474 - Antidepressants in Pregnancy, Screening for OSA, Professional Grief

From the Literature

1)  Antidepressant Use During Pregnancy and Effect on Children

Depression is very common in the US and is of particular concern in the prenatal and perinatal period because of the association with post-partum depression, impaired maternal-infant bonding, and suicidal/infanticidal ideation. While the use of antidepressant medications is generally very effective for depression, there has been concern from prior large-scale observational studies that it may lead to adverse child neurodevelopmental (ND) outcomes such as autism spectrum disorder (ASD), attention deficit/hyperactivity disorder (ADHD), behavioral disorders, learning and communication disorders, and intellectual disability. The recommendations for clinical use of these medications in pregnancy have been to weigh the benefits/risks of these medications carefully in a discussion with the patient to decide on the appropriate course.

A pharmacoepidemiology group decided to tackle the question of harm from antidepressants (AD) with a carefully constructed retrospective cohort study using a large Medicaid patient cohort and a combined commercial insurance cohort. The investigators used a primary exposure definition of AD use after 19 weeks of pregnancy but also analyzed those that discontinued AD medications prior to pregnancy as well as those who used in early pregnancy only. Medication adherence was defined as 2 fills of the medication during pregnancy. Outcomes were assessed from claims data using validated algorithms to ensure the best data. The analysis was detailed and used several methods for adjusting for measured and unmeasured confounders and used sensitivity analyses to check their assumptions.

Overall, the crude (unadjusted) analysis did show an association between AD use and ND outcomes (the statistically significant hazard ratios ranged between 1.32 and 2.02). However, after several different methods were applied to adjust for confounders, the results decreased in magnitude (to just above 1.0), and, for most groups, when comparisons with AD discontinuers and between siblings (where one used AD meds and one did not) were performed, the associations became non-significant.

The authors conclude that there is no significant concern of ND harm due directly to AD medications. However, it is important to look at the other factors associated with taking AD medication – social determinants of health, relationships, support, etc. – to assess a possible effect on ND outcomes.

John’s Comments:

This kind of large dataset observational evidence is potentially very useful to point out directions for future research, but its application to clinical care must be very carefully considered. This study is a great example of how observational data can mislead when confounders are uncontrolled, and how a thoughtful analysis can cause us to think more deeply about the problem. The clinical syndrome of depression can have multiple inputs and varied effects, and just focusing on the prescription of medication oversimplifies the issue. Neurodevelopmental harms can certainly arise from toxic exposures in utero, but our role in primary care is to carefully examine the family unit for other salient factors: maternal-infant bonding, resources to support child care and development, the role of violence and relationship issues – and try to help ameliorate these factors. This support is especially important if the mother is impaired by a history of depression.

Reference:

·         Suarez EA, Bateman BT, Hernández-Díaz S, et al. Association of Antidepressant Use During Pregnancy With Risk of Neurodevelopmental Disorders in Children. JAMA Intern Med. 2022;182(11):1149-1160. Link

From the USPSTF

2)  Screening for Obstructive Sleep Apnea (OSA)

Sleep apnea is a sleep-related breathing disorder characterized by abnormal breathing patterns during sleep.  Signs and symptoms of include snoring, witnessed apnea, excessive daytime sleepiness, morning headaches, decreased libido, impaired cognition, mood changes, or gasping or choking while asleep. 

Based on cohort and survey data from 2007-2010, the estimated prevalence of mild OSA (defined as an apnea-hypoxia index [AHI] > 5) among adults aged 30 to 70 years was 14% for men and 5% for women, and the estimated prevalence of moderate to severe OSA (defined as AHI > 15) was 13% for men and 6% for women.  The AHI is the combined average number of apneas and hypopneas that occur per hour of sleep.  Severe OSA is associated with increased all-cause mortality.  Untreated OSA has also been associated with cardiovascular disease and cerebrovascular events, T2D, cognitive impairment, decreased quality of life, and motor vehicle crashes.  The role of OSA as an independent risk factor for all-cause mortality separate from other risk factors, such as older age, higher BMI, and other cardiovascular risk factors, is unclear.

Individuals at increased risk for OSA include men, postmenopausal women, older adults (aged 40 to 70 years), persons with a higher body mass index, and persons with a physical irregularity that could affect their upper airway and breathing.  In addition, Black, Hispanic/Latino, and Native American/Alaska Native persons have higher rates of sleep apnea compared with White persons.

The USPSTF recently updated their 2017 recommendations regarding the utilization of screening for OSA, and concluded that in the general asymptomatic adult population, the current evidence is insufficient to assess the balance of benefits and harms of screening. (I Recommendation)

There are several screening questionnaires and clinical prediction tools that attempt to identify persons at higher risk of OSA.  Many combine questions about clinical findings (eg, BMI and neck circumference) with questions about symptoms associated with OSA.  Commonly used screening questionnaires and clinical prediction tools include the Epworth Sleepiness Scale (ESS), STOP questionnaire (snoring, tiredness, observed apnea, high blood pressure), STOPBANG questionnaire (STOP questionnaire plus BMI, age, neck circumference, and gender), Berlin Questionnaire, Mallampati Score, and Multivariable Apnea Prediction tool.  The USPSTF found inadequate evidence on the accuracy of screening questionnaires and multistep screening approaches to identify adults at increased risk for OSA.

Although there is some evidence that treatment of OSA with positive airway pressure or mandibular advancement devices may affect intermediate outcomes (ie, apnea-hypopnea index and blood pressure) and health outcomes (ie, quality of life) in patients referred for OSA treatment, evidence of this impact in screen-detected populations is lacking. 

Most groups do not recommend routine screening in primary care settings among populations without signs or symptoms of OSA.  The US Department of Veterans Affairs guidelines suggest using the STOP questionnaire to stratify the risk of OSA among patients who report sleep issues (weak recommendation) and also suggest assessing for sleep-disordered breathing in patients with a history of cardiovascular or cerebrovascular events, CHF, and chronic opioid use (weak recommendation). 

In 2017, the American Academy of Sleep Medicine (AASM) issued a health advisory recommending annual OSA screening for adult patients who belong to certain high-risk groups, including those with heart failure, elevated blood pressure, a-fib, resistant hypertension, T2D, and stroke.  This advisory also recommended screening for those with a BMI > 30, those who have nocturnal dysrhythmias, pulmonary hypertension, or coronary artery disease, as well as those who are preparing for bariatric surgery. 

The AASM recommends those at high risk for OSA, based on an initial screening, should receive a comprehensive sleep evaluation that includes an overnight sleep study in an accredited sleep center or a home sleep apnea test. 

The American Heart Association released a scientific statement in 2021 advocating for screening in patients with resistant or poorly controlled hypertension, pulmonary hypertension, and recurrent atrial fibrillation after either cardioversion or ablation. 

Mark’s Comments:

This recommendation highlights the fact that severe OSA is quite prevalent and likely presently underdiagnosed.  At the same time, there is need for rigorous research to identify optimal screening strategies for OSA in the primary care setting and to determine who will benefit from screening and treatment, particularly in asymptomatic or mildly symptomatic patients.  The AASM “health advisory,” without providing an evidence basis and strength of recommendation for their screening parameters, far exceeds the present evidence, and could create conditions for both overdiagnosis and overtreatment.  At the same time, it is encouraging that clinicians are becoming more cognizant of the importance of adequate sleep to overall health.  Given the estimated prevalence of OSA, being aware of risk factors and asking about symptoms, particularly in higher risk patients, would be considered an essential aspect of good clinical care.  If symptoms exist, additional evaluation would certainly be appropriate.  

References:

·         USPSTF.  Screening for Obstructive Sleep Apnea in Adults:  USPSTF Recommendation Statement.  JAMA. November 15, 2022;328(19):1945-1950.  Link

·         Gottlieb D.  Screening for Obstructive Sleep Apnea in Adults.  JAMA. 2022;328(19):1908-1910.  Link

From PeerRxMed ( www.PeerRxMed.org )

3)  To Grieve is Normal … No One Should Grieve Alone

“Your loss is not a test, a lesson, something to handle, a gift, or a blessing.  Loss is simply what happens to you in life.  Meaning is what you make happen.”   David Kessler, author of Finding Meaning: The Sixth Stage of Grief

How do you grieve?  Or for many of us, perhaps the better question would be “do you grieve?”  Though we typically associate grieving with the death of a loved one, that is a very narrow view of loss and grief.  Indeed, loss comes in many forms, including changes in relationships, changes in physical health, and changes in life circumstances, and we’ve all certainly had plenty of losses, particularly over the past almost 3 years since COVID-19 became a household word. 

In our professional work, we are daily surrounded by loss.  In the midst of such loss, my experience is that many physicians and other healthcare professionals, including myself, don’t grieve effectively, if we even consciously grieve at all.   Note that last sentence didn’t say “correctly,” but rather “effectively.”  We rarely allow ourselves permission to experience the wide range of complex and often “unlovely” emotions that can accompany loss, including anger, shock, guilt, shame, and even relief.  Instead, we often dismiss, bury, or deny them rather than providing ourselves the space and grace to process them. 

But where did we “learn” to grieve as healthcare professionals?  As I’ve researched this question, my conclusion is that for most of us the answer is we didn’t, or at least not in any explicit way.  Instead, what was modeled for us is that clinicians don’t grieve; that somehow we are either immune to the emotional impact of loss or should be able to transcend it, and that those of us who do experience and express grief are “weak,” too enmeshed, overly emotional, or even “unprofessional.” 

In the process, we deny our humanity and instead of learning how to grieve, we experience emotional consequences of suppressed and unresolved grief, including irritability, anger, guilt, shame, fear, confusion, and emotional distance.  You’ve likely seen these being expressed by many of our colleagues over the past 3 years – and perhaps by yourself as well.     

Over the next few weeks in Take 3, I’m going to be exploring the role of grief in our professional lives, recognizing that how we process the inevitable losses which are part of our work matters greatly.  For some (and likely many), this may bring up memories you’ve been carrying with you for a long time.  If so, be gentle with yourself, and consider using this as an opportunity to process these memories in a more healthy and meaningful way, including inviting other colleagues into dialogue with you.  As you do so, remember grief is normal, natural, and necessary.  And most importantly, embrace the wisdom that no one should grieve alone … including you.    

______________

Mark and John

Carilion Clinic Department of Family and Community Medicine

Feel free to forward Take 3 to your colleagues. Glad to add them to the distribution list.

Email: mhgreenawald@carilionclinic.org