Pregnancy & Psychiatric Medications: a WritePharma Quick Guide

**This content is part of our May is for Mental Health campaign: to raise awareness regarding mental illness, stigma, and providing hope throughout the month of May 2024.

• Psychiatric Illness and Pregnancy

• Use of psychotropics before, during, and after pregnancy, is of concern because of potential risks of perinatal and postnatal harm.

• Discontinuing medications when pregnant amid untreated psychiatric illness carries its own set of risks - risk vs. benefit analysis with psychiatrist is always recommended. Focus on patient-centered decision making to ensure patient is informed.
  

• Treatment Concepts

• Decisions should be made prior to conception if possible

• Use of a single medication at higher doses is recommended over use of multiple agents (avoid polypharmacy, increased risk of adverse reactions/potential fetal harm)

• Changing medications after pregnancy should be avoided to reduce exposure to multiple medications

• For Professionals: Medications with fewer metabolites, higher protein binding, and few drug interactions are preferred 

• Pregnancy + Depression

• 1 in 10 risk of developing peripartum depression exists during any month of pregnancy as well as within the first year of delivery 

• Peripartum Mood Changes

• Postpartum Blues → 80%

  • less severe than the others

• Postpartum Depression → 10-15%

• Postpartum Psychosis → 1-2% 

  • presence of psychotic symptoms: hallucinations (sensory) or delusions (thoughts)

• Diagnosis of Peripartum Depression

• Patient meets DSM-V criteria for MDD

  • DSM-V = Diagnostic Statistical Manual, 5th Edition - Diagnostic handbook for psychiatric illness designed for healthcare providers.

• Onset of symptoms occurs during pregnancy, or within 4 weeks following delivery

• 4 of the following symptoms + depressed mood/anhedonia for at least 2 weeks

• Sleep problems

• Interest deficit

• Guilt, worthlessness, hopelessness, regret

• Energy deficit 

• Concentration

• Appetite disorder

• Psychomotor retardation or agitation

• Suicidality 

• Treatment Options

• Mild → Psychotherapy (ex: Cognitive Behavioral Therapy)

• Moderate → Pharmacotherapy (Medications)

• Severe → Electroconvulsive Therapy (ECT) 

  • often the safest option for severe depression.

  • Consider TMS (Transcranial Magnetic Stimulation) which is a less intimidating alternative to ECT.

• Risk vs Benefit

• Severity of maternal illness vs. Risk to the fetus 

• If mother is having severe symptoms - may often be a safer choice to medicate or utilize other treatment modalities

• Treatment of Peripartum Depression 

• Guidance Available to Prescribers:

• FDA Pregnancy Categories

• ACOG: American College of OBGYNs

• APA: American  Psych Association 

• Emerging literature 

• SSRIs → 1st Line Therapy
  

• Fluoxetine, Citalopram,  Sertraline, Fluvoxamine 

• AVOID PAROXETINE IF POSSIBLE
  

• SNRIs

• Duloxetine, Venlafaxine, Desvenlafaxine, Milnacipran

• Other Options

• Bupropion

• Mirtazapine 

• Trazodone, Nefazodone, Vilazodone 

• TCAs

• MAOIs 

• PPHN In Newborns

• Persistent pulmonary hypertension of the newborn is defined as the failure of the normal circulatory transition that occurs after birth.

• Risk is present with all SSRIs, 2nd and 3rd trimester

• Paroxetine During Pregnancy - Class D 

• Paroxetine exposure during first trimester of pregnancy may increase the risk of congenital malformations

• Cardiac malformations 

• No specific recommendations from ACOG for this scenario

• Patient specific decision to switch prior to/after conception 

• New-Onset Depression During Pregnancy: ACOG/APA Recommendations 

• Prior to initiating the medication, risk-benefit discussion should take place

• Tread mild-moderate depression with psychotherapy

• Pharmacotherapy is appropriate if the patient will benefit

• Safety profile of antidepressants should be considered and an individualized decision should be made 

• 1. Consider risk/benefit of continuing or discontinuing therapy

• 2. Consider severity of current and past depression

• Asymptomatic /mild patients → can consider taper/discontinuing medication

• Women with severe depression → remain on medication 

• “Severe” = prior suicide attempt, functional incapacitation, weight loss

• Lactation + Depression

• Medications with HIGHEST Concentrations in Breast Milk:

• Fluoxetine, SNRIs, Mirtazapine, Bupropion 

• Minimal levels in Breast Milk (Better):

• Imipramine, Nortriptyline, and Citalopram ( Citalopram is dose dependent)

• Undetectable in Breast Milk (BEST)

• Sertraline, Paroxetine 

• Anxiety + Pregnancy

• Benzodiazepine (BDZ) Use in Pregnancy/Lactation

• Use of BDZ’s does NOT carry a teratogenic risk 

• Risk of “Floppy Infant Syndrome”

• If administered shortly before birth

• Hypothermia, lethargy, poor respiratory effort, feeding difficulties

• Withdrawal Syndromes are Possible

• Seen in Alprazolam, Chlordiazepoxide, Diazepam 

• Use of BDZs during nursing - SAFE 

• Does not typically affect the infant 

• Bipolar Disorder + Pregnancy

• Postpartum risk of relapse: 32-67%

• Perinatal episodes tend to be depressive

• More likely in subsequent pregnancies

• 46% increase risk of postpartum psychosis 

• Lithium during Pregnancy

• Use during pregnancy is associated with CONGENITAL CARDIAC MALFORMATIONS → Ebstein’s Anomaly

• Pregnancy Category D

• ACOG Recommendations for Lithium use during Pregnancy:

• Mild/Infrequent Episodes → 

• Gradually taper lithium prior to conception

• Moderate Relapse Risk/History of Severe Episodes

• Gradually taper lithium

• Reinitiate after organogenesis 

• Severe/Frequent Episodes → 

• Continue lithium throughout gestation

• Counsel on reproductive risks 

• *Monitor levels closely, as physiologic changes in pregnancy may affect lithium levels 

• AVOID VPA and CBZ IN PREGNANCY

• VPA Derivatives:

• Rate of major malformations > 10%

• Neural tube defects, craniofacial and cardiac anomalies, fetal growth restriction

• Cognitive impairment

• Poor neurodevelopmental outcomes

• Increased risk of Autism Spectrum Disorder

• Carbamazepine (CBZ)

• “Fetal CBZ Syndrome” - associated with facial dysmorphism and fingernail hypoplasia 

• AVOID USE

• Lamotrigine 

• No major fetal abnormalities associated with use

• Pregnancy increases drug clearance by 30% 

• Pregnancy Category C

• Bipolar Disorder + Lactation

• Measuring concentrations in neonates is ineffective 

• D/C nursing if neonate develops ADRs

• ADRs associated with lithium during nursing should be avoided

• WHO working group on drugs and human lactation

• VPA - “Compatible with Breastfeeding”

• CBZ - “probably safe”

• Schizophrenia (SCZ) + Pregnancy 

• Pregnancy outcomes in SCZ

• ADRs Reported

• Low birth weight

• Preterm delivery

• Placental abnormality

• Higher incidence of postnatal death

• Congenital malformations

• It is imperative to CONTINUE TREATMENT during pregnancy

• If untreated, there are risks to mother and child

• Maternal self-mutilation, denial of pregnancy/prenatal care, infanticide (killing of the fetus)

• All Antipsychotics are FDA Pregnancy Category C

• Exception: Clozapine/Lurasidone are Category B

• Lactation: there is limited evidence on APs in nursing - risk vs. benefit should be considered

• First Generation Anti Psychotics (FGA) > Second Generation Antipsychotics (SGA)

• High Potency FGAs > Low Potency FGAs 

• Routine use of SGAs is NOT recommended in pregnancy and lactation 

• BUT - this is really just because we have more data available for FGAs + Pregnancy (older drug, more documented uses)

• Risperidone may increase risk of major malformations - AVOID WHEN POSSIBLE

• Treatment Approach

• 1. Weigh risks of continuing drugs against risk of symptom relapse

• 2. Use monotherapy (1 drug) at lowest effective doses

• 3. In the case of chronic schizophrenia  → Maintain therapy before and during pregnancy

• 4. If a patient is stable on SGAs prior to pregnancy → Risk/Benefit required

• Summary

• Advising a pregnant patient to discontinue any psychotropic drugs exchanges the risk of fetal harm vs. the risk of untreated maternal illness

• Risk of maternal illness should be considered when deciding to continue/initiate pharmacotherapy

• Pharmacotherapy/Medication should be selected based on available literature in conjunction with maternal medication history/exposure 

• Risk & Benefit of pharmacotherapy should be discussed with patient prior to initiation/continuation of psychotropics during pregnancy. Patient-centered counseling and informed consent is necessary.