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

Screening for Perinatal Depression

Perinatal depression is defined as major and minor depressive episodes that occur during pregnancy or in the first 12 months after delivery. It is very common, affecting approximately 9% of women in pregnancy and up to 37% at any point in the first year postpartum

Clinical Actions

USPSTF (2019) recommends that

…clinicians provide or refer pregnant and postpartum persons who are at increased risk of perinatal depression to counseling interventions (Grade B Guidance)

Moderate net benefit

Note: Definition of Grade B Guidance

The USPSTF recommends the service | There is high certainty that the net benefit is moderate or there is moderate certainty that the net benefit is moderate to substantial
Suggestions for Practice: Offer or provide this service
Recommendation based on ‘convincing evidence’
- Counseling interventions (e.g., cognitive behavioral therapy and interpersonal therapy) are effective in the prevention of perinatal depression

ACOG recommendations include the following

ObGyns and other obstetric care providers should screen patients for perinatal depression and anxiety “at the initial prenatal visit, later in pregnancy, and at postpartum visits”
Use a validated screening tool to identify the presence of depression or anxiety

Antepartum Depression Risk Factors

FACTOR	STRENGTH OF ASSOCIATION
Maternal anxiety	Medium – Large
Negative life events	Medium – Large
Unintended pregnancy	Medium
Medicaid (US)	Medium
Poor relationship quality	Medium
History of depression	Medium
Domestic violence	Small – Medium
Lack of social support	Small – Medium
Smoking	Small
Lower income	Small
Lower education	Small

Postpartum Depression Risk Factors:

Depression during pregnancy
Anxiety during pregnancy
Experiencing stressful life events during pregnancy or the early postpartum period
Traumatic birth experience
Preterm birth/infant admission to neonatal intensive care
Low levels of social support
Previous history of depression
Breastfeeding problems
Multiparity

Synopsis:

Left untreated, the results of depression can be devastating for both the child and the mother. Proactive screening is necessary because often depression can go unnoticed. Changes in libido, mood and sleep may incorrectly be attributed to the pregnancy or the birth of the child rather than underlying depression

Key Points:

Screening alone has potential for clinical benefit In the context of a positive screening test, follow up with appropriate medical interventions and referrals provides maximal benefit
Gauge depression by paying attention to flat affect, noting unusual anxiety or tearfulness in addition to using a screening instrument
Anxiety and insomnia can be significant indicators of depression
Women with a history or with common risk factors for depression are more likely to be affected by perinatal depression and extra caution is warranted
Management including evaluation and close follow up are required for women with
- Current depression or anxiety
- History of perinatal mood disorders
- Risk factors for perinatal mood disorders
- Suicidal ideation
The Edinburgh post-natal depression scale (EPDS) and the PHQ-9 screening tool (see ‘Learn More – Primary Sources’ below)
- Are validated for use in the primary care setting
- Take a relatively short time to complete
- EPDS: Sensitivity 55% to 98% | Specificity 68% to 97%
- PHQ-9: Sensitivity 53% to 77% | Specificity 85% to 94%
Other screening tools, unlike the EPDS, include constitutional symptoms
- Constitutional symptoms such as altered sleep patterns are associated with pregnancy/postpartum period in general, and therefore can reduce screening specificity
Systems should be in place to ensure follow up, diagnosis and treatment

Learn More – Primary Sources:

ACOG Clinical Practice Guideline 4: Screening and Diagnosis of Mental Health Conditions During Pregnancy and Postpartum

ACOG Guide for Integrating Mental Health Care into Obstetric Practice

USPSTF Recommendation Statement (JAMA): Interventions to Prevent Perinatal Depression

USPSTF Perinatal Depression: Preventive Interventions (2019)

Edinburgh Postnatal Depression Scale

PHQ-9 Screening Tool

American Psychological Association: Depression Assessment Instruments

Risk factors for depressive symptoms during pregnancy: a systematic review

Risk factors in pregnancy for post-traumatic stress and depression after childbirth

USPSTF: Depression and Suicide Risk in Adults Screening