Photo credit: Studio Romantic/Shutterstock
Photo credit: Studio Romantic/Shutterstock

This article is sponsored by Otsuka America Pharmaceutical, Inc.

In long-term care environments, it’s not uncommon for site staff including nurses, administrators, physical therapists, physicians and others to work closely with patients living with various neurological conditions. Along with this comes the potentially complex task of both recognizing and appropriately diagnosing health conditions that may present similarly but require different care. Of note, one neurological condition that is often mistaken for depression is Pseudobulbar Affect (PBA), which impacts an estimated 1.8 million people in the US1. Therefore, the proper identification of this condition among at-risk patients within the long-term environment requires a lot of communication and a deeper understanding of the unique nuances that may differentiate PBA and depression. 

Understanding Pseudobulbar Affect (PBA)

While not well known, PBA is a secondary condition that manifests as sudden, frequent, uncontrollable episodes of crying and/or laughing, which are disproportionate or incongruent to a patient’s actual emotional state1, 2.These episodes can result from various primary neurological conditions, including Alzheimer’s disease, stroke, traumatic brain injury, multiple sclerosis, or Parkinson’s disease1. While PBA’s prevalence in these neurological conditions is notable, it’s easy to understand how its symptoms can be mistaken for other mood disorders like depression1, 2.

As a result, an important factor in properly diagnosing PBA within the long-term setting lies in the staff’s ability to both recognize its symptoms and share them with a resident’s healthcare provider. For example, facility staff that interact with and manage patients on a day-to-day basis may interpret an individual’s uncontrollable outbursts of crying or laughter as a part of their daily struggle to cope with their primary neurological condition. This can result in misdiagnosis of PBA symptoms among at-risk patients1, 3, 4

The PBA Symptom Confusion with Depression

The symptom overlap, particularly the uncontrollable crying associated with PBA, can easily be mistaken for depression3, 5, 6. It should be noted, that while crying is a common expression of emotional distress, it is not exclusively a symptom of depression4, 5, 6. This can be especially challenging when considering the fact that in one study, 57.5% of patients who were diagnosed with PBA had comorbid depression7,I,II. Therefore, the presence of uncontrollable crying in PBA patients can be misleading for staff, healthcare providers, patients and their loved ones when working toward a proper diagnosis3

It’s important to understand that PBA is a distinct, but treatable neurological condition that can significantly impact a person’s daily life and interpersonal relationships. Fortunately, clinical screening can help facility staff and healthcare providers to properly identify PBA among those patients most at risk for the condition. This includes asking the key clinical questions and considering the patient’s entire neurological and psychological health background to appropriately differentiate PBA from other mood disorders1, 4, 8.

Following is a summary of common guidance in assessing PBA versus depression:

Crying in DepressionCrying in PBA
Matches how the patient feelsDisproportionate to or inconsistent with how the patient feels
Mostly controllable; stops when mood changesUncontrollable
Onset and duration defined by moodHappens frequently, suddenly, and may be brief

These are not all the diagnostic features of depression9. Formal diagnosis of depression or PBA can only be made by a qualified healthcare practitioner.

Clinical Screening Criteria 

Effective screening for PBA includes a thorough understanding of a patient’s medical history, particularly any underlying neurological conditions that could put them at risk such as Alzheimer’s disease, stroke and traumatic brain injury. It is possible to first start with a primary question that can help better facilitate conversations between the healthcare staff and a patient’s healthcare provider to help them reach a possible diagnosis around PBA1, 2, 4, 10, 11

Do I ever observe my resident crying or laughing but it seems odd or out of place?

This question can help spark a dialogue among facility staff that explores the nature, frequency, and emotional context of these episodes based on the patient’s experience. While challenging, healthcare providers who foster a sense of curiosity, take the time to engage in conversations with the patient, and employ targeted questioning about specific episodes – such as using the Center for Neurologic Study-Lability Scale (CNS-LS)1, can help uncover PBA. 

NUEDEXTA: FDA-Approved for PBA

If PBA is identified and diagnosed,

NUEDEXTA® (dextromethorphan HBr and quinidine sulfate) is an available treatment option. As the only FDA-approved treatment for PBA, NUEDEXTA is clinically proven to reduce PBA episodes and has a demonstrated safety profile12, 13. In a 12-week pivotal trial, NUEDEXTA was found to significantly reduce PBA episode rates compared with a placebo13. Do not take NUEDEXTA if you are taking other drugs that contain quinidine, quinine, or mefloquine. The most common side effects were diarrhea and dizziness. These are not all the risks from use of NUEDEXTA. Please see additional Important Safety Information below. For additional information, visit https://www.nuedextahcp.com/

Key Insights and Future Direction

In conclusion, distinguishing PBA from depression among at-risk residents in long-term care settings is a multifaceted challenge that requires a greater understanding of the condition, keen observations, and an ongoing dialogue between facility staff, patients, caregivers, and providers4.

INDICATION and IMPORTANT SAFETY INFORMATION for NUEDEXTA®(dextromethorphan HBr and quinidine sulfate)

Indication

NUEDEXTA is indicated for the treatment of pseudobulbar affect (PBA).

PBA occurs secondary to a variety of otherwise unrelated neurologic conditions, and is characterized by involuntary, sudden, and frequent episodes of laughing and/or crying. PBA episodes typically occur out of proportion or incongruent to the underlying emotional state. PBA is a specific condition, distinct from other types of emotional lability that may occur in patients with neurologic disease or injury.

IMPORTANT SAFETY INFORMATION

CONTRAINDICATIONS:

  • Quinidine and Related Drugs: NUEDEXTA contains quinidine and should not be used concomitantly with other drugs containing quinidine, quinine, or mefloquine.
  • Hypersensitivity: NUEDEXTA is contraindicated in patients with a history of NUEDEXTA-, quinine-, mefloquine-, or quinidine-induced thrombocytopenia, hepatitis, bone-marrow depression, lupus-like syndrome, or known hypersensitivity to dextromethorphan (e.g., rash, hives).
  • MAOIs: NUEDEXTA is contraindicated in patients taking monoamine oxidase inhibitors (MAOIs), or in patients who have taken MAOIs within the preceding 14 days, due to the risk of serious and possibly fatal drug interactions, including serotonin syndrome. Allow at least 14 days after stopping NUEDEXTA before starting an MAOI.
  • Cardiovascular: NUEDEXTA is contraindicated in patients with a prolonged QT interval, congenital long QT syndrome, history suggestive of torsades de pointes, heart failure, patients receiving drugs that both prolong QT interval and are metabolized by CYP2D6 (e.g., thioridazine and pimozide), patients with complete atrioventricular (AV) block without implanted pacemaker, or at high risk of complete AV block.

Thrombocytopenia and Other Hypersensitivity Reactions: Quinidine can cause immune-mediated thrombocytopenia that can be severe or fatal. Non-specific symptoms, such as lightheadedness, chills, fever, nausea, and vomiting, can precede or occur with thrombocytopenia. NUEDEXTA should be discontinued immediately if thrombocytopenia occurs.

Hepatotoxicity: Hepatitis, including granulomatous hepatitis, has been reported in patients receiving quinidine, generally during the first few weeks of therapy. Discontinue immediately if this occurs.

Cardiac Effects: NUEDEXTA causes dose-dependent QTc prolongation. QT prolongation can cause torsades de pointes–type ventricular tachycardia, with the risk increasing as the degree of prolongation increases. When initiating NUEDEXTA in patients at risk for QT prolongation and torsades de pointes, electrocardiographic (ECG) evaluation of QT interval should be conducted at baseline and 3 to 4 hours after the first dose. Some risk factors include use with CYP3A4 inhibitors or drugs that prolong QT interval, electrolyte abnormalities, bradycardia, or left ventricular hypertrophy or dysfunction. If patients taking NUEDEXTA experience symptoms that could indicate the occurrence of cardiac arrhythmias (e.g., syncope or palpitations), NUEDEXTA should be discontinued, and the patient further evaluated.

Concomitant Use of CYP2D6 Substrates: NUEDEXTA inhibits CYP2D6 and may interact with other drugs metabolized by CYP2D6. Adjust dose of CYP2D6 substrates as needed.

Dizziness: NUEDEXTA may cause dizziness. Take precautions to reduce the risk of falls.

Serotonin Syndrome: Use of NUEDEXTA with selective serotonin reuptake inhibitors (SSRIs) or tricyclic antidepressants increases the risk of “serotonin syndrome.”

Anticholinergic Effects of Quinidine: Monitor for worsening in myasthenia gravis.

Adverse Reactions: The most common adverse reactions (incidence of ≥3% and two-fold greater than placebo) in patients taking NUEDEXTA are diarrhea, dizziness, cough, vomiting, asthenia, peripheral edema, urinary tract infection, influenza, increased gamma-glutamyltransferase, and flatulence.

These are not all the risks for use of NUEDEXTA.

To report SUSPECTED ADVERSE REACTIONS, contact Otsuka America Pharmaceutical, Inc. at 1-800-438-9927 or FDA at 1-800-FDA-1088 (www.fda.gov/medwatch).

Please see FULL PRESCRIBING INFORMATION.

References

  1. Ahmed A, Simmons Z. Pseudobulbar Affect: Prevalence and Management. Ther Clin Risk Manag. 2013;9:483-489. doi:10.2147/TCRM.S53906.
  2. Brooks BR, Crumpacker D, Fellus J, Kantor D, Kaye RE. PRISM: A Novel Research Tool to Assess the Prevalence of Pseudobulbar Affect Symptoms across Neurological Conditions. Zhang XY, ed. PLoS ONE. 2013;8(8):e72232. doi:https://doi.org/10.1371/journal.pone.0072232
  3. Foley K., Konetzka R., Bunin A., Yonan C. Prevalence of pseudobulbar affect symptoms and clinical correlates in nursing home residents. Int J Geriatr Psychiatry. 2016;31(7):694-701. doi:10.1002/gps.4374.
  4. Turell W, Roc A, Pioro E, Howson A. Living With the Burden of Pseudobulbar Affect: A Qualitative Analysis of the Effects of Education on Patient Experience. Journal of Patient Experience. Published online March 2, 2020:237437351989959. doi:https://doi.org/10.1177/2374373519899597
  5. Differentiating PBA from Depression – PBA Voices. Accessed February 8, 2024. https://pbavoices.org/understanding-pba/differentiating-pba-from-depression/
  6. PBA (Pseudobulbar Affect). Brain Injury Association of America. https://www.biausa.org/brain-injury/about-brain-injury/pba
  7. Hammond FM, Alexander DN, Cutler AJ, et al. PRISM II: an open-label study to assess effectiveness of dextromethorphan/quinidine for pseudobulbar affect in patients with dementia, stroke or traumatic brain injury. BMC Neurol. 2016;16:89. 
  8. Tammie Lee Demler P. Introduction to Pseudobulbar Affect: Setting the Stage for Recognition and Familiarity With This Challenging Disorder. wwwajmccom. 2017;23. Accessed February 8, 2024. https://www.ajmc.com/view/introduction-to-pseudobulbar-affect-setting-the-stage-for-recognition-and-familiarity-with-this-challenging-disorder
  9. Cummings JL, Arciniegas DB, Brooks BR, et al. Defining and diagnosing involuntary emotional expression disorder. CNS Spectr. 2006;11(S6):1-7.
  10. Hammond FM, Alexander DN, Cutler AJ, et al. PRISM II: an open-label study to assess effectiveness of dextromethorphan/quinidine for pseudobulbar affect in patients with dementia, stroke or traumatic brain injury. BMC Neurology. 2016;16(1). doi:https://doi.org/10.1186/s12883-016-0609-0
  11. CENTER for NEUROLOGIC STUDY-LABILITY SCALE (CNS-LS) for PSEUDOBULBAR AFFECT (PBA). https://www.nuedextahcp.com/documents/CNS-LS-English.pdf
  12. NUEDEXTA [package insert]. Rockville, MD: Otsuka America Pharmaceutical, Inc.
  13. Pioro EP, Brooks BR, Cummings J, et al. Dextromethorphan plus ultra-low quinidine reduces pseudobulbar affect. Ann Neurol. 2010;68(5):693-702.

 IN = 367 participants.

IIParticipants in this open-label, multicenter, 90-day trial received DM/Q 20/10 mg twice daily. The primary outcome was the Center for Neurologic Study-Lability Scale (CNS-LS), assessing change in PBA episode frequency and severity. The CNS-LS final visit score was compared to baseline (primary analysis) and to the response in a previously conducted placebo-controlled trial with DM/Q in patients with ALS or MS. Secondary outcomes included change in PBA episode count and Clinical Global Impression of Change with respect to PBA as rated by a clinician (CGI-C) and by the patient or caregiver (PGI-C).

April 2024          18US24EBC0004