Treatment of Perinatal and Postpartum Depression

SUMMARY:

Perinatal mental health conditions may occur prior to pregnancy or up to twelve months after delivery. The prevalence of any kind of mental illness in women in the US is more than one in four, and about 20% will develop a mental health condition during pregnancy or in the postpartum period. Obstetricians should be able to counsel about benefits of psychopharmacotherapy and use a validated screening tool to titrate medications. First-line treatments include psychotherapy, selective serotonin uptake inhibitors, and newer medications such as zuranolone.

Types of Perinatal Depression

Depressive disorders
- During pregnancy and up to 12 months postpartum
- Pregnancy and childbirth can exacerbate depression
- One quarter of women will continue to have depression for the following three years
- Counseling is helpful to prevent depression
Bipolar disorders
- Onset during reproductive years
- May or may not include psychotic features
- About 25% of those with depression have a bipolar disorder and should be screened for this
  - Before prescribing medication for depression, screening should be performed for a bipolar disorder, which can cause self harm or infanticide
- The risk of relapse postpartum is 39%
  - The risk of relapse is three times higher in women who have discontinued therapy
  - Continution of therapy is strongly recommended in the prenatal and the postpartum period
Anxiety
- Includes: Generalized anxiety | Panic | Agoraphobia | Mutism | Separation anxiety | Social phobia and phobia related disorders
- All share fear, anticipatory anxiety, and avoidance behaviors
- 20% of all women have one or more anxiety disorders
- Are often combined with perinatal depression
Postpartum psychosis
- Rare and occur about 1/1000 to 2/1000 pregnancies
- Often occur with a bipolar disorder or depression
- Typical onset 2 to 10 days postpartum through the first four weeks after delivery
- Most do not have a prior psychiatric history
- Those with a bipolar disorder and a prior history have the highest recurrent risk
- Given its association with suicide and infanticide, psychiatric hospitalization is indicated with high dose lithium
- Full remission by 2 months postpartum

Treatment

Generalized Treatment Approach

Begin with lowest possible effective dose
Avoid polypharmacy
Minimize switching medications
If using an SSRI: Taper over 2 to 4 weeks vs abrupt discontinuation
Lactation considerations
- Do not discourage breastfeeding if it is a patient’s preferred method of infant feeding
- If patient stable on a particular medication during pregnancy
  - Do not routinely change medication postpartum
- When initiating pharmacotherapy during lactation consider
  - Medication’s transfer into breast milk
  - Anticipated therapeutic effectiveness

First line therapy for PTSD, Anxiety or Depression

Sertraline
- Starting dose 25 mgs
- After 4 days 50 mgs
- In 7 days 100 mgs
- Therapeutic range 50 to 200mgs
Fluoxetine
- Starting dose 10 mgs
- In four days increase to 20 mgs
- Therapuetic range 20 to 80 mgs
Citalopram
- 10 mgs starting dose
- Monthly increases by 10 mgs
- Therapeutic range 20 to 40 mgs
Escitalopram
- 5 mgs starting dose
- In four days increase to 10 mg
- Reassessment monthly and increase by 10 mgs
- Therapeutic range 10 to 20 mgs

Zuranolone

Consider zuranolone within 12 months postpartum period for depression with onset
- In 3^rd trimester or
- Within 4 weeks postpartum
Zuranolone (see ‘Learn More – Primary Sources’ below) is approved for use for postpartum depression | The FDA does not specify or refer to degree of severity in the ‘Indications and Usage’ section
Benefits: Improved and rapidly resolved symptoms
- Oral administration
Risks: Potential suicidal ideation | Sedation and CNS-depressant effects that can restrict common activities of daily living (e.g., driving)
Common side effects
- Dizziness | Fatigue | Drowsiness | Diarrhea | Common cold-like symptoms | UTIs
Can be used with other oral antidepressants like SSRIs and SNRIs
Avoid other CNS-depressing substances
May cause fetal harms
Requires use effective contraception during treatment course and for 1 week after final dose
Breast Feeding
- Passes into breast milk
- Limited data
- Use shared decision making regarding continuation, pumping and discarding milk through 1-week past treatment completion
Dosing
- 50 mg daily in the evening for 14 days
- With a fatty meal
- 400 to 1,000 calories | 25% to 50% fat for 14 days
- If CNS-depressant effects occur (somnolence and confusion): Reduce dose to 40 mg
- Severe hepatic or moderate to severe renal impairment: 30 mg

Note: Adjust dose if patient taking strong CYP3A4 inhibitors | Avoid concomitant use with CYP3A4 inducers

CYP3A4 Inducers: Phenobarbital | Phenytoin | Rifampicin | St. John’s wort | Glucocorticoids

KEY POINTS:

Benzodiazepines
- Use sparingly or be avoided in treatment of perinatal depression
Valproate
- Do not use for treatment of bipolar disorder during pregnancy
Lithium
- Can be used during the first trimester of pregnancy
- Pregnancy should include a detailed second trimester ultrasound
- Odds ratio for birth defects: 1.86 (95% CI, 1.16 to 2.96)
Zuranolone
- If not effective or symptoms recur following treatment, do not repeat medication course | Consider other management options
Postpartum psychosis is a psychiatric emergency

Learn More – Primary Sources

ACOG Clinical Practice Guideline 5: Treatment and Management of Mental Health Conditions During Pregnancy and Postpartum

ACOG Statement on the Benefit of Access to SSRIs During Pregnancy

ACOG Clinical Practice Update: Zuranolone and Brexanolone for the Treatment of Postpartum Depression

University of North Carolina – NC MATTERS Program – Perinatal Depression Toolkit

FDA: ZURZUVA (zuranolone) capsules, for oral use