Actor portrayal of a patient with Pseudobulbar Affect, or PBA, crying symptoms

Pseudobulbar Affect (PBA) is commonly comorbid with depression and other mood or behavioral disorders 1

Depression is highly prevalent among patients with neurologic conditions such as dementia and multiple sclerosis (MS). 4 Since PBA occurs secondary to neurologic conditions or brain injuries, it makes sense that PBA is also commonly comorbid with depression. It is crucial to evaluate your patients with complex neurologic conditions for all possible diagnoses to ensure that they get the right treatment to reduce their symptoms.


In a 90-day, open-label, single-arm study, more than half of patients who were diagnosed with PBA had comorbid depression (N=367). 70.8% of patients in the study were taking psychopharmacologic medications. 5, a, b

a PRISM II was a 90-day, open-label, single-arm, 74-site, U.S. trial in adult patients with dementia, stroke, or TBI. All patients received a clinical diagnosis of PBA by their physician and had a Center for Neurologic Study-Lability Scale (CNS-LS) score of 13 or greater at baseline. CNS-LS is a seven-item self-report rating scale that measures perceived frequency and control over laughing and/or crying episodes. It was validated as a PBA screening tool in amyotrophic lateral sclerosis (ALS) and multiple sclerosis (MS) populations. CNS-LS of 13 or greater may suggest PBA but does not confer a PBA diagnosis. 5-7

b Based on Patient Health Questionnaire-9 (PHQ-9), a nine-item assessment of depressive symptoms. Scores range from 0 to 27, with higher scores indicating increased depression severity. 5

Depression and PBA may be difficult to distinguish 1

While depression and PBA can occur together, it is common to mistake PBA crying episodes for symptoms of depression and other disorders with symptoms of mood lability. But there are many clinical features that distinguish PBA episodes from depression symptoms. The most prominent feature is duration. Depression symptoms last weeks to months, whereas PBA episodes last seconds to minutes. 1


In a web-based survey of 265 caregivers working at geriatric long-term care facilities, 80.4% of participants reported that they would have attributed PBA episodes to depression before gaining knowledge and experience with PBA. To learn more, visit our PBA in Long-Term Care Settings page.

Recognize the different characteristics of crying 8

PBA is a neurologic condition, not a psychologic or psychiatric disorder. One of the major differences between PBA and depression is the relationship between crying episodes and mood. PBA alters a patient’s expression, or affect, causing involuntary crying that is exaggerated or incongruent with their underlying mood. 8 A patient with PBA may cry when they’re not sad, or they may cry uncontrollably when they’re only a little sad. If you suspect your patient has mood lability, consider asking them whether their crying matches how they feel.

  • Matches how the patient feels
  • Mostly controllable; stops when mood changes
  • Onset and duration defined by mood
  • Disproportionate to or inconsistent with how the patient feels
  • Uncontrollable
  • Happens frequently, suddenly, and may be brief

These are not all the diagnostic features of depression. 8 Formal diagnosis of depression or PBA can only be made by a qualified healthcare practitioner.

When to screen for PBA

Use the Center for Neurologic Study-Lability Scale (CNS-LS) c or review the Steps to Diagnosis to screen for PBA when patients with neurologic conditions or brain injury are diagnosed with and treated for depression but are still experiencing involuntary, sudden, frequent laughing and/or crying episodes. 1-4

When evaluating a patient, review their chart for medications commonly prescribed for mood or behavioral disorders. These many include tricyclic antidepressants, nontricyclic antidepressants (e.g., SSRIs, SNRIs), and antipsychotics.

In the PRISM study, psychotropic medication use was significantly higher in patients with symptoms suggestive of PBA (CNS-LS score ≥ 13) compared to use in patients without (CNS-LS score <13). 4, c The reason for psychotropic medication use was not captured in the study.

Score* Proportion of patients taking at least one antidepressant or antipsychotic medication
CNS-LS ≥ 13 (N=1,944) 53%
CNS-LS ≥ 21 (N=492) 61.6%
CNS-LS < 13 (N=3,346) 35.4%

* The proportion of patients taking at least one antidepressant or antipsychotic medication was significantly higher among those with scores suggestive of PBA versus those without scores suggestive of PBA (P < 0.0001 for both comparisons, chi-square test).

c CNS-LS is a seven-item self-report rating scale that measures perceived frequency and control over laughing and/or crying episodes. It was validated as a PBA screening tool in ALS and MS populations. The presence of PBA symptoms (uncontrollable episodes of laughing and/or crying) was defined as a CNS-LS score of 13 or greater. Higher CNS-LS scores are indicative of more frequent uncontrollable laughing and/or crying episodes. This scale does not confer a PBA diagnosis. 6, 7

Various mood and behavioral disorders can affect patients with neurologic conditions or brain injury. 2

Depression is only one of the mood disorders that has signs and symptoms similar to PBA. Crying and other episodes are common among mood and behavioral disorders that often co-occur with a patient's underlying condition.1, 3, 4, 8-10

Patients with traumatic brain injury may experience anxiety or post-traumatic stress disorder, and patients with dementia may experience aggression, delusions, and personality changes.9,10 If your neurologic patient's chart includes symptoms of affective or mood lability, consider screening them for PBA too.

It could be time to screen for PBA.

Learn more about the Steps to Diagnosis

Crying and other episodes can be common among patients with anxiety, post-traumatic stress disorder, depression, delusions, aggression, and personality changes, which can complicate the diagnosis of Pseudobulbar Affect
Co-Pay Card & Sample Requests

References: 1. Miller A, Pratt H, Schiffer RB. Pseudobulbar affect: the spectrum of clinical presentations, etiologies and treatments. Expert Rev Neurother. 2011;11(7):1077-1088. 2. Colamonico J, Formella A, Bradley W. Pseudobulbar affect: burden of illness in the USA. Adv Ther. 2012;29(9):775-798. 3. Parvizi J, Arciniegas DB, Bernardini GL, et al. Diagnosis and management of pathological laughter and crying. Mayo Clin Proc. 2006;81(11):1482-1486. 4. 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. PLoS ONE. 2013;8(8):e72232. 5. 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. 6. Moore SR, Gresham LS, Bromberg MB, Kasarkis EJ, Smith RA. A self report measure of affective lability. J Neurol Neurosurg Psychiatry. 1997;63(1):89-93. 7. Smith RA, Berg JE, Pope LE, Callahan JD, Wynn D, Thisted RA. Validation of the CNS emotional lability scale for pseudobulbar affect (pathological laughing and crying) in multiple sclerosis patients. Mult Scler. 2004;10(6):679-685. 8. Cummings JL, Arciniegas DB, Brooks BR, et al. Defining and diagnosing involuntary emotional expression disorder. CNS Spectr. 2006;11(S6):1-7. 9. Engelman WA, Hammond FM, Malec JF. Diagnosing pseudobulbar affect in traumatic brain injury. Neuropsychiatr Dis Treat. 2014;10:1903-1910. 10. Crumpacker DW, Engelman WA. Identifying pseudobulbar affect in Alzheimer’s disease and dementia. US Neurol. 2014;10(1):10-14 11. Vernon M, Poon JL, Dornberger S, Frandsen B, Kulus J, Eliopoulos C, Yonan C. Burden of care for patients with symptoms of pseudobulbar affect residing in long-term care facilities: Results of a caregiver survey. Poster presented at: The 46th Annual Meeting and Exhibition of the American Society of Consultant Pharmacists; October 30 – November 1, 2015; Las Vegas, NV.

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


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.



  • 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 (