Espresso: Zuranolone for Postpartum Depression

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We’re back! While we’ll operate for a bit on a reduced schedule (new episodes every-other-week), we are so excited to get back to podcasting and covering the need-to-know in OB/GYN. Thanks for all the love and support over the last few months! <3 Nick & Fei

Reading: Zuranolone for the Treatment of Postpartum Depression (ACOG Practice Advisory)

What is zuranolone and why is it important? 

    • We know that postpartum/perinatal mental health conditions and some of the leading causes of preventable maternal mortality 

      • PPD affects approximately 14% of women 

      • Understanding/discussing/recommending medication and treatment can potentially decrease maternal morbidity and mortality 

  • Medication type

    • Neuroactive steroid gamma-aminobutyric acid (GABA) A receptor positive modulator 

    • Oral medication  

    • Recent FDA approval for use in PPD 

Why is zuranolone recommended, and what else is out there? 

  • Why is it recommended? 

    • Two phase 3 randomized double-blind, placebo-controlled multicenter studies 

    • Primary endpoint in both: change in depressive symptoms in the Hamilton depression rating scale (HAMD-17) 

      • 17 point scale 

      • Assesses somatic (physical ie. loss of appetite), affective (mood ie. sadness), cognitive (thinking, ie. difficulty concentrating), and behavioral (ie. social withdrawal) symptoms of depression 

      • Reliable and valid method of assessing and measuring depression 

    • In both studies, those on Zuranolone showed significantly more improvement in their symptoms compared those in placebo 

      • Treatment effect maintained at day 42 (4 weeks after last dose of zuranolone) 

  • Why the HAMD-17? 

    • More used in research settings, but anticipated that other validated tools (like EPDS or PHQ9) will be used in clinical settings 

  • What else is out there? 

    • Brexanolone - first FDA approved medication specifically for postpartum depression

      • However, unlike zuranolone which is oral, brexanolone consists of a 60 hour in-hospital IV infusion, which may not be readily accessible 

        • May be difficult to arrange inpatient admission 

        • May also be difficult for patients to leave their newborns for 60 hours to get infusion 

    • SSRIs 

      • Not specific for postpartum/perinatal depression 

      • Can be effective, but also may be difficult to find the correct SSRI

      • Many SSRIs also require uptitration of dosage 

  • What to consider when prescribing zuranolone 

    • Consideration of zuranolone in the postpartum period (within 12 months postpartum) for depression that has onset in the third trimester or within 4 weeks postpartum

    • Benefits: 

      • Significantly improved and rapid resolution of symptoms 

    • Risks: 

      • Potential suicidal thoughts or behavior 

      • Sedation - can make it so you can’t drive 

      • Lack of efficacy data beyond 42 days 

  • How to prescribe and take zuranolone 

    • Daily recommended dose is 50 mg 

      • Take in evening with fatty meal (400-1000 calories, 25-50% fat) for 14 days 

      • Can reduce dose to 40 mg if CNS depression effects occur 

      • If hepatic or renal impairment, start dose at 30 mg 

    • Can be used alone or as an adjunct to other oral antidepressant therapy like SSRIs 

    • Recommendation is to have effective contraception during treatment and for 1 week after final dose. There is a registry if pregnancy occurs 

    • Warn patients about adverse reactions 

      • Impaired ability to drive 

      • CNS depressant effects 

      • Increased suicidal thoughts and behaviors 

    • Zuranolone does pass into breastmilk, but relative infant dose is smaller than that of SSRIs 

Perinatal Mental Health, feat. Dr. Tiffany Moore-Simas and Dr. Nancy Byatt

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Today on the podcast, we’re addressing perinatal mental health. While we’ve talked about depression on the show before, there’s so much more in this sphere as we’ll discuss today.

 

Joining us are two experts in this field who share their passion for this work with us. Dr. Tiffany Moore Simas is Chair and Professor of OB/GYN at UMass Memorial Health and UMass Chan Medical School as well as co-Chair of the ACOG Maternal Mental Health Expert Work Group. And Dr. Nancy Byatt is a tenured Professor of Psychiatry and OB/GYN at UMass Memorial Health and UMass Chan Medical School. Both serve as senior leaders with the Massachusetts Perinatal Psychiatry Access Program, MCPAP for Moms, and Lifeline For Moms.

 

Importance of Perinatal Mental Health

  • Mental health conditions are the most common complications of pregnancy – 1 in 5!

    • More common in adolescents, veterans, marginalized populations (BIPOC, poverty).

  • Untreated mental health conditions carry both short- and long-term consequences that can affect whole family:

    • o   Less engagement in medical care

    • o   Smoking, substance use

    • o   Preterm delivery, low birth weight, NICU admission

    • o   Lactation challenges, bonding issues

      • Parent with untreated mental health disorder is considered an Adverse Childhood Experience (ACE) for the infant.

    • o   Adverse partner relationships

  • Mortality: leading cause of preventable maternal mortality.

    • 100% of maternal deaths due to mental health, including suicide, overdose, are preventable!

  • Underdetected and undertreated

  • OB/GYNs can screen and help manage mental health conditions. The majority (80%) of depression, for example, is managed by primary care providers, not psychiatrists. As obstetric care clinicians, we are the primary care providers to pregnant and postpartum individuals and thus, we should be providing mental health care!

Screening for Perinatal Mood and Anxiety Disorders

  • In this context, perinatal refers to during pregnancy and the first year after pregnancy ends

  • Perinatal Mood and Anxiety Disorders primarily include depression, bipolar disorder, and anxiety or anxiety-related conditions (generalized anxiety disorder, PTSD, OCD).

  • Screens should be performed with validated tools that query the last 7-14 days of symptoms for anxiety and depression.

    • o   Validated tools:

      • PHQ-9, EPDS (depression)

      • GAD-7 (generalized anxiety)

    • o   ACOG recommends screening patients at least once during the perinatal period for depression and anxiety symptoms. If a patient is screened during pregnancy, additional screening should occur during the comprehensive postpartum visit.

      • We recommend screening: new OB visit, later in pregnancy (i.e., 3rd trimester) and postpartum given the almost even distribution of onset predating pregnancy, onset in pregnancy, and onset postpartum.

    • o   Data suggests that early detection and treatment improves outcomes.

  • Bipolar disorder screening:

    • o   In one study, 1 in 5 patients screening positive for postpartum depression actually had bipolar disorder.

      • Recall: bipolar disorder can worsen with antidepressant treatment (unopposed SSRIs) – thus, need to screen for bipolar before initiating pharmacotherapy and ideally universally to prevent harm!

    • o   Patients with bipolar disorder have higher risk of postpartum psychosis

      • Rare: 1-2/1000 perinatal individuals; but 70% have bipolar disorder!

      • 4% risk of infanticide with postpartum psychosis

      • This is a psychiatric emergency.

        • Often occurs within the first days of delivery and most cases occur within the first 3 weeks.

    • o   Screening options:

      • Mood Disorder Question (MDQ) – self administered

      • CIDI – clinician administered with branching logic

    • o   Appropriate to refer to psychiatry if bipolar disorder is suspected – more on resources to help later!

Positive Screening   General Principles of Treatment

  • Just like a glucola, our questionnaires for mental health concerns are screening tests. Subsequent assessment is critical to confirm diagnosis.

    • o   See resources collection at the end of these notes for help!

  • For depression and anxiety, there are three pillars of treatment:

    • o   Psychotherapy

    • o   Pharmacotherapy or medication

      • o   Adjunctive interventions

  • Treat based on level of severity. For information on assessing and treating perinatal mental health conditions, visit the ACOG website.

  • If pharmacotherapy is indicated/started, patients may have some concerns:

    • o   Provide reassurance

    • o   Frame risk/benefit discussion in treated disease vs. untreated disease as not treating is associated with risks - just like any other disease!

    • o   Use lowest effective dose and monotherapy when able

  • Find more information on educating patients about treatment on ACOG’s website.

Concerns for Suicidality or Harm To Baby

  • These can represent urgent clinical scenarios and further assessment and response is critical:

    • o   Thoughts of harming self or baby are common yet not all are necessarily a psychiatric emergency.

    • o   When assessing for risk of harm to self or others it is important to assess:

      • Ideation – Do they have thoughts of harming themselves or someone else?  Are the thoughts fleeting or do they persist?

      • Intent – Are they intending to act on it? Have they thought of how they could do harm themselves or someone else or die by suicide?

      • Plan - Are they planning to act on it?  Have they developed a plan for how to die by suicide or to harm someone else?

    • o   If you are concerned that the patient is at risk of harm to self or others, then it is important to obtain further assessment which includes an evaluation for whether the patient may need psychiatric hospitalization

    • o   Regardless of whether these are a psychiatric emergency, the presence of thoughts of harming self or baby are indicative of higher illness severity.

  • More information on ACOG’s website.

 Resources for Integrating Perinatal Mental Health Care into Your Practice

 

Perinatal Depression

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Depression is a major health disorder affecting around 10% of women, particularly in the perinatal and postpartum periods. Depression is twice as common in women as in men, and OB/GYNs should be familiar with its diagnosis and management, particularly in the perinatal period. You can read more with ACOG CO 757.

There are many different types of depression diagnoses, including: major depressive disorder, persistent depressive disorder, seasonal affective disorder, perinatal (postpartum) depression, premenstrual dysphoric disorder (PMDD), etc. According to the DSM-V, a major depressive episode is diagnosed when one has: 

  • Five (or more) of the following symptoms have been present for a 2-week period and represent a change from previous functioning; at least one of the symptoms is either depressed mood or loss of interest/pleasure. 

  • Symptoms cannot be explained by medications or another medical illness (i.e., hypothyroidism).

  • The remaining (need 4+ from this list):

    • Depressed most of the day, nearly every day as indicated by subjective report or observation made by others;

    • Diminished interest or pleasure in all, or almost all, activities most of the day, nearly every day;

    • Significant weight loss when not dieting or weight gain, or increase/decrease in appetite nearly every day;

    • Insomnia or hypersomnia;

    • Psychomotor agitation or retardation; 

    • Fatigue or loss of energy;

    • Feelings of worthlessness or inappropriate guilt;

    • Decreased ability to think/concentrate;

    • Recurrent thoughts of death/suicidal ideation.

Perinatal depression is defined separately as major and minor depressive episodes that occur during pregnancy or in the first 12 months after delivery. This is one of the most common medical complications during pregnancy and the postpartum period, affecting 1/7 women. 

Depression and other mood disorders can have devastating effects on women and their families: maternal suicide exceeds hemorrhage and hypertensive disorders as a cause of maternal mortality 

SO how do we screen for perinatal depression? ACOG recommends that obstetric care providers screen patients at least once during the perinatal period for depression and anxiety symptoms using a standardized tool, and again in the postpartum period during a comprehensive postpartum visit. There is evidence that screening alone can have clinical benefits for patients suffering with depression.

One of the most commonly used is the Edinburgh Postnatal Depression Screen, which is a 10 item survey that takes less than 5 minutes to complete. The sensitivity is estimated between: 59-100%, and specificity: 49-100%. A Spanish version is available.

The Patient Health Questionnaire 9 (PHQ-9) is another acceptable tool. Other items like the Postpartum Depression Screening Scale (PDSS) is more sensitive (91-94%) and specific (72-98%), but it is a 35 item survey and thus more time intensive.

Management of perinatal depression is a team sport, requiring multiple additional support members and medical team members. Medication prescription will vary for OB/GYNs and their comfort with this. In brief:

  • Women with current depression/anxiety or a history of perinatal mood disorder should have close monitoring, evaluation, and assessment.

  • Some OB/GYNs are comfortable starting antidepressant medication and following their patients, most commonly an SSRI. Psychiatry referral is also acceptable.

  • Referral to social work and behavioral health - possibly for psychotherapy, which alone is a reasonable alternative to antidepressants if needed.

  • For those with severe postpartum depression, another possibility is brexanolone.

    • Limited clinical experience and restricted availability 

    • Usually restricted to patients who do not improve with antidepressants