512 - Screening for EPSE, Treatment of PPD, What Are You Feeding?
Take 3 – Practical Practice Pointers©
From a Clinical Question
1) Screening for Movement Disorders/Extrapyramidal Side Effects in Patients on Antipsychotic Medications
Prescribing of 2nd generation antipsychotics has become much more common in primary care for indications such as bipolar disorder (types 1 and 2), anxiety, treatment-resistant depression, agitation in dementia, and even insomnia. In our health system, we are evaluating the usefulness of an electronic health record (EHR)-based reminder to administer the Abnormal Involuntary Movement Scale (AIMS) to patients taking antipsychotic medications at least once per year.
Tardive dyskinesia, akathisia, and parkinsonian symptoms (collectively called extrapyramidal side effects, EPSE) are movement disorders that occur mainly as a complication of antipsychotic therapy. The newer (“atypical”, 2nd generation) antipsychotics were developed in the hopes that these complications would be eliminated, but while there is a reduced incidence of EPSE compared to 1st generation antipsychotics, reports of their prevalence vary between <10% to 50%.
Because of this concern, the American Psychiatric Association guidelines for the management of schizophrenia advise regular assessment for EPSE symptoms every 12 months and every 6 months for patients at high risk of EPSE (“older than 55 years; women; individuals with a mood disorder, substance use disorder, intellectual disability, or central nervous system injury; high cumulative exposure to antipsychotic medications, high potency dopamine receptor antagonists; and patients who experience acute dystonic reactions, clinically significant parkinsonism, or akathisia”). This assessment can be performed with several different scales, but no particular scale is recommended and no specific score on these scales is defined as a threshold for diagnosis.
Studies looking only at tardive dyskinesia (TD) report very low prevalence (< 1% in some studies), but a systematic review of studies looking at all ESPE found a 37% prevalence (7% for TD alone). There was some publication bias found in this review, which could have artificially raised the prevalence estimates.
A recent systematic review of screening/diagnostic instruments for assessing movement disorders reviewed 133 articles that examined 23 different scales. The evidence supporting each was subjected to a rating scheme, and no scale was rated higher than “recommended with caveats.” The principal caveat about the AIMS, as an example, is that it did not include questions about tremor or parkinsonian movements, missing a large category of EPSEs.
There are more treatments available these days for EPSEs. For TD alone, which may not resolve with dose reduction and switching of the antipsychotic medications, there are 2 new medications - VMAT2 inhibitors (deutetrabenazine or valbenazine) - that can be used. For Parkinsonian symptoms, these usually resolve after discontinuation of the antipsychotic medication.
The AIMS instrument has been the most frequently used instrument to detect EPSEs, including in FDA sponsored studies of treatment of ESPEs from antipsychotic medications. However, this whole area suffers from a lack of a definitive instrument for detection of all relevant EPSEs, clarification of terminology about EPSEs, clear treatment options, and favorable prognoses. Trials evaluating the utility of screening for movement disorders (vs. recognizing them as they occur) are lacking. As with all prescribed medicines, it is important for clinicians to be conscious of the common and serious side effects of medications, to counsel patients carefully about these side effects, and dutifully monitor patients for subtle signs of these EPSEs so that appropriate dose reduction measures or additional treatment can be undertaken.
· American Psychiatric Association. Practice Guideline for the Treatment of Patients With Schizophrenia. 3rd ed. American Psychiatric Publishing; 2021. Link
· Ali T, Sisay M, Tariku M, Mekuria AN, Desalew A. Antipsychotic-induced extrapyramidal side effects: A systematic review and meta-analysis of observational studies. PLoS One. 2021;16(9):e0257129. Link
· Martino D, Karnik V, Bhidayasiri R, et al. Scales for Antipsychotic-Associated Movement Disorders: Systematic Review, Critique, and Recommendations. Movement Disorders. 2023;38(6):1008-1026. Link
· Bergman H, Walker DM, Nikolakopoulou A, Soares-Weiser K, Adams CE. Systematic review of interventions for treating or preventing antipsychotic-induced tardive dyskinesia. Health Technol Assess. 2017;21(43):1-218. Link
From the Guidelines and the FDA
2) Treatment for Postpartum Depression (PPD)
In our June 30, 2023 Edition of Take 3 we reviewed the most recent USPSTF recommendations regarding screening for depression in adults, include those who are pregnant and in the postpartum period. The Task Force recommendation was to screen all adults for depression (B Recommendation), and favored using the Edinburgh Postnatal Depression Scale (EPDS) for pregnancy and postpartum care.
Depressive symptoms such as dysphoria, insomnia, fatigue, impaired concentration, anhedonia, changes in appetite, or crying spells can occur in both postpartum major depression and postpartum blues. The symptoms of postpartum blues are mild and self-limited, typically developing within 2-3 days of delivery, peaking over the next few days, and resolving within two weeks of onset. By contrast, the diagnosis of major depression requires a minimum of five symptoms that must be present for at least two weeks. Symptoms of postpartum blues that persist beyond two weeks are best viewed as postpartum depression. Postpartum depression (PPD) affects approximately 10–15% of adult mothers yearly with depressive symptoms lasting more than 6 months among 25–50% of those affected.
In June of 2023, the American College of Obstetrics and Gynecology (ACOG) released an updated clinical practice guideline on the treatment and management of mental health conditions during pregnancy and postpartum. The guideline included the recommendation for the use of either the Patient Health Questionnaire (PHQ-9) or the EPDS (Edinburgh) as tools to both diagnose and follow clinical depression. Other recommendations include:
· Psychotherapy should be considered a first-line treatment for mild-moderate perinatal unipolar depression (Strong/Moderate Quality)
· SSRIs should be used as first-line pharmacotherapy for perinatal unipolar depression. SNRIs are reasonable alternatives. If there is no pharmacotherapy history, sertraline or escitalopram are reasonable first-line medications. (Strong/Low Quality)
· Consideration should be given for the use of brexanolone (Zulresso), a GABA-A receptor agonist, in the postpartum period for moderate-to-severe perinatal depression with onset in the third trimester or within 4 weeks postpartum. The decision to use brexanolone should balance the benefits (eg. rapid onset of action) with the risks and challenges (eg. limited access, high cost ($34,000/infusion just for the medication), lack of data supporting safety with breastfeeding, requirement for inpatient monitoring during the infusion, lack of efficacy data beyond 30 days (Strong/Moderate Quality)
The ACOG guideline has a more aggressive dosage adjustment schedule for medications than many who treat depression are accustomed to. See the table below.
The FDA recently approved zuranolone (Zurzuvae), a new oral medication with an indication for PPD, which was not covered in the guideline. While more attractive because of its pill form and lower cost than IV brexanolone (Zulresso), it would still likely be reserved for 3rd or even 4th line treatment. The recommended dosing is 50 mg (one pill) daily for 14 days. The packaging will include a boxed warning noting that the drug can affect a user's ability to drive and perform other potentially hazardous activities, possibly without their knowledge of the impairment. As a result, the FDA indicates that people who use Zurzuvae should not drive or operate heavy machinery for at least 12 hours after taking the pill. The cost is not yet known, but early speculation indicates it could be up to $10,000 for a course of therapy (yes, you read that correctly).
Given the limitations of obstetrical care in many regions of the country (including our own in rural areas), it will be important for we who provide women’s health services to stay up to date on the care of the postpartum patient.
It should also be noted that while zuranolone will be likely marketed as the only oral treatment approved exclusively for postpartum depression, that is only because its application for the treatment of major depressive disorder was denied by the FDA pending further studies.
· ACOG Clinical Practice Guideline. Treatment and Management of Mental Health Conditions During Pregnancy and Postpartum. Number 5. June 2023. Link (by subscription only)
From PeerRxMed ( www.PeerRxMed.org )
3) What Thoughts Are You Feeding?
“Where attention goes, energy flows.” Variations of this quote credited to many
I enjoy listening to podcasts when I exercise, and one that is regularly on my playlist is called "The One You Feed". Each episode starts with the host, Eric Zimmer, reading a parable and asking the guest what it means to them in life and in the work that they do. The parable, which has many circulating versions, goes something like this:
A grandparent is talking with their grandchild. The grandparent says, “In life, there are two wolves inside of us which are always at battle. One is a good wolf which represents things like kindness, bravery, and love. The other is a bad wolf which represents things like greed, hatred, and fear”.
The grandchild stops and thinks about it for a second then then asks, “Which one wins.”
The grandparent replies, “The one you feed.”
What has struck me about the resulting conversation is how many different and rich interpretations emerge from this simple story from the guests, who include scientists, authors, researchers, teachers, thought leaders, and public figures. What has also impressed me is how my own interpretations (pleural) of it have evolved over time as I have reflected on their answers and my own life journey.
One thing the story regularly reminds me of is how easy it is for my thoughts to “go negative” regarding certain topics, circumstances, or people, particularly when I’m experiencing increased stress and/or haven’t been practicing self-care, and how, without conscious effort to change that, it can become an automatic “reflex.” Indeed, neuroscience teaches that such a “negativity bias” is “wired” into our neurocircuitry as a survival mechanism.
Take some time this week to reflect on the parable; what you might consider your “good and bad wolves,” what they represent to you, and in what ways you are feeding them (or not). Do you have some “thought habits” that are not serving your desired outcome? Afterall, if your thought energy is going to be feeding something, you might as well be doing it by design rather than by default. Chose regularly … and wisely.
Mark and John
Carilion Clinic Department of Family and Community Medicine
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