproate may produce congenital malformations (e.g., neural tube
defects) at a rate higher than other antiepileptic drugs; other
complications include neonatal hepatic failure and hypoglycemia;

33. MOOD STABILIZERS/ ANTIEPILEPTIC
DRUGS
• long-term effects include low IQ and a greater risk for autism
spectrum disorderin children.
• Valproate should not be used to treat women with epilepsy who are
pregnant or who plan to become pregnant.
• If a woman becomes pregnant while taking trimethadione, termination
of the pregnancy should be considered.

34. MOOD STABILIZERS/ ANTIEPILEPTIC
DRUGS
• Trimethadione and phenytoin may be associated with a neonatal
coagulation defect that may cause bleeding during the early neonatal
period (prophylactic Vitamin K may be indicated).
• Prenatal exposure to phenytoin is associated with a greater risk of
neuroblastoma.
• Risk of use of this class of medications appears particularly high in the
1st trimester.
• However, abrupt discontinuation of antiepileptic drugs in mothers who
use them to prevent major seizures should be avoided as this also
creates risk.

35. SEDATIVES AND HYPNOTICS
• In animal studies, there is no evidence of teratogenic effects.
• Offspring of rats exposed to doses higher than the MRHD showed
some evidence of delayed ossification, and decreased pup
weights/survival.
• Fewer adverse effects have been found in studies using rabbits.
• There are no adequate and well-controlled studies in pregnant women.
• Cases of severe neonatal respiratory depression have been reported
when Zolpidem was used at the end of pregnancy, especially when
taken with other CNS-depressants

36. Fetal and Neonatal Effects: TCAs
• Thalidomide tragedy and the advent of the Lithium Registry of Babies
• There are studies that have used TCAs as a study drug that reported
that exposure did not cause anatomical, skeletal, or cardiac
abnormalities in animal models

37. Long-Term Developmental Outcomes:
TCAs
• Prenatal TCA exposure has been linked to behavioral teratogenicity in
animal models, which has been measured by assessing locomotor
activity/exploration, social interaction and cognition.
• These measures test exploration of and habituation to novel situations,
and may uncover anxiety-like behavior.

38. Fetal and Neonatal Effects: SRIs
• Animal models used to investigate the fetal/neonatal outcomes studied and
observed in human TCA research began with intense focus on fluoxetine,
the first SRI.
• Studies in rats showed that fluoxetine caused
• Pulmonary hypertension and structural abnormalities in the vascular system and an
• Increase in postnatal mortality at the highest doses enlarged heart, and this was at a
much lower dose

39. Fetal and Neonatal Effects: SRIs
• Animal research that focused on the typical human pregnancy
outcomes such as gestational length, birth weight, and litter size
showed mixed results.
• Fluoxetine exposure shortened gestation time decreased litter sizes and
lowered birth weights
• However, there are also multiple studies, some by the same
researchers, that report no significant effects, and these differences
appear to depend on differing doses, route of administration, and time
of exposure during gestation

40. Long-Term Developmental Outcomes:
SRIs
• In most of the animal studies cited above that measured fetal/neonatal
effects of fluoxetine exposure, long-term behavioral tests were also
conducted.
• Vorhees evaluated neurobehavioral outcomes at three developmental
stages (preweaning, juvenile, adult), and found no significant effects
on any behavioral tests at any stage of development.
• Noorlander et al. however, found that neonatal fluoxetine caused
permanent cardiac anomalies that were accompanied by long-term
behavioral deficits demonstrated by depression- and anxiety-like
behaviors that were dose-dependent

41. Breastfeeding &
Psychiatric Medications

42. Facts
• A significant number of women may require pharmacological
treatment while nursing.
• While many women with postpartum illness delay treatment
because they are worried that the medications they take may
harm the nursing infant
• The accumulated data indicates that the risk of adverse events
in the nursing infant is low.

43. Breast milk and anti depressants
• Most anti depressants taken by the mother are secreted into the breast
milk, and there is no evidence to suggest that certain antidepressants
pose significant risks to the nursing infant.
• Sertraline and paroxetine (among SSRIs) and nortriptyline and
imipramine (among TCAs) are the most evidence-based medications
for use during breastfeeding because of similar findings across
multiple laboratories, usually undetectable infant serum levels and no
reports of short term adverse events

44. Anti-Anxiety Agents and breast feeding
• Sedation,
• Poor feeding,
• Respiratory distress
• Serious complications not yet reported

45. Mood Stabilizers
• On-demand breastfeeding may significantly disrupt the mother’s sleep
and thus may increase her vulnerability to relapse during the acute
postpartum period.
• Stevens-Johnson syndrome (SJS) in 0.1% case on Lamotrigine
• Toxicity in nursing infants related to exposure to various mood
stabilizers, including lithium and carbamazepine are
• Cyanosis
• Hypotonia
• Hypothermia
• Thyroid dysfunction
• Renal damage

46. Antipsychotic Agents and breast feeding
• Chlorpromazine has been associated with adverse events including
sedation and developmental delay
• No evidence of adverse effect with Atypical antipsychotics

47. Conclusion
• The use of psychotropic medications in pregnant women is a concern
because of the risks of adverse perinatal and postnatal outcomes.
• Advising these women to discontinue medication presents new risks
associated with untreated or inadequately treated mental illness, such as poor
adherence to prenatal care, inadequate nutrition, and increased alcohol and
tobacco use.
• Ideally, decisions about psychiatric medication use during and after
pregnancy should be made before conception.
• The use of a single medication at a higher dosage is preferred over multiple
medications, and those with fewer metabolites, higher protein binding, and
fewer interactions with other medications are also preferred.
• All psychotropic medications cross the placenta, are present in amniotic
fluid, and can enter breast milk.