Ms. D, age 32, recently gave birth to her second child. Her psychiatric history includes major depressive disorder. She had been stable on mirtazapine 30 mg at bedtime for 3 years. Based on clinical stability and patient preference, Ms. D elected to taper off mirtazapine 1 month prior to delivery. Now at 1 month postdelivery, Ms. D notes the reemergence of her depressive symptoms; during her child’s latest pediatrician visit, she scores 15 on the Edinburgh Postnatal Depression Scale (EPDS). She breastfeeds her baby and wants more information on the safety of taking an antidepressant while breastfeeding.

Ms. D discusses her previous use of mirtazapine with her treatment team. The team reviews the available resources with Ms. D and together they plan to make a shared decision regarding treatment of her depression at her next appointment.

The American Academy of Pediatrics¹ and World Health Organization² recommend exclusive breastfeeding of infants for their first 6 months of life and support it as a complement to other foods through and beyond age 2. Untreated conditions such as postpartum depression impact maternal well-being and may interfere with parenting and child development. In fact, untreated maternal mental health leads to an increased risk of suicide, reduced maternal economic productivity, and worsened health for both mother and child.³

Because many women experience psychiatric symptoms before they become pregnant as well as during the perinatal period, questions often arise regardingthe use of psychiatric medications—specifically antidepressants—and their safety in patients who are breastfeeding. Key considerations regarding medication management should include the patient’s previous response to medications, the risks of untreated maternal mental illness, and evidence regarding risks and benefits in lactation. This article summarizes where to find evidence-based lactation information, how to interpret that information, and what information is available for select antidepressants.

Locating lactation information

Start by checking the manufacturer’s medication labeling (“prescribing information”) and medication information resources such as Micromedex (www.micromedexsolutions.com) and Lexicomp (www.wolterskluwer.com/en/solutions/lexicomp). The updated labeling includes a risk/benefit assessment of available data on the risk for continued use of a medication during pregnancy compared to the risk if a medication is discontinued and the disorder goes untreated.⁴ The “breastfeeding considerations” section of medication labeling include details regarding the presence of the medication and the amount of it in breastmilk, adverse events in infants exposed to the medication through breastmilk, and additional pertinent data as applicable. Lexicomp includes information regarding breastfeeding considerations, and a subscription may also include access to Briggs Drugs in Pregnancy and Lactation’s information pages. Micromedex includes its own lactation safety rating scale score.

Several other resources can help guide clinicians toward patient-specific recommendations. From the National Library of Medicine, LactMed (https://www.ncbi.nlm.nih.gov/books/NBK501922/) allows clinicians to search for specific medications to see what information exists pertaining to medication levels in breastmilk and infant blood as well as potential adverse effects in the nursing infant and/or on lactation and breastmilk.⁵ LactMed provides information regarding alternative medications to consider and references from which the information was gathered.

Another helpful resource is the InfantRisk Center from Texas Tech University Health Sciences Center, which includes a free call center for parents and clinicians who have questions about medications and breastfeeding (806-352-2519; Monday through Friday, 8 am to 5 pm CST). The InfantRisk Center also offers smartphone apps for clinicians as well as individuals who are pregnant or breastfeeding.⁶ Two commonly referenced textbooks on medications and breastfeeding include Hale’s Medication and Mother’s Milk 2023: A Manual of Lactational Pharmacology⁷ and Briggs Drugs in Pregnancy and Lactation: A Reference Guide to Fetal and Neonatal Risk.⁸

Continue to: How to interpret the information

How to interpret the information

Medication levels in breastmilk are affected by several properties, such as the medication’s molecular weight, protein binding, pKa, and volume of distribution. A few commonly used terms in lactation literature for medications include the relative infant dose (RID) and milk/plasma (M/P) ratio.

RID provides information about relative medication exposure for the infant. It is calculated by dividing the infant’s dose of a medication via breastmilk (mg/kg/d) by the mother’s dose (mg/kg/d).⁷ Most consider an RID <10% to be safe.⁷

M/P is the ratio of medication concentration in the mother’s milk divided by the medication concentration in the mother’s plasma. A ratio <1 is preferable and generally indicates that a low level of medication has been transferred to human milk.⁷

Another factor that can be evaluated is protein binding. Medications that are highly protein-bound do not tend to pass as easily into breastmilk and can minimize infant exposure.

Several risk categorization systems are available, depending upon the resource used to obtain lactation information. One common system is Hale’s Lactation Risk Categories, with 5 safety levels ranging from L1 (breastfeeding compatible) to L5 (hazardous) (Table 1⁷). Briggs et al⁸ utilize 7 categories to summarize recommendations ranging from breastfeeding-compatible to contraindicated; however, it is important to read the full medication monograph in the context of the rating provided. Table 2^7,8 provides breastfeeding information from Hale’s⁷ and from Briggs et al⁸ for some commonly used antidepressants.

In addition to interpreting available literature, it is also important to consider patient-specific factors, including (but not limited to) the severity of the patient’s psychiatric disorder and their previous response to medication. If a mother achieved remission on a particular antidepressant in the past, it may be preferable to restart that agent rather than trial a new medication.

CASE CONTINUED

Two weeks later and following the use of a variety of resources, Ms. D’s treatment team finds that mirtazapine is rated Probably Compatible (L3 in Hale’s Lactation Risk Categories), with an M/P ratio of 0.76.⁷ The RID of mirtazapine ranges from 1.6% to 6.3%, and limited data from infants exposed to maternal use of mirtazapine during breastfeeding have not shown adverse effects.⁵ The treatment team administers the EDPS to Ms. D again and she scores 18. Given Ms. D’s previous remission with mirtazapine, current severity of depressive symptoms, and the risk/benefit assessment from lactation resources, the decision is made to restart mirtazapine 15 mg/d at bedtime with the option to titrate up if indicated. Ms. D plans to continue breastfeeding and will monitor for signs of any adverse effects in her infant. The Figure provides a summary of navigating this individualized decision with patients.

Related Resources

• MotherToBaby. Medication fact sheets, option to contact for no-charge consultation, free patient education information materials. www.mothertobaby.org
• Reprotox. Summaries on effects of medications on pregnancy, reproduction, and development (subscription required). www.reprotox.org

Drug Brand Names

Bupropion • Wellbutrin
Citalopram • Celexa
Duloxetine • Cymbalta
Escitalopram • Lexapro
Fluoxetine • Prozac
Mirtazapine • Remeron
Nortriptyline • Pamelor
Paroxetine • Paxil
Sertraline • Zoloft
Trazodone • Oleptro
Venlafaxine • Effexor
Vortioxetine • Trintellix

Ms. D, age 32, recently gave birth to her second child. Her psychiatric history includes major depressive disorder. She had been stable on mirtazapine 30 mg at bedtime for 3 years. Based on clinical stability and patient preference, Ms. D elected to taper off mirtazapine 1 month prior to delivery. Now at 1 month postdelivery, Ms. D notes the reemergence of her depressive symptoms; during her child’s latest pediatrician visit, she scores 15 on the Edinburgh Postnatal Depression Scale (EPDS). She breastfeeds her baby and wants more information on the safety of taking an antidepressant while breastfeeding.

Ms. D discusses her previous use of mirtazapine with her treatment team. The team reviews the available resources with Ms. D and together they plan to make a shared decision regarding treatment of her depression at her next appointment.

The American Academy of Pediatrics¹ and World Health Organization² recommend exclusive breastfeeding of infants for their first 6 months of life and support it as a complement to other foods through and beyond age 2. Untreated conditions such as postpartum depression impact maternal well-being and may interfere with parenting and child development. In fact, untreated maternal mental health leads to an increased risk of suicide, reduced maternal economic productivity, and worsened health for both mother and child.³

Because many women experience psychiatric symptoms before they become pregnant as well as during the perinatal period, questions often arise regardingthe use of psychiatric medications—specifically antidepressants—and their safety in patients who are breastfeeding. Key considerations regarding medication management should include the patient’s previous response to medications, the risks of untreated maternal mental illness, and evidence regarding risks and benefits in lactation. This article summarizes where to find evidence-based lactation information, how to interpret that information, and what information is available for select antidepressants.

Locating lactation information

Start by checking the manufacturer’s medication labeling (“prescribing information”) and medication information resources such as Micromedex (www.micromedexsolutions.com) and Lexicomp (www.wolterskluwer.com/en/solutions/lexicomp). The updated labeling includes a risk/benefit assessment of available data on the risk for continued use of a medication during pregnancy compared to the risk if a medication is discontinued and the disorder goes untreated.⁴ The “breastfeeding considerations” section of medication labeling include details regarding the presence of the medication and the amount of it in breastmilk, adverse events in infants exposed to the medication through breastmilk, and additional pertinent data as applicable. Lexicomp includes information regarding breastfeeding considerations, and a subscription may also include access to Briggs Drugs in Pregnancy and Lactation’s information pages. Micromedex includes its own lactation safety rating scale score.

Several other resources can help guide clinicians toward patient-specific recommendations. From the National Library of Medicine, LactMed (https://www.ncbi.nlm.nih.gov/books/NBK501922/) allows clinicians to search for specific medications to see what information exists pertaining to medication levels in breastmilk and infant blood as well as potential adverse effects in the nursing infant and/or on lactation and breastmilk.⁵ LactMed provides information regarding alternative medications to consider and references from which the information was gathered.

Another helpful resource is the InfantRisk Center from Texas Tech University Health Sciences Center, which includes a free call center for parents and clinicians who have questions about medications and breastfeeding (806-352-2519; Monday through Friday, 8 am to 5 pm CST). The InfantRisk Center also offers smartphone apps for clinicians as well as individuals who are pregnant or breastfeeding.⁶ Two commonly referenced textbooks on medications and breastfeeding include Hale’s Medication and Mother’s Milk 2023: A Manual of Lactational Pharmacology⁷ and Briggs Drugs in Pregnancy and Lactation: A Reference Guide to Fetal and Neonatal Risk.⁸

Continue to: How to interpret the information

How to interpret the information

Medication levels in breastmilk are affected by several properties, such as the medication’s molecular weight, protein binding, pKa, and volume of distribution. A few commonly used terms in lactation literature for medications include the relative infant dose (RID) and milk/plasma (M/P) ratio.

RID provides information about relative medication exposure for the infant. It is calculated by dividing the infant’s dose of a medication via breastmilk (mg/kg/d) by the mother’s dose (mg/kg/d).⁷ Most consider an RID <10% to be safe.⁷

M/P is the ratio of medication concentration in the mother’s milk divided by the medication concentration in the mother’s plasma. A ratio <1 is preferable and generally indicates that a low level of medication has been transferred to human milk.⁷

Another factor that can be evaluated is protein binding. Medications that are highly protein-bound do not tend to pass as easily into breastmilk and can minimize infant exposure.

Several risk categorization systems are available, depending upon the resource used to obtain lactation information. One common system is Hale’s Lactation Risk Categories, with 5 safety levels ranging from L1 (breastfeeding compatible) to L5 (hazardous) (Table 1⁷). Briggs et al⁸ utilize 7 categories to summarize recommendations ranging from breastfeeding-compatible to contraindicated; however, it is important to read the full medication monograph in the context of the rating provided. Table 2^7,8 provides breastfeeding information from Hale’s⁷ and from Briggs et al⁸ for some commonly used antidepressants.

In addition to interpreting available literature, it is also important to consider patient-specific factors, including (but not limited to) the severity of the patient’s psychiatric disorder and their previous response to medication. If a mother achieved remission on a particular antidepressant in the past, it may be preferable to restart that agent rather than trial a new medication.

CASE CONTINUED

Two weeks later and following the use of a variety of resources, Ms. D’s treatment team finds that mirtazapine is rated Probably Compatible (L3 in Hale’s Lactation Risk Categories), with an M/P ratio of 0.76.⁷ The RID of mirtazapine ranges from 1.6% to 6.3%, and limited data from infants exposed to maternal use of mirtazapine during breastfeeding have not shown adverse effects.⁵ The treatment team administers the EDPS to Ms. D again and she scores 18. Given Ms. D’s previous remission with mirtazapine, current severity of depressive symptoms, and the risk/benefit assessment from lactation resources, the decision is made to restart mirtazapine 15 mg/d at bedtime with the option to titrate up if indicated. Ms. D plans to continue breastfeeding and will monitor for signs of any adverse effects in her infant. The Figure provides a summary of navigating this individualized decision with patients.

Related Resources

• MotherToBaby. Medication fact sheets, option to contact for no-charge consultation, free patient education information materials. www.mothertobaby.org
• Reprotox. Summaries on effects of medications on pregnancy, reproduction, and development (subscription required). www.reprotox.org

Drug Brand Names

Bupropion • Wellbutrin
Citalopram • Celexa
Duloxetine • Cymbalta
Escitalopram • Lexapro
Fluoxetine • Prozac
Mirtazapine • Remeron
Nortriptyline • Pamelor
Paroxetine • Paxil
Sertraline • Zoloft
Trazodone • Oleptro
Venlafaxine • Effexor
Vortioxetine • Trintellix

Ms. D, age 32, recently gave birth to her second child. Her psychiatric history includes major depressive disorder. She had been stable on mirtazapine 30 mg at bedtime for 3 years. Based on clinical stability and patient preference, Ms. D elected to taper off mirtazapine 1 month prior to delivery. Now at 1 month postdelivery, Ms. D notes the reemergence of her depressive symptoms; during her child’s latest pediatrician visit, she scores 15 on the Edinburgh Postnatal Depression Scale (EPDS). She breastfeeds her baby and wants more information on the safety of taking an antidepressant while breastfeeding.

Ms. D discusses her previous use of mirtazapine with her treatment team. The team reviews the available resources with Ms. D and together they plan to make a shared decision regarding treatment of her depression at her next appointment.

The American Academy of Pediatrics¹ and World Health Organization² recommend exclusive breastfeeding of infants for their first 6 months of life and support it as a complement to other foods through and beyond age 2. Untreated conditions such as postpartum depression impact maternal well-being and may interfere with parenting and child development. In fact, untreated maternal mental health leads to an increased risk of suicide, reduced maternal economic productivity, and worsened health for both mother and child.³

Because many women experience psychiatric symptoms before they become pregnant as well as during the perinatal period, questions often arise regardingthe use of psychiatric medications—specifically antidepressants—and their safety in patients who are breastfeeding. Key considerations regarding medication management should include the patient’s previous response to medications, the risks of untreated maternal mental illness, and evidence regarding risks and benefits in lactation. This article summarizes where to find evidence-based lactation information, how to interpret that information, and what information is available for select antidepressants.

Locating lactation information

Start by checking the manufacturer’s medication labeling (“prescribing information”) and medication information resources such as Micromedex (www.micromedexsolutions.com) and Lexicomp (www.wolterskluwer.com/en/solutions/lexicomp). The updated labeling includes a risk/benefit assessment of available data on the risk for continued use of a medication during pregnancy compared to the risk if a medication is discontinued and the disorder goes untreated.⁴ The “breastfeeding considerations” section of medication labeling include details regarding the presence of the medication and the amount of it in breastmilk, adverse events in infants exposed to the medication through breastmilk, and additional pertinent data as applicable. Lexicomp includes information regarding breastfeeding considerations, and a subscription may also include access to Briggs Drugs in Pregnancy and Lactation’s information pages. Micromedex includes its own lactation safety rating scale score.

Several other resources can help guide clinicians toward patient-specific recommendations. From the National Library of Medicine, LactMed (https://www.ncbi.nlm.nih.gov/books/NBK501922/) allows clinicians to search for specific medications to see what information exists pertaining to medication levels in breastmilk and infant blood as well as potential adverse effects in the nursing infant and/or on lactation and breastmilk.⁵ LactMed provides information regarding alternative medications to consider and references from which the information was gathered.

Another helpful resource is the InfantRisk Center from Texas Tech University Health Sciences Center, which includes a free call center for parents and clinicians who have questions about medications and breastfeeding (806-352-2519; Monday through Friday, 8 am to 5 pm CST). The InfantRisk Center also offers smartphone apps for clinicians as well as individuals who are pregnant or breastfeeding.⁶ Two commonly referenced textbooks on medications and breastfeeding include Hale’s Medication and Mother’s Milk 2023: A Manual of Lactational Pharmacology⁷ and Briggs Drugs in Pregnancy and Lactation: A Reference Guide to Fetal and Neonatal Risk.⁸

Continue to: How to interpret the information

How to interpret the information

Medication levels in breastmilk are affected by several properties, such as the medication’s molecular weight, protein binding, pKa, and volume of distribution. A few commonly used terms in lactation literature for medications include the relative infant dose (RID) and milk/plasma (M/P) ratio.

RID provides information about relative medication exposure for the infant. It is calculated by dividing the infant’s dose of a medication via breastmilk (mg/kg/d) by the mother’s dose (mg/kg/d).⁷ Most consider an RID <10% to be safe.⁷

M/P is the ratio of medication concentration in the mother’s milk divided by the medication concentration in the mother’s plasma. A ratio <1 is preferable and generally indicates that a low level of medication has been transferred to human milk.⁷

Another factor that can be evaluated is protein binding. Medications that are highly protein-bound do not tend to pass as easily into breastmilk and can minimize infant exposure.

Several risk categorization systems are available, depending upon the resource used to obtain lactation information. One common system is Hale’s Lactation Risk Categories, with 5 safety levels ranging from L1 (breastfeeding compatible) to L5 (hazardous) (Table 1⁷). Briggs et al⁸ utilize 7 categories to summarize recommendations ranging from breastfeeding-compatible to contraindicated; however, it is important to read the full medication monograph in the context of the rating provided. Table 2^7,8 provides breastfeeding information from Hale’s⁷ and from Briggs et al⁸ for some commonly used antidepressants.

In addition to interpreting available literature, it is also important to consider patient-specific factors, including (but not limited to) the severity of the patient’s psychiatric disorder and their previous response to medication. If a mother achieved remission on a particular antidepressant in the past, it may be preferable to restart that agent rather than trial a new medication.

CASE CONTINUED

Two weeks later and following the use of a variety of resources, Ms. D’s treatment team finds that mirtazapine is rated Probably Compatible (L3 in Hale’s Lactation Risk Categories), with an M/P ratio of 0.76.⁷ The RID of mirtazapine ranges from 1.6% to 6.3%, and limited data from infants exposed to maternal use of mirtazapine during breastfeeding have not shown adverse effects.⁵ The treatment team administers the EDPS to Ms. D again and she scores 18. Given Ms. D’s previous remission with mirtazapine, current severity of depressive symptoms, and the risk/benefit assessment from lactation resources, the decision is made to restart mirtazapine 15 mg/d at bedtime with the option to titrate up if indicated. Ms. D plans to continue breastfeeding and will monitor for signs of any adverse effects in her infant. The Figure provides a summary of navigating this individualized decision with patients.

Related Resources

• MotherToBaby. Medication fact sheets, option to contact for no-charge consultation, free patient education information materials. www.mothertobaby.org
• Reprotox. Summaries on effects of medications on pregnancy, reproduction, and development (subscription required). www.reprotox.org

Drug Brand Names

Bupropion • Wellbutrin
Citalopram • Celexa
Duloxetine • Cymbalta
Escitalopram • Lexapro
Fluoxetine • Prozac
Mirtazapine • Remeron
Nortriptyline • Pamelor
Paroxetine • Paxil
Sertraline • Zoloft
Trazodone • Oleptro
Venlafaxine • Effexor
Vortioxetine • Trintellix

Bipolar disorder (BD) is a recurrent, life-long psychiatric illness affecting nearly 2% of the world population^1,2 that is characterized by episodes of mania and depression interspersed among periods of relative mood stability.³ The illness causes an enormous health burden, which makes understanding its pathophysiology and treatment patterns a substantial priority.⁴ In the 1950s, lithium was found to be effective for treating acute manic episodes and preventing relapse in BD.⁵ Since then, valproate and carbamazepine also have been FDA-approved for treating mania.^6,7 Antipsychotics have also shown evidence of efficacy in BD treatment,^8,9 particularly for use in acute settings for more rapid effect or for a limited duration,¹⁰ which has led some to refer to them as “mood stabilizers.”¹¹

In this article, we describe changes in trends of prescribing medications to treat BD, the role of ion dysregulation in the disorder, and how a better understanding of this dysregulation might impact the choice of treatment.

Changes in pharmacotherapy for bipolar disorder

From 1997 through 2016, the use of lithium for BD decreased from >30% of patients to 17.6% (with a nadir of 13.9% from 2009 to 2012).¹² Over the same period, the use of nonlithium mood stabilizers decreased from 30.4% to approximately 4.8%, while second-generation antipsychotic (SGAs) use increased from 12.4% to 50.4%.¹² Distressingly, antidepressant use increased from approximately 47% to 56.8%, and antidepressant use without concomitant mood stabilizers increased from 38% to 40.8%, although the rate of antidepressants without either a mood stabilizer or an antipsychotic remained relatively stable (14.9% to 16.8%).¹² In randomized trials, when added to mood stabilizers, antidepressants have consistently failed to separate from placebo,^13-15 but they can destabilize the illness, resulting in increases in mania, depression, and subsyndromal mixed symptoms.^16-18

It is easy to understand clinicians’ attempts to address their patients’ distress due to depressive symptoms that do not resolve with mood stabilizers.^19,20 Similarly, the increased use of antipsychotics is driven by evidence that antipsychotics are effective for treating bipolar depression and preventing the recurrence of manic and (for some antipsychotics) depressive episodes.^21,22 However, long-term antipsychotic use causes brain volume change in patients with schizophrenia²³ or major depressive disorder²⁴ and in nonhuman primates^25,26; metabolic abnormalities^27-31; and cardiovascular adverse effects.³² Antipsychotics are believed to be associated with withdrawal psychosis.^33,34 In the head-to-head Clinical Health Outcomes Initiative in Comparative Effectiveness for Bipolar Disorder (Bipolar CHOICE) study, quetiapine was as effective as lithium but associated with more adverse effects.³⁵ Importantly, the estimated disability-adjusted life years of patients with BD increased by 54.4% from 6.02 million in 1990 to 9.29 million in 2017, which is greater than the increase in the incidence of BD (47.74%) over the same time.³⁶ This means that despite the dramatic increase in treatment options for people with BD, functional outcomes have declined.

One major difference between antipsychotics and mood stabilizers is that antipsychotics do not alter the underlying abnormal pathology of BD.³⁷ An ideal pharmacologic intervention is one that corrects a known pathophysiologic anomaly of the condition being treated. There are no demonstrated abnormalities in the dopamine or serotonin systems in individuals with BD, but long-term use of antipsychotics may create dopaminergic alterations.³³ One of the most reproducible biomarkers associated with manic and bipolar depressed mood states is increased intracellular sodium^38,39 and reduced ability to correct a sodium challenge.^40-42 By normalizing intracellular sodium levels, lithium and the mood-stabilizing anticonvulsants uniquely and specifically counter known physiologic abnormalities in patients with BD.^37,43

The role of ion dysregulation

The pathophysiology of BD remains elusive. A multitude of lines of evidence link BD to abnormal neuroimaging findings,^22,44,45 oxidative stress,⁴⁶ inflammation,⁴⁷ and mitochondrial disease,⁴⁸ but there is still no unifying understanding of these findings. Ion dysregulation appears to be central to understanding and treating BD.^38,39

Despite extensive genetic studies, no genes have been identified that mediate >5% of the risk for BD. Nonetheless, 74% of all genes identified as mediating risk for BD code for proteins essential for the regulation of ion transport and membrane potential.⁴⁹ The 2 genes that contribute the greatest risk are CACNA1C and ANK3, which code for a calcium channel and a cytoskeletal protein, respectively.⁵⁰ ANK3 codes for ankyrin G, which plays a role in proper coupling of the voltage-gated sodium channels to the cytoskeleton.⁵¹ An additional risk gene, TRANK1, contains multiple ankyrin-like repeat domains, which suggests some shared functions with ANK3.⁵² More importantly, the most reproducible pathophysiologic findings in BD are dysregulation of sodium, potassium, hydrogen, and calcium transport, with consequent alteration of depolarization potential, neuronal excitability, and calcium-mediated processes.^38,39,53-56 For example, increased sodium and calcium within cells have been observed in both mania and bipolar depression, and these levels normalize during euthymia. All medications that are effective for treating BD may reduce intracellular sodium or calcium; traditional mood stabilizers do so directly by inhibiting voltage-sensitive sodium channels in an activity-dependent manner or displacing intracellular sodium,^43,57 whereas antipsychotics do so indirectly by increasing sodium pump activity through inhibition of second messengers of the dopamine D2 family of receptors.³⁷

Continue to: The extent of ion dysregulation...

The extent of ion dysregulation is directly associated with the expressed mood state of the illness. A small reduction in the activity of the sodium pump results in a small increase in intracellular sodium (approximately 10 mM).^39,58 This led to the hypothesis that increased intracellular sodium causes the transmembrane potential to increase closer to membrane depolarization threshold, which increases excitability of affected neurons.^38,39,58 Neurons are likely to fire and propagate signals more easily, which may manifest as symptoms of mania, such as increased energy, activity, lability, excitability, irritability, tangentiality, and looseness of associations. As the process of increased intracellular sodium progresses, a minority of neurons are expected to have their transmembrane potentials depolarize sufficiently for the resting membrane potential to go beyond threshold potential.⁵⁹ Such neurons are in a state of constant depolarization (also known as depolarization block), which disrupts neuronal circuits. The difficulty in progression of these signals results in the classic bipolar depression symptoms of low energy, reduced activity, and slowing of all brain activity that is seen as psychomotor slowing.³⁸

Implications for treatment

Medications for treating bipolar illness include lithium, anticonvulsants, benzodiazepines, first-generation antipsychotics, and SGAs.^37,43

Mood stabilizers (lithium and certain anticonvulsants) correct the previously mentioned sodium abnormality by reducing sodium entry into the cell in an activity-dependent manner.⁴³ As the only agents that directly address a known pathophysiologic abnormality, they are foundational in the treatment of BD.⁶⁰ Lithium effectively treats acute mania and prevents relapse.⁶¹ It preferentially targets the active neurons, entering through both voltage-responsive and neurotransmitter-coupled channels.^43,62 This results in an increase of intracellular lithium concentrations to as much as 8 times that of the extracellular concentration.⁶³ These ions displace intracellular sodium ions in a 1:1 ratio, which results in a reduced intracellular sodium concentration that reduces the excitability of neurons.^43,57,62

Substantial evidence supports the use of valproic acid for initial and maintenance treatment of BD.⁶⁴ It inhibits the voltage-sensitive sodium channel when the channel is open, which results in an activity-dependent action that selectively impacts rapidly firing neurons.⁴³ The voltage-gated sodium channels exist nearly exclusively on the axon, beyond the hillock⁶⁵; as such, valproic acid will only inhibit neurons that fire, whereas lithium accumulates throughout the neuron and will affect depolarization in the neuronal soma as well as the firing in the axon.⁴³ Additionally, valproic acid has been observed to enhance gamma-aminobutyric acid (GABA) levels and transmission.^43,66,67 A meta-analysis that included 6 randomized controlled trials illustrated that, acutely, valproate was not different from lithium’s overall efficacy (RR 1.02; 95% CI, 0.87 to 1.20), but was associated with reduced dropout rates compared with placebo or lithium (RR 0.82; 95% CI, 0.71 to 0.95 and RR 0.87; 95% CI, 0.77 to 0.98, respectively).⁶⁴

Lamotrigine is an anticonvulsant used for initial and maintenance treatment of BD, with greater efficacy for depressive episodes⁶⁸; it also has notable effect for treating bipolar depression, although it is not FDA-approved for this indication.⁶⁹ Lamotrigine inhibits sodium influx by binding to open voltage-gated sodium channels⁷⁰ but also appears to reduce N-methyl-D-aspartate–mediated sodium entry,⁷¹ thereby acting both prehillock and posthillock.

Continue to: Carbamazepine is an anticonvulsant...

Carbamazepine is an anticonvulsant FDA-approved for treating BD.⁷ Like valproate, it acts by inhibiting voltage-gated sodium channels in an activity-dependent manner,⁷² which means it preferentially inhibits the most active neurons and those with higher intracellular sodium.⁴³

Benzodiazepines, which have shown to be effective for treating acute mania,⁷³ potentiate synaptic GABA receptors accruing an elevation in intracellular chloride influx.⁷⁴ Despite acute efficacy, benzodiazepine use is limited because these agents are associated with worsening long-term, substance use–related outcomes.^75,76

Antipsychotics are effective for treating mood disorders,^60,76 and their use has been rising dramatically.¹² The antimanic effect of all antipsychotics is believed to be mediated through dopamine D2 blockade, since use of a dose sufficient to block D2 receptors is required, and haloperidol, which acts exclusively on the D2 receptor, is equal to SGAs in its antimanic effect.⁷⁷ Blockade of the D2 receptor will increase the activity of the sodium pump (sodium and potassium-activated adenosine triphosphatase) thus reducing intracellular sodium and calcium concentrations.³⁷ When antipsychotics are used as antidepressants, they are generally used at doses lower than those used to treat mania.⁷⁸

Antipsychotics are effective for treating BD, and may work more quickly than other agents for treating acute mania.⁷⁹ However, maintenance or prevention trials tend to favor mood stabilizers.^35,60,80 Several add-on studies have found the combination of a mood stabilizer plus an antipsychotic is superior to a mood stabilizer alone or an antipsychotic alone.⁸¹

An argument for mood stabilizers

Evidence suggests mood stabilizers and other approaches, such as antipsychotics, are almost equivalent for treating acute mania, with a small clinical advantage of mood stabilizers for preventing relapse. In general, current treatment guidelines do not distinguish mood stabilizers from antipsychotics as the first-line treatment.⁸² Over the past 20 years, antipsychotic use has increased while mood stabilizer use has decreased, so that presently a patient with BD is more likely to be prescribed an antipsychotic than a mood stabilizer.¹² Over the same time, dysfunction among patients with BD has increased.³³ Antipsychotics are appealing because they appear to be equally effective and generally well tolerated. But these agents cause problems that are difficult to see in routine visits, such as metabolic^27-31 and cardiovascular adverse effects²⁹ as well as reductions in brain volume.^23-26 Mechanistic research suggests that mood stabilizers directly correct known pathophysiologic anomalies with additional protective effects, whereas antipsychotics appear to create new abnormalities and contribute to medical problems. Clinicians need to look beyond the similarities in acute efficacy and make a more broadly supported, evidence-based choice for managing BD, which clearly places mood stabilizers as the first-line agent and antipsychotics as reasonable alternatives. At a minimum, mood stabilizers should be viewed as the foundation to which antipsychotics can be added.

Bottom Line

Traditional mood stabilizers—lithium and some anticonvulsants—are the only agents that directly address physiologic abnormalities associated with both mania and bipolar depression, including mood state–associated elevations of intracellular sodium. Because of their specificity, these agents maximize mood stabilization and minimize adverse effects.

Related Resources

• Karas A, Stummer L, Freedberg A. Psychiatric and nonpsychiatric indications for mood stabilizers and select antiepileptics. Current Psychiatry. 2022;21(4):34-38. doi:10.12788/cp.0230
• Koch J. Mood stabilizers: balancing tolerability, serum levels, and dosage. Current Psychiatry. 2021;20(7):37-40. doi:10.12788/cp.0147

Drug Brand Names

Carbamazepine • Tegretol
Haloperidol • Haldol
Lamotrigine • Lamictal
Lithium • Eskalith, Lithobid
Quetiapine • Seroquel
Valproate • Depakote, Depakene

Bipolar disorder (BD) is a recurrent, life-long psychiatric illness affecting nearly 2% of the world population^1,2 that is characterized by episodes of mania and depression interspersed among periods of relative mood stability.³ The illness causes an enormous health burden, which makes understanding its pathophysiology and treatment patterns a substantial priority.⁴ In the 1950s, lithium was found to be effective for treating acute manic episodes and preventing relapse in BD.⁵ Since then, valproate and carbamazepine also have been FDA-approved for treating mania.^6,7 Antipsychotics have also shown evidence of efficacy in BD treatment,^8,9 particularly for use in acute settings for more rapid effect or for a limited duration,¹⁰ which has led some to refer to them as “mood stabilizers.”¹¹

In this article, we describe changes in trends of prescribing medications to treat BD, the role of ion dysregulation in the disorder, and how a better understanding of this dysregulation might impact the choice of treatment.

Changes in pharmacotherapy for bipolar disorder

From 1997 through 2016, the use of lithium for BD decreased from >30% of patients to 17.6% (with a nadir of 13.9% from 2009 to 2012).¹² Over the same period, the use of nonlithium mood stabilizers decreased from 30.4% to approximately 4.8%, while second-generation antipsychotic (SGAs) use increased from 12.4% to 50.4%.¹² Distressingly, antidepressant use increased from approximately 47% to 56.8%, and antidepressant use without concomitant mood stabilizers increased from 38% to 40.8%, although the rate of antidepressants without either a mood stabilizer or an antipsychotic remained relatively stable (14.9% to 16.8%).¹² In randomized trials, when added to mood stabilizers, antidepressants have consistently failed to separate from placebo,^13-15 but they can destabilize the illness, resulting in increases in mania, depression, and subsyndromal mixed symptoms.^16-18

It is easy to understand clinicians’ attempts to address their patients’ distress due to depressive symptoms that do not resolve with mood stabilizers.^19,20 Similarly, the increased use of antipsychotics is driven by evidence that antipsychotics are effective for treating bipolar depression and preventing the recurrence of manic and (for some antipsychotics) depressive episodes.^21,22 However, long-term antipsychotic use causes brain volume change in patients with schizophrenia²³ or major depressive disorder²⁴ and in nonhuman primates^25,26; metabolic abnormalities^27-31; and cardiovascular adverse effects.³² Antipsychotics are believed to be associated with withdrawal psychosis.^33,34 In the head-to-head Clinical Health Outcomes Initiative in Comparative Effectiveness for Bipolar Disorder (Bipolar CHOICE) study, quetiapine was as effective as lithium but associated with more adverse effects.³⁵ Importantly, the estimated disability-adjusted life years of patients with BD increased by 54.4% from 6.02 million in 1990 to 9.29 million in 2017, which is greater than the increase in the incidence of BD (47.74%) over the same time.³⁶ This means that despite the dramatic increase in treatment options for people with BD, functional outcomes have declined.

One major difference between antipsychotics and mood stabilizers is that antipsychotics do not alter the underlying abnormal pathology of BD.³⁷ An ideal pharmacologic intervention is one that corrects a known pathophysiologic anomaly of the condition being treated. There are no demonstrated abnormalities in the dopamine or serotonin systems in individuals with BD, but long-term use of antipsychotics may create dopaminergic alterations.³³ One of the most reproducible biomarkers associated with manic and bipolar depressed mood states is increased intracellular sodium^38,39 and reduced ability to correct a sodium challenge.^40-42 By normalizing intracellular sodium levels, lithium and the mood-stabilizing anticonvulsants uniquely and specifically counter known physiologic abnormalities in patients with BD.^37,43

The role of ion dysregulation

The pathophysiology of BD remains elusive. A multitude of lines of evidence link BD to abnormal neuroimaging findings,^22,44,45 oxidative stress,⁴⁶ inflammation,⁴⁷ and mitochondrial disease,⁴⁸ but there is still no unifying understanding of these findings. Ion dysregulation appears to be central to understanding and treating BD.^38,39

Despite extensive genetic studies, no genes have been identified that mediate >5% of the risk for BD. Nonetheless, 74% of all genes identified as mediating risk for BD code for proteins essential for the regulation of ion transport and membrane potential.⁴⁹ The 2 genes that contribute the greatest risk are CACNA1C and ANK3, which code for a calcium channel and a cytoskeletal protein, respectively.⁵⁰ ANK3 codes for ankyrin G, which plays a role in proper coupling of the voltage-gated sodium channels to the cytoskeleton.⁵¹ An additional risk gene, TRANK1, contains multiple ankyrin-like repeat domains, which suggests some shared functions with ANK3.⁵² More importantly, the most reproducible pathophysiologic findings in BD are dysregulation of sodium, potassium, hydrogen, and calcium transport, with consequent alteration of depolarization potential, neuronal excitability, and calcium-mediated processes.^38,39,53-56 For example, increased sodium and calcium within cells have been observed in both mania and bipolar depression, and these levels normalize during euthymia. All medications that are effective for treating BD may reduce intracellular sodium or calcium; traditional mood stabilizers do so directly by inhibiting voltage-sensitive sodium channels in an activity-dependent manner or displacing intracellular sodium,^43,57 whereas antipsychotics do so indirectly by increasing sodium pump activity through inhibition of second messengers of the dopamine D2 family of receptors.³⁷

Continue to: The extent of ion dysregulation...

The extent of ion dysregulation is directly associated with the expressed mood state of the illness. A small reduction in the activity of the sodium pump results in a small increase in intracellular sodium (approximately 10 mM).^39,58 This led to the hypothesis that increased intracellular sodium causes the transmembrane potential to increase closer to membrane depolarization threshold, which increases excitability of affected neurons.^38,39,58 Neurons are likely to fire and propagate signals more easily, which may manifest as symptoms of mania, such as increased energy, activity, lability, excitability, irritability, tangentiality, and looseness of associations. As the process of increased intracellular sodium progresses, a minority of neurons are expected to have their transmembrane potentials depolarize sufficiently for the resting membrane potential to go beyond threshold potential.⁵⁹ Such neurons are in a state of constant depolarization (also known as depolarization block), which disrupts neuronal circuits. The difficulty in progression of these signals results in the classic bipolar depression symptoms of low energy, reduced activity, and slowing of all brain activity that is seen as psychomotor slowing.³⁸

Implications for treatment

Medications for treating bipolar illness include lithium, anticonvulsants, benzodiazepines, first-generation antipsychotics, and SGAs.^37,43

Mood stabilizers (lithium and certain anticonvulsants) correct the previously mentioned sodium abnormality by reducing sodium entry into the cell in an activity-dependent manner.⁴³ As the only agents that directly address a known pathophysiologic abnormality, they are foundational in the treatment of BD.⁶⁰ Lithium effectively treats acute mania and prevents relapse.⁶¹ It preferentially targets the active neurons, entering through both voltage-responsive and neurotransmitter-coupled channels.^43,62 This results in an increase of intracellular lithium concentrations to as much as 8 times that of the extracellular concentration.⁶³ These ions displace intracellular sodium ions in a 1:1 ratio, which results in a reduced intracellular sodium concentration that reduces the excitability of neurons.^43,57,62

Substantial evidence supports the use of valproic acid for initial and maintenance treatment of BD.⁶⁴ It inhibits the voltage-sensitive sodium channel when the channel is open, which results in an activity-dependent action that selectively impacts rapidly firing neurons.⁴³ The voltage-gated sodium channels exist nearly exclusively on the axon, beyond the hillock⁶⁵; as such, valproic acid will only inhibit neurons that fire, whereas lithium accumulates throughout the neuron and will affect depolarization in the neuronal soma as well as the firing in the axon.⁴³ Additionally, valproic acid has been observed to enhance gamma-aminobutyric acid (GABA) levels and transmission.^43,66,67 A meta-analysis that included 6 randomized controlled trials illustrated that, acutely, valproate was not different from lithium’s overall efficacy (RR 1.02; 95% CI, 0.87 to 1.20), but was associated with reduced dropout rates compared with placebo or lithium (RR 0.82; 95% CI, 0.71 to 0.95 and RR 0.87; 95% CI, 0.77 to 0.98, respectively).⁶⁴

Lamotrigine is an anticonvulsant used for initial and maintenance treatment of BD, with greater efficacy for depressive episodes⁶⁸; it also has notable effect for treating bipolar depression, although it is not FDA-approved for this indication.⁶⁹ Lamotrigine inhibits sodium influx by binding to open voltage-gated sodium channels⁷⁰ but also appears to reduce N-methyl-D-aspartate–mediated sodium entry,⁷¹ thereby acting both prehillock and posthillock.

Continue to: Carbamazepine is an anticonvulsant...

Carbamazepine is an anticonvulsant FDA-approved for treating BD.⁷ Like valproate, it acts by inhibiting voltage-gated sodium channels in an activity-dependent manner,⁷² which means it preferentially inhibits the most active neurons and those with higher intracellular sodium.⁴³

Benzodiazepines, which have shown to be effective for treating acute mania,⁷³ potentiate synaptic GABA receptors accruing an elevation in intracellular chloride influx.⁷⁴ Despite acute efficacy, benzodiazepine use is limited because these agents are associated with worsening long-term, substance use–related outcomes.^75,76

Antipsychotics are effective for treating mood disorders,^60,76 and their use has been rising dramatically.¹² The antimanic effect of all antipsychotics is believed to be mediated through dopamine D2 blockade, since use of a dose sufficient to block D2 receptors is required, and haloperidol, which acts exclusively on the D2 receptor, is equal to SGAs in its antimanic effect.⁷⁷ Blockade of the D2 receptor will increase the activity of the sodium pump (sodium and potassium-activated adenosine triphosphatase) thus reducing intracellular sodium and calcium concentrations.³⁷ When antipsychotics are used as antidepressants, they are generally used at doses lower than those used to treat mania.⁷⁸

Antipsychotics are effective for treating BD, and may work more quickly than other agents for treating acute mania.⁷⁹ However, maintenance or prevention trials tend to favor mood stabilizers.^35,60,80 Several add-on studies have found the combination of a mood stabilizer plus an antipsychotic is superior to a mood stabilizer alone or an antipsychotic alone.⁸¹

An argument for mood stabilizers

Evidence suggests mood stabilizers and other approaches, such as antipsychotics, are almost equivalent for treating acute mania, with a small clinical advantage of mood stabilizers for preventing relapse. In general, current treatment guidelines do not distinguish mood stabilizers from antipsychotics as the first-line treatment.⁸² Over the past 20 years, antipsychotic use has increased while mood stabilizer use has decreased, so that presently a patient with BD is more likely to be prescribed an antipsychotic than a mood stabilizer.¹² Over the same time, dysfunction among patients with BD has increased.³³ Antipsychotics are appealing because they appear to be equally effective and generally well tolerated. But these agents cause problems that are difficult to see in routine visits, such as metabolic^27-31 and cardiovascular adverse effects²⁹ as well as reductions in brain volume.^23-26 Mechanistic research suggests that mood stabilizers directly correct known pathophysiologic anomalies with additional protective effects, whereas antipsychotics appear to create new abnormalities and contribute to medical problems. Clinicians need to look beyond the similarities in acute efficacy and make a more broadly supported, evidence-based choice for managing BD, which clearly places mood stabilizers as the first-line agent and antipsychotics as reasonable alternatives. At a minimum, mood stabilizers should be viewed as the foundation to which antipsychotics can be added.

Bottom Line

Traditional mood stabilizers—lithium and some anticonvulsants—are the only agents that directly address physiologic abnormalities associated with both mania and bipolar depression, including mood state–associated elevations of intracellular sodium. Because of their specificity, these agents maximize mood stabilization and minimize adverse effects.

Related Resources

• Karas A, Stummer L, Freedberg A. Psychiatric and nonpsychiatric indications for mood stabilizers and select antiepileptics. Current Psychiatry. 2022;21(4):34-38. doi:10.12788/cp.0230
• Koch J. Mood stabilizers: balancing tolerability, serum levels, and dosage. Current Psychiatry. 2021;20(7):37-40. doi:10.12788/cp.0147

Drug Brand Names

Carbamazepine • Tegretol
Haloperidol • Haldol
Lamotrigine • Lamictal
Lithium • Eskalith, Lithobid
Quetiapine • Seroquel
Valproate • Depakote, Depakene

Bipolar disorder (BD) is a recurrent, life-long psychiatric illness affecting nearly 2% of the world population^1,2 that is characterized by episodes of mania and depression interspersed among periods of relative mood stability.³ The illness causes an enormous health burden, which makes understanding its pathophysiology and treatment patterns a substantial priority.⁴ In the 1950s, lithium was found to be effective for treating acute manic episodes and preventing relapse in BD.⁵ Since then, valproate and carbamazepine also have been FDA-approved for treating mania.^6,7 Antipsychotics have also shown evidence of efficacy in BD treatment,^8,9 particularly for use in acute settings for more rapid effect or for a limited duration,¹⁰ which has led some to refer to them as “mood stabilizers.”¹¹

In this article, we describe changes in trends of prescribing medications to treat BD, the role of ion dysregulation in the disorder, and how a better understanding of this dysregulation might impact the choice of treatment.

Changes in pharmacotherapy for bipolar disorder

From 1997 through 2016, the use of lithium for BD decreased from >30% of patients to 17.6% (with a nadir of 13.9% from 2009 to 2012).¹² Over the same period, the use of nonlithium mood stabilizers decreased from 30.4% to approximately 4.8%, while second-generation antipsychotic (SGAs) use increased from 12.4% to 50.4%.¹² Distressingly, antidepressant use increased from approximately 47% to 56.8%, and antidepressant use without concomitant mood stabilizers increased from 38% to 40.8%, although the rate of antidepressants without either a mood stabilizer or an antipsychotic remained relatively stable (14.9% to 16.8%).¹² In randomized trials, when added to mood stabilizers, antidepressants have consistently failed to separate from placebo,^13-15 but they can destabilize the illness, resulting in increases in mania, depression, and subsyndromal mixed symptoms.^16-18

It is easy to understand clinicians’ attempts to address their patients’ distress due to depressive symptoms that do not resolve with mood stabilizers.^19,20 Similarly, the increased use of antipsychotics is driven by evidence that antipsychotics are effective for treating bipolar depression and preventing the recurrence of manic and (for some antipsychotics) depressive episodes.^21,22 However, long-term antipsychotic use causes brain volume change in patients with schizophrenia²³ or major depressive disorder²⁴ and in nonhuman primates^25,26; metabolic abnormalities^27-31; and cardiovascular adverse effects.³² Antipsychotics are believed to be associated with withdrawal psychosis.^33,34 In the head-to-head Clinical Health Outcomes Initiative in Comparative Effectiveness for Bipolar Disorder (Bipolar CHOICE) study, quetiapine was as effective as lithium but associated with more adverse effects.³⁵ Importantly, the estimated disability-adjusted life years of patients with BD increased by 54.4% from 6.02 million in 1990 to 9.29 million in 2017, which is greater than the increase in the incidence of BD (47.74%) over the same time.³⁶ This means that despite the dramatic increase in treatment options for people with BD, functional outcomes have declined.

One major difference between antipsychotics and mood stabilizers is that antipsychotics do not alter the underlying abnormal pathology of BD.³⁷ An ideal pharmacologic intervention is one that corrects a known pathophysiologic anomaly of the condition being treated. There are no demonstrated abnormalities in the dopamine or serotonin systems in individuals with BD, but long-term use of antipsychotics may create dopaminergic alterations.³³ One of the most reproducible biomarkers associated with manic and bipolar depressed mood states is increased intracellular sodium^38,39 and reduced ability to correct a sodium challenge.^40-42 By normalizing intracellular sodium levels, lithium and the mood-stabilizing anticonvulsants uniquely and specifically counter known physiologic abnormalities in patients with BD.^37,43

The role of ion dysregulation

The pathophysiology of BD remains elusive. A multitude of lines of evidence link BD to abnormal neuroimaging findings,^22,44,45 oxidative stress,⁴⁶ inflammation,⁴⁷ and mitochondrial disease,⁴⁸ but there is still no unifying understanding of these findings. Ion dysregulation appears to be central to understanding and treating BD.^38,39

Despite extensive genetic studies, no genes have been identified that mediate >5% of the risk for BD. Nonetheless, 74% of all genes identified as mediating risk for BD code for proteins essential for the regulation of ion transport and membrane potential.⁴⁹ The 2 genes that contribute the greatest risk are CACNA1C and ANK3, which code for a calcium channel and a cytoskeletal protein, respectively.⁵⁰ ANK3 codes for ankyrin G, which plays a role in proper coupling of the voltage-gated sodium channels to the cytoskeleton.⁵¹ An additional risk gene, TRANK1, contains multiple ankyrin-like repeat domains, which suggests some shared functions with ANK3.⁵² More importantly, the most reproducible pathophysiologic findings in BD are dysregulation of sodium, potassium, hydrogen, and calcium transport, with consequent alteration of depolarization potential, neuronal excitability, and calcium-mediated processes.^38,39,53-56 For example, increased sodium and calcium within cells have been observed in both mania and bipolar depression, and these levels normalize during euthymia. All medications that are effective for treating BD may reduce intracellular sodium or calcium; traditional mood stabilizers do so directly by inhibiting voltage-sensitive sodium channels in an activity-dependent manner or displacing intracellular sodium,^43,57 whereas antipsychotics do so indirectly by increasing sodium pump activity through inhibition of second messengers of the dopamine D2 family of receptors.³⁷

Continue to: The extent of ion dysregulation...

The extent of ion dysregulation is directly associated with the expressed mood state of the illness. A small reduction in the activity of the sodium pump results in a small increase in intracellular sodium (approximately 10 mM).^39,58 This led to the hypothesis that increased intracellular sodium causes the transmembrane potential to increase closer to membrane depolarization threshold, which increases excitability of affected neurons.^38,39,58 Neurons are likely to fire and propagate signals more easily, which may manifest as symptoms of mania, such as increased energy, activity, lability, excitability, irritability, tangentiality, and looseness of associations. As the process of increased intracellular sodium progresses, a minority of neurons are expected to have their transmembrane potentials depolarize sufficiently for the resting membrane potential to go beyond threshold potential.⁵⁹ Such neurons are in a state of constant depolarization (also known as depolarization block), which disrupts neuronal circuits. The difficulty in progression of these signals results in the classic bipolar depression symptoms of low energy, reduced activity, and slowing of all brain activity that is seen as psychomotor slowing.³⁸

Implications for treatment

Medications for treating bipolar illness include lithium, anticonvulsants, benzodiazepines, first-generation antipsychotics, and SGAs.^37,43

Mood stabilizers (lithium and certain anticonvulsants) correct the previously mentioned sodium abnormality by reducing sodium entry into the cell in an activity-dependent manner.⁴³ As the only agents that directly address a known pathophysiologic abnormality, they are foundational in the treatment of BD.⁶⁰ Lithium effectively treats acute mania and prevents relapse.⁶¹ It preferentially targets the active neurons, entering through both voltage-responsive and neurotransmitter-coupled channels.^43,62 This results in an increase of intracellular lithium concentrations to as much as 8 times that of the extracellular concentration.⁶³ These ions displace intracellular sodium ions in a 1:1 ratio, which results in a reduced intracellular sodium concentration that reduces the excitability of neurons.^43,57,62

Substantial evidence supports the use of valproic acid for initial and maintenance treatment of BD.⁶⁴ It inhibits the voltage-sensitive sodium channel when the channel is open, which results in an activity-dependent action that selectively impacts rapidly firing neurons.⁴³ The voltage-gated sodium channels exist nearly exclusively on the axon, beyond the hillock⁶⁵; as such, valproic acid will only inhibit neurons that fire, whereas lithium accumulates throughout the neuron and will affect depolarization in the neuronal soma as well as the firing in the axon.⁴³ Additionally, valproic acid has been observed to enhance gamma-aminobutyric acid (GABA) levels and transmission.^43,66,67 A meta-analysis that included 6 randomized controlled trials illustrated that, acutely, valproate was not different from lithium’s overall efficacy (RR 1.02; 95% CI, 0.87 to 1.20), but was associated with reduced dropout rates compared with placebo or lithium (RR 0.82; 95% CI, 0.71 to 0.95 and RR 0.87; 95% CI, 0.77 to 0.98, respectively).⁶⁴

Lamotrigine is an anticonvulsant used for initial and maintenance treatment of BD, with greater efficacy for depressive episodes⁶⁸; it also has notable effect for treating bipolar depression, although it is not FDA-approved for this indication.⁶⁹ Lamotrigine inhibits sodium influx by binding to open voltage-gated sodium channels⁷⁰ but also appears to reduce N-methyl-D-aspartate–mediated sodium entry,⁷¹ thereby acting both prehillock and posthillock.

Continue to: Carbamazepine is an anticonvulsant...

Carbamazepine is an anticonvulsant FDA-approved for treating BD.⁷ Like valproate, it acts by inhibiting voltage-gated sodium channels in an activity-dependent manner,⁷² which means it preferentially inhibits the most active neurons and those with higher intracellular sodium.⁴³

Benzodiazepines, which have shown to be effective for treating acute mania,⁷³ potentiate synaptic GABA receptors accruing an elevation in intracellular chloride influx.⁷⁴ Despite acute efficacy, benzodiazepine use is limited because these agents are associated with worsening long-term, substance use–related outcomes.^75,76

Antipsychotics are effective for treating mood disorders,^60,76 and their use has been rising dramatically.¹² The antimanic effect of all antipsychotics is believed to be mediated through dopamine D2 blockade, since use of a dose sufficient to block D2 receptors is required, and haloperidol, which acts exclusively on the D2 receptor, is equal to SGAs in its antimanic effect.⁷⁷ Blockade of the D2 receptor will increase the activity of the sodium pump (sodium and potassium-activated adenosine triphosphatase) thus reducing intracellular sodium and calcium concentrations.³⁷ When antipsychotics are used as antidepressants, they are generally used at doses lower than those used to treat mania.⁷⁸

Antipsychotics are effective for treating BD, and may work more quickly than other agents for treating acute mania.⁷⁹ However, maintenance or prevention trials tend to favor mood stabilizers.^35,60,80 Several add-on studies have found the combination of a mood stabilizer plus an antipsychotic is superior to a mood stabilizer alone or an antipsychotic alone.⁸¹

An argument for mood stabilizers

Evidence suggests mood stabilizers and other approaches, such as antipsychotics, are almost equivalent for treating acute mania, with a small clinical advantage of mood stabilizers for preventing relapse. In general, current treatment guidelines do not distinguish mood stabilizers from antipsychotics as the first-line treatment.⁸² Over the past 20 years, antipsychotic use has increased while mood stabilizer use has decreased, so that presently a patient with BD is more likely to be prescribed an antipsychotic than a mood stabilizer.¹² Over the same time, dysfunction among patients with BD has increased.³³ Antipsychotics are appealing because they appear to be equally effective and generally well tolerated. But these agents cause problems that are difficult to see in routine visits, such as metabolic^27-31 and cardiovascular adverse effects²⁹ as well as reductions in brain volume.^23-26 Mechanistic research suggests that mood stabilizers directly correct known pathophysiologic anomalies with additional protective effects, whereas antipsychotics appear to create new abnormalities and contribute to medical problems. Clinicians need to look beyond the similarities in acute efficacy and make a more broadly supported, evidence-based choice for managing BD, which clearly places mood stabilizers as the first-line agent and antipsychotics as reasonable alternatives. At a minimum, mood stabilizers should be viewed as the foundation to which antipsychotics can be added.

Bottom Line

Traditional mood stabilizers—lithium and some anticonvulsants—are the only agents that directly address physiologic abnormalities associated with both mania and bipolar depression, including mood state–associated elevations of intracellular sodium. Because of their specificity, these agents maximize mood stabilization and minimize adverse effects.

Related Resources

• Karas A, Stummer L, Freedberg A. Psychiatric and nonpsychiatric indications for mood stabilizers and select antiepileptics. Current Psychiatry. 2022;21(4):34-38. doi:10.12788/cp.0230
• Koch J. Mood stabilizers: balancing tolerability, serum levels, and dosage. Current Psychiatry. 2021;20(7):37-40. doi:10.12788/cp.0147

Drug Brand Names

Carbamazepine • Tegretol
Haloperidol • Haldol
Lamotrigine • Lamictal
Lithium • Eskalith, Lithobid
Quetiapine • Seroquel
Valproate • Depakote, Depakene

CASE Depressed and anxious

Five years ago, Ms. X, age 60, was diagnosed with treatment-resistant major depressive disorder (MDD) with anxiety. This diagnosis was established by a previous psychiatrist. She presents to a clinic for a second opinion.

Since her diagnosis, Ms. X has experienced sad mood, anhedonia, difficulty falling asleep, increased appetite and weight, and decreased concentration and attention. Her anxiety stems from her inability to work, which causes her to worry about her children. In the clinic, the treatment team conducts the Patient Health Questionnaire-9 (PHQ-9) and Generalized Anxiety Disorder-7 item scale (GAD-7) with Ms. X. She scores 16 on the PHQ-9, indicating moderately severe depression, and scores 12 on the GAD-7, indicating moderate anxiety.

Ms. X’s current medication regimen consists of venlafaxine extended-release (XR) 225 mg/d, trazodone 100 mg/d at bedtime, and clonazepam 1 mg twice daily. She reports no significant improvement of her symptoms from these medications. Additionally, Ms. X reports that in the past she had been prescribed fluoxetine, citalopram, and duloxetine, but she cannot recall the dosages.

Ms. X appears appropriately groomed, maintains appropriate eye contact, has clear speech, and does not show evidence of internal stimulation; however, she has difficulty following instructions. She makes negative comments about herself such as “I’m worthless” and “Nobody cares about me.” The treatment team decides to taper Ms. X off venlafaxine XR and initiates sertraline 50 mg/d, while continuing trazodone 50 mg/d at bedtime and clonazepam 1 mg twice daily. The team refers her for cognitive-behavioral therapy (CBT) to address her cognitive distortions, sad mood, and anxiety. Ms. X is asked to follow up with Psychiatry in 1 week.

EVALUATION Unusual behavior

At her CBT intake, Ms. X endorses depression and anxiety. Her PHQ-9 score at this visit is 19 (moderately severe depression) and GAD-7 score is 16 (severe anxiety). The psychologist notes that Ms. X is able to complete activities of daily living and instrumental activities of daily living without assistance. Ms. X denies any use of illicit substances or alcohol. No gross memory impairment is noted during this appointment, though Ms. X exhibits unusual behavior, including exiting and re-entering the clinic multiple times to repeatedly ask about follow-up appointments. The psychologist concludes that Ms. X’s presentation and behavior can be explained by MDD and pseudodementia.

[polldaddy:12189562]

The authors’ observations

Pseudodementia gained recognition in clinical research >100 years ago.¹ Officially coined by Kiloh in 1961, the term was used broadly to categorize psychiatric cases that present like dementia but are the result of reversible causes. More recently, it has been used to describe older adults who present with cognitive deficits in the context of depressive symptoms.² The goal of evaluation is to determine if the primary issue is a cognitive disorder or a depressive episode. DSM-5-TR does not classify pseudodementia as a distinct diagnosis, but instead categorizes its symptoms as components under other major diagnostic categories. Patients can present with MDD and associated cognitive symptoms, or with a cognitive disorder with depressive symptoms, which would be diagnosed as a cognitive disorder with a major depressive-like episode.³

Pseudodementia is rare. Brodaty et al⁴ found the prevalence of pseudodementia in primary care settings was 0.6%. Older adults (age >65) who live alone are at increased risk of developing pseudodementia, which can be worsened by poor social support and acute psychosocial and environmental changes.⁵ A key characteristic of this disorder is that as the patient’s depressed mood improves, their memory and cognition also improve.⁶ Table 1^3,6 outlines overlapping features of MDD and pseudodementia.

Continue to: EVALUATION Worsening depression

 

 

EVALUATION Worsening depression

At her Psychiatry follow-up appointment, Ms. X reports that her mood is worse since she ended the relationship with her partner and she feels anxious because the partner was financially supporting her. Her PHQ-9 score is 24 (severe depression) and her GAD-7 score is 12 (moderate anxiety). Ms. X reports tolerating her transition from venlafaxine XR 225 mg/d to sertraline 50 mg/d well.

Additionally, Ms. X reports her children have called her “useless” since she continues to have difficulties following through on household tasks, even though she has no physical impairments that prevent her from completing them. The Psychiatry team observes that Ms. X has no problems walking or moving her arms or legs.

The Psychiatry team administers the Montreal Cognitive Assessment (MoCA). Ms. X scores 22, indicating mild impairment.

The team recommends a neuropsychological assessment to determine if this MoCA score is due to a cognitive disorder or is rooted in her mood symptoms. The team also recommends an MRI of the brain, complete blood count (CBC), comprehensive metabolic panel (CMP), and urinalysis (UA).

[polldaddy:12189567]

Continue to: The authors' observations

 

 

The authors’ observations

Neuropsychological assessments are important tools for exploring the behavioral manifestations of brain dysfunction (Table 2).⁷ These assessments factor in elements of neurology, psychiatry, and psychology to provide information about the diagnosis, prognosis, and functional status of patients with medical conditions, especially those with neurocognitive and psychiatric disorders. They combine information from the patient and collateral interviews, behavioral observations, a review of patient records, and objective tests of motor, emotional, and cognitive function.

Among other uses, neuropsychological assessments can help identify depression in patients with neurologic impairment, determine the diagnosis and plan of care for patients with concussions, determine the risk of a motor vehicle crash in patients with cognitive impairment, and distinguish Alzheimer disease from vascular dementia.⁸ Components of such assessments include the Beck Anxiety Inventory (BAI) to assess anxiety, the Dementia Rating Scale-2 and Neuropsychological Assessment Battery-Screening Module to assess dementia, and the Beck Depression Inventory (BDI) to assess depression.⁹

EVALUATION Continued cognitive decline

A different psychologist performs the neuro­psychological assessment, who conducts the Repeatable Battery for the Assessment of Neuropsychological Status Update to determine if Ms. X is experiencing cognitive impairment. Her immediate memory, visuospatial/constructions, language, attention, and delayed memory are significantly impaired for someone her age. The psychologist also administers the Wechsler Adult Intelligence Scale IV and finds Ms. X’s general cognitive ability is within the low average range of intellectual functioning as measured by Full-Scale IQ. Ms. X scores 29 on the BDI-II, indicating significant depressive symptoms, and 13 on the BAI, indicating mild anxiety symptoms.

Ms. X is diagnosed with MDD and an unspecified neurocognitive disorder. The psychologist recommends she start CBT to address her mood and anxiety symptoms.

Upon reviewing the results with Ms. X, the treatment team again recommends a brain MRI, CBC, CMP, and UA to rule out organic causes of her cognitive decline. Ms. X decides against the MRI and laboratory workup and elects to continue her present medication regimen and CBT.

Several weeks later, Ms. X’s family brings her to the emergency department (ED) for evaluation of worsening mood, decreased personal hygiene, increased irritability, and further cognitive decline. They report she is having an increasingly difficult time remembering things such as where she parked her car. The ED team decides to discontinue clonazepam but continues sertraline and trazodone.

Continue to: CBC, CMP, and UA...

CBC, CMP, and UA are unremarkable. Ms. X undergoes a brain CT scan without contrast, which reveals hyperdense lesions in the inferior left tentorium, posterior fossa. A subsequent brain MRI with contrast reveals a dural-based enhancing mass, inferior to the left tentorium, in the left posterior fossa measuring 2.2 cm x 2.1 cm, suggestive of a meningioma. The team orders a Neurosurgery consult.

[polldaddy:12189571]

The authors’ observations

While most brain tumors are secondary to metastasis, meningiomas are the most common primary CNS tumor. Typically, they are asymptomatic; their diagnosis is often delayed until the patient presents with psychiatric symptoms without any focal neurologic findings. The frontal lobe is the most common location of meningioma. Data from 48 case reports of patients with meningiomas and psychiatric symptoms suggest symptoms do not always correlate with specific brain regions.^10,11

Indications for neuroimaging in cases such as Ms. X include an abrupt change in behavior or personality, lack of response to psychiatric treatment, presence of focal neurologic signs, and an unusual psychiatric presentation and development of symptoms.¹¹

TREATMENT Neurosurgery

Neurosurgery recommends and performs a suboccipital craniotomy for biopsy and resection. Ms. X tolerates the procedure well. A meningioma is found in the posterior fossa, near the cerebellar convexity. A biopsy finds no evidence of malignancies.

At her postoperative follow-up appointment several days after the procedure, Ms. X reports new-onset hearing loss and tinnitus.

[polldaddy:12189747]

Continue to: The authors' observations

 

 

The authors’ observations

Patients who require neurosurgery typically already carry a heavy psychiatric burden, which makes it challenging to determine the exact psychiatric consequences of neuro­surgery.^12-14 For example, research shows that temporal lobe resection and temporal lobectomy for treatment-resistant epilepsy can lead to an exacerbation of baseline psychiatric symptoms and the development of new symptoms (31% to 34%).^15,16 However, Bommakanti et al¹³ found no new psychiatric symptoms after resection of meningiomas, and surgery seemed to play a role in ameliorating psychiatric symptoms in patients with intracranial tumors. Research attempting to document the psychiatric sequelae of neurosurgery has had mixed results, and it is difficult to determine what effects brain surgery has on mental health.

OUTCOME Minimal improvement

Several weeks after neurosurgery, Ms. X and her family report her mood is improved. Her PHQ-9 score improves to 15, but her GAD-7 score increases to 13, 1 point above her previous score.

The treatment team recommends Ms. X continue taking sertraline 50 mg/d and trazodone 50 mg/d at bedtime. Ms. X’s family reports her cognition and memory have not improved; her MoCA score increases by 1 point to 23. The treatment team discusses with Ms. X and her family the possibility that her cognitive problems maybe better explained as a neurocognitive disorder rather than as a result of the meningioma, since her MoCA score has not significantly improved. Ms. X and her family decide to seek a second opinion from a neurologist.

Bottom Line

Pseudodementia is a term used to describe older adults who present with cognitive issues in the context of depressive symptoms. Even in the absence of focal findings, neuroimaging should be considered as part of the workup in patients who continue to experience a progressive decline in mood and cognitive function.

Related Resources

• Moller MD, Parmenter BA, Lane DW. Neuropsychological testing: a useful but underutilized resource. Current Psychiatry. 2019;18(11):40-46,51.
• Pollak J. Psychological/neuropsychological testing: when to refer for reexamination. Current Psychiatry. 2021;20(9):18- 19,30-31,37. doi:10.12788/cp.0157

Drug Brand Names

Citalopram • Celexa
Clonazepam • Klonopin
Duloxetine • Cymbalta
Fluoxetine • Prozac
Sertraline • Zoloft
Trazodone • Oleptro
Venlafaxine extended- release • Effexor XR

CASE Depressed and anxious

Five years ago, Ms. X, age 60, was diagnosed with treatment-resistant major depressive disorder (MDD) with anxiety. This diagnosis was established by a previous psychiatrist. She presents to a clinic for a second opinion.

Since her diagnosis, Ms. X has experienced sad mood, anhedonia, difficulty falling asleep, increased appetite and weight, and decreased concentration and attention. Her anxiety stems from her inability to work, which causes her to worry about her children. In the clinic, the treatment team conducts the Patient Health Questionnaire-9 (PHQ-9) and Generalized Anxiety Disorder-7 item scale (GAD-7) with Ms. X. She scores 16 on the PHQ-9, indicating moderately severe depression, and scores 12 on the GAD-7, indicating moderate anxiety.

Ms. X’s current medication regimen consists of venlafaxine extended-release (XR) 225 mg/d, trazodone 100 mg/d at bedtime, and clonazepam 1 mg twice daily. She reports no significant improvement of her symptoms from these medications. Additionally, Ms. X reports that in the past she had been prescribed fluoxetine, citalopram, and duloxetine, but she cannot recall the dosages.

Ms. X appears appropriately groomed, maintains appropriate eye contact, has clear speech, and does not show evidence of internal stimulation; however, she has difficulty following instructions. She makes negative comments about herself such as “I’m worthless” and “Nobody cares about me.” The treatment team decides to taper Ms. X off venlafaxine XR and initiates sertraline 50 mg/d, while continuing trazodone 50 mg/d at bedtime and clonazepam 1 mg twice daily. The team refers her for cognitive-behavioral therapy (CBT) to address her cognitive distortions, sad mood, and anxiety. Ms. X is asked to follow up with Psychiatry in 1 week.

EVALUATION Unusual behavior

At her CBT intake, Ms. X endorses depression and anxiety. Her PHQ-9 score at this visit is 19 (moderately severe depression) and GAD-7 score is 16 (severe anxiety). The psychologist notes that Ms. X is able to complete activities of daily living and instrumental activities of daily living without assistance. Ms. X denies any use of illicit substances or alcohol. No gross memory impairment is noted during this appointment, though Ms. X exhibits unusual behavior, including exiting and re-entering the clinic multiple times to repeatedly ask about follow-up appointments. The psychologist concludes that Ms. X’s presentation and behavior can be explained by MDD and pseudodementia.

[polldaddy:12189562]

The authors’ observations

Pseudodementia gained recognition in clinical research >100 years ago.¹ Officially coined by Kiloh in 1961, the term was used broadly to categorize psychiatric cases that present like dementia but are the result of reversible causes. More recently, it has been used to describe older adults who present with cognitive deficits in the context of depressive symptoms.² The goal of evaluation is to determine if the primary issue is a cognitive disorder or a depressive episode. DSM-5-TR does not classify pseudodementia as a distinct diagnosis, but instead categorizes its symptoms as components under other major diagnostic categories. Patients can present with MDD and associated cognitive symptoms, or with a cognitive disorder with depressive symptoms, which would be diagnosed as a cognitive disorder with a major depressive-like episode.³

Pseudodementia is rare. Brodaty et al⁴ found the prevalence of pseudodementia in primary care settings was 0.6%. Older adults (age >65) who live alone are at increased risk of developing pseudodementia, which can be worsened by poor social support and acute psychosocial and environmental changes.⁵ A key characteristic of this disorder is that as the patient’s depressed mood improves, their memory and cognition also improve.⁶ Table 1^3,6 outlines overlapping features of MDD and pseudodementia.

Continue to: EVALUATION Worsening depression

 

 

EVALUATION Worsening depression

At her Psychiatry follow-up appointment, Ms. X reports that her mood is worse since she ended the relationship with her partner and she feels anxious because the partner was financially supporting her. Her PHQ-9 score is 24 (severe depression) and her GAD-7 score is 12 (moderate anxiety). Ms. X reports tolerating her transition from venlafaxine XR 225 mg/d to sertraline 50 mg/d well.

Additionally, Ms. X reports her children have called her “useless” since she continues to have difficulties following through on household tasks, even though she has no physical impairments that prevent her from completing them. The Psychiatry team observes that Ms. X has no problems walking or moving her arms or legs.

The Psychiatry team administers the Montreal Cognitive Assessment (MoCA). Ms. X scores 22, indicating mild impairment.

The team recommends a neuropsychological assessment to determine if this MoCA score is due to a cognitive disorder or is rooted in her mood symptoms. The team also recommends an MRI of the brain, complete blood count (CBC), comprehensive metabolic panel (CMP), and urinalysis (UA).

[polldaddy:12189567]

Continue to: The authors' observations

 

 

The authors’ observations

Neuropsychological assessments are important tools for exploring the behavioral manifestations of brain dysfunction (Table 2).⁷ These assessments factor in elements of neurology, psychiatry, and psychology to provide information about the diagnosis, prognosis, and functional status of patients with medical conditions, especially those with neurocognitive and psychiatric disorders. They combine information from the patient and collateral interviews, behavioral observations, a review of patient records, and objective tests of motor, emotional, and cognitive function.

Among other uses, neuropsychological assessments can help identify depression in patients with neurologic impairment, determine the diagnosis and plan of care for patients with concussions, determine the risk of a motor vehicle crash in patients with cognitive impairment, and distinguish Alzheimer disease from vascular dementia.⁸ Components of such assessments include the Beck Anxiety Inventory (BAI) to assess anxiety, the Dementia Rating Scale-2 and Neuropsychological Assessment Battery-Screening Module to assess dementia, and the Beck Depression Inventory (BDI) to assess depression.⁹

EVALUATION Continued cognitive decline

A different psychologist performs the neuro­psychological assessment, who conducts the Repeatable Battery for the Assessment of Neuropsychological Status Update to determine if Ms. X is experiencing cognitive impairment. Her immediate memory, visuospatial/constructions, language, attention, and delayed memory are significantly impaired for someone her age. The psychologist also administers the Wechsler Adult Intelligence Scale IV and finds Ms. X’s general cognitive ability is within the low average range of intellectual functioning as measured by Full-Scale IQ. Ms. X scores 29 on the BDI-II, indicating significant depressive symptoms, and 13 on the BAI, indicating mild anxiety symptoms.

Ms. X is diagnosed with MDD and an unspecified neurocognitive disorder. The psychologist recommends she start CBT to address her mood and anxiety symptoms.

Upon reviewing the results with Ms. X, the treatment team again recommends a brain MRI, CBC, CMP, and UA to rule out organic causes of her cognitive decline. Ms. X decides against the MRI and laboratory workup and elects to continue her present medication regimen and CBT.

Several weeks later, Ms. X’s family brings her to the emergency department (ED) for evaluation of worsening mood, decreased personal hygiene, increased irritability, and further cognitive decline. They report she is having an increasingly difficult time remembering things such as where she parked her car. The ED team decides to discontinue clonazepam but continues sertraline and trazodone.

Continue to: CBC, CMP, and UA...

CBC, CMP, and UA are unremarkable. Ms. X undergoes a brain CT scan without contrast, which reveals hyperdense lesions in the inferior left tentorium, posterior fossa. A subsequent brain MRI with contrast reveals a dural-based enhancing mass, inferior to the left tentorium, in the left posterior fossa measuring 2.2 cm x 2.1 cm, suggestive of a meningioma. The team orders a Neurosurgery consult.

[polldaddy:12189571]

The authors’ observations

While most brain tumors are secondary to metastasis, meningiomas are the most common primary CNS tumor. Typically, they are asymptomatic; their diagnosis is often delayed until the patient presents with psychiatric symptoms without any focal neurologic findings. The frontal lobe is the most common location of meningioma. Data from 48 case reports of patients with meningiomas and psychiatric symptoms suggest symptoms do not always correlate with specific brain regions.^10,11

Indications for neuroimaging in cases such as Ms. X include an abrupt change in behavior or personality, lack of response to psychiatric treatment, presence of focal neurologic signs, and an unusual psychiatric presentation and development of symptoms.¹¹

TREATMENT Neurosurgery

Neurosurgery recommends and performs a suboccipital craniotomy for biopsy and resection. Ms. X tolerates the procedure well. A meningioma is found in the posterior fossa, near the cerebellar convexity. A biopsy finds no evidence of malignancies.

At her postoperative follow-up appointment several days after the procedure, Ms. X reports new-onset hearing loss and tinnitus.

[polldaddy:12189747]

Continue to: The authors' observations

 

 

The authors’ observations

Patients who require neurosurgery typically already carry a heavy psychiatric burden, which makes it challenging to determine the exact psychiatric consequences of neuro­surgery.^12-14 For example, research shows that temporal lobe resection and temporal lobectomy for treatment-resistant epilepsy can lead to an exacerbation of baseline psychiatric symptoms and the development of new symptoms (31% to 34%).^15,16 However, Bommakanti et al¹³ found no new psychiatric symptoms after resection of meningiomas, and surgery seemed to play a role in ameliorating psychiatric symptoms in patients with intracranial tumors. Research attempting to document the psychiatric sequelae of neurosurgery has had mixed results, and it is difficult to determine what effects brain surgery has on mental health.

OUTCOME Minimal improvement

Several weeks after neurosurgery, Ms. X and her family report her mood is improved. Her PHQ-9 score improves to 15, but her GAD-7 score increases to 13, 1 point above her previous score.

The treatment team recommends Ms. X continue taking sertraline 50 mg/d and trazodone 50 mg/d at bedtime. Ms. X’s family reports her cognition and memory have not improved; her MoCA score increases by 1 point to 23. The treatment team discusses with Ms. X and her family the possibility that her cognitive problems maybe better explained as a neurocognitive disorder rather than as a result of the meningioma, since her MoCA score has not significantly improved. Ms. X and her family decide to seek a second opinion from a neurologist.

Bottom Line

Pseudodementia is a term used to describe older adults who present with cognitive issues in the context of depressive symptoms. Even in the absence of focal findings, neuroimaging should be considered as part of the workup in patients who continue to experience a progressive decline in mood and cognitive function.

Related Resources

• Moller MD, Parmenter BA, Lane DW. Neuropsychological testing: a useful but underutilized resource. Current Psychiatry. 2019;18(11):40-46,51.
• Pollak J. Psychological/neuropsychological testing: when to refer for reexamination. Current Psychiatry. 2021;20(9):18- 19,30-31,37. doi:10.12788/cp.0157

Drug Brand Names

Citalopram • Celexa
Clonazepam • Klonopin
Duloxetine • Cymbalta
Fluoxetine • Prozac
Sertraline • Zoloft
Trazodone • Oleptro
Venlafaxine extended- release • Effexor XR

CASE Depressed and anxious

Five years ago, Ms. X, age 60, was diagnosed with treatment-resistant major depressive disorder (MDD) with anxiety. This diagnosis was established by a previous psychiatrist. She presents to a clinic for a second opinion.

Since her diagnosis, Ms. X has experienced sad mood, anhedonia, difficulty falling asleep, increased appetite and weight, and decreased concentration and attention. Her anxiety stems from her inability to work, which causes her to worry about her children. In the clinic, the treatment team conducts the Patient Health Questionnaire-9 (PHQ-9) and Generalized Anxiety Disorder-7 item scale (GAD-7) with Ms. X. She scores 16 on the PHQ-9, indicating moderately severe depression, and scores 12 on the GAD-7, indicating moderate anxiety.

Ms. X’s current medication regimen consists of venlafaxine extended-release (XR) 225 mg/d, trazodone 100 mg/d at bedtime, and clonazepam 1 mg twice daily. She reports no significant improvement of her symptoms from these medications. Additionally, Ms. X reports that in the past she had been prescribed fluoxetine, citalopram, and duloxetine, but she cannot recall the dosages.

Ms. X appears appropriately groomed, maintains appropriate eye contact, has clear speech, and does not show evidence of internal stimulation; however, she has difficulty following instructions. She makes negative comments about herself such as “I’m worthless” and “Nobody cares about me.” The treatment team decides to taper Ms. X off venlafaxine XR and initiates sertraline 50 mg/d, while continuing trazodone 50 mg/d at bedtime and clonazepam 1 mg twice daily. The team refers her for cognitive-behavioral therapy (CBT) to address her cognitive distortions, sad mood, and anxiety. Ms. X is asked to follow up with Psychiatry in 1 week.

EVALUATION Unusual behavior

At her CBT intake, Ms. X endorses depression and anxiety. Her PHQ-9 score at this visit is 19 (moderately severe depression) and GAD-7 score is 16 (severe anxiety). The psychologist notes that Ms. X is able to complete activities of daily living and instrumental activities of daily living without assistance. Ms. X denies any use of illicit substances or alcohol. No gross memory impairment is noted during this appointment, though Ms. X exhibits unusual behavior, including exiting and re-entering the clinic multiple times to repeatedly ask about follow-up appointments. The psychologist concludes that Ms. X’s presentation and behavior can be explained by MDD and pseudodementia.

[polldaddy:12189562]

The authors’ observations

Pseudodementia gained recognition in clinical research >100 years ago.¹ Officially coined by Kiloh in 1961, the term was used broadly to categorize psychiatric cases that present like dementia but are the result of reversible causes. More recently, it has been used to describe older adults who present with cognitive deficits in the context of depressive symptoms.² The goal of evaluation is to determine if the primary issue is a cognitive disorder or a depressive episode. DSM-5-TR does not classify pseudodementia as a distinct diagnosis, but instead categorizes its symptoms as components under other major diagnostic categories. Patients can present with MDD and associated cognitive symptoms, or with a cognitive disorder with depressive symptoms, which would be diagnosed as a cognitive disorder with a major depressive-like episode.³

Pseudodementia is rare. Brodaty et al⁴ found the prevalence of pseudodementia in primary care settings was 0.6%. Older adults (age >65) who live alone are at increased risk of developing pseudodementia, which can be worsened by poor social support and acute psychosocial and environmental changes.⁵ A key characteristic of this disorder is that as the patient’s depressed mood improves, their memory and cognition also improve.⁶ Table 1^3,6 outlines overlapping features of MDD and pseudodementia.

Continue to: EVALUATION Worsening depression

 

 

EVALUATION Worsening depression

At her Psychiatry follow-up appointment, Ms. X reports that her mood is worse since she ended the relationship with her partner and she feels anxious because the partner was financially supporting her. Her PHQ-9 score is 24 (severe depression) and her GAD-7 score is 12 (moderate anxiety). Ms. X reports tolerating her transition from venlafaxine XR 225 mg/d to sertraline 50 mg/d well.

Additionally, Ms. X reports her children have called her “useless” since she continues to have difficulties following through on household tasks, even though she has no physical impairments that prevent her from completing them. The Psychiatry team observes that Ms. X has no problems walking or moving her arms or legs.

The Psychiatry team administers the Montreal Cognitive Assessment (MoCA). Ms. X scores 22, indicating mild impairment.

The team recommends a neuropsychological assessment to determine if this MoCA score is due to a cognitive disorder or is rooted in her mood symptoms. The team also recommends an MRI of the brain, complete blood count (CBC), comprehensive metabolic panel (CMP), and urinalysis (UA).

[polldaddy:12189567]

Continue to: The authors' observations

 

 

The authors’ observations

Neuropsychological assessments are important tools for exploring the behavioral manifestations of brain dysfunction (Table 2).⁷ These assessments factor in elements of neurology, psychiatry, and psychology to provide information about the diagnosis, prognosis, and functional status of patients with medical conditions, especially those with neurocognitive and psychiatric disorders. They combine information from the patient and collateral interviews, behavioral observations, a review of patient records, and objective tests of motor, emotional, and cognitive function.

Among other uses, neuropsychological assessments can help identify depression in patients with neurologic impairment, determine the diagnosis and plan of care for patients with concussions, determine the risk of a motor vehicle crash in patients with cognitive impairment, and distinguish Alzheimer disease from vascular dementia.⁸ Components of such assessments include the Beck Anxiety Inventory (BAI) to assess anxiety, the Dementia Rating Scale-2 and Neuropsychological Assessment Battery-Screening Module to assess dementia, and the Beck Depression Inventory (BDI) to assess depression.⁹

EVALUATION Continued cognitive decline

A different psychologist performs the neuro­psychological assessment, who conducts the Repeatable Battery for the Assessment of Neuropsychological Status Update to determine if Ms. X is experiencing cognitive impairment. Her immediate memory, visuospatial/constructions, language, attention, and delayed memory are significantly impaired for someone her age. The psychologist also administers the Wechsler Adult Intelligence Scale IV and finds Ms. X’s general cognitive ability is within the low average range of intellectual functioning as measured by Full-Scale IQ. Ms. X scores 29 on the BDI-II, indicating significant depressive symptoms, and 13 on the BAI, indicating mild anxiety symptoms.

Ms. X is diagnosed with MDD and an unspecified neurocognitive disorder. The psychologist recommends she start CBT to address her mood and anxiety symptoms.

Upon reviewing the results with Ms. X, the treatment team again recommends a brain MRI, CBC, CMP, and UA to rule out organic causes of her cognitive decline. Ms. X decides against the MRI and laboratory workup and elects to continue her present medication regimen and CBT.

Several weeks later, Ms. X’s family brings her to the emergency department (ED) for evaluation of worsening mood, decreased personal hygiene, increased irritability, and further cognitive decline. They report she is having an increasingly difficult time remembering things such as where she parked her car. The ED team decides to discontinue clonazepam but continues sertraline and trazodone.

Continue to: CBC, CMP, and UA...

CBC, CMP, and UA are unremarkable. Ms. X undergoes a brain CT scan without contrast, which reveals hyperdense lesions in the inferior left tentorium, posterior fossa. A subsequent brain MRI with contrast reveals a dural-based enhancing mass, inferior to the left tentorium, in the left posterior fossa measuring 2.2 cm x 2.1 cm, suggestive of a meningioma. The team orders a Neurosurgery consult.

[polldaddy:12189571]

The authors’ observations

While most brain tumors are secondary to metastasis, meningiomas are the most common primary CNS tumor. Typically, they are asymptomatic; their diagnosis is often delayed until the patient presents with psychiatric symptoms without any focal neurologic findings. The frontal lobe is the most common location of meningioma. Data from 48 case reports of patients with meningiomas and psychiatric symptoms suggest symptoms do not always correlate with specific brain regions.^10,11

Indications for neuroimaging in cases such as Ms. X include an abrupt change in behavior or personality, lack of response to psychiatric treatment, presence of focal neurologic signs, and an unusual psychiatric presentation and development of symptoms.¹¹

TREATMENT Neurosurgery

Neurosurgery recommends and performs a suboccipital craniotomy for biopsy and resection. Ms. X tolerates the procedure well. A meningioma is found in the posterior fossa, near the cerebellar convexity. A biopsy finds no evidence of malignancies.

At her postoperative follow-up appointment several days after the procedure, Ms. X reports new-onset hearing loss and tinnitus.

[polldaddy:12189747]

Continue to: The authors' observations

 

 

The authors’ observations

Patients who require neurosurgery typically already carry a heavy psychiatric burden, which makes it challenging to determine the exact psychiatric consequences of neuro­surgery.^12-14 For example, research shows that temporal lobe resection and temporal lobectomy for treatment-resistant epilepsy can lead to an exacerbation of baseline psychiatric symptoms and the development of new symptoms (31% to 34%).^15,16 However, Bommakanti et al¹³ found no new psychiatric symptoms after resection of meningiomas, and surgery seemed to play a role in ameliorating psychiatric symptoms in patients with intracranial tumors. Research attempting to document the psychiatric sequelae of neurosurgery has had mixed results, and it is difficult to determine what effects brain surgery has on mental health.

OUTCOME Minimal improvement

Several weeks after neurosurgery, Ms. X and her family report her mood is improved. Her PHQ-9 score improves to 15, but her GAD-7 score increases to 13, 1 point above her previous score.

The treatment team recommends Ms. X continue taking sertraline 50 mg/d and trazodone 50 mg/d at bedtime. Ms. X’s family reports her cognition and memory have not improved; her MoCA score increases by 1 point to 23. The treatment team discusses with Ms. X and her family the possibility that her cognitive problems maybe better explained as a neurocognitive disorder rather than as a result of the meningioma, since her MoCA score has not significantly improved. Ms. X and her family decide to seek a second opinion from a neurologist.

Bottom Line

Pseudodementia is a term used to describe older adults who present with cognitive issues in the context of depressive symptoms. Even in the absence of focal findings, neuroimaging should be considered as part of the workup in patients who continue to experience a progressive decline in mood and cognitive function.

Related Resources

• Moller MD, Parmenter BA, Lane DW. Neuropsychological testing: a useful but underutilized resource. Current Psychiatry. 2019;18(11):40-46,51.
• Pollak J. Psychological/neuropsychological testing: when to refer for reexamination. Current Psychiatry. 2021;20(9):18- 19,30-31,37. doi:10.12788/cp.0157

Drug Brand Names

Citalopram • Celexa
Clonazepam • Klonopin
Duloxetine • Cymbalta
Fluoxetine • Prozac
Sertraline • Zoloft
Trazodone • Oleptro
Venlafaxine extended- release • Effexor XR

Attending psychiatrists who work night shift in a psychiatric emergency department (ED) or medical ED require a different set of skills than when working daytime or evening shifts, especially when working full-time or solo. While all patients should be treated carefully and meticulously regardless of the shift, this article offers tips for efficiency for solo attending psychiatrists who work night shift in an ED.

Check orders. Typically, multiple psychiatric clinicians are available on other shifts, but only 1 at night. This can lead to significant variability and potential errors in patients’ orders. Such errors filter down to night shift and often must be addressed by the solo clinician, who can’t say “that person is not my patient” because there are no other clinicians available to help. Carefully check orders (ideally, on all patients every shift) to ensure there are no errors or omissions.

Use note templates. While it is important to avoid using mere checklists, with electronic medical record systems, create templates for typical notes. This will save time when the pace of patients increases.

Be brief in your documentation. Brevity is key when documenting at night. Focus on what is necessary and sufficient.

Conduct thorough but efficient interviews. Be aware of how much time you spend on patient interviews. While still thorough, interviews must often be shorter due to a higher staff-to-patient ratio at night.

Be aware of potential medical issues. Many psychiatric EDs are not attached to a hospital. With other medical consultants not readily available in the middle of the night, be particularly alert for any acute medical issues that may arise, and act accordingly.

Focus on the order of tasks. Be aware of which tasks you complete and in what order. For example, at night you may need to medicate sooner for agitation because other patients are sleeping, instead of letting one patient’s agitation disrupt the entire night milieu.

Continue to: Don't let tasks pile up

Don’t let tasks pile up. Time management and multitasking are key skills at night. Take care of clinical issues as they arise. Finish documentation as you go along. Don’t let things pile up throughout your shift and then spend significant time after your shift to catch up.

Know your staff. The staff around you are your eyes and ears. Get to know your clinical and nonclinical staff’s tendencies. This can be immensely helpful in picking up any different patterns when interviewing and observing patients.

Know your limits. You may not be able to solve everything or obtain the ideal collateral at night. Don’t get caught up in definitively trying to resolve things and end up wasting precious time at night. Let it go. Don’t overthink. If all else fails, hold the patient overnight.

Prioritize self-care. Night shift work has been shown to negatively impact one’s health.^1-3 If you choose this type of work, either part-time or full-time, maintain your own health by exercising regularly, eating a healthy diet, obtaining adequate rest between shifts, and seeing your health care team often.

Attending psychiatrists who work night shift in a psychiatric emergency department (ED) or medical ED require a different set of skills than when working daytime or evening shifts, especially when working full-time or solo. While all patients should be treated carefully and meticulously regardless of the shift, this article offers tips for efficiency for solo attending psychiatrists who work night shift in an ED.

Check orders. Typically, multiple psychiatric clinicians are available on other shifts, but only 1 at night. This can lead to significant variability and potential errors in patients’ orders. Such errors filter down to night shift and often must be addressed by the solo clinician, who can’t say “that person is not my patient” because there are no other clinicians available to help. Carefully check orders (ideally, on all patients every shift) to ensure there are no errors or omissions.

Use note templates. While it is important to avoid using mere checklists, with electronic medical record systems, create templates for typical notes. This will save time when the pace of patients increases.

Be brief in your documentation. Brevity is key when documenting at night. Focus on what is necessary and sufficient.

Conduct thorough but efficient interviews. Be aware of how much time you spend on patient interviews. While still thorough, interviews must often be shorter due to a higher staff-to-patient ratio at night.

Be aware of potential medical issues. Many psychiatric EDs are not attached to a hospital. With other medical consultants not readily available in the middle of the night, be particularly alert for any acute medical issues that may arise, and act accordingly.

Focus on the order of tasks. Be aware of which tasks you complete and in what order. For example, at night you may need to medicate sooner for agitation because other patients are sleeping, instead of letting one patient’s agitation disrupt the entire night milieu.

Continue to: Don't let tasks pile up

Don’t let tasks pile up. Time management and multitasking are key skills at night. Take care of clinical issues as they arise. Finish documentation as you go along. Don’t let things pile up throughout your shift and then spend significant time after your shift to catch up.

Know your staff. The staff around you are your eyes and ears. Get to know your clinical and nonclinical staff’s tendencies. This can be immensely helpful in picking up any different patterns when interviewing and observing patients.

Know your limits. You may not be able to solve everything or obtain the ideal collateral at night. Don’t get caught up in definitively trying to resolve things and end up wasting precious time at night. Let it go. Don’t overthink. If all else fails, hold the patient overnight.

Prioritize self-care. Night shift work has been shown to negatively impact one’s health.^1-3 If you choose this type of work, either part-time or full-time, maintain your own health by exercising regularly, eating a healthy diet, obtaining adequate rest between shifts, and seeing your health care team often.

Attending psychiatrists who work night shift in a psychiatric emergency department (ED) or medical ED require a different set of skills than when working daytime or evening shifts, especially when working full-time or solo. While all patients should be treated carefully and meticulously regardless of the shift, this article offers tips for efficiency for solo attending psychiatrists who work night shift in an ED.

Check orders. Typically, multiple psychiatric clinicians are available on other shifts, but only 1 at night. This can lead to significant variability and potential errors in patients’ orders. Such errors filter down to night shift and often must be addressed by the solo clinician, who can’t say “that person is not my patient” because there are no other clinicians available to help. Carefully check orders (ideally, on all patients every shift) to ensure there are no errors or omissions.

Use note templates. While it is important to avoid using mere checklists, with electronic medical record systems, create templates for typical notes. This will save time when the pace of patients increases.

Be brief in your documentation. Brevity is key when documenting at night. Focus on what is necessary and sufficient.

Conduct thorough but efficient interviews. Be aware of how much time you spend on patient interviews. While still thorough, interviews must often be shorter due to a higher staff-to-patient ratio at night.

Be aware of potential medical issues. Many psychiatric EDs are not attached to a hospital. With other medical consultants not readily available in the middle of the night, be particularly alert for any acute medical issues that may arise, and act accordingly.

Focus on the order of tasks. Be aware of which tasks you complete and in what order. For example, at night you may need to medicate sooner for agitation because other patients are sleeping, instead of letting one patient’s agitation disrupt the entire night milieu.

Continue to: Don't let tasks pile up

Don’t let tasks pile up. Time management and multitasking are key skills at night. Take care of clinical issues as they arise. Finish documentation as you go along. Don’t let things pile up throughout your shift and then spend significant time after your shift to catch up.

Know your staff. The staff around you are your eyes and ears. Get to know your clinical and nonclinical staff’s tendencies. This can be immensely helpful in picking up any different patterns when interviewing and observing patients.

Know your limits. You may not be able to solve everything or obtain the ideal collateral at night. Don’t get caught up in definitively trying to resolve things and end up wasting precious time at night. Let it go. Don’t overthink. If all else fails, hold the patient overnight.

Prioritize self-care. Night shift work has been shown to negatively impact one’s health.^1-3 If you choose this type of work, either part-time or full-time, maintain your own health by exercising regularly, eating a healthy diet, obtaining adequate rest between shifts, and seeing your health care team often.

Sound moral principles are essential in the development of all physicians. Given how heavily each clinical encounter is laden with ethical implications, this is taught early in medical school. The medical student and resident physician must be able to make ethical and moral decisions on a consistent basis.

Speaking as a psychiatrist in training, there is an intimate relationship between psychiatry and moral questions.¹ Issues such as determining an individual’s ability to make decisions about their medical care, hospitalizing patients against their will, and involuntarily administering medication are an almost-daily occurrence.² Physicians, especially those who practice psychiatric medicine, must be ethically grounded to properly make these difficult but common decisions. It is also imperative that residents are given proper guidance in ethical practice in structured didactics and hands-on training.

However, many residents may be unfamiliar with ethics in research, more specifically ethical authorship. While some trainees might have participated in scholarly activities before residency, residency is the time to discover one’s interests, and residents are encouraged to engage in research. Unfortunately, many of the considerations surrounding ethical authorship are not emphasized, and questionable practices are common.³ In this article, I summarize the different faces of unethical authorship, and call for a greater emphasis on ethical authorship in medical residency training programs.

What drives unethical authorship practices

One of the main drivers for the increase in unethical practices is the need to publish to advance one’s academic career. The academic principle of “publish or perish” pressures many faculty researchers.³ The impact of this expectation plays a significant role in potentially unethical authorship practices, and also has increased the number of publications of mediocre quality or fraudulent data.⁴ This mindset has also seeped into the clinical world because promotions and financial bonuses are incentives for attending physicians to perform scholarly work. Due to these incentives and pressures, a senior academician might compel a junior researcher to include them as a coauthor on the junior researcher’s paper, even when the senior’s contributions to the paper might be limited.⁵

Most journals have specific criteria for authorship. The International Committee of Medical Journal Editors (ICMJE) has 4 core criteria for authorship: 1) substantial contributions to the conception or design of the work, or the acquisition, analysis, or interpretation of data for the work; 2) drafting the work or revising it critically for important intellectual content; 3) providing final approval of the version to be published, and 4) agreement to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.^5,6 One survey found that in certain journals, approximately 15% of authors met full ICMJE authorship criteria, while one-half claimed there were substantial contributions but did not state anything more specific.⁷

There are several types of authorship abuse.⁵ Gift authorship is when authorship is awarded to a friend either out of respect or in hopes that friend will return the favor (quid pro quo). Ghost authorship occurs when a third party commissions an author to write or help write a paper (eg, when a pharmaceutical company hires writers to produce a paper about a medication they manufacture) or when legitimate authors are denied recognition on a paper. Honorary authorship occurs when authorship is granted with the hope that the reputation of the honorary author will increase the chances of the paper getting published and possibly boost citations.

While these forms of authorship abuse occur with unsettling frequency, they might not be common among physician trainees who do not engage in full-time research.⁵ Resident authors might be more likely to experience coercive authorship.

Continue to: Coercive authorship is when...

Coercive authorship is when an individual in a superior position (such as an attending physician) forces their name onto a paper of a junior individual (such as a resident). Kwok⁸ called this “The White Bull effect,” based on Greek mythology in which Zeus transformed himself into a white bull to seduce Europa. The White Bull represents the predatory nature of the senior individual who exploits ambiguous institutional research regulations to their benefit.⁸ They stretch out the ICMJE criteria, only superficially satisfying them to justify authorship. In this scenario, the attending physician with promotional incentives notices the work of a resident and demands authorship, given their role as the “supervising” physician (akin to general supervision of a research group). This is not justification for authorship per the ICMJE or any major medical journal criteria. However, a resident with limited research experience may agree to include the attending as a coauthor for a variety of reasons, including fear of a poor performance evaluation or professionalism complaints, or just to maintain a positive working relationship.

Serious implications

While there are countless reasons to be concerned about this behavior, the central issue is the attending physician’s role to train and/or mentor the resident. As previously stated, a physician—especially one practicing psychiatric medicine—must be of morally sound mind. A resident being taught unethical behaviors by their attending physician has dangerous implications. Academic dishonesty does not occur in vacuum. It is likely that dishonest and unethical behavior in research matters can cross over into the clinical arena. One study found that individuals who exhibit dishonest academic behavior are more likely to violate workplace policies.⁹ Also, these behaviors lead to increased moral disengagement in all areas.^10,11 Imagining a morally disengaged attending psychiatrist practicing medicine and training the next generation of psychiatrists is unsettling.

My hope is that residency programs discourage this detrimental conduct in their departments and support those trying to uphold integrity.

Sound moral principles are essential in the development of all physicians. Given how heavily each clinical encounter is laden with ethical implications, this is taught early in medical school. The medical student and resident physician must be able to make ethical and moral decisions on a consistent basis.

Speaking as a psychiatrist in training, there is an intimate relationship between psychiatry and moral questions.¹ Issues such as determining an individual’s ability to make decisions about their medical care, hospitalizing patients against their will, and involuntarily administering medication are an almost-daily occurrence.² Physicians, especially those who practice psychiatric medicine, must be ethically grounded to properly make these difficult but common decisions. It is also imperative that residents are given proper guidance in ethical practice in structured didactics and hands-on training.

However, many residents may be unfamiliar with ethics in research, more specifically ethical authorship. While some trainees might have participated in scholarly activities before residency, residency is the time to discover one’s interests, and residents are encouraged to engage in research. Unfortunately, many of the considerations surrounding ethical authorship are not emphasized, and questionable practices are common.³ In this article, I summarize the different faces of unethical authorship, and call for a greater emphasis on ethical authorship in medical residency training programs.

What drives unethical authorship practices

One of the main drivers for the increase in unethical practices is the need to publish to advance one’s academic career. The academic principle of “publish or perish” pressures many faculty researchers.³ The impact of this expectation plays a significant role in potentially unethical authorship practices, and also has increased the number of publications of mediocre quality or fraudulent data.⁴ This mindset has also seeped into the clinical world because promotions and financial bonuses are incentives for attending physicians to perform scholarly work. Due to these incentives and pressures, a senior academician might compel a junior researcher to include them as a coauthor on the junior researcher’s paper, even when the senior’s contributions to the paper might be limited.⁵

Most journals have specific criteria for authorship. The International Committee of Medical Journal Editors (ICMJE) has 4 core criteria for authorship: 1) substantial contributions to the conception or design of the work, or the acquisition, analysis, or interpretation of data for the work; 2) drafting the work or revising it critically for important intellectual content; 3) providing final approval of the version to be published, and 4) agreement to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.^5,6 One survey found that in certain journals, approximately 15% of authors met full ICMJE authorship criteria, while one-half claimed there were substantial contributions but did not state anything more specific.⁷

There are several types of authorship abuse.⁵ Gift authorship is when authorship is awarded to a friend either out of respect or in hopes that friend will return the favor (quid pro quo). Ghost authorship occurs when a third party commissions an author to write or help write a paper (eg, when a pharmaceutical company hires writers to produce a paper about a medication they manufacture) or when legitimate authors are denied recognition on a paper. Honorary authorship occurs when authorship is granted with the hope that the reputation of the honorary author will increase the chances of the paper getting published and possibly boost citations.

While these forms of authorship abuse occur with unsettling frequency, they might not be common among physician trainees who do not engage in full-time research.⁵ Resident authors might be more likely to experience coercive authorship.

Continue to: Coercive authorship is when...

Coercive authorship is when an individual in a superior position (such as an attending physician) forces their name onto a paper of a junior individual (such as a resident). Kwok⁸ called this “The White Bull effect,” based on Greek mythology in which Zeus transformed himself into a white bull to seduce Europa. The White Bull represents the predatory nature of the senior individual who exploits ambiguous institutional research regulations to their benefit.⁸ They stretch out the ICMJE criteria, only superficially satisfying them to justify authorship. In this scenario, the attending physician with promotional incentives notices the work of a resident and demands authorship, given their role as the “supervising” physician (akin to general supervision of a research group). This is not justification for authorship per the ICMJE or any major medical journal criteria. However, a resident with limited research experience may agree to include the attending as a coauthor for a variety of reasons, including fear of a poor performance evaluation or professionalism complaints, or just to maintain a positive working relationship.

Serious implications

While there are countless reasons to be concerned about this behavior, the central issue is the attending physician’s role to train and/or mentor the resident. As previously stated, a physician—especially one practicing psychiatric medicine—must be of morally sound mind. A resident being taught unethical behaviors by their attending physician has dangerous implications. Academic dishonesty does not occur in vacuum. It is likely that dishonest and unethical behavior in research matters can cross over into the clinical arena. One study found that individuals who exhibit dishonest academic behavior are more likely to violate workplace policies.⁹ Also, these behaviors lead to increased moral disengagement in all areas.^10,11 Imagining a morally disengaged attending psychiatrist practicing medicine and training the next generation of psychiatrists is unsettling.

My hope is that residency programs discourage this detrimental conduct in their departments and support those trying to uphold integrity.

Sound moral principles are essential in the development of all physicians. Given how heavily each clinical encounter is laden with ethical implications, this is taught early in medical school. The medical student and resident physician must be able to make ethical and moral decisions on a consistent basis.

Speaking as a psychiatrist in training, there is an intimate relationship between psychiatry and moral questions.¹ Issues such as determining an individual’s ability to make decisions about their medical care, hospitalizing patients against their will, and involuntarily administering medication are an almost-daily occurrence.² Physicians, especially those who practice psychiatric medicine, must be ethically grounded to properly make these difficult but common decisions. It is also imperative that residents are given proper guidance in ethical practice in structured didactics and hands-on training.

However, many residents may be unfamiliar with ethics in research, more specifically ethical authorship. While some trainees might have participated in scholarly activities before residency, residency is the time to discover one’s interests, and residents are encouraged to engage in research. Unfortunately, many of the considerations surrounding ethical authorship are not emphasized, and questionable practices are common.³ In this article, I summarize the different faces of unethical authorship, and call for a greater emphasis on ethical authorship in medical residency training programs.

What drives unethical authorship practices

One of the main drivers for the increase in unethical practices is the need to publish to advance one’s academic career. The academic principle of “publish or perish” pressures many faculty researchers.³ The impact of this expectation plays a significant role in potentially unethical authorship practices, and also has increased the number of publications of mediocre quality or fraudulent data.⁴ This mindset has also seeped into the clinical world because promotions and financial bonuses are incentives for attending physicians to perform scholarly work. Due to these incentives and pressures, a senior academician might compel a junior researcher to include them as a coauthor on the junior researcher’s paper, even when the senior’s contributions to the paper might be limited.⁵

Most journals have specific criteria for authorship. The International Committee of Medical Journal Editors (ICMJE) has 4 core criteria for authorship: 1) substantial contributions to the conception or design of the work, or the acquisition, analysis, or interpretation of data for the work; 2) drafting the work or revising it critically for important intellectual content; 3) providing final approval of the version to be published, and 4) agreement to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.^5,6 One survey found that in certain journals, approximately 15% of authors met full ICMJE authorship criteria, while one-half claimed there were substantial contributions but did not state anything more specific.⁷

There are several types of authorship abuse.⁵ Gift authorship is when authorship is awarded to a friend either out of respect or in hopes that friend will return the favor (quid pro quo). Ghost authorship occurs when a third party commissions an author to write or help write a paper (eg, when a pharmaceutical company hires writers to produce a paper about a medication they manufacture) or when legitimate authors are denied recognition on a paper. Honorary authorship occurs when authorship is granted with the hope that the reputation of the honorary author will increase the chances of the paper getting published and possibly boost citations.

While these forms of authorship abuse occur with unsettling frequency, they might not be common among physician trainees who do not engage in full-time research.⁵ Resident authors might be more likely to experience coercive authorship.

Continue to: Coercive authorship is when...

Coercive authorship is when an individual in a superior position (such as an attending physician) forces their name onto a paper of a junior individual (such as a resident). Kwok⁸ called this “The White Bull effect,” based on Greek mythology in which Zeus transformed himself into a white bull to seduce Europa. The White Bull represents the predatory nature of the senior individual who exploits ambiguous institutional research regulations to their benefit.⁸ They stretch out the ICMJE criteria, only superficially satisfying them to justify authorship. In this scenario, the attending physician with promotional incentives notices the work of a resident and demands authorship, given their role as the “supervising” physician (akin to general supervision of a research group). This is not justification for authorship per the ICMJE or any major medical journal criteria. However, a resident with limited research experience may agree to include the attending as a coauthor for a variety of reasons, including fear of a poor performance evaluation or professionalism complaints, or just to maintain a positive working relationship.

Serious implications

While there are countless reasons to be concerned about this behavior, the central issue is the attending physician’s role to train and/or mentor the resident. As previously stated, a physician—especially one practicing psychiatric medicine—must be of morally sound mind. A resident being taught unethical behaviors by their attending physician has dangerous implications. Academic dishonesty does not occur in vacuum. It is likely that dishonest and unethical behavior in research matters can cross over into the clinical arena. One study found that individuals who exhibit dishonest academic behavior are more likely to violate workplace policies.⁹ Also, these behaviors lead to increased moral disengagement in all areas.^10,11 Imagining a morally disengaged attending psychiatrist practicing medicine and training the next generation of psychiatrists is unsettling.

My hope is that residency programs discourage this detrimental conduct in their departments and support those trying to uphold integrity.

Introduction

Dysphagia is the sensation of difficulty swallowing food or liquid in the acute or chronic setting. The prevalence of dysphagia ranges based on the type and etiology but may impact up to one in six adults.^1,2 Dysphagia can cause a significant impact on a patient’s health and overall quality of life. A recent study found that only 50% of symptomatic adults seek medical care despite modifying their eating habits by either eating slowly or changing to softer foods or liquids.¹ The most common, serious complications of dysphagia include aspiration pneumonia, malnutrition, and dehydration.³ According to the Agency for Healthcare Research and Quality, dysphagia may be responsible for up to 60,000 deaths annually.³

History

The diagnosis of dysphagia begins with a thorough history. Questions about the timing, onset, progression, localization of symptoms, and types of food that are difficult to swallow are essential in differentiating oropharyngeal and esophageal dysphagia.^3,4 Further history taking must include medication and allergy review, smoking history, and review of prior radiation or surgical therapies to the head and neck.

Briefly, oropharyngeal dysphagia is difficulty initiating a swallow or passing food from the mouth or throat and can be caused by structural or functional etiologies.⁵ Clinical presentations include a sensation of food stuck in the back of the throat, coughing or choking while eating, or drooling. Structural causes include head and neck cancer, Zenker diverticulum, Killian Jamieson diverticula, prolonged intubation, or changes secondary to prior surgery or radiation.³ Functional causes may include neurologic, rheumatologic, or muscular disorders.⁶

Esophageal dysphagia refers to difficulty transporting food or liquid down the esophagus and can be caused by structural, inflammatory, or functional disorders.⁵ Patients typically localize symptoms of heartburn, regurgitation, nausea, vomiting, cough, or chest pain along the sternum or epigastric region. Alarm signs concerning for malignancy include unintentional weight loss, fevers, or night sweats.^3,7 Aside from symptoms, medication review is essential, as dysphagia is a common side effect of antipsychotics, anticholinergics, antimuscarinics, narcotics, and immunosuppressant drugs.⁸ Larger pills such as NSAIDs, antibiotics, bisphosphonates, potassium supplements, and methylxanthines can cause drug-induced esophagitis, which can initially present as dysphagia.⁸ Inflammatory causes can be elucidated by obtaining a history about allergies, tobacco use, and recent infections such as thrush or pneumonia. Patients with a history of recurrent pneumonias may be silently aspirating, a complication of dysphagia.³ Once esophageal dysphagia is clinically suspected based on history, workup can begin. 

Differentiating etiologies of esophageal dysphagia 

The next step in diagnosing esophageal dysphagia is differentiating between structural, inflammatory, or dysmotility etiology (Figure 1). 

Courtesy Tanisha Ronnie, MD, Lauren Bloomberg, MD, and Mukund Venu, MD

Patients with a structural cause typically have difficulty swallowing solids but are able to swallow liquids unless the disease progresses. Symptoms can rapidly worsen and lead to odynophagia, weight loss, and vomiting. In comparison, patients with motility disorders typically have difficulty swallowing both solids and liquids initially, and symptoms can be constant or intermittent.⁵ 

Prior to diagnostic studies, a 4-week trial of a proton pump inhibitor (PPI) is appropriate for patients with reflux symptoms who are younger than 50 with no alarm features concerning for malignancy.^7,9 If symptoms persist after a PPI trial, then an upper endoscopy (EGD) is indicated. An EGD allows for visualization of structural etiologies, obtaining biopsies to rule out inflammatory etiologies, and the option to therapeutically treat reduced luminal diameter with dilatation.¹⁰ The most common structural and inflammatory etiologies noted on EGD include strictures, webs, carcinomas, Schatzki rings, and gastroesophageal reflux or eosinophilic esophagitis.⁴

If upper endoscopy is normal and clinical suspicion for an obstructive cause remains high, barium esophagram can be utilized as an adjunctive study. Previously, barium esophagram was the initial test to distinguish between structural and motility disorders. The benefits of endoscopy over barium esophagram as the first diagnostic study include higher diagnostic yield, higher sensitivity and specificity, and lower costs.⁷ However, barium studies may be more sensitive for lower esophageal rings or extrinsic esophageal compression.3 

 

Evaluation of esophageal motility disorder

If a structural or inflammatory etiology of dysphagia is not identified, investigation for an esophageal motility disorder (EMD) is warranted. Examples of motility disorders include achalasia, ineffective esophageal motility, hypercontractility, spasticity, or esophagogastric junction outflow obstruction (EGJOO).^10,11 High-resolution esophageal manometry (HRM) remains the gold standard in diagnosis of EMD.¹² An HRM catheter utilizes 36 sensors placed two centimeters apart and is placed in the esophagus to evaluate pressure and peristalsis between the upper and lower esophageal sphincters.¹³ In 2009, the Chicago Classification System was developed to provide a diagnostic algorithm that categorizes EMD based on HRM testing, with the most recent version (4.0) being published in 2020.^12,14 Motility diagnoses are divided into two general classifications of disorders of body peristalsis and disorders of EGJ outflow. The most recent updates also include changes in swallow protocols, patient positioning, targeted symptoms, addition of impedance sensors, and consideration of supplemental testing when HRM is inconclusive based on the clinical context.¹² There are some limitations of HRM to highlight. One of the main diagnostic values used with HRM is the integrated relaxation pressure (IRP). Despite standardization, IRP measurements vary based on the recorder and patient position. A minority of patients with achalasia may have IRP that does not approach the accepted cutoff and, therefore, the EGJ is not accurately assessed on HRM.^15,16 In addition, some swallow protocols have lower sensitivity and specificity for certain motility disorders, and the test can result as inconclusive.14 In these scenarios, supplemental testing with timed barium esophagram or functional luminal imaging probe (EndoFLIP) is indicated.^10,11

Loyola University Chicago

Over the past decade, EndoFLIP has emerged as a novel diagnostic tool in evaluating EMD. EndoFLIP is usually completed during an upper endoscopy and utilizes impedance planimetry to measure cross-sectional area and esophageal distensibility and evaluate contractile patterns.¹⁶ During the procedure, a small catheter with an inflatable balloon is inserted into the esophagus with the distal end in the stomach, traversing the esophagogastric junction (EGJ). The pressure transducer has electrodes every centimeter to allow for a three-dimensional construction of the esophagus and EGJ.¹⁷ EndoFLIP has been shown to accurately measure pyloric diameter, pressure, and distensibility at certain balloon volumes.¹⁸ In addition, FLIP is being used to further identify aspects of esophageal dysmotility in patients with eosinophilic esophagitis, thought primarily to be an inflammatory disorder.¹⁹ However, limitations include minimal accessibility of EndoFLIP within clinical practice and a specific computer program needed to generate the topographic plots.²⁰ 

When used in conjunction with HRM, EndoFLIP provides complementary data that can be used to better detect major motility disorders.^15,20,21 Each study adds unique information about the different physiologic events comprising the esophageal response to distention. Overall, the benefits of EndoFLIP include expediting workup during index endoscopy, patient comfort with sedation, and real-time diagnostic data that supplement results obtained during HRM.^{10,16,20,2223}

Of note, if the diagnostic evaluation for structural, inflammatory, and motility disorders are unrevealing, investigating for atypical reflux symptoms can be pursued for patients with persistent dysphagia. Studies investigating pH, or acidity in the esophagus, in relation to symptoms, can be conducted wirelessly via a capsule fixed to the mucosa or with a nasal catheter.³

Normal workup – hypervigilance

In a subset of patients, all diagnostic testing for structural, inflammatory, or motility disorders is normal. These patients are classified as having a functional esophageal disorder. Despite normal testing, patients still have significant symptoms including epigastric pain, chest pain, globus sensation, or difficulty swallowing. It is theorized that a degree of visceral hypersensitivity between the brain-gut axis contributes to ongoing symptoms.²⁴ Studies for effective treatments are ongoing but typically include cognitive-behavioral therapy, brain-gut behavioral therapy, swallow therapy antidepressants, or short courses of proton pump inhibitors.⁹

Conclusion

In this review article, we discussed the diagnostic approach for esophageal dysphagia. Initial assessment requires a thorough history, differentiation between oropharyngeal and esophageal dysphagia, and determination of who warrants an upper endoscopy. Upper endoscopy may reveal structural or inflammatory causes of dysphagia, including strictures, masses, or esophagitis, to name a few. If a structural or inflammatory cause is ruled out, this warrants investigation for esophageal motility disorders. The current gold standard for diagnosing EMD is manometry, and supplemental studies, including EndoFLIP, barium esophagram, and pH studies, may provide complimentary data. If workup for dysphagia is normal, evaluation for esophageal hypervigilance causing increased sensitivity to normal or mild sensations may be warranted. In conclusion, the diagnosis of dysphagia is challenging and requires investigation with a systematic approach to ensure timely diagnosis and treatment

Dr. Ronnie and Dr. Bloomberg are in the department of internal medicine at Loyola University Chicago, Maywood, Ill. Dr. Venu is in the division of gastroenterology at Loyola. He is on the speakers bureau at Medtronic.

References 

1. Adkins C et al. Clin Gastroenterol Hepatol. 2020;18(9):1970-9.e2. 

2. Bhattacharyya N. Otolaryngol Head Neck Surg. 2014;151(5):765-9. 

3. McCarty EB and Chao TN. Med Clin North Am. 2021;105(5):939-54. 

4. Thiyagalingam S et al. Mayo Clin Proc. 2021;96(2):488-97. 

5. Malagelada JR et al. J Clin Gastroenterol. 2015;49(5):370-8.

6. Rommel, N and Hamdy S. Nat Rev Gastroenterol Hepatol. 2016;13(1):49-59. 

7. Liu LWC et al. J Can Assoc Gastroenterol. 2018;1(1):5-19. 

8. Schwemmle C et al. HNO. 2015;63(7):504-10. 

9. Moayyedi P et al. Am J Gastroenterol. 2017;112(7):988-1013. 

10. Triggs J and Pandolfino J. F1000Res. 2019 Aug 29. doi: 10.12688/f1000research.18900.1. 

11. Yadlapati R et al. Neurogastroenterol Motil. 2021;33(1):e14058. 

12. Yadlapati R et al. Neurogastroenterol Motil. 2021;33(1):e14053. 

13. Fox M et al. Neurogastroenterol Motil. 2004;16(5):533-42. 

14. Sweis R and Fox M. Curr Gastroenterol Rep. 2020;22(10):49. 

15. Carlson DA et al. Gastroenterology. 2015;149(7):1742-51. 

16. Donnan EN and Pandolfino JE. Gastroenterol Clin North Am. 2020;49(3):427-35. 

17. Carlson DA. Curr Opin Gastroenterol. 2016;32(4):310-8.
 

18. Zheng T et al. Neurogastroenterol Motil. 2022;34(10):e14386.

19. Carlson DA et al. Clin Gastroenterol Hepatol. 2022;20(8):1719-28.e3.

20. Carlson DA et al. Am J Gastroenterol. 2016;111(12):1726-35.

21. Carlson DA et al. Neurogastroenterol Motil. 2021;33(10):e14116.

22. Carlson DA et al. Gastrointest Endosc. 2019;90(6):915-923.e1.

23. Fox MR et al. Neurogastroenterol Motil. 2021;33(4):e14120.

24. Aziz Q et al. Gastroenterology. 2016 Feb 15. doi: 10.1053/j.gastro.2016.02.012.

Introduction

Dysphagia is the sensation of difficulty swallowing food or liquid in the acute or chronic setting. The prevalence of dysphagia ranges based on the type and etiology but may impact up to one in six adults.^1,2 Dysphagia can cause a significant impact on a patient’s health and overall quality of life. A recent study found that only 50% of symptomatic adults seek medical care despite modifying their eating habits by either eating slowly or changing to softer foods or liquids.¹ The most common, serious complications of dysphagia include aspiration pneumonia, malnutrition, and dehydration.³ According to the Agency for Healthcare Research and Quality, dysphagia may be responsible for up to 60,000 deaths annually.³

History

The diagnosis of dysphagia begins with a thorough history. Questions about the timing, onset, progression, localization of symptoms, and types of food that are difficult to swallow are essential in differentiating oropharyngeal and esophageal dysphagia.^3,4 Further history taking must include medication and allergy review, smoking history, and review of prior radiation or surgical therapies to the head and neck.

Briefly, oropharyngeal dysphagia is difficulty initiating a swallow or passing food from the mouth or throat and can be caused by structural or functional etiologies.⁵ Clinical presentations include a sensation of food stuck in the back of the throat, coughing or choking while eating, or drooling. Structural causes include head and neck cancer, Zenker diverticulum, Killian Jamieson diverticula, prolonged intubation, or changes secondary to prior surgery or radiation.³ Functional causes may include neurologic, rheumatologic, or muscular disorders.⁶

Esophageal dysphagia refers to difficulty transporting food or liquid down the esophagus and can be caused by structural, inflammatory, or functional disorders.⁵ Patients typically localize symptoms of heartburn, regurgitation, nausea, vomiting, cough, or chest pain along the sternum or epigastric region. Alarm signs concerning for malignancy include unintentional weight loss, fevers, or night sweats.^3,7 Aside from symptoms, medication review is essential, as dysphagia is a common side effect of antipsychotics, anticholinergics, antimuscarinics, narcotics, and immunosuppressant drugs.⁸ Larger pills such as NSAIDs, antibiotics, bisphosphonates, potassium supplements, and methylxanthines can cause drug-induced esophagitis, which can initially present as dysphagia.⁸ Inflammatory causes can be elucidated by obtaining a history about allergies, tobacco use, and recent infections such as thrush or pneumonia. Patients with a history of recurrent pneumonias may be silently aspirating, a complication of dysphagia.³ Once esophageal dysphagia is clinically suspected based on history, workup can begin. 

Differentiating etiologies of esophageal dysphagia 

The next step in diagnosing esophageal dysphagia is differentiating between structural, inflammatory, or dysmotility etiology (Figure 1). 

Courtesy Tanisha Ronnie, MD, Lauren Bloomberg, MD, and Mukund Venu, MD

Patients with a structural cause typically have difficulty swallowing solids but are able to swallow liquids unless the disease progresses. Symptoms can rapidly worsen and lead to odynophagia, weight loss, and vomiting. In comparison, patients with motility disorders typically have difficulty swallowing both solids and liquids initially, and symptoms can be constant or intermittent.⁵ 

Prior to diagnostic studies, a 4-week trial of a proton pump inhibitor (PPI) is appropriate for patients with reflux symptoms who are younger than 50 with no alarm features concerning for malignancy.^7,9 If symptoms persist after a PPI trial, then an upper endoscopy (EGD) is indicated. An EGD allows for visualization of structural etiologies, obtaining biopsies to rule out inflammatory etiologies, and the option to therapeutically treat reduced luminal diameter with dilatation.¹⁰ The most common structural and inflammatory etiologies noted on EGD include strictures, webs, carcinomas, Schatzki rings, and gastroesophageal reflux or eosinophilic esophagitis.⁴

If upper endoscopy is normal and clinical suspicion for an obstructive cause remains high, barium esophagram can be utilized as an adjunctive study. Previously, barium esophagram was the initial test to distinguish between structural and motility disorders. The benefits of endoscopy over barium esophagram as the first diagnostic study include higher diagnostic yield, higher sensitivity and specificity, and lower costs.⁷ However, barium studies may be more sensitive for lower esophageal rings or extrinsic esophageal compression.3 

 

Evaluation of esophageal motility disorder

If a structural or inflammatory etiology of dysphagia is not identified, investigation for an esophageal motility disorder (EMD) is warranted. Examples of motility disorders include achalasia, ineffective esophageal motility, hypercontractility, spasticity, or esophagogastric junction outflow obstruction (EGJOO).^10,11 High-resolution esophageal manometry (HRM) remains the gold standard in diagnosis of EMD.¹² An HRM catheter utilizes 36 sensors placed two centimeters apart and is placed in the esophagus to evaluate pressure and peristalsis between the upper and lower esophageal sphincters.¹³ In 2009, the Chicago Classification System was developed to provide a diagnostic algorithm that categorizes EMD based on HRM testing, with the most recent version (4.0) being published in 2020.^12,14 Motility diagnoses are divided into two general classifications of disorders of body peristalsis and disorders of EGJ outflow. The most recent updates also include changes in swallow protocols, patient positioning, targeted symptoms, addition of impedance sensors, and consideration of supplemental testing when HRM is inconclusive based on the clinical context.¹² There are some limitations of HRM to highlight. One of the main diagnostic values used with HRM is the integrated relaxation pressure (IRP). Despite standardization, IRP measurements vary based on the recorder and patient position. A minority of patients with achalasia may have IRP that does not approach the accepted cutoff and, therefore, the EGJ is not accurately assessed on HRM.^15,16 In addition, some swallow protocols have lower sensitivity and specificity for certain motility disorders, and the test can result as inconclusive.14 In these scenarios, supplemental testing with timed barium esophagram or functional luminal imaging probe (EndoFLIP) is indicated.^10,11

Loyola University Chicago

Over the past decade, EndoFLIP has emerged as a novel diagnostic tool in evaluating EMD. EndoFLIP is usually completed during an upper endoscopy and utilizes impedance planimetry to measure cross-sectional area and esophageal distensibility and evaluate contractile patterns.¹⁶ During the procedure, a small catheter with an inflatable balloon is inserted into the esophagus with the distal end in the stomach, traversing the esophagogastric junction (EGJ). The pressure transducer has electrodes every centimeter to allow for a three-dimensional construction of the esophagus and EGJ.¹⁷ EndoFLIP has been shown to accurately measure pyloric diameter, pressure, and distensibility at certain balloon volumes.¹⁸ In addition, FLIP is being used to further identify aspects of esophageal dysmotility in patients with eosinophilic esophagitis, thought primarily to be an inflammatory disorder.¹⁹ However, limitations include minimal accessibility of EndoFLIP within clinical practice and a specific computer program needed to generate the topographic plots.²⁰ 

When used in conjunction with HRM, EndoFLIP provides complementary data that can be used to better detect major motility disorders.^15,20,21 Each study adds unique information about the different physiologic events comprising the esophageal response to distention. Overall, the benefits of EndoFLIP include expediting workup during index endoscopy, patient comfort with sedation, and real-time diagnostic data that supplement results obtained during HRM.^{10,16,20,2223}

Of note, if the diagnostic evaluation for structural, inflammatory, and motility disorders are unrevealing, investigating for atypical reflux symptoms can be pursued for patients with persistent dysphagia. Studies investigating pH, or acidity in the esophagus, in relation to symptoms, can be conducted wirelessly via a capsule fixed to the mucosa or with a nasal catheter.³

Normal workup – hypervigilance

In a subset of patients, all diagnostic testing for structural, inflammatory, or motility disorders is normal. These patients are classified as having a functional esophageal disorder. Despite normal testing, patients still have significant symptoms including epigastric pain, chest pain, globus sensation, or difficulty swallowing. It is theorized that a degree of visceral hypersensitivity between the brain-gut axis contributes to ongoing symptoms.²⁴ Studies for effective treatments are ongoing but typically include cognitive-behavioral therapy, brain-gut behavioral therapy, swallow therapy antidepressants, or short courses of proton pump inhibitors.⁹

Conclusion

In this review article, we discussed the diagnostic approach for esophageal dysphagia. Initial assessment requires a thorough history, differentiation between oropharyngeal and esophageal dysphagia, and determination of who warrants an upper endoscopy. Upper endoscopy may reveal structural or inflammatory causes of dysphagia, including strictures, masses, or esophagitis, to name a few. If a structural or inflammatory cause is ruled out, this warrants investigation for esophageal motility disorders. The current gold standard for diagnosing EMD is manometry, and supplemental studies, including EndoFLIP, barium esophagram, and pH studies, may provide complimentary data. If workup for dysphagia is normal, evaluation for esophageal hypervigilance causing increased sensitivity to normal or mild sensations may be warranted. In conclusion, the diagnosis of dysphagia is challenging and requires investigation with a systematic approach to ensure timely diagnosis and treatment

Dr. Ronnie and Dr. Bloomberg are in the department of internal medicine at Loyola University Chicago, Maywood, Ill. Dr. Venu is in the division of gastroenterology at Loyola. He is on the speakers bureau at Medtronic.

References 

1. Adkins C et al. Clin Gastroenterol Hepatol. 2020;18(9):1970-9.e2. 

2. Bhattacharyya N. Otolaryngol Head Neck Surg. 2014;151(5):765-9. 

3. McCarty EB and Chao TN. Med Clin North Am. 2021;105(5):939-54. 

4. Thiyagalingam S et al. Mayo Clin Proc. 2021;96(2):488-97. 

5. Malagelada JR et al. J Clin Gastroenterol. 2015;49(5):370-8.

6. Rommel, N and Hamdy S. Nat Rev Gastroenterol Hepatol. 2016;13(1):49-59. 

7. Liu LWC et al. J Can Assoc Gastroenterol. 2018;1(1):5-19. 

8. Schwemmle C et al. HNO. 2015;63(7):504-10. 

9. Moayyedi P et al. Am J Gastroenterol. 2017;112(7):988-1013. 

10. Triggs J and Pandolfino J. F1000Res. 2019 Aug 29. doi: 10.12688/f1000research.18900.1. 

11. Yadlapati R et al. Neurogastroenterol Motil. 2021;33(1):e14058. 

12. Yadlapati R et al. Neurogastroenterol Motil. 2021;33(1):e14053. 

13. Fox M et al. Neurogastroenterol Motil. 2004;16(5):533-42. 

14. Sweis R and Fox M. Curr Gastroenterol Rep. 2020;22(10):49. 

15. Carlson DA et al. Gastroenterology. 2015;149(7):1742-51. 

16. Donnan EN and Pandolfino JE. Gastroenterol Clin North Am. 2020;49(3):427-35. 

17. Carlson DA. Curr Opin Gastroenterol. 2016;32(4):310-8.
 

18. Zheng T et al. Neurogastroenterol Motil. 2022;34(10):e14386.

19. Carlson DA et al. Clin Gastroenterol Hepatol. 2022;20(8):1719-28.e3.

20. Carlson DA et al. Am J Gastroenterol. 2016;111(12):1726-35.

21. Carlson DA et al. Neurogastroenterol Motil. 2021;33(10):e14116.

22. Carlson DA et al. Gastrointest Endosc. 2019;90(6):915-923.e1.

23. Fox MR et al. Neurogastroenterol Motil. 2021;33(4):e14120.

24. Aziz Q et al. Gastroenterology. 2016 Feb 15. doi: 10.1053/j.gastro.2016.02.012.

Introduction

Dysphagia is the sensation of difficulty swallowing food or liquid in the acute or chronic setting. The prevalence of dysphagia ranges based on the type and etiology but may impact up to one in six adults.^1,2 Dysphagia can cause a significant impact on a patient’s health and overall quality of life. A recent study found that only 50% of symptomatic adults seek medical care despite modifying their eating habits by either eating slowly or changing to softer foods or liquids.¹ The most common, serious complications of dysphagia include aspiration pneumonia, malnutrition, and dehydration.³ According to the Agency for Healthcare Research and Quality, dysphagia may be responsible for up to 60,000 deaths annually.³

History

The diagnosis of dysphagia begins with a thorough history. Questions about the timing, onset, progression, localization of symptoms, and types of food that are difficult to swallow are essential in differentiating oropharyngeal and esophageal dysphagia.^3,4 Further history taking must include medication and allergy review, smoking history, and review of prior radiation or surgical therapies to the head and neck.

Briefly, oropharyngeal dysphagia is difficulty initiating a swallow or passing food from the mouth or throat and can be caused by structural or functional etiologies.⁵ Clinical presentations include a sensation of food stuck in the back of the throat, coughing or choking while eating, or drooling. Structural causes include head and neck cancer, Zenker diverticulum, Killian Jamieson diverticula, prolonged intubation, or changes secondary to prior surgery or radiation.³ Functional causes may include neurologic, rheumatologic, or muscular disorders.⁶

Esophageal dysphagia refers to difficulty transporting food or liquid down the esophagus and can be caused by structural, inflammatory, or functional disorders.⁵ Patients typically localize symptoms of heartburn, regurgitation, nausea, vomiting, cough, or chest pain along the sternum or epigastric region. Alarm signs concerning for malignancy include unintentional weight loss, fevers, or night sweats.^3,7 Aside from symptoms, medication review is essential, as dysphagia is a common side effect of antipsychotics, anticholinergics, antimuscarinics, narcotics, and immunosuppressant drugs.⁸ Larger pills such as NSAIDs, antibiotics, bisphosphonates, potassium supplements, and methylxanthines can cause drug-induced esophagitis, which can initially present as dysphagia.⁸ Inflammatory causes can be elucidated by obtaining a history about allergies, tobacco use, and recent infections such as thrush or pneumonia. Patients with a history of recurrent pneumonias may be silently aspirating, a complication of dysphagia.³ Once esophageal dysphagia is clinically suspected based on history, workup can begin. 

Differentiating etiologies of esophageal dysphagia 

The next step in diagnosing esophageal dysphagia is differentiating between structural, inflammatory, or dysmotility etiology (Figure 1). 

Courtesy Tanisha Ronnie, MD, Lauren Bloomberg, MD, and Mukund Venu, MD

Patients with a structural cause typically have difficulty swallowing solids but are able to swallow liquids unless the disease progresses. Symptoms can rapidly worsen and lead to odynophagia, weight loss, and vomiting. In comparison, patients with motility disorders typically have difficulty swallowing both solids and liquids initially, and symptoms can be constant or intermittent.⁵ 

Prior to diagnostic studies, a 4-week trial of a proton pump inhibitor (PPI) is appropriate for patients with reflux symptoms who are younger than 50 with no alarm features concerning for malignancy.^7,9 If symptoms persist after a PPI trial, then an upper endoscopy (EGD) is indicated. An EGD allows for visualization of structural etiologies, obtaining biopsies to rule out inflammatory etiologies, and the option to therapeutically treat reduced luminal diameter with dilatation.¹⁰ The most common structural and inflammatory etiologies noted on EGD include strictures, webs, carcinomas, Schatzki rings, and gastroesophageal reflux or eosinophilic esophagitis.⁴

If upper endoscopy is normal and clinical suspicion for an obstructive cause remains high, barium esophagram can be utilized as an adjunctive study. Previously, barium esophagram was the initial test to distinguish between structural and motility disorders. The benefits of endoscopy over barium esophagram as the first diagnostic study include higher diagnostic yield, higher sensitivity and specificity, and lower costs.⁷ However, barium studies may be more sensitive for lower esophageal rings or extrinsic esophageal compression.3 

 

Evaluation of esophageal motility disorder

If a structural or inflammatory etiology of dysphagia is not identified, investigation for an esophageal motility disorder (EMD) is warranted. Examples of motility disorders include achalasia, ineffective esophageal motility, hypercontractility, spasticity, or esophagogastric junction outflow obstruction (EGJOO).^10,11 High-resolution esophageal manometry (HRM) remains the gold standard in diagnosis of EMD.¹² An HRM catheter utilizes 36 sensors placed two centimeters apart and is placed in the esophagus to evaluate pressure and peristalsis between the upper and lower esophageal sphincters.¹³ In 2009, the Chicago Classification System was developed to provide a diagnostic algorithm that categorizes EMD based on HRM testing, with the most recent version (4.0) being published in 2020.^12,14 Motility diagnoses are divided into two general classifications of disorders of body peristalsis and disorders of EGJ outflow. The most recent updates also include changes in swallow protocols, patient positioning, targeted symptoms, addition of impedance sensors, and consideration of supplemental testing when HRM is inconclusive based on the clinical context.¹² There are some limitations of HRM to highlight. One of the main diagnostic values used with HRM is the integrated relaxation pressure (IRP). Despite standardization, IRP measurements vary based on the recorder and patient position. A minority of patients with achalasia may have IRP that does not approach the accepted cutoff and, therefore, the EGJ is not accurately assessed on HRM.^15,16 In addition, some swallow protocols have lower sensitivity and specificity for certain motility disorders, and the test can result as inconclusive.14 In these scenarios, supplemental testing with timed barium esophagram or functional luminal imaging probe (EndoFLIP) is indicated.^10,11

Loyola University Chicago

Over the past decade, EndoFLIP has emerged as a novel diagnostic tool in evaluating EMD. EndoFLIP is usually completed during an upper endoscopy and utilizes impedance planimetry to measure cross-sectional area and esophageal distensibility and evaluate contractile patterns.¹⁶ During the procedure, a small catheter with an inflatable balloon is inserted into the esophagus with the distal end in the stomach, traversing the esophagogastric junction (EGJ). The pressure transducer has electrodes every centimeter to allow for a three-dimensional construction of the esophagus and EGJ.¹⁷ EndoFLIP has been shown to accurately measure pyloric diameter, pressure, and distensibility at certain balloon volumes.¹⁸ In addition, FLIP is being used to further identify aspects of esophageal dysmotility in patients with eosinophilic esophagitis, thought primarily to be an inflammatory disorder.¹⁹ However, limitations include minimal accessibility of EndoFLIP within clinical practice and a specific computer program needed to generate the topographic plots.²⁰ 

When used in conjunction with HRM, EndoFLIP provides complementary data that can be used to better detect major motility disorders.^15,20,21 Each study adds unique information about the different physiologic events comprising the esophageal response to distention. Overall, the benefits of EndoFLIP include expediting workup during index endoscopy, patient comfort with sedation, and real-time diagnostic data that supplement results obtained during HRM.^{10,16,20,2223}

Of note, if the diagnostic evaluation for structural, inflammatory, and motility disorders are unrevealing, investigating for atypical reflux symptoms can be pursued for patients with persistent dysphagia. Studies investigating pH, or acidity in the esophagus, in relation to symptoms, can be conducted wirelessly via a capsule fixed to the mucosa or with a nasal catheter.³

Normal workup – hypervigilance

In a subset of patients, all diagnostic testing for structural, inflammatory, or motility disorders is normal. These patients are classified as having a functional esophageal disorder. Despite normal testing, patients still have significant symptoms including epigastric pain, chest pain, globus sensation, or difficulty swallowing. It is theorized that a degree of visceral hypersensitivity between the brain-gut axis contributes to ongoing symptoms.²⁴ Studies for effective treatments are ongoing but typically include cognitive-behavioral therapy, brain-gut behavioral therapy, swallow therapy antidepressants, or short courses of proton pump inhibitors.⁹

Conclusion

In this review article, we discussed the diagnostic approach for esophageal dysphagia. Initial assessment requires a thorough history, differentiation between oropharyngeal and esophageal dysphagia, and determination of who warrants an upper endoscopy. Upper endoscopy may reveal structural or inflammatory causes of dysphagia, including strictures, masses, or esophagitis, to name a few. If a structural or inflammatory cause is ruled out, this warrants investigation for esophageal motility disorders. The current gold standard for diagnosing EMD is manometry, and supplemental studies, including EndoFLIP, barium esophagram, and pH studies, may provide complimentary data. If workup for dysphagia is normal, evaluation for esophageal hypervigilance causing increased sensitivity to normal or mild sensations may be warranted. In conclusion, the diagnosis of dysphagia is challenging and requires investigation with a systematic approach to ensure timely diagnosis and treatment

Dr. Ronnie and Dr. Bloomberg are in the department of internal medicine at Loyola University Chicago, Maywood, Ill. Dr. Venu is in the division of gastroenterology at Loyola. He is on the speakers bureau at Medtronic.

References 

1. Adkins C et al. Clin Gastroenterol Hepatol. 2020;18(9):1970-9.e2. 

2. Bhattacharyya N. Otolaryngol Head Neck Surg. 2014;151(5):765-9. 

3. McCarty EB and Chao TN. Med Clin North Am. 2021;105(5):939-54. 

4. Thiyagalingam S et al. Mayo Clin Proc. 2021;96(2):488-97. 

5. Malagelada JR et al. J Clin Gastroenterol. 2015;49(5):370-8.

6. Rommel, N and Hamdy S. Nat Rev Gastroenterol Hepatol. 2016;13(1):49-59. 

7. Liu LWC et al. J Can Assoc Gastroenterol. 2018;1(1):5-19. 

8. Schwemmle C et al. HNO. 2015;63(7):504-10. 

9. Moayyedi P et al. Am J Gastroenterol. 2017;112(7):988-1013. 

10. Triggs J and Pandolfino J. F1000Res. 2019 Aug 29. doi: 10.12688/f1000research.18900.1. 

11. Yadlapati R et al. Neurogastroenterol Motil. 2021;33(1):e14058. 

12. Yadlapati R et al. Neurogastroenterol Motil. 2021;33(1):e14053. 

13. Fox M et al. Neurogastroenterol Motil. 2004;16(5):533-42. 

14. Sweis R and Fox M. Curr Gastroenterol Rep. 2020;22(10):49. 

15. Carlson DA et al. Gastroenterology. 2015;149(7):1742-51. 

16. Donnan EN and Pandolfino JE. Gastroenterol Clin North Am. 2020;49(3):427-35. 

17. Carlson DA. Curr Opin Gastroenterol. 2016;32(4):310-8.
 

18. Zheng T et al. Neurogastroenterol Motil. 2022;34(10):e14386.

19. Carlson DA et al. Clin Gastroenterol Hepatol. 2022;20(8):1719-28.e3.

20. Carlson DA et al. Am J Gastroenterol. 2016;111(12):1726-35.

21. Carlson DA et al. Neurogastroenterol Motil. 2021;33(10):e14116.

22. Carlson DA et al. Gastrointest Endosc. 2019;90(6):915-923.e1.

23. Fox MR et al. Neurogastroenterol Motil. 2021;33(4):e14120.

24. Aziz Q et al. Gastroenterology. 2016 Feb 15. doi: 10.1053/j.gastro.2016.02.012.

Each May, the gastroenterology community gathers for Digestive Disease Week® to be inspired, meet up with friends and colleagues from across the globe, and learn the latest in scientific advances to inform how we care for our patients in the clinic, on inpatient wards, and in our endoscopy suites. DDW® 2023, held in the Windy City of Chicago, does not disappoint. This year’s conference features a dizzying array of offerings, including 3,500 poster and ePoster presentations and 1,300 abstract lectures, as well as the perennially well-attended AGA Post-Graduate Course and other offerings.

This year’s AGA Presidential Plenary, hosted on May 8 by outgoing AGA President Dr. John M. Carethers, is not to be missed. The session will honor the 125-year history of the AGA and recognizes the barriers overcome in diversifying the practice of gastroenterology. You will learn about individuals such as Alexis St. Martin, MD; Basil Hirschowitz, MD, AGAF; Leonidas Berry, MD; Sadye Curry, MD; and, other barrier-breakers in GI who have been instrumental in shaping the modern practice of gastroenterology. I hope you will join me in attending.

In this month’s issue of GIHN, we introduce the winner of the 2023 AGA Shark Tank innovation competition, which was held during the 2023 AGA Tech Summit. We also report on a landmark phase 4, double-blind randomized trial published in the New England Journal of Medicine demonstrating the effectiveness of vedolizumab in inducing remission in chronic pouchitis, and a new AGA clinical practice update on the role of EUS-guided gallbladder drainage in acute cholecystitis.

The AGA Government Affairs Committee also updates us on their advocacy to reform prior authorization policies affecting GI practice, and explains how you can assist in these efforts. In our Member Spotlight, we introduce you to gastroenterologist Sharmila Anandasabapthy, MD, who shares her passion for global health and the one piece of career advice she’s glad she ignored.

Finally, GIHN Associate Editor Dr. Avi Ketwaroo presents our quarterly Perspectives column highlighting differing approaches to clinical management of pancreatic cystic lesions. We hope you enjoy all of the exciting content featured in this issue and look forward to seeing you in Chicago (or, virtually) for DDW.
 

Megan A. Adams, MD, JD, MSc
Editor-in-Chief

Each May, the gastroenterology community gathers for Digestive Disease Week® to be inspired, meet up with friends and colleagues from across the globe, and learn the latest in scientific advances to inform how we care for our patients in the clinic, on inpatient wards, and in our endoscopy suites. DDW® 2023, held in the Windy City of Chicago, does not disappoint. This year’s conference features a dizzying array of offerings, including 3,500 poster and ePoster presentations and 1,300 abstract lectures, as well as the perennially well-attended AGA Post-Graduate Course and other offerings.

This year’s AGA Presidential Plenary, hosted on May 8 by outgoing AGA President Dr. John M. Carethers, is not to be missed. The session will honor the 125-year history of the AGA and recognizes the barriers overcome in diversifying the practice of gastroenterology. You will learn about individuals such as Alexis St. Martin, MD; Basil Hirschowitz, MD, AGAF; Leonidas Berry, MD; Sadye Curry, MD; and, other barrier-breakers in GI who have been instrumental in shaping the modern practice of gastroenterology. I hope you will join me in attending.

In this month’s issue of GIHN, we introduce the winner of the 2023 AGA Shark Tank innovation competition, which was held during the 2023 AGA Tech Summit. We also report on a landmark phase 4, double-blind randomized trial published in the New England Journal of Medicine demonstrating the effectiveness of vedolizumab in inducing remission in chronic pouchitis, and a new AGA clinical practice update on the role of EUS-guided gallbladder drainage in acute cholecystitis.

The AGA Government Affairs Committee also updates us on their advocacy to reform prior authorization policies affecting GI practice, and explains how you can assist in these efforts. In our Member Spotlight, we introduce you to gastroenterologist Sharmila Anandasabapthy, MD, who shares her passion for global health and the one piece of career advice she’s glad she ignored.

Finally, GIHN Associate Editor Dr. Avi Ketwaroo presents our quarterly Perspectives column highlighting differing approaches to clinical management of pancreatic cystic lesions. We hope you enjoy all of the exciting content featured in this issue and look forward to seeing you in Chicago (or, virtually) for DDW.
 

Megan A. Adams, MD, JD, MSc
Editor-in-Chief

Each May, the gastroenterology community gathers for Digestive Disease Week® to be inspired, meet up with friends and colleagues from across the globe, and learn the latest in scientific advances to inform how we care for our patients in the clinic, on inpatient wards, and in our endoscopy suites. DDW® 2023, held in the Windy City of Chicago, does not disappoint. This year’s conference features a dizzying array of offerings, including 3,500 poster and ePoster presentations and 1,300 abstract lectures, as well as the perennially well-attended AGA Post-Graduate Course and other offerings.

This year’s AGA Presidential Plenary, hosted on May 8 by outgoing AGA President Dr. John M. Carethers, is not to be missed. The session will honor the 125-year history of the AGA and recognizes the barriers overcome in diversifying the practice of gastroenterology. You will learn about individuals such as Alexis St. Martin, MD; Basil Hirschowitz, MD, AGAF; Leonidas Berry, MD; Sadye Curry, MD; and, other barrier-breakers in GI who have been instrumental in shaping the modern practice of gastroenterology. I hope you will join me in attending.

In this month’s issue of GIHN, we introduce the winner of the 2023 AGA Shark Tank innovation competition, which was held during the 2023 AGA Tech Summit. We also report on a landmark phase 4, double-blind randomized trial published in the New England Journal of Medicine demonstrating the effectiveness of vedolizumab in inducing remission in chronic pouchitis, and a new AGA clinical practice update on the role of EUS-guided gallbladder drainage in acute cholecystitis.

The AGA Government Affairs Committee also updates us on their advocacy to reform prior authorization policies affecting GI practice, and explains how you can assist in these efforts. In our Member Spotlight, we introduce you to gastroenterologist Sharmila Anandasabapthy, MD, who shares her passion for global health and the one piece of career advice she’s glad she ignored.

Finally, GIHN Associate Editor Dr. Avi Ketwaroo presents our quarterly Perspectives column highlighting differing approaches to clinical management of pancreatic cystic lesions. We hope you enjoy all of the exciting content featured in this issue and look forward to seeing you in Chicago (or, virtually) for DDW.
 

Megan A. Adams, MD, JD, MSc
Editor-in-Chief

Dear colleagues,

Pancreas cysts have become almost ubiquitous in this era of high-resolution cross-sectional imaging. They are a common GI consult with patients and providers worried about the potential risk of malignant transformation. Despite significant research over the past few decades, predicting the natural history of these cysts, especially the side-branch intraductal papillary mucinous neoplasms (IPMNs), remains difficult. There have been a variety of expert recommendations and guidelines, but heterogeneity exists in management especially regarding timing of endoscopic ultrasound, imaging surveillance, and cessation of surveillance. Some centers will present these cysts at multidisciplinary conferences, while others will follow general or local algorithms. In this issue of Perspectives, Dr. Lauren G. Khanna, assistant professor of medicine at NYU Langone Health, New York, and Dr. Santhi Vege, professor of medicine at the Mayo Clinic, Rochester, Minn., present updated and differing approaches to managing these cysts. Which side of the debate are you on? We welcome your thoughts, questions and input– share with us on Twitter @AGA_GIHN

Continuing pancreas cyst surveillance indefinitely is reasonable

BY LAUREN G. KHANNA, MD, MS

Pancreas cysts remain a clinical challenge. The true incidence of pancreas cysts is unknown, but from MRI and autopsy series, may be up to 50%. Patients presenting with a pancreas cyst often have significant anxiety about their risk of pancreas cancer. We as a medical community initially did too; but over the past few decades as we have gathered more data, we have become more comfortable observing many pancreas cysts. Yet our recommendations for how, how often, and for how long to evaluate pancreas cysts are still very much under debate; there are multiple guidelines with discordant recommendations. In this article, I will discuss my approach to patients with a pancreas cyst.

NYU Langone Health

At the first evaluation, I review available imaging to see if there are characteristic features to determine the type of pancreas cyst: IPMN (including main duct, branch duct, or mixed type), serous cystic neoplasm (SCA), mucinous cystic neoplasm (MCN), solid pseudopapillary neoplasm (SPN), cystic neuroendocrine tumor (NET), or pseudocyst. I also review symptoms, including abdominal pain, weight loss, history of pancreatitis, and onset of diabetes, and check hemoglobin A1c and Ca19-9. I often recommend magnetic resonance cholangiopancreatography (MRCP) if it has not already been obtained and is feasible (that is, if a patient does not have severe claustrophobia or a medical device incompatible with MRI). If a patient is not a candidate for treatment should a pancreatic malignancy be identified, because of age, comorbidities, or preference, I recommend no further evaluation.

Where cyst type remains unclear despite MRCP, and for cysts over 2 cm, I recommend endoscopic ultrasound (EUS) for fluid sampling to assist in determining cyst type and to rule out any other high-risk features. In accordance with international guidelines, if a patient has any concerning imaging features, including main pancreatic duct dilation >5 mm, solid component or mural nodule, or thickened or enhancing duct walls, regardless of cyst size, I recommend EUS to assess for and biopsy any solid component and to sample cyst fluid to examine for dysplasia. Given the lower sensitivity of CT for high-risk features, if MRCP is not feasible, for cysts 1-2 cm, I recommend EUS for better evaluation.

If a cyst is determined to be a cystic NET; main duct or mixed-type IPMN; MCN; or SPN; or a branch duct IPMN with mural nodule, high-grade dysplasia, or adenocarcinoma, and the patient is a surgical candidate, I refer the patient for surgical evaluation. If a cyst is determined to be an SCA, the malignant potential is minimal, and patients do not require follow-up. Patients with a pseudocyst are managed according to their clinical scenario.

Many patients have a proven or suspected branch duct IPMN, an indeterminate cyst, or multiple cysts. Cyst management during surveillance is then determined by the size of the largest cyst and stability of the cyst(s). Of note, patients with an IPMN also have been shown to have an elevated risk of concurrent pancreas adenocarcinoma, which I believe is one of the strongest arguments for heightened surveillance of the entire pancreas in pancreas cyst patients. EUS in particular can identify small or subtle lesions that are not detected by cross-sectional imaging.

If a patient has no prior imaging, in accordance with international and European guidelines, I recommend the first surveillance MRCP at a 6-month interval for cysts <2 cm, which may offer the opportunity to identify rapidly progressing cysts. If a patient has previous imaging available demonstrating stability, I recommend surveillance on an annual basis for cysts <2 cm. For patients with a cyst >2 cm, as above, I recommend EUS, and if there are no concerning features on imaging or EUS, I then recommend annual surveillance.

While the patient is under surveillance, if there is more than minimal cyst growth, a change in cyst appearance, or development of any imaging high-risk feature, pancreatitis, new onset or worsening diabetes, or elevation of Ca19-9, I recommend EUS for further evaluation and consideration of surgery based on EUS findings. If an asymptomatic cyst <2 cm remains stable for 5 years, I offer patients the option to extend imaging to every 2 years, if they are comfortable. In my experience, though, many patients prefer to continue annual imaging. The American Gastroenterological Association guidelines promote stopping surveillance after 5 years of stability, however there are studies demonstrating development of malignancy in cysts that were initially stable over the first 5 years of surveillance. Therefore, I discuss with patients that it is reasonable to continue cyst surveillance indefinitely, until they would no longer be interested in pursuing treatment of any kind if a malignant lesion were to be identified.

There are two special groups of pancreas cyst patients who warrant specific attention. Patients who are at elevated risk of pancreas adenocarcinoma because of an associated genetic mutation or a family history of pancreatic cancer already may be undergoing annual pancreas cancer screening with either MRCP, EUS, or alternating MRCP and EUS. When these high-risk patients also have pancreas cysts, I utilize whichever strategy would image their pancreas most frequently and do not extend beyond 1-year intervals. Another special group is patients who have undergone partial pancreatectomy for IPMN. As discussed above, given the elevated risk of concurrent pancreas adenocarcinoma in IPMN patients, I recommend indefinite continued surveillance of the remaining pancreas parenchyma in these patients.

Given the prevalence of pancreas cysts, it certainly would be convenient if guidelines were straightforward enough for primary care physicians to manage pancreas cyst surveillance, as they do for breast cancer screening. However, the complexities of pancreas cysts necessitate the expertise of gastroenterologists and pancreas surgeons, and a multidisciplinary team approach is best where possible.

Dr. Khanna is chief, advanced endoscopy, Tisch Hospital; director, NYU Advanced Endoscopy Fellowship; assistant professor of medicine, NYU Langone Health. Email: [email protected]. There are no relevant conflicts to disclose.
 

References

Tanaka M et al. Pancreatology. 2017 Sep-Oct;17(5):738-75.

Sahora K et al. Eur J Surg Oncol. 2016 Feb;42(2):197-204.

Del Chiaro M et al. Gut. 2018 May;67(5):789-804

Vege SS et al. Gastroenterology. 2015 Apr;148(4):819-22

Petrone MC et al. Clin Transl Gastroenterol. 2018 Jun 13;9(6):158

Pancreas cysts: More is not necessarily better!

BY SANTHI SWAROOP VEGE, MD

Pancreas cysts (PC) are very common, incidental findings on cross-sectional imaging, performed for non–pancreas-related symptoms. The important issues in management of patients with PC in my practice are the prevalence, natural history, frequency of occurrence of high-grade dysplasia (HGD) and/or pancreatic cancer (PDAC), concerning clinical symptoms and imaging findings, indications for EUS and fine-needle aspiration cytology, ideal method and frequency of surveillance, indications for surgery (up front and during follow-up), follow-up after surgery, stopping surveillance, costs, and unintentional harms of management. Good population-based evidence regarding many of the issues described above does not exist, and all information is from selected clinic, radiology, EUS, and surgical cohorts (very important when trying to assess the publications). Cohort studies should start with all PC undergoing surveillance and assess various outcomes, rather than looking backward from EUS or surgical cohorts.

The 2015 American Gastroenterological Association guidelines on asymptomatic neoplastic pancreas cysts, which I coauthored, recommend, consistent with principles of High Value Care (minimal unintentional harms and cost effectiveness), that two of three high-risk features (mural nodule, cyst size greater than 3 cm, and dilated pancreatic duct) be present for EUS-guided fine-needle aspiration (EUS-FNA). By the same token, they advise surgery for those with two of three high-risk features and or concerning features on EUS and cytology. Finally, they suggest stopping surveillance at 5 years if there are no significant changes. Rigorous GRADE methodology along with systematic review of all relevant questions (rather than cohorts of 500 or fewer patients) formed the basis of the guidelines. Those meta-analyses showed that risk of PDAC in mural nodules, cyst size >3 cm, and dilated pancreatic duct, while elevated, still is very low in absolute terms. Less than 20% of resections for highly selected, high-risk cysts showed PDAC. The guidelines were met with a lot of resistance from several societies and physician groups. The recommendations for stopping surveillance after 5 years and no surveillance for absent or low-grade dysplasia after surgery are hotly contested, and these areas need larger, long-term studies.

The whole area of cyst fluid molecular markers that would suggest mucinous type (KRAS and GNAS mutations) and, more importantly, the presence or imminent development of PDAC (next-generation sequencing or NGS) is an exciting field. One sincerely hopes that there will be a breakthrough in this area to achieve the holy grail. Cost effectiveness studies demonstrate the futility of existing guidelines and favor a less intensive approach. Guidelines are only a general framework, and management of individual patients in the clinic is entirely at the discretion of the treating physician. One should make every attempt to detect advanced lesions in PC, but such effort should not subject a large majority of patients to unintentional harms by overtreatment and add further to the burgeoning health care costs in the country.

Mayo Clinic

PC are extremely common (10% of all abdominal imaging), increase with age, are seen in as many as 40%-50% of MRI examinations for nonpancreatic indications, and most (>50%) are IPMNs. Most of the debate centers around the concerns of PDAC and/or HGD associated with mucinous cysts (MCN, IPMN, side-branch, main duct, or mixed).

The various guidelines by multiple societies differ in some aspects, such as in selection of patients based on clinical, laboratory, and imaging findings for up-front surgery or surveillance, the frequency of surveillance based on the size of the cyst and the presence of other concerning cyst features (usually with MRCP), the indications for EUS (both initial and subsequent), importance of the magnitude of growth (most IPMNs slowly grow over a period of time), indications for surgery during surveillance and postsurgery surveillance, and the decision to stop surveillance at some point in time. The literature is replete with small case series reporting a proportion of cancers detected and often ignoring the harms of surgery. Incidence of and mortality caused by PDAC are very low (about 1% for both) in a large national cohort of VA pancreatic cyst patients with long-term follow-up and other studies.

Marcov modeling suggests that none of the guidelines would lead to cost-effective care with low mortality because of overtreatment of low-risk lesions, and a specificity of 67% or more for PDAC/HGB is required. AGA guidelines came close to it but with low sensitivity. Monte Carlo modeling suggests that less intensive strategies, compared with more intensive, result in a similar number of deaths at a much lower cost. While molecular markers in PC fluid are reported to increase the specificity of PDAC/HGD to greater than 70%, it should be observed that such validation was done in a small percentage of patients who had both those markers and resection.

The costs of expensive procedures like EUS, MRI, and surgery, the 3% complication rate with EUS-FNA (primarily acute pancreatitis), and the 1% mortality and approximately 20%-30% morbidity with surgery (bleeding, infection, fistula) and postpancreatectomy diabetes of approximately 30% in the long run need special attention.

In conclusion, one could say pancreas cysts are extremely frequent, most of the neoplastic cysts are mucinous (IPMN and MCN) and slowly growing over time without an associated cancer, and the greatest need at this time is to identify the small proportion of such cysts with PDAC and/or HGD. Until such time, judicious selection of patients for surveillance and reasonable intervals of such surveillance with selective use of EUS will help identify patients requiring resection. In our enthusiasm to detect every possible pancreatic cancer, we should not ignore the unintentional outcomes of surgery to a large majority of patients who would never develop PDAC and the astronomical costs associated with such practice.

Dr. Vege is professor of medicine at the Mayo Clinic. He reported having no conflicts of interest regarding this article.
 

References

Vege SS et al. Gastroenterology. 2015;148:819-22.

Lobo JM et al. Surgery. 2020;168:601-9.

Lennon AM and Vege SS. Clin Gastroenterol Hepatol. 2022;20:1663-7.

Harris RP. Ann Intern Med. 2015;162:787-9.

Dear colleagues,

Pancreas cysts have become almost ubiquitous in this era of high-resolution cross-sectional imaging. They are a common GI consult with patients and providers worried about the potential risk of malignant transformation. Despite significant research over the past few decades, predicting the natural history of these cysts, especially the side-branch intraductal papillary mucinous neoplasms (IPMNs), remains difficult. There have been a variety of expert recommendations and guidelines, but heterogeneity exists in management especially regarding timing of endoscopic ultrasound, imaging surveillance, and cessation of surveillance. Some centers will present these cysts at multidisciplinary conferences, while others will follow general or local algorithms. In this issue of Perspectives, Dr. Lauren G. Khanna, assistant professor of medicine at NYU Langone Health, New York, and Dr. Santhi Vege, professor of medicine at the Mayo Clinic, Rochester, Minn., present updated and differing approaches to managing these cysts. Which side of the debate are you on? We welcome your thoughts, questions and input– share with us on Twitter @AGA_GIHN

Continuing pancreas cyst surveillance indefinitely is reasonable

BY LAUREN G. KHANNA, MD, MS

Pancreas cysts remain a clinical challenge. The true incidence of pancreas cysts is unknown, but from MRI and autopsy series, may be up to 50%. Patients presenting with a pancreas cyst often have significant anxiety about their risk of pancreas cancer. We as a medical community initially did too; but over the past few decades as we have gathered more data, we have become more comfortable observing many pancreas cysts. Yet our recommendations for how, how often, and for how long to evaluate pancreas cysts are still very much under debate; there are multiple guidelines with discordant recommendations. In this article, I will discuss my approach to patients with a pancreas cyst.

NYU Langone Health

At the first evaluation, I review available imaging to see if there are characteristic features to determine the type of pancreas cyst: IPMN (including main duct, branch duct, or mixed type), serous cystic neoplasm (SCA), mucinous cystic neoplasm (MCN), solid pseudopapillary neoplasm (SPN), cystic neuroendocrine tumor (NET), or pseudocyst. I also review symptoms, including abdominal pain, weight loss, history of pancreatitis, and onset of diabetes, and check hemoglobin A1c and Ca19-9. I often recommend magnetic resonance cholangiopancreatography (MRCP) if it has not already been obtained and is feasible (that is, if a patient does not have severe claustrophobia or a medical device incompatible with MRI). If a patient is not a candidate for treatment should a pancreatic malignancy be identified, because of age, comorbidities, or preference, I recommend no further evaluation.

Where cyst type remains unclear despite MRCP, and for cysts over 2 cm, I recommend endoscopic ultrasound (EUS) for fluid sampling to assist in determining cyst type and to rule out any other high-risk features. In accordance with international guidelines, if a patient has any concerning imaging features, including main pancreatic duct dilation >5 mm, solid component or mural nodule, or thickened or enhancing duct walls, regardless of cyst size, I recommend EUS to assess for and biopsy any solid component and to sample cyst fluid to examine for dysplasia. Given the lower sensitivity of CT for high-risk features, if MRCP is not feasible, for cysts 1-2 cm, I recommend EUS for better evaluation.

If a cyst is determined to be a cystic NET; main duct or mixed-type IPMN; MCN; or SPN; or a branch duct IPMN with mural nodule, high-grade dysplasia, or adenocarcinoma, and the patient is a surgical candidate, I refer the patient for surgical evaluation. If a cyst is determined to be an SCA, the malignant potential is minimal, and patients do not require follow-up. Patients with a pseudocyst are managed according to their clinical scenario.

Many patients have a proven or suspected branch duct IPMN, an indeterminate cyst, or multiple cysts. Cyst management during surveillance is then determined by the size of the largest cyst and stability of the cyst(s). Of note, patients with an IPMN also have been shown to have an elevated risk of concurrent pancreas adenocarcinoma, which I believe is one of the strongest arguments for heightened surveillance of the entire pancreas in pancreas cyst patients. EUS in particular can identify small or subtle lesions that are not detected by cross-sectional imaging.

If a patient has no prior imaging, in accordance with international and European guidelines, I recommend the first surveillance MRCP at a 6-month interval for cysts <2 cm, which may offer the opportunity to identify rapidly progressing cysts. If a patient has previous imaging available demonstrating stability, I recommend surveillance on an annual basis for cysts <2 cm. For patients with a cyst >2 cm, as above, I recommend EUS, and if there are no concerning features on imaging or EUS, I then recommend annual surveillance.

While the patient is under surveillance, if there is more than minimal cyst growth, a change in cyst appearance, or development of any imaging high-risk feature, pancreatitis, new onset or worsening diabetes, or elevation of Ca19-9, I recommend EUS for further evaluation and consideration of surgery based on EUS findings. If an asymptomatic cyst <2 cm remains stable for 5 years, I offer patients the option to extend imaging to every 2 years, if they are comfortable. In my experience, though, many patients prefer to continue annual imaging. The American Gastroenterological Association guidelines promote stopping surveillance after 5 years of stability, however there are studies demonstrating development of malignancy in cysts that were initially stable over the first 5 years of surveillance. Therefore, I discuss with patients that it is reasonable to continue cyst surveillance indefinitely, until they would no longer be interested in pursuing treatment of any kind if a malignant lesion were to be identified.

There are two special groups of pancreas cyst patients who warrant specific attention. Patients who are at elevated risk of pancreas adenocarcinoma because of an associated genetic mutation or a family history of pancreatic cancer already may be undergoing annual pancreas cancer screening with either MRCP, EUS, or alternating MRCP and EUS. When these high-risk patients also have pancreas cysts, I utilize whichever strategy would image their pancreas most frequently and do not extend beyond 1-year intervals. Another special group is patients who have undergone partial pancreatectomy for IPMN. As discussed above, given the elevated risk of concurrent pancreas adenocarcinoma in IPMN patients, I recommend indefinite continued surveillance of the remaining pancreas parenchyma in these patients.

Given the prevalence of pancreas cysts, it certainly would be convenient if guidelines were straightforward enough for primary care physicians to manage pancreas cyst surveillance, as they do for breast cancer screening. However, the complexities of pancreas cysts necessitate the expertise of gastroenterologists and pancreas surgeons, and a multidisciplinary team approach is best where possible.

Dr. Khanna is chief, advanced endoscopy, Tisch Hospital; director, NYU Advanced Endoscopy Fellowship; assistant professor of medicine, NYU Langone Health. Email: [email protected]. There are no relevant conflicts to disclose.
 

References

Tanaka M et al. Pancreatology. 2017 Sep-Oct;17(5):738-75.

Sahora K et al. Eur J Surg Oncol. 2016 Feb;42(2):197-204.

Del Chiaro M et al. Gut. 2018 May;67(5):789-804

Vege SS et al. Gastroenterology. 2015 Apr;148(4):819-22

Petrone MC et al. Clin Transl Gastroenterol. 2018 Jun 13;9(6):158

Pancreas cysts: More is not necessarily better!

BY SANTHI SWAROOP VEGE, MD

Pancreas cysts (PC) are very common, incidental findings on cross-sectional imaging, performed for non–pancreas-related symptoms. The important issues in management of patients with PC in my practice are the prevalence, natural history, frequency of occurrence of high-grade dysplasia (HGD) and/or pancreatic cancer (PDAC), concerning clinical symptoms and imaging findings, indications for EUS and fine-needle aspiration cytology, ideal method and frequency of surveillance, indications for surgery (up front and during follow-up), follow-up after surgery, stopping surveillance, costs, and unintentional harms of management. Good population-based evidence regarding many of the issues described above does not exist, and all information is from selected clinic, radiology, EUS, and surgical cohorts (very important when trying to assess the publications). Cohort studies should start with all PC undergoing surveillance and assess various outcomes, rather than looking backward from EUS or surgical cohorts.

The 2015 American Gastroenterological Association guidelines on asymptomatic neoplastic pancreas cysts, which I coauthored, recommend, consistent with principles of High Value Care (minimal unintentional harms and cost effectiveness), that two of three high-risk features (mural nodule, cyst size greater than 3 cm, and dilated pancreatic duct) be present for EUS-guided fine-needle aspiration (EUS-FNA). By the same token, they advise surgery for those with two of three high-risk features and or concerning features on EUS and cytology. Finally, they suggest stopping surveillance at 5 years if there are no significant changes. Rigorous GRADE methodology along with systematic review of all relevant questions (rather than cohorts of 500 or fewer patients) formed the basis of the guidelines. Those meta-analyses showed that risk of PDAC in mural nodules, cyst size >3 cm, and dilated pancreatic duct, while elevated, still is very low in absolute terms. Less than 20% of resections for highly selected, high-risk cysts showed PDAC. The guidelines were met with a lot of resistance from several societies and physician groups. The recommendations for stopping surveillance after 5 years and no surveillance for absent or low-grade dysplasia after surgery are hotly contested, and these areas need larger, long-term studies.

The whole area of cyst fluid molecular markers that would suggest mucinous type (KRAS and GNAS mutations) and, more importantly, the presence or imminent development of PDAC (next-generation sequencing or NGS) is an exciting field. One sincerely hopes that there will be a breakthrough in this area to achieve the holy grail. Cost effectiveness studies demonstrate the futility of existing guidelines and favor a less intensive approach. Guidelines are only a general framework, and management of individual patients in the clinic is entirely at the discretion of the treating physician. One should make every attempt to detect advanced lesions in PC, but such effort should not subject a large majority of patients to unintentional harms by overtreatment and add further to the burgeoning health care costs in the country.

Mayo Clinic

PC are extremely common (10% of all abdominal imaging), increase with age, are seen in as many as 40%-50% of MRI examinations for nonpancreatic indications, and most (>50%) are IPMNs. Most of the debate centers around the concerns of PDAC and/or HGD associated with mucinous cysts (MCN, IPMN, side-branch, main duct, or mixed).

The various guidelines by multiple societies differ in some aspects, such as in selection of patients based on clinical, laboratory, and imaging findings for up-front surgery or surveillance, the frequency of surveillance based on the size of the cyst and the presence of other concerning cyst features (usually with MRCP), the indications for EUS (both initial and subsequent), importance of the magnitude of growth (most IPMNs slowly grow over a period of time), indications for surgery during surveillance and postsurgery surveillance, and the decision to stop surveillance at some point in time. The literature is replete with small case series reporting a proportion of cancers detected and often ignoring the harms of surgery. Incidence of and mortality caused by PDAC are very low (about 1% for both) in a large national cohort of VA pancreatic cyst patients with long-term follow-up and other studies.

Marcov modeling suggests that none of the guidelines would lead to cost-effective care with low mortality because of overtreatment of low-risk lesions, and a specificity of 67% or more for PDAC/HGB is required. AGA guidelines came close to it but with low sensitivity. Monte Carlo modeling suggests that less intensive strategies, compared with more intensive, result in a similar number of deaths at a much lower cost. While molecular markers in PC fluid are reported to increase the specificity of PDAC/HGD to greater than 70%, it should be observed that such validation was done in a small percentage of patients who had both those markers and resection.

The costs of expensive procedures like EUS, MRI, and surgery, the 3% complication rate with EUS-FNA (primarily acute pancreatitis), and the 1% mortality and approximately 20%-30% morbidity with surgery (bleeding, infection, fistula) and postpancreatectomy diabetes of approximately 30% in the long run need special attention.

In conclusion, one could say pancreas cysts are extremely frequent, most of the neoplastic cysts are mucinous (IPMN and MCN) and slowly growing over time without an associated cancer, and the greatest need at this time is to identify the small proportion of such cysts with PDAC and/or HGD. Until such time, judicious selection of patients for surveillance and reasonable intervals of such surveillance with selective use of EUS will help identify patients requiring resection. In our enthusiasm to detect every possible pancreatic cancer, we should not ignore the unintentional outcomes of surgery to a large majority of patients who would never develop PDAC and the astronomical costs associated with such practice.

Dr. Vege is professor of medicine at the Mayo Clinic. He reported having no conflicts of interest regarding this article.
 

References

Vege SS et al. Gastroenterology. 2015;148:819-22.

Lobo JM et al. Surgery. 2020;168:601-9.

Lennon AM and Vege SS. Clin Gastroenterol Hepatol. 2022;20:1663-7.

Harris RP. Ann Intern Med. 2015;162:787-9.

Dear colleagues,

Pancreas cysts have become almost ubiquitous in this era of high-resolution cross-sectional imaging. They are a common GI consult with patients and providers worried about the potential risk of malignant transformation. Despite significant research over the past few decades, predicting the natural history of these cysts, especially the side-branch intraductal papillary mucinous neoplasms (IPMNs), remains difficult. There have been a variety of expert recommendations and guidelines, but heterogeneity exists in management especially regarding timing of endoscopic ultrasound, imaging surveillance, and cessation of surveillance. Some centers will present these cysts at multidisciplinary conferences, while others will follow general or local algorithms. In this issue of Perspectives, Dr. Lauren G. Khanna, assistant professor of medicine at NYU Langone Health, New York, and Dr. Santhi Vege, professor of medicine at the Mayo Clinic, Rochester, Minn., present updated and differing approaches to managing these cysts. Which side of the debate are you on? We welcome your thoughts, questions and input– share with us on Twitter @AGA_GIHN

Continuing pancreas cyst surveillance indefinitely is reasonable

BY LAUREN G. KHANNA, MD, MS

Pancreas cysts remain a clinical challenge. The true incidence of pancreas cysts is unknown, but from MRI and autopsy series, may be up to 50%. Patients presenting with a pancreas cyst often have significant anxiety about their risk of pancreas cancer. We as a medical community initially did too; but over the past few decades as we have gathered more data, we have become more comfortable observing many pancreas cysts. Yet our recommendations for how, how often, and for how long to evaluate pancreas cysts are still very much under debate; there are multiple guidelines with discordant recommendations. In this article, I will discuss my approach to patients with a pancreas cyst.

NYU Langone Health

At the first evaluation, I review available imaging to see if there are characteristic features to determine the type of pancreas cyst: IPMN (including main duct, branch duct, or mixed type), serous cystic neoplasm (SCA), mucinous cystic neoplasm (MCN), solid pseudopapillary neoplasm (SPN), cystic neuroendocrine tumor (NET), or pseudocyst. I also review symptoms, including abdominal pain, weight loss, history of pancreatitis, and onset of diabetes, and check hemoglobin A1c and Ca19-9. I often recommend magnetic resonance cholangiopancreatography (MRCP) if it has not already been obtained and is feasible (that is, if a patient does not have severe claustrophobia or a medical device incompatible with MRI). If a patient is not a candidate for treatment should a pancreatic malignancy be identified, because of age, comorbidities, or preference, I recommend no further evaluation.

Where cyst type remains unclear despite MRCP, and for cysts over 2 cm, I recommend endoscopic ultrasound (EUS) for fluid sampling to assist in determining cyst type and to rule out any other high-risk features. In accordance with international guidelines, if a patient has any concerning imaging features, including main pancreatic duct dilation >5 mm, solid component or mural nodule, or thickened or enhancing duct walls, regardless of cyst size, I recommend EUS to assess for and biopsy any solid component and to sample cyst fluid to examine for dysplasia. Given the lower sensitivity of CT for high-risk features, if MRCP is not feasible, for cysts 1-2 cm, I recommend EUS for better evaluation.

If a cyst is determined to be a cystic NET; main duct or mixed-type IPMN; MCN; or SPN; or a branch duct IPMN with mural nodule, high-grade dysplasia, or adenocarcinoma, and the patient is a surgical candidate, I refer the patient for surgical evaluation. If a cyst is determined to be an SCA, the malignant potential is minimal, and patients do not require follow-up. Patients with a pseudocyst are managed according to their clinical scenario.

Many patients have a proven or suspected branch duct IPMN, an indeterminate cyst, or multiple cysts. Cyst management during surveillance is then determined by the size of the largest cyst and stability of the cyst(s). Of note, patients with an IPMN also have been shown to have an elevated risk of concurrent pancreas adenocarcinoma, which I believe is one of the strongest arguments for heightened surveillance of the entire pancreas in pancreas cyst patients. EUS in particular can identify small or subtle lesions that are not detected by cross-sectional imaging.

If a patient has no prior imaging, in accordance with international and European guidelines, I recommend the first surveillance MRCP at a 6-month interval for cysts <2 cm, which may offer the opportunity to identify rapidly progressing cysts. If a patient has previous imaging available demonstrating stability, I recommend surveillance on an annual basis for cysts <2 cm. For patients with a cyst >2 cm, as above, I recommend EUS, and if there are no concerning features on imaging or EUS, I then recommend annual surveillance.

While the patient is under surveillance, if there is more than minimal cyst growth, a change in cyst appearance, or development of any imaging high-risk feature, pancreatitis, new onset or worsening diabetes, or elevation of Ca19-9, I recommend EUS for further evaluation and consideration of surgery based on EUS findings. If an asymptomatic cyst <2 cm remains stable for 5 years, I offer patients the option to extend imaging to every 2 years, if they are comfortable. In my experience, though, many patients prefer to continue annual imaging. The American Gastroenterological Association guidelines promote stopping surveillance after 5 years of stability, however there are studies demonstrating development of malignancy in cysts that were initially stable over the first 5 years of surveillance. Therefore, I discuss with patients that it is reasonable to continue cyst surveillance indefinitely, until they would no longer be interested in pursuing treatment of any kind if a malignant lesion were to be identified.

There are two special groups of pancreas cyst patients who warrant specific attention. Patients who are at elevated risk of pancreas adenocarcinoma because of an associated genetic mutation or a family history of pancreatic cancer already may be undergoing annual pancreas cancer screening with either MRCP, EUS, or alternating MRCP and EUS. When these high-risk patients also have pancreas cysts, I utilize whichever strategy would image their pancreas most frequently and do not extend beyond 1-year intervals. Another special group is patients who have undergone partial pancreatectomy for IPMN. As discussed above, given the elevated risk of concurrent pancreas adenocarcinoma in IPMN patients, I recommend indefinite continued surveillance of the remaining pancreas parenchyma in these patients.

Given the prevalence of pancreas cysts, it certainly would be convenient if guidelines were straightforward enough for primary care physicians to manage pancreas cyst surveillance, as they do for breast cancer screening. However, the complexities of pancreas cysts necessitate the expertise of gastroenterologists and pancreas surgeons, and a multidisciplinary team approach is best where possible.

Dr. Khanna is chief, advanced endoscopy, Tisch Hospital; director, NYU Advanced Endoscopy Fellowship; assistant professor of medicine, NYU Langone Health. Email: [email protected]. There are no relevant conflicts to disclose.
 

References

Tanaka M et al. Pancreatology. 2017 Sep-Oct;17(5):738-75.

Sahora K et al. Eur J Surg Oncol. 2016 Feb;42(2):197-204.

Del Chiaro M et al. Gut. 2018 May;67(5):789-804

Vege SS et al. Gastroenterology. 2015 Apr;148(4):819-22

Petrone MC et al. Clin Transl Gastroenterol. 2018 Jun 13;9(6):158

Pancreas cysts: More is not necessarily better!

BY SANTHI SWAROOP VEGE, MD

Pancreas cysts (PC) are very common, incidental findings on cross-sectional imaging, performed for non–pancreas-related symptoms. The important issues in management of patients with PC in my practice are the prevalence, natural history, frequency of occurrence of high-grade dysplasia (HGD) and/or pancreatic cancer (PDAC), concerning clinical symptoms and imaging findings, indications for EUS and fine-needle aspiration cytology, ideal method and frequency of surveillance, indications for surgery (up front and during follow-up), follow-up after surgery, stopping surveillance, costs, and unintentional harms of management. Good population-based evidence regarding many of the issues described above does not exist, and all information is from selected clinic, radiology, EUS, and surgical cohorts (very important when trying to assess the publications). Cohort studies should start with all PC undergoing surveillance and assess various outcomes, rather than looking backward from EUS or surgical cohorts.

The 2015 American Gastroenterological Association guidelines on asymptomatic neoplastic pancreas cysts, which I coauthored, recommend, consistent with principles of High Value Care (minimal unintentional harms and cost effectiveness), that two of three high-risk features (mural nodule, cyst size greater than 3 cm, and dilated pancreatic duct) be present for EUS-guided fine-needle aspiration (EUS-FNA). By the same token, they advise surgery for those with two of three high-risk features and or concerning features on EUS and cytology. Finally, they suggest stopping surveillance at 5 years if there are no significant changes. Rigorous GRADE methodology along with systematic review of all relevant questions (rather than cohorts of 500 or fewer patients) formed the basis of the guidelines. Those meta-analyses showed that risk of PDAC in mural nodules, cyst size >3 cm, and dilated pancreatic duct, while elevated, still is very low in absolute terms. Less than 20% of resections for highly selected, high-risk cysts showed PDAC. The guidelines were met with a lot of resistance from several societies and physician groups. The recommendations for stopping surveillance after 5 years and no surveillance for absent or low-grade dysplasia after surgery are hotly contested, and these areas need larger, long-term studies.

The whole area of cyst fluid molecular markers that would suggest mucinous type (KRAS and GNAS mutations) and, more importantly, the presence or imminent development of PDAC (next-generation sequencing or NGS) is an exciting field. One sincerely hopes that there will be a breakthrough in this area to achieve the holy grail. Cost effectiveness studies demonstrate the futility of existing guidelines and favor a less intensive approach. Guidelines are only a general framework, and management of individual patients in the clinic is entirely at the discretion of the treating physician. One should make every attempt to detect advanced lesions in PC, but such effort should not subject a large majority of patients to unintentional harms by overtreatment and add further to the burgeoning health care costs in the country.

Mayo Clinic

PC are extremely common (10% of all abdominal imaging), increase with age, are seen in as many as 40%-50% of MRI examinations for nonpancreatic indications, and most (>50%) are IPMNs. Most of the debate centers around the concerns of PDAC and/or HGD associated with mucinous cysts (MCN, IPMN, side-branch, main duct, or mixed).

The various guidelines by multiple societies differ in some aspects, such as in selection of patients based on clinical, laboratory, and imaging findings for up-front surgery or surveillance, the frequency of surveillance based on the size of the cyst and the presence of other concerning cyst features (usually with MRCP), the indications for EUS (both initial and subsequent), importance of the magnitude of growth (most IPMNs slowly grow over a period of time), indications for surgery during surveillance and postsurgery surveillance, and the decision to stop surveillance at some point in time. The literature is replete with small case series reporting a proportion of cancers detected and often ignoring the harms of surgery. Incidence of and mortality caused by PDAC are very low (about 1% for both) in a large national cohort of VA pancreatic cyst patients with long-term follow-up and other studies.

Marcov modeling suggests that none of the guidelines would lead to cost-effective care with low mortality because of overtreatment of low-risk lesions, and a specificity of 67% or more for PDAC/HGB is required. AGA guidelines came close to it but with low sensitivity. Monte Carlo modeling suggests that less intensive strategies, compared with more intensive, result in a similar number of deaths at a much lower cost. While molecular markers in PC fluid are reported to increase the specificity of PDAC/HGD to greater than 70%, it should be observed that such validation was done in a small percentage of patients who had both those markers and resection.

The costs of expensive procedures like EUS, MRI, and surgery, the 3% complication rate with EUS-FNA (primarily acute pancreatitis), and the 1% mortality and approximately 20%-30% morbidity with surgery (bleeding, infection, fistula) and postpancreatectomy diabetes of approximately 30% in the long run need special attention.

In conclusion, one could say pancreas cysts are extremely frequent, most of the neoplastic cysts are mucinous (IPMN and MCN) and slowly growing over time without an associated cancer, and the greatest need at this time is to identify the small proportion of such cysts with PDAC and/or HGD. Until such time, judicious selection of patients for surveillance and reasonable intervals of such surveillance with selective use of EUS will help identify patients requiring resection. In our enthusiasm to detect every possible pancreatic cancer, we should not ignore the unintentional outcomes of surgery to a large majority of patients who would never develop PDAC and the astronomical costs associated with such practice.

Dr. Vege is professor of medicine at the Mayo Clinic. He reported having no conflicts of interest regarding this article.
 

References

Vege SS et al. Gastroenterology. 2015;148:819-22.

Lobo JM et al. Surgery. 2020;168:601-9.

Lennon AM and Vege SS. Clin Gastroenterol Hepatol. 2022;20:1663-7.

Harris RP. Ann Intern Med. 2015;162:787-9.

Dear friends,

Spring is coming to an end, and in this time with the upcoming summer usually racing by, I always find myself reflecting on the past year. I celebrate my achievements (both personal and work related), try not to be too hard on myself with unaccomplished tasks, and plan goals for the upcoming year. Most importantly, it’s a time to be grateful for both opportunities and challenges. Thank you for your engagement with The New Gastroenterologist, and as you go through this issue, I hope you can find time for some spring reflections as well!

In this issue’s In Focus, Dr. Tanisha Ronnie, Dr. Lauren Bloomberg, and Dr. Mukund Venu break down the approach to a patient with dysphagia, a common and difficult encounter in GI practice. They emphasize the importance of a good clinical history as well as understanding the role of diagnostic testing. In our Short Clinical Review section, Dr. Noa Krugliak Cleveland and Dr. David Rubin review the rising role of intestinal ultrasound in inflammatory bowel disease, how to be trained, and how to incorporate it in clinical practice.

As early-career gastroenterologists, Dr. Samad Soudagar and Dr. Mohammad Bilal were tasked with establishing an advanced endoscopy practice, which may be overwhelming for many. They synthesized their experiences into 10 practical tips to build a successful practice. Our Post-fellowship Pathways article highlights Dr. Katie Hutchins’s journey from private practice to academic medicine; she provides insights into the life-changing decision and what she learned about herself to make that pivot.

In our Finance section, Dr. Kelly Hathorn and Dr. David Creighton reflect on navigating as new parents while both working full time in medicine; their article weighs the pros and cons of various childcare options in the post–COVID pandemic world.

In an additional contribution this issue, gastroenterology and hepatology fellowship program leaders at the University of Florida, Gainesville, describe their experience with virtual recruitment, including feedback from their candidates, especially as we enter another cycle of GI Match.

If you are interested in contributing or have ideas for future TNG topics, please contact me ([email protected]), or Jillian Schweitzer ([email protected]), managing editor of TNG.

Until next time, I leave you with a historical fun fact, because we would not be where we are without appreciating where we were: The first formalized gastroenterology fellowship curriculum was a joint publication by four major GI and hepatology societies in 1996 – just 27 years ago!
 

Yours truly,

Judy A Trieu, MD, MPH



Editor-in-Chief

Advanced Endoscopy Fellow

Division of gastroenterology & hepatology

University of North Carolina at Chapel Hill
 

Dear friends,

Spring is coming to an end, and in this time with the upcoming summer usually racing by, I always find myself reflecting on the past year. I celebrate my achievements (both personal and work related), try not to be too hard on myself with unaccomplished tasks, and plan goals for the upcoming year. Most importantly, it’s a time to be grateful for both opportunities and challenges. Thank you for your engagement with The New Gastroenterologist, and as you go through this issue, I hope you can find time for some spring reflections as well!

In this issue’s In Focus, Dr. Tanisha Ronnie, Dr. Lauren Bloomberg, and Dr. Mukund Venu break down the approach to a patient with dysphagia, a common and difficult encounter in GI practice. They emphasize the importance of a good clinical history as well as understanding the role of diagnostic testing. In our Short Clinical Review section, Dr. Noa Krugliak Cleveland and Dr. David Rubin review the rising role of intestinal ultrasound in inflammatory bowel disease, how to be trained, and how to incorporate it in clinical practice.

As early-career gastroenterologists, Dr. Samad Soudagar and Dr. Mohammad Bilal were tasked with establishing an advanced endoscopy practice, which may be overwhelming for many. They synthesized their experiences into 10 practical tips to build a successful practice. Our Post-fellowship Pathways article highlights Dr. Katie Hutchins’s journey from private practice to academic medicine; she provides insights into the life-changing decision and what she learned about herself to make that pivot.

In our Finance section, Dr. Kelly Hathorn and Dr. David Creighton reflect on navigating as new parents while both working full time in medicine; their article weighs the pros and cons of various childcare options in the post–COVID pandemic world.

In an additional contribution this issue, gastroenterology and hepatology fellowship program leaders at the University of Florida, Gainesville, describe their experience with virtual recruitment, including feedback from their candidates, especially as we enter another cycle of GI Match.

If you are interested in contributing or have ideas for future TNG topics, please contact me ([email protected]), or Jillian Schweitzer ([email protected]), managing editor of TNG.

Until next time, I leave you with a historical fun fact, because we would not be where we are without appreciating where we were: The first formalized gastroenterology fellowship curriculum was a joint publication by four major GI and hepatology societies in 1996 – just 27 years ago!
 

Yours truly,

Judy A Trieu, MD, MPH



Editor-in-Chief

Advanced Endoscopy Fellow

Division of gastroenterology & hepatology

University of North Carolina at Chapel Hill
 

Dear friends,

Spring is coming to an end, and in this time with the upcoming summer usually racing by, I always find myself reflecting on the past year. I celebrate my achievements (both personal and work related), try not to be too hard on myself with unaccomplished tasks, and plan goals for the upcoming year. Most importantly, it’s a time to be grateful for both opportunities and challenges. Thank you for your engagement with The New Gastroenterologist, and as you go through this issue, I hope you can find time for some spring reflections as well!

In this issue’s In Focus, Dr. Tanisha Ronnie, Dr. Lauren Bloomberg, and Dr. Mukund Venu break down the approach to a patient with dysphagia, a common and difficult encounter in GI practice. They emphasize the importance of a good clinical history as well as understanding the role of diagnostic testing. In our Short Clinical Review section, Dr. Noa Krugliak Cleveland and Dr. David Rubin review the rising role of intestinal ultrasound in inflammatory bowel disease, how to be trained, and how to incorporate it in clinical practice.

As early-career gastroenterologists, Dr. Samad Soudagar and Dr. Mohammad Bilal were tasked with establishing an advanced endoscopy practice, which may be overwhelming for many. They synthesized their experiences into 10 practical tips to build a successful practice. Our Post-fellowship Pathways article highlights Dr. Katie Hutchins’s journey from private practice to academic medicine; she provides insights into the life-changing decision and what she learned about herself to make that pivot.

In our Finance section, Dr. Kelly Hathorn and Dr. David Creighton reflect on navigating as new parents while both working full time in medicine; their article weighs the pros and cons of various childcare options in the post–COVID pandemic world.

In an additional contribution this issue, gastroenterology and hepatology fellowship program leaders at the University of Florida, Gainesville, describe their experience with virtual recruitment, including feedback from their candidates, especially as we enter another cycle of GI Match.

If you are interested in contributing or have ideas for future TNG topics, please contact me ([email protected]), or Jillian Schweitzer ([email protected]), managing editor of TNG.

Until next time, I leave you with a historical fun fact, because we would not be where we are without appreciating where we were: The first formalized gastroenterology fellowship curriculum was a joint publication by four major GI and hepatology societies in 1996 – just 27 years ago!
 

Yours truly,

Judy A Trieu, MD, MPH



Editor-in-Chief

Advanced Endoscopy Fellow

Division of gastroenterology & hepatology

University of North Carolina at Chapel Hill
 

Sharmila Anandasabapathy, MD, knew she wanted to focus on endoscopy when she first started her career. Her passion would someday translate into a worldwide effort to expand and test this technology.

While leading an endoscopy unit in New York City, Dr. Anandasabapathy began developing endoscopic and imaging technologies for underresourced and underserved areas. These technologies eventually made their way into global clinical trials.

“We’ve gone to clinical trial in over 2,000 patients worldwide. When I made that jump into global GI, I was able to make that jump into global health in general,” said Dr. Anandasabapathy.

Baylor College of Medicine

As vice president for global programs at Baylor College of Medicine in Houston, Dr. Anandasabapathy currently focuses on clinical and translational research.

“We’re looking at the development of new, low-cost devices for early cancer detection in GI globally. I oversee our global programs across the whole college, so it’s GI, it’s surgery, it’s anesthesia, it’s obstetrics, it’s everything.”

In an interview, Dr. Anandasabapathy discussed what attracted her to gastroenterology and why she always takes the time to smile at her patients.
 

Q: Why did you choose GI? 

A: There’s two questions in there: Why I chose GI and why I chose endoscopy.

I chose GI because when I was in my internal medicine training, they seemed like the happiest people in the hospital. They liked what they did. You could make a meaningful impact even at 3 a.m. if you were coming in for a variceal bleed. Everybody seemed happy with their choice of specialty. I was ready to be an oncologist, and I ended up becoming a gastroenterologist.

I chose endoscopy because it was where I wanted to be when I woke up in the morning. I was happy there. I love the procedures; I love the hand-eye coordination. I liked the fact that these were relatively shorter procedures, that it was technology based, and there was infinite growth.
 

Q: Was there a time when you really helped a patient by doing that endoscopy, preventing Barrett’s esophagus or even cancer?

A: I can think of several times where we had early cancers and it was a question between endoscopic treatment or surgery. It was always discussed with the surgeons. We made the decision within a multidisciplinary group and with the patient, but we usually went with the endoscopic options and the patients have done great. We’ve given them a greater quality of life, and I think that’s really rewarding.

Q: What gives you the most joy in your day-to-day practice?

A: My patients. I work with Barrett’s esophagus patients, and they tend to be well informed about the research and the science. I’m lucky to have a patient population that is really interested and willing to participate in that. I also like my students, my junior faculty. I like teaching and the global application of teaching.

Q: What fears did you have to push past to get to where you are in your career?

A: That I would never become an independent researcher and do it alone. I was able to, over time. The ability to transition from being independent to teaching others and making them independent is a wonderful one.

Early on when I was doing GI, I remember looking at my division, and there were about 58 gastroenterologists and only 2 women. I thought at the time, “Well, can I do it? Is this a field that is conducive with being a woman and having a family?” It turned out that it is. Today, I’m really gratified to see that there are more women in GI than there ever were before.
 

Q: Have you ever received advice that you’ve ignored?A: Yes. Early in my training in internal medicine, I was told that I smiled too much and that my personality was such that patients and others would think I was too glib. Medicine was a serious business, and you shouldn’t be smiling. That’s not my personality – I’m not Eeyore. I think it’s served me well to be positive, and it’s served me well with patients to be smiling. Especially when you’re dealing with patients who have precancer or dysplasia and are scared – they want reassurance and they want a level of confidence. I’m glad I ignored that advice.

Q: What would be your advice to medical students?

A: Think about where you want to be when you wake up in the morning. If it’s either in a GI practice or doing GI research or doing endoscopy, then you should absolutely do it.

Lightning round

Cat person or dog person

Dog



Favorite sport

Tennis



What song do you have to sing along with when you hear it?

Dancing Queen



Favorite music genre

1980s pop



Favorite movie, show, or book

Wuthering Heights
 

Dr. Anandasabapathy is on LinkedIn and on Twitter at @anandasabapathy , @bcmglobalhealth , and @bcm_gihep .

Sharmila Anandasabapathy, MD, knew she wanted to focus on endoscopy when she first started her career. Her passion would someday translate into a worldwide effort to expand and test this technology.

While leading an endoscopy unit in New York City, Dr. Anandasabapathy began developing endoscopic and imaging technologies for underresourced and underserved areas. These technologies eventually made their way into global clinical trials.

“We’ve gone to clinical trial in over 2,000 patients worldwide. When I made that jump into global GI, I was able to make that jump into global health in general,” said Dr. Anandasabapathy.

Baylor College of Medicine

As vice president for global programs at Baylor College of Medicine in Houston, Dr. Anandasabapathy currently focuses on clinical and translational research.

“We’re looking at the development of new, low-cost devices for early cancer detection in GI globally. I oversee our global programs across the whole college, so it’s GI, it’s surgery, it’s anesthesia, it’s obstetrics, it’s everything.”

In an interview, Dr. Anandasabapathy discussed what attracted her to gastroenterology and why she always takes the time to smile at her patients.
 

Q: Why did you choose GI? 

A: There’s two questions in there: Why I chose GI and why I chose endoscopy.

I chose GI because when I was in my internal medicine training, they seemed like the happiest people in the hospital. They liked what they did. You could make a meaningful impact even at 3 a.m. if you were coming in for a variceal bleed. Everybody seemed happy with their choice of specialty. I was ready to be an oncologist, and I ended up becoming a gastroenterologist.

I chose endoscopy because it was where I wanted to be when I woke up in the morning. I was happy there. I love the procedures; I love the hand-eye coordination. I liked the fact that these were relatively shorter procedures, that it was technology based, and there was infinite growth.
 

Q: Was there a time when you really helped a patient by doing that endoscopy, preventing Barrett’s esophagus or even cancer?

A: I can think of several times where we had early cancers and it was a question between endoscopic treatment or surgery. It was always discussed with the surgeons. We made the decision within a multidisciplinary group and with the patient, but we usually went with the endoscopic options and the patients have done great. We’ve given them a greater quality of life, and I think that’s really rewarding.

Q: What gives you the most joy in your day-to-day practice?

A: My patients. I work with Barrett’s esophagus patients, and they tend to be well informed about the research and the science. I’m lucky to have a patient population that is really interested and willing to participate in that. I also like my students, my junior faculty. I like teaching and the global application of teaching.

Q: What fears did you have to push past to get to where you are in your career?

A: That I would never become an independent researcher and do it alone. I was able to, over time. The ability to transition from being independent to teaching others and making them independent is a wonderful one.

Early on when I was doing GI, I remember looking at my division, and there were about 58 gastroenterologists and only 2 women. I thought at the time, “Well, can I do it? Is this a field that is conducive with being a woman and having a family?” It turned out that it is. Today, I’m really gratified to see that there are more women in GI than there ever were before.
 

Q: Have you ever received advice that you’ve ignored?A: Yes. Early in my training in internal medicine, I was told that I smiled too much and that my personality was such that patients and others would think I was too glib. Medicine was a serious business, and you shouldn’t be smiling. That’s not my personality – I’m not Eeyore. I think it’s served me well to be positive, and it’s served me well with patients to be smiling. Especially when you’re dealing with patients who have precancer or dysplasia and are scared – they want reassurance and they want a level of confidence. I’m glad I ignored that advice.

Q: What would be your advice to medical students?

A: Think about where you want to be when you wake up in the morning. If it’s either in a GI practice or doing GI research or doing endoscopy, then you should absolutely do it.

Lightning round

Cat person or dog person

Dog



Favorite sport

Tennis



What song do you have to sing along with when you hear it?

Dancing Queen



Favorite music genre

1980s pop



Favorite movie, show, or book

Wuthering Heights
 

Dr. Anandasabapathy is on LinkedIn and on Twitter at @anandasabapathy , @bcmglobalhealth , and @bcm_gihep .

Sharmila Anandasabapathy, MD, knew she wanted to focus on endoscopy when she first started her career. Her passion would someday translate into a worldwide effort to expand and test this technology.

While leading an endoscopy unit in New York City, Dr. Anandasabapathy began developing endoscopic and imaging technologies for underresourced and underserved areas. These technologies eventually made their way into global clinical trials.

“We’ve gone to clinical trial in over 2,000 patients worldwide. When I made that jump into global GI, I was able to make that jump into global health in general,” said Dr. Anandasabapathy.

Baylor College of Medicine

As vice president for global programs at Baylor College of Medicine in Houston, Dr. Anandasabapathy currently focuses on clinical and translational research.

“We’re looking at the development of new, low-cost devices for early cancer detection in GI globally. I oversee our global programs across the whole college, so it’s GI, it’s surgery, it’s anesthesia, it’s obstetrics, it’s everything.”

In an interview, Dr. Anandasabapathy discussed what attracted her to gastroenterology and why she always takes the time to smile at her patients.
 

Q: Why did you choose GI? 

A: There’s two questions in there: Why I chose GI and why I chose endoscopy.

I chose GI because when I was in my internal medicine training, they seemed like the happiest people in the hospital. They liked what they did. You could make a meaningful impact even at 3 a.m. if you were coming in for a variceal bleed. Everybody seemed happy with their choice of specialty. I was ready to be an oncologist, and I ended up becoming a gastroenterologist.

I chose endoscopy because it was where I wanted to be when I woke up in the morning. I was happy there. I love the procedures; I love the hand-eye coordination. I liked the fact that these were relatively shorter procedures, that it was technology based, and there was infinite growth.
 

Q: Was there a time when you really helped a patient by doing that endoscopy, preventing Barrett’s esophagus or even cancer?

A: I can think of several times where we had early cancers and it was a question between endoscopic treatment or surgery. It was always discussed with the surgeons. We made the decision within a multidisciplinary group and with the patient, but we usually went with the endoscopic options and the patients have done great. We’ve given them a greater quality of life, and I think that’s really rewarding.

Q: What gives you the most joy in your day-to-day practice?

A: My patients. I work with Barrett’s esophagus patients, and they tend to be well informed about the research and the science. I’m lucky to have a patient population that is really interested and willing to participate in that. I also like my students, my junior faculty. I like teaching and the global application of teaching.

Q: What fears did you have to push past to get to where you are in your career?

A: That I would never become an independent researcher and do it alone. I was able to, over time. The ability to transition from being independent to teaching others and making them independent is a wonderful one.

Early on when I was doing GI, I remember looking at my division, and there were about 58 gastroenterologists and only 2 women. I thought at the time, “Well, can I do it? Is this a field that is conducive with being a woman and having a family?” It turned out that it is. Today, I’m really gratified to see that there are more women in GI than there ever were before.
 

Q: Have you ever received advice that you’ve ignored?A: Yes. Early in my training in internal medicine, I was told that I smiled too much and that my personality was such that patients and others would think I was too glib. Medicine was a serious business, and you shouldn’t be smiling. That’s not my personality – I’m not Eeyore. I think it’s served me well to be positive, and it’s served me well with patients to be smiling. Especially when you’re dealing with patients who have precancer or dysplasia and are scared – they want reassurance and they want a level of confidence. I’m glad I ignored that advice.

Q: What would be your advice to medical students?

A: Think about where you want to be when you wake up in the morning. If it’s either in a GI practice or doing GI research or doing endoscopy, then you should absolutely do it.

Lightning round

Cat person or dog person

Dog



Favorite sport

Tennis



What song do you have to sing along with when you hear it?

Dancing Queen



Favorite music genre

1980s pop



Favorite movie, show, or book

Wuthering Heights
 

Dr. Anandasabapathy is on LinkedIn and on Twitter at @anandasabapathy , @bcmglobalhealth , and @bcm_gihep .