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  • Nathan Riley, MD

Obgyno Wino Podcast Episode 77 - Use of Psychiatrics Medications During Pregnancy and Lactation

We must eradicate from the soul all fear and terror of what comes towards man out of the future.

We must acquire serenity in all feelings and sensations about the future.

We must look forward with absolute equanimity to everything that may come.

And we must think only that whatever comes is given to us by a world-directive full of wisdom.

It is part of what we must learn in this age, namely, to live out of pure trust, without any security in existence.

Trust in the ever present help of the spiritual world.

Truly, nothing else will do if our courage is not to fail us.

And let us seek the awakening from within ourselves every morning and every evening."

- Rudolf Steiner, A Verse for Our Time


2015 Pinot Noir Carneros from Steele Wines




PB#92 - Published October 2009 (Reaffirmed 2016)


Five Pearls

1. mismanagement of maternal psychiatric illness can be an obstacle to appropriate prenatal follow-up, inadequate nutrition, increased alcohol and illicit drug abuse, deficits in mother-infant bonding, family environment disruptions, along with adverse pregnancy outcome like prematurity and low birth weight

2. all psychotropic drugs cross the placenta, are found in amniotic fluid, and can enter human breast milk (but likely in VERY low levels in the case of breastmilk)

3. In selecting any medications, those with fewer metabolites, higher protein binding (less placental passage), and fewer interactions with other medications are always a better bet.

4. Late in pregnancy, exposure to SSRIs associated with neonatal jitteriness, mild respiratory distress, transient tachypnea, weak cry, poor tone, and NICU admission.

5. Higher doses of folic acid supplementation (4mg/day) has not been shown to prevent drug-associated NTDs, but, according to ACOG, it should still be offered pre-conception and through the first trimester.


Major depressive disorder

- 17% prevalence among adults in the U.S.

- women 2x higher risk than man

- higher in women age 25-44

- 10-16% of pregnant women will meet criteria for diagnosis of MDD; up to 70% will have some symptoms

- poorly managed depression in pregnancy is associated with preterm birth and low birth weight, especially when depression in late 2nd trimester or early 3rd trimester

- many symptoms of depression overlap with symptoms of pregnancy, so they go overlooked

- for women who are taking anti-depressants pre-conception, ~70% experience recurrence in pregnancy if meds are discontinued (versus 25% if meds continued)

- postpartum depression: major depressive episode that occurs within the first 6 weeks postpartum

- screening tools: Edinburgh Postnatal Depression Scale, Beck Depression Inventory, and Postpartum Depression Screening Scale

- 68-100% detection rate using these screening tools (better for severe symptoms); 78-96% specificity


Bipolar disorder

- 4-6.5% of the population affected; even split between men and women

- distinct periods of abnormally high and low moods

- women are more likely than men to experience depressive episodes in bipolar disorder and rapid cycling up and down

- in women, typical onset in late teens to early twenties

- 32% of women relapse in postpartum period (they tend to be depressive in nature)

- high likelihood of recurrence in pregnancy with history of episode in prior pregnancy

- risk of postpartum psychosis is as high as 50%


Anxiety disorders

- most common class of psych disorders: 18% prevalence among adults

- panic disorder, GAD, PTSD, and phobias are 2x more likely in women than men

- anxiety/stress are risk factors for SAB, preterm delivery, prolonged labor, precipitous labor, fetal distress, and need for operative delivery (NO CAUSAL RELATIONSHIP)

- panic disorder: recurrent panic attacks that arise in situations that shouldn't provoke anxiety; highest risk in pregnancy is in the postpartum period

- PTSD: 3rd most common psych dx among underserved pregnant women, ~8% prevalence; common to have co-morbid condition like GAD

- traumatic obstetric experiences can trigger PTSD (e.g. emergency c-section, miscarriage)

- OCD worsens postpartum


Schizophrenia spectrum disorders

- schizophrenia: severe, persistent mental illness characterized by psychosis OR catatonia

- associated with preterm delivery, low birth weight, placental abnormalities including abruption, congenital malformations (esp CV system), and postnatal death

- more likely to require interventions on L&D including induction, operative assistance, or c-section


Treatment in pregnancy and while lactating

- some meds can be teratogenic if taken during embryogenesis (i.e. 3rd-8th week gestation)

- available toxicity/teratogenicity profiles in pregnancy/breastfeeding are available in Table 2 below

- you can additionally reference www.reprotox.org and TERIS for even more info



Note: In selecting any medications, those with fewer metabolites, higher protein binding (less placental passage), and fewer interactions with other medications are always a better bet. Ask for help from a friendly MFM or psychiatrist when in doubt!


Specific notes on treatment considerations of various disorders

Depression

- paroxetine: 1-2x higher risk of congenital cardiac malformations if fetus exposed in 1st trimester (Cat D)

- other small possible malformative associations have been suggested (e.g. paroxetine/sertraline --> omphalocele); however, these correlations have only been found after MANY statistical tests

- late in pregnancy, exposure to SSRIs associated with neonatal jitteriness, mild respiratory distress, transient tachypnea, weak cry, poor tone, and NICU admission

- risk of relapse must be weighed against these risks: higher risk of relapse if >5 year depression history or history of relapse >4x

- if stopping SSRI or SNRI, best to taper to avoid withdrawal


Note: length of taper depends dependent on half-life, shorter half life requires longer taper, e.g. decrease by 25% every 2-6 weeks


- TCAs: associated with limb anomalies in early studies, but this hasn't panned out; otherwise acute effects like fetal tachycardia and neonatal irritability haven't panned out in recent studies

- SNRIs and other agents: no adverse effects documented

- structured psychotherapy is also effective as adjuvant therapy for pregnant women with major depression


Bipolar disorder

- lithium: associated with fetal cardiac malformations (1.2-7.7 risk ratio) and other congenital malformations (1.5-3 risk ratio) early in pregnancy;

- later exposure associated with fetal and neonatal cardiac arrhythmias, hypoglycemia, nephrogenic DI, polyhydramnios, thyroid issues, prematurity, and floppy infant syndrome if exposed later in pregnancy

- if exposed as a neonate (e.g. breastmilk), lithium toxicity may present as flaccidity, lethargy, and poor suck reflexes; no long-term issues on 5-year follow-up

- these risks must be balanced against the risk of discontinuation while pregnant

- abruptly stopping lithium carries high risk of relapse

- if tapering pre-conception in mild disease: gradually taper before conception

- in more severe disease but relatively lower risk of relapse: taper before conception but reinstituted after embryogenesis (~8th week gestation)

- in the most severe disease: just keep them on lithium

- if fetus was exposed to lithium in the 1st trimester, fetal echo is recommended to evaluate for cardiac malformation

- valproate, carbamazepine, and lamotrigene: these drugs were designed as anticonvulsants for epilepsy but work to stabilize mood in bipolar; any teratogenic effects of either drug are hard to distinguish from the adverse effects of the underlying seizure disorder

- valproate and carbamazepine --> better than lithium for mixed episodes; avoid in 1st trimester given advsere effects to fetal development

- valproate: up to 4% risk of neural tube defects (lesser risk for other malformations like craniofacial anomalies, limb abnormalities, CV anomalies, and varying degrees of cognitive impairment --> "fetal valproate syndrome"); acute neonatal risks include hepatotoxicity, coagulopathies, hypoglycemia, and withdrawal symptoms

- carbamazepine: exposure in pregnancy may manifest as "carbamazepine syndrome" --> dysmorphism and fingernail hypoplasia; insufficient evidence to remark on any association with neural tube defects or developmental delay

- lamotrigene --> better for bipolar depression; better tolerability and safety profile

- lamotrigene: insufficient evidence to suggest association with congenital anomalies, though some registries have found midline facial clefts at higher doses


Note: Higher doses of folic acid supplementation (4mg/day) has not been shown to prevent drug-associated NTDs, but, according to ACOG, it should still be offered pre-conception and through the first trimester


Anxiety disorders

- benzodiazepines: no significant risk of teratogenesis

- there is a risk of floppy infant syndrome (hypothermia, lethargy, poor feeding, and poor respiratory effort) when benzos are used close to birth

- neonatal withdrawal syndrome has also been documented (restlessness, hypoertonia, hyperreflexia, tremulousness, apnea, diarrhea, and vomiting); can last for up to 3 months postpartum

- if stopping a benzo, do it gradually and get help from a pyschiatrist


Schizophrenia

- the atypical anti-psychotics have generally replaced the typicals

- the atypicals are better at managing the negative symptoms of schizophrenia (e.g. catatonia); they are also tolerated better and have better side effect profile

- they are also used increasingly for tx of bipolar disorder, OCD, and treatment-resistant depression

- very little safety data in pregnancy and breastfeeding --> ACOG recommends not using them in pregnancy or while breastfeeding (but if well-managed while taking an atypical antipsychotic during conception, best to keep your patient on it)

- the typical antipsychotics have more safety data

- no significant teratogenic effects associated with chlorpromazine, haloperidol, or perphenazine

- with haloperidol, no risk of prematurity, fetal viability, or low birth weight has been found

- with (prochlorperazine, chlorpromazine), likewise not an increased risk of neonatal survival rates or severe anomalies (maybe some issues with these two and major anomalies per other subanalysis...but hey...the data sucks)

- available data for the typical antipsychotic shows no neurobehavioral in neonates exposed in-utero

- the one caution: EPS, neuroleptic malignant syndrome, and dyskinesia in the neonate (diphenhydramine used to treat EPS also not associated with issues)

- if needed postpartum, ACOG recommends limiting the administration of typical antipsychotics in order to minimize the need for additional administration of medications to treat EPS


What is my patient is taking meds while breastfeeding?

- if mother's symptoms are well-controlled, no reason to believe that stopping breastfeeding is of any benefit unless neonate develop any abnormal signs

- anti-depressants are not likely to be an issue

- lithium is also best to continue if symptoms well-controlled

- valproate and carbamazepine are also best to continue according to the WHO

- benzos probably OK at low doses

- insufficient data on antipsychotics

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