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Aggressive outbursts and emotional lability in a 16-year-old boy
Mr. X, age 16, has cerebral palsy (CP), idiopathic normal pressure hydrocephalus (iNPH), and a history of impulse control disorder and behavioral instability, including episodes of aggression or combativeness. Mr. X’s mother reports that these episodes are almost always preceded by inappropriate laughing or crying. His outbursts and emotional lability have gotten worse during the last 6 months. Due to his disruptive behaviors, Mr. X has been unable to attend school, and his parents are considering group home placement. Although they were previously able to control their son’s aggressive behaviors, they fear for his safety, and after one such episode, they call 911. Mr. X is transported by police in handcuffs to the comprehensive psychiatric emergency room (CPEP) for evaluation.
While in CPEP, Mr. X remains uncooperative and disruptive; subsequently, he is placed in 4-point restraints and given
[polldaddy:9991896]
The authors’ observations
Pseudobulbar affect (PBA) is a disorder characterized by sporadic episodes of inappropriate laughing and/or crying that are incongruent with situational context and are frequently exaggerated in comparison with the actual feelings of the patient. The duration of PBA episodes can last seconds to minutes and arise unpredictably.
PBA typically develops secondary to a neurologic disorder, most commonly Alzheimer’s disease (AD), amyotrophic lateral sclerosis (ALS), multiple sclerosis (MS), Parkinson’s disease (PD), stroke, or traumatic brain injury (TBI).1 PBA symptoms are present in an estimated 29.3% of patients with AD, 44.8% of patients with ALS, 45.8% of patients with MS, 26% of patients with PD, 37.8% of patients with stroke, and 52.4% of patients with TBI.2 Although PBA appears far more frequently in patients with MS or ALS compared with those with PD, PD represents an under-recognized and larger patient population. A small fraction of patients also develops PBA secondary to hyperthyroidism, hypothyroidism, Graves’ disease, Wilson’s disease, brain tumors, and a multitude of encephalopathies.3 These neurologic disorders cause dysregulation of the corticopontine-cerebellar circuitry, resulting in functional impediment to the normal affect modulator action of the cerebellum.4
The neurologic insults that can result in PBA may include CP or iNPH. Cerebellar injury is a frequent pathological finding in CP.5 In patients with iNPH, in addition to altered CSF flow, enlarged ventricles compress the corticospinal tracts in the lateral ventricles,6 which is theorized to induce PBA symptoms.
PBA is diagnosed by subjective clinical evaluation and by using the Center for Neurologic Study–Lability Scale (CNS-LS). The CNS-LS is a 7-question survey that addresses the severity of affect lability (Table 17). It may be completed by the patient or caregiver. Each question ranges in score from 1 to 5, with the total score ranging from 7 to 35. The minimum score required for the diagnosis of PBA is 13.7
PBA is frequently misdiagnosed as depression, although the 2 disorders can occur simultaneously (Table 21,8). A crucial distinguishing factor between depression and PBA is the extent of symptoms. Depression presents as feelings of sadness associated with crying and disinterest that occur for weeks to months. In contrast, PBA presents as brief, uncontrollable episodes of laughing and/or crying that last seconds to minutes. Unlike depression, the behaviors associated with PBA are exaggerated or do not match the patient’s feelings. Furthermore, a neurologic disease or brain injury is always present in a patient with PBA, but is not imperative for the diagnosis of depression.
Continue to: Compared with individuals without PBA...
Compared with individuals without PBA, patients with PBA also experience more distress, embarrassment, and social disability, and are consequently more likely to suffer from other psychiatric conditions, including depression, anxiety/panic attacks, bipolar disorder, posttraumatic stress disorder, psychotic disorder, and schizophrenia.1 The Patient Health Questionnaire (PHQ-9), a tool for measuring depression severity, can be used in addition to the CNS-LS to determine if the patient has both depression and PBA.
HISTORY Poor response to anxiolytics and antipsychotics
Mr. X previously received a ventriculoperitoneal shunt for treating iNPH. He was not taking any medications for CP. To address his impulse control disorder, he was prescribed olanzapine, 20 mg/d, risperidone, 2 mg/d, and diazepam, 5 mg three times a day. Mr. X is uncontrolled on these medications, experiencing frequent behavioral outbursts at home. His mother completes a CNS-LS for him. He receives a score of 20, which suggests a diagnosis of PBA. His PHQ-9 score is 8, indicating mild depression.
[polldaddy:9991899]
TREATMENT Introducing a new medication
Mr. X is started on
Continue to: The authors' observations
The authors’ observations
Decreasing the severity and frequency of episodes constitutes the mainstay of treating PBA. In the past, off-label treatments, including selective serotonin reuptake inhibitors (SSRIs) and tricyclic antidepressants, were prescribed to reduce PBA symptoms.5 Currently, dextromethorphan/quinidine is the only FDA-approved medication for treating PBA; however, its use in patients younger than age 18 is considered investigational.
Atypical antipsychotics, such as olanzapine and risperidone, have more warnings and precautions than dextromethorphan/quinidine. Risperidone has a “black-box” warning for QT prolongation, in addition to death and stroke in elderly patients.10 Although dextromethorphan/quinidine does not have a black-box warning, it does increase the risk of QT prolongation, and patients with cardiac risk factors should undergo an electrocardiogram before starting this medication. Additionally, risperidone and olanzapine are known to cause significant weight gain, which can increase the risk of developing hyperlipidemia, metabolic syndrome, and type 2 diabetes mellitus.10,11 Neuroleptic malignant syndrome (NMS) is a potentially life-threatening adverse effect of all antipsychotics. NMS is characterized by fever, rigidity, altered consciousness, and increased heart and respiratory rates.12
Quinidine increases the bioavailability of dextromethorphan by inhibiting CYP2D6. When dextromethorphan/quinidine is simultaneously used with an SSRI that also inhibits CYP2D6, such as paroxetine or fluoxetine, the patient may be at increased risk for developing adverse effects such as respiratory depression and serotonin syndrome.13
[polldaddy:9991902]
Continue to: The authors' observations
The authors’ observations
Although the exact pathophysiology of PBA is unknown, multiple theories may explain the principle elements of the condition. In the absence of a neurologic insult, the cerebellum acts as an affect regulator, inhibiting laughter and crying at times in which they are considered inappropriate. Parvizi et al4 have theorized that the lesions involved in PBA disrupt the corticopontine-cerebellar circuitry, which impedes the ability of the cerebellum to function as an affect modulator.3 In addition to the dysregulation of cerebellar circuitry, altered serotonin and glutamate levels are believed to contribute to the deficient affect regulation observed in PBA; therefore, adding dextromethorphan/quinidine potentiates serotonin and glutamate levels in the synaptic cleft, resulting in a reduction in PBA episodes.4
OUTCOME Affect stability
Seven months after beginning dextromethorphan/quinidine, Mr. X has experienced resolution of his PBA episodes. His PHQ-9 score was reduced to 0 (no clinical signs of depression) within 1 month of starting this medication and his PHQ-9 scores remain below 5, representing minimal depressive severity. The CNS-LS scale is not conducted at further visits because the patient’s mother reported no further PBA episodes. Mr. X no longer exhibits episodes of aggression. These episodes seemed to have been a manifestation of his frustration and difficulty in controlling his PBA episodes. Furthermore, his dosage of diazepam was reduced, and he was weaned off risperidone. Mr. X’s parents report that he has a drastically improved affect. He continues to tolerate his medication well and no longer demonstrates any exacerbations of his psychiatric symptoms.
Bottom Line
Pseudobulbar affect (PBA) may occur secondary to various neurologic insults, including cerebral palsy and idiopathic normal pressure hydrocephalus. The condition is diagnosed by a subjective clinical evaluation and use of the Center for Neurologic Study–Lability Scale. Dextromethorphan/quinidine can significantly reduce PBA symptoms.
Acknowledgements
The authors thank Anthony S. Graziano and Rachel M. Watt, both Physician Assistant students, Daemen College, Amherst, New York.
Related Resources
- Frock B, Williams A, Caplan JP. Pseudobulbar affect: when patients laugh or cry, but don’t know why. Current Psychiatry. 2016;15(9):56-60,63.
- Crumpacker DW. Enhancing approaches to the identification and management of pseudobulbar affect. J Clin Psychiatry. 2016;77(9):e1155.
Drug Brand Names
Dextromethorphan/quinidine • Nuedexta
Diazepam • Valium
Fluoxetine • Prozac
Haloperidol • Haldol
Lorazepam • Ativan
Olanzapine • Zyprexa
Paroxetine • Paxil
Risperidone • Risperdal
1. Colamonico J, Formella A, Bradley W. Pseudobulbar affect: burden of illness in the USA. Adv Ther. 2012;29(9):775-798.
2. Brooks BR, Crumpacker D, Fellus J, et al. PRISM: a novel research tool to assess the prevalence of pseudobulbar affect symptoms across neurological conditions. PLoS One. 2013;8(8):e72232. doi: 10.1371/journal.pone.0072232.
3. Schiffer R, Pope LE. Review of pseudobulbar affect including a novel and potential therapy. J Neuropsychiatry Clin Neurosci. 2005;17(4):447-454.
4. Parvizi J, Anderson SW, Martin CO, et al. Pathological laughter and crying: a link to the cerebellum. Brain. 2001;124(pt 9):1708-1719.
5. Johnsen SD, Bodensteiner JB, Lotze TE. Frequency and nature of cerebellar injury in the extremely premature survivor with cerebral palsy. J Child Neurol. 2005;20(1):60-64.
6. Kamiya K, Hori M, Miyajima M, et al. Axon diameter and intra-axonal volume fraction of the corticospinal tract in idiopathic normal pressure hydrocephalus measured by Q-Space imaging. PLoS One. 2014;9(8):e103842. doi: 10.1371/journal.pone.0103842.
7. Moore SR, Gresham LS, Bromberg MB, et al. A self report measuredextromethorphan of affective lability. J Neurol Neurosurg Psychiatry. 1997;63(1):89-93.
8. Ahmed A, Simmons Z. Pseudobulbar affect: prevalence and management. Ther Clinical Risk Manag. 2013;9:483-489.
9. Cruz MP. Nuedexta for the treatment of pseudobulbar affect. A condition of involuntary crying or laughing. P T. 2013;38(6):325-328.
10. Goëb JL, Marco S, Duhamel A, et al. Metabolic side effects of risperidone in children and adolescents with early onset schizophrenia. Prim Care Companion J Clin Psychiatry. 2008;10(6):486-487.
11. Nemeroff CB. Dosing the antipsychotic medication olanzapine. J Clin Psychiatry. 1997;58(suppl 10):45-49.
12. Troller JN, Chen X, Sachdev PS. Neuroleptic malignant syndrome associated with atypical antipsychotic drugs. CNS Drugs. 2009;23(6):477-492.
13. Schoedel KA, Pope LE, Sellers EM. Randomized open-label drug-drug interaction trial of dextromethorphan/quinidine and paroxetine in healthy volunteers. Clin Drug Investig. 2012;32(3):157-169.
Mr. X, age 16, has cerebral palsy (CP), idiopathic normal pressure hydrocephalus (iNPH), and a history of impulse control disorder and behavioral instability, including episodes of aggression or combativeness. Mr. X’s mother reports that these episodes are almost always preceded by inappropriate laughing or crying. His outbursts and emotional lability have gotten worse during the last 6 months. Due to his disruptive behaviors, Mr. X has been unable to attend school, and his parents are considering group home placement. Although they were previously able to control their son’s aggressive behaviors, they fear for his safety, and after one such episode, they call 911. Mr. X is transported by police in handcuffs to the comprehensive psychiatric emergency room (CPEP) for evaluation.
While in CPEP, Mr. X remains uncooperative and disruptive; subsequently, he is placed in 4-point restraints and given
[polldaddy:9991896]
The authors’ observations
Pseudobulbar affect (PBA) is a disorder characterized by sporadic episodes of inappropriate laughing and/or crying that are incongruent with situational context and are frequently exaggerated in comparison with the actual feelings of the patient. The duration of PBA episodes can last seconds to minutes and arise unpredictably.
PBA typically develops secondary to a neurologic disorder, most commonly Alzheimer’s disease (AD), amyotrophic lateral sclerosis (ALS), multiple sclerosis (MS), Parkinson’s disease (PD), stroke, or traumatic brain injury (TBI).1 PBA symptoms are present in an estimated 29.3% of patients with AD, 44.8% of patients with ALS, 45.8% of patients with MS, 26% of patients with PD, 37.8% of patients with stroke, and 52.4% of patients with TBI.2 Although PBA appears far more frequently in patients with MS or ALS compared with those with PD, PD represents an under-recognized and larger patient population. A small fraction of patients also develops PBA secondary to hyperthyroidism, hypothyroidism, Graves’ disease, Wilson’s disease, brain tumors, and a multitude of encephalopathies.3 These neurologic disorders cause dysregulation of the corticopontine-cerebellar circuitry, resulting in functional impediment to the normal affect modulator action of the cerebellum.4
The neurologic insults that can result in PBA may include CP or iNPH. Cerebellar injury is a frequent pathological finding in CP.5 In patients with iNPH, in addition to altered CSF flow, enlarged ventricles compress the corticospinal tracts in the lateral ventricles,6 which is theorized to induce PBA symptoms.
PBA is diagnosed by subjective clinical evaluation and by using the Center for Neurologic Study–Lability Scale (CNS-LS). The CNS-LS is a 7-question survey that addresses the severity of affect lability (Table 17). It may be completed by the patient or caregiver. Each question ranges in score from 1 to 5, with the total score ranging from 7 to 35. The minimum score required for the diagnosis of PBA is 13.7
PBA is frequently misdiagnosed as depression, although the 2 disorders can occur simultaneously (Table 21,8). A crucial distinguishing factor between depression and PBA is the extent of symptoms. Depression presents as feelings of sadness associated with crying and disinterest that occur for weeks to months. In contrast, PBA presents as brief, uncontrollable episodes of laughing and/or crying that last seconds to minutes. Unlike depression, the behaviors associated with PBA are exaggerated or do not match the patient’s feelings. Furthermore, a neurologic disease or brain injury is always present in a patient with PBA, but is not imperative for the diagnosis of depression.
Continue to: Compared with individuals without PBA...
Compared with individuals without PBA, patients with PBA also experience more distress, embarrassment, and social disability, and are consequently more likely to suffer from other psychiatric conditions, including depression, anxiety/panic attacks, bipolar disorder, posttraumatic stress disorder, psychotic disorder, and schizophrenia.1 The Patient Health Questionnaire (PHQ-9), a tool for measuring depression severity, can be used in addition to the CNS-LS to determine if the patient has both depression and PBA.
HISTORY Poor response to anxiolytics and antipsychotics
Mr. X previously received a ventriculoperitoneal shunt for treating iNPH. He was not taking any medications for CP. To address his impulse control disorder, he was prescribed olanzapine, 20 mg/d, risperidone, 2 mg/d, and diazepam, 5 mg three times a day. Mr. X is uncontrolled on these medications, experiencing frequent behavioral outbursts at home. His mother completes a CNS-LS for him. He receives a score of 20, which suggests a diagnosis of PBA. His PHQ-9 score is 8, indicating mild depression.
[polldaddy:9991899]
TREATMENT Introducing a new medication
Mr. X is started on
Continue to: The authors' observations
The authors’ observations
Decreasing the severity and frequency of episodes constitutes the mainstay of treating PBA. In the past, off-label treatments, including selective serotonin reuptake inhibitors (SSRIs) and tricyclic antidepressants, were prescribed to reduce PBA symptoms.5 Currently, dextromethorphan/quinidine is the only FDA-approved medication for treating PBA; however, its use in patients younger than age 18 is considered investigational.
Atypical antipsychotics, such as olanzapine and risperidone, have more warnings and precautions than dextromethorphan/quinidine. Risperidone has a “black-box” warning for QT prolongation, in addition to death and stroke in elderly patients.10 Although dextromethorphan/quinidine does not have a black-box warning, it does increase the risk of QT prolongation, and patients with cardiac risk factors should undergo an electrocardiogram before starting this medication. Additionally, risperidone and olanzapine are known to cause significant weight gain, which can increase the risk of developing hyperlipidemia, metabolic syndrome, and type 2 diabetes mellitus.10,11 Neuroleptic malignant syndrome (NMS) is a potentially life-threatening adverse effect of all antipsychotics. NMS is characterized by fever, rigidity, altered consciousness, and increased heart and respiratory rates.12
Quinidine increases the bioavailability of dextromethorphan by inhibiting CYP2D6. When dextromethorphan/quinidine is simultaneously used with an SSRI that also inhibits CYP2D6, such as paroxetine or fluoxetine, the patient may be at increased risk for developing adverse effects such as respiratory depression and serotonin syndrome.13
[polldaddy:9991902]
Continue to: The authors' observations
The authors’ observations
Although the exact pathophysiology of PBA is unknown, multiple theories may explain the principle elements of the condition. In the absence of a neurologic insult, the cerebellum acts as an affect regulator, inhibiting laughter and crying at times in which they are considered inappropriate. Parvizi et al4 have theorized that the lesions involved in PBA disrupt the corticopontine-cerebellar circuitry, which impedes the ability of the cerebellum to function as an affect modulator.3 In addition to the dysregulation of cerebellar circuitry, altered serotonin and glutamate levels are believed to contribute to the deficient affect regulation observed in PBA; therefore, adding dextromethorphan/quinidine potentiates serotonin and glutamate levels in the synaptic cleft, resulting in a reduction in PBA episodes.4
OUTCOME Affect stability
Seven months after beginning dextromethorphan/quinidine, Mr. X has experienced resolution of his PBA episodes. His PHQ-9 score was reduced to 0 (no clinical signs of depression) within 1 month of starting this medication and his PHQ-9 scores remain below 5, representing minimal depressive severity. The CNS-LS scale is not conducted at further visits because the patient’s mother reported no further PBA episodes. Mr. X no longer exhibits episodes of aggression. These episodes seemed to have been a manifestation of his frustration and difficulty in controlling his PBA episodes. Furthermore, his dosage of diazepam was reduced, and he was weaned off risperidone. Mr. X’s parents report that he has a drastically improved affect. He continues to tolerate his medication well and no longer demonstrates any exacerbations of his psychiatric symptoms.
Bottom Line
Pseudobulbar affect (PBA) may occur secondary to various neurologic insults, including cerebral palsy and idiopathic normal pressure hydrocephalus. The condition is diagnosed by a subjective clinical evaluation and use of the Center for Neurologic Study–Lability Scale. Dextromethorphan/quinidine can significantly reduce PBA symptoms.
Acknowledgements
The authors thank Anthony S. Graziano and Rachel M. Watt, both Physician Assistant students, Daemen College, Amherst, New York.
Related Resources
- Frock B, Williams A, Caplan JP. Pseudobulbar affect: when patients laugh or cry, but don’t know why. Current Psychiatry. 2016;15(9):56-60,63.
- Crumpacker DW. Enhancing approaches to the identification and management of pseudobulbar affect. J Clin Psychiatry. 2016;77(9):e1155.
Drug Brand Names
Dextromethorphan/quinidine • Nuedexta
Diazepam • Valium
Fluoxetine • Prozac
Haloperidol • Haldol
Lorazepam • Ativan
Olanzapine • Zyprexa
Paroxetine • Paxil
Risperidone • Risperdal
Mr. X, age 16, has cerebral palsy (CP), idiopathic normal pressure hydrocephalus (iNPH), and a history of impulse control disorder and behavioral instability, including episodes of aggression or combativeness. Mr. X’s mother reports that these episodes are almost always preceded by inappropriate laughing or crying. His outbursts and emotional lability have gotten worse during the last 6 months. Due to his disruptive behaviors, Mr. X has been unable to attend school, and his parents are considering group home placement. Although they were previously able to control their son’s aggressive behaviors, they fear for his safety, and after one such episode, they call 911. Mr. X is transported by police in handcuffs to the comprehensive psychiatric emergency room (CPEP) for evaluation.
While in CPEP, Mr. X remains uncooperative and disruptive; subsequently, he is placed in 4-point restraints and given
[polldaddy:9991896]
The authors’ observations
Pseudobulbar affect (PBA) is a disorder characterized by sporadic episodes of inappropriate laughing and/or crying that are incongruent with situational context and are frequently exaggerated in comparison with the actual feelings of the patient. The duration of PBA episodes can last seconds to minutes and arise unpredictably.
PBA typically develops secondary to a neurologic disorder, most commonly Alzheimer’s disease (AD), amyotrophic lateral sclerosis (ALS), multiple sclerosis (MS), Parkinson’s disease (PD), stroke, or traumatic brain injury (TBI).1 PBA symptoms are present in an estimated 29.3% of patients with AD, 44.8% of patients with ALS, 45.8% of patients with MS, 26% of patients with PD, 37.8% of patients with stroke, and 52.4% of patients with TBI.2 Although PBA appears far more frequently in patients with MS or ALS compared with those with PD, PD represents an under-recognized and larger patient population. A small fraction of patients also develops PBA secondary to hyperthyroidism, hypothyroidism, Graves’ disease, Wilson’s disease, brain tumors, and a multitude of encephalopathies.3 These neurologic disorders cause dysregulation of the corticopontine-cerebellar circuitry, resulting in functional impediment to the normal affect modulator action of the cerebellum.4
The neurologic insults that can result in PBA may include CP or iNPH. Cerebellar injury is a frequent pathological finding in CP.5 In patients with iNPH, in addition to altered CSF flow, enlarged ventricles compress the corticospinal tracts in the lateral ventricles,6 which is theorized to induce PBA symptoms.
PBA is diagnosed by subjective clinical evaluation and by using the Center for Neurologic Study–Lability Scale (CNS-LS). The CNS-LS is a 7-question survey that addresses the severity of affect lability (Table 17). It may be completed by the patient or caregiver. Each question ranges in score from 1 to 5, with the total score ranging from 7 to 35. The minimum score required for the diagnosis of PBA is 13.7
PBA is frequently misdiagnosed as depression, although the 2 disorders can occur simultaneously (Table 21,8). A crucial distinguishing factor between depression and PBA is the extent of symptoms. Depression presents as feelings of sadness associated with crying and disinterest that occur for weeks to months. In contrast, PBA presents as brief, uncontrollable episodes of laughing and/or crying that last seconds to minutes. Unlike depression, the behaviors associated with PBA are exaggerated or do not match the patient’s feelings. Furthermore, a neurologic disease or brain injury is always present in a patient with PBA, but is not imperative for the diagnosis of depression.
Continue to: Compared with individuals without PBA...
Compared with individuals without PBA, patients with PBA also experience more distress, embarrassment, and social disability, and are consequently more likely to suffer from other psychiatric conditions, including depression, anxiety/panic attacks, bipolar disorder, posttraumatic stress disorder, psychotic disorder, and schizophrenia.1 The Patient Health Questionnaire (PHQ-9), a tool for measuring depression severity, can be used in addition to the CNS-LS to determine if the patient has both depression and PBA.
HISTORY Poor response to anxiolytics and antipsychotics
Mr. X previously received a ventriculoperitoneal shunt for treating iNPH. He was not taking any medications for CP. To address his impulse control disorder, he was prescribed olanzapine, 20 mg/d, risperidone, 2 mg/d, and diazepam, 5 mg three times a day. Mr. X is uncontrolled on these medications, experiencing frequent behavioral outbursts at home. His mother completes a CNS-LS for him. He receives a score of 20, which suggests a diagnosis of PBA. His PHQ-9 score is 8, indicating mild depression.
[polldaddy:9991899]
TREATMENT Introducing a new medication
Mr. X is started on
Continue to: The authors' observations
The authors’ observations
Decreasing the severity and frequency of episodes constitutes the mainstay of treating PBA. In the past, off-label treatments, including selective serotonin reuptake inhibitors (SSRIs) and tricyclic antidepressants, were prescribed to reduce PBA symptoms.5 Currently, dextromethorphan/quinidine is the only FDA-approved medication for treating PBA; however, its use in patients younger than age 18 is considered investigational.
Atypical antipsychotics, such as olanzapine and risperidone, have more warnings and precautions than dextromethorphan/quinidine. Risperidone has a “black-box” warning for QT prolongation, in addition to death and stroke in elderly patients.10 Although dextromethorphan/quinidine does not have a black-box warning, it does increase the risk of QT prolongation, and patients with cardiac risk factors should undergo an electrocardiogram before starting this medication. Additionally, risperidone and olanzapine are known to cause significant weight gain, which can increase the risk of developing hyperlipidemia, metabolic syndrome, and type 2 diabetes mellitus.10,11 Neuroleptic malignant syndrome (NMS) is a potentially life-threatening adverse effect of all antipsychotics. NMS is characterized by fever, rigidity, altered consciousness, and increased heart and respiratory rates.12
Quinidine increases the bioavailability of dextromethorphan by inhibiting CYP2D6. When dextromethorphan/quinidine is simultaneously used with an SSRI that also inhibits CYP2D6, such as paroxetine or fluoxetine, the patient may be at increased risk for developing adverse effects such as respiratory depression and serotonin syndrome.13
[polldaddy:9991902]
Continue to: The authors' observations
The authors’ observations
Although the exact pathophysiology of PBA is unknown, multiple theories may explain the principle elements of the condition. In the absence of a neurologic insult, the cerebellum acts as an affect regulator, inhibiting laughter and crying at times in which they are considered inappropriate. Parvizi et al4 have theorized that the lesions involved in PBA disrupt the corticopontine-cerebellar circuitry, which impedes the ability of the cerebellum to function as an affect modulator.3 In addition to the dysregulation of cerebellar circuitry, altered serotonin and glutamate levels are believed to contribute to the deficient affect regulation observed in PBA; therefore, adding dextromethorphan/quinidine potentiates serotonin and glutamate levels in the synaptic cleft, resulting in a reduction in PBA episodes.4
OUTCOME Affect stability
Seven months after beginning dextromethorphan/quinidine, Mr. X has experienced resolution of his PBA episodes. His PHQ-9 score was reduced to 0 (no clinical signs of depression) within 1 month of starting this medication and his PHQ-9 scores remain below 5, representing minimal depressive severity. The CNS-LS scale is not conducted at further visits because the patient’s mother reported no further PBA episodes. Mr. X no longer exhibits episodes of aggression. These episodes seemed to have been a manifestation of his frustration and difficulty in controlling his PBA episodes. Furthermore, his dosage of diazepam was reduced, and he was weaned off risperidone. Mr. X’s parents report that he has a drastically improved affect. He continues to tolerate his medication well and no longer demonstrates any exacerbations of his psychiatric symptoms.
Bottom Line
Pseudobulbar affect (PBA) may occur secondary to various neurologic insults, including cerebral palsy and idiopathic normal pressure hydrocephalus. The condition is diagnosed by a subjective clinical evaluation and use of the Center for Neurologic Study–Lability Scale. Dextromethorphan/quinidine can significantly reduce PBA symptoms.
Acknowledgements
The authors thank Anthony S. Graziano and Rachel M. Watt, both Physician Assistant students, Daemen College, Amherst, New York.
Related Resources
- Frock B, Williams A, Caplan JP. Pseudobulbar affect: when patients laugh or cry, but don’t know why. Current Psychiatry. 2016;15(9):56-60,63.
- Crumpacker DW. Enhancing approaches to the identification and management of pseudobulbar affect. J Clin Psychiatry. 2016;77(9):e1155.
Drug Brand Names
Dextromethorphan/quinidine • Nuedexta
Diazepam • Valium
Fluoxetine • Prozac
Haloperidol • Haldol
Lorazepam • Ativan
Olanzapine • Zyprexa
Paroxetine • Paxil
Risperidone • Risperdal
1. Colamonico J, Formella A, Bradley W. Pseudobulbar affect: burden of illness in the USA. Adv Ther. 2012;29(9):775-798.
2. Brooks BR, Crumpacker D, Fellus J, et al. PRISM: a novel research tool to assess the prevalence of pseudobulbar affect symptoms across neurological conditions. PLoS One. 2013;8(8):e72232. doi: 10.1371/journal.pone.0072232.
3. Schiffer R, Pope LE. Review of pseudobulbar affect including a novel and potential therapy. J Neuropsychiatry Clin Neurosci. 2005;17(4):447-454.
4. Parvizi J, Anderson SW, Martin CO, et al. Pathological laughter and crying: a link to the cerebellum. Brain. 2001;124(pt 9):1708-1719.
5. Johnsen SD, Bodensteiner JB, Lotze TE. Frequency and nature of cerebellar injury in the extremely premature survivor with cerebral palsy. J Child Neurol. 2005;20(1):60-64.
6. Kamiya K, Hori M, Miyajima M, et al. Axon diameter and intra-axonal volume fraction of the corticospinal tract in idiopathic normal pressure hydrocephalus measured by Q-Space imaging. PLoS One. 2014;9(8):e103842. doi: 10.1371/journal.pone.0103842.
7. Moore SR, Gresham LS, Bromberg MB, et al. A self report measuredextromethorphan of affective lability. J Neurol Neurosurg Psychiatry. 1997;63(1):89-93.
8. Ahmed A, Simmons Z. Pseudobulbar affect: prevalence and management. Ther Clinical Risk Manag. 2013;9:483-489.
9. Cruz MP. Nuedexta for the treatment of pseudobulbar affect. A condition of involuntary crying or laughing. P T. 2013;38(6):325-328.
10. Goëb JL, Marco S, Duhamel A, et al. Metabolic side effects of risperidone in children and adolescents with early onset schizophrenia. Prim Care Companion J Clin Psychiatry. 2008;10(6):486-487.
11. Nemeroff CB. Dosing the antipsychotic medication olanzapine. J Clin Psychiatry. 1997;58(suppl 10):45-49.
12. Troller JN, Chen X, Sachdev PS. Neuroleptic malignant syndrome associated with atypical antipsychotic drugs. CNS Drugs. 2009;23(6):477-492.
13. Schoedel KA, Pope LE, Sellers EM. Randomized open-label drug-drug interaction trial of dextromethorphan/quinidine and paroxetine in healthy volunteers. Clin Drug Investig. 2012;32(3):157-169.
1. Colamonico J, Formella A, Bradley W. Pseudobulbar affect: burden of illness in the USA. Adv Ther. 2012;29(9):775-798.
2. Brooks BR, Crumpacker D, Fellus J, et al. PRISM: a novel research tool to assess the prevalence of pseudobulbar affect symptoms across neurological conditions. PLoS One. 2013;8(8):e72232. doi: 10.1371/journal.pone.0072232.
3. Schiffer R, Pope LE. Review of pseudobulbar affect including a novel and potential therapy. J Neuropsychiatry Clin Neurosci. 2005;17(4):447-454.
4. Parvizi J, Anderson SW, Martin CO, et al. Pathological laughter and crying: a link to the cerebellum. Brain. 2001;124(pt 9):1708-1719.
5. Johnsen SD, Bodensteiner JB, Lotze TE. Frequency and nature of cerebellar injury in the extremely premature survivor with cerebral palsy. J Child Neurol. 2005;20(1):60-64.
6. Kamiya K, Hori M, Miyajima M, et al. Axon diameter and intra-axonal volume fraction of the corticospinal tract in idiopathic normal pressure hydrocephalus measured by Q-Space imaging. PLoS One. 2014;9(8):e103842. doi: 10.1371/journal.pone.0103842.
7. Moore SR, Gresham LS, Bromberg MB, et al. A self report measuredextromethorphan of affective lability. J Neurol Neurosurg Psychiatry. 1997;63(1):89-93.
8. Ahmed A, Simmons Z. Pseudobulbar affect: prevalence and management. Ther Clinical Risk Manag. 2013;9:483-489.
9. Cruz MP. Nuedexta for the treatment of pseudobulbar affect. A condition of involuntary crying or laughing. P T. 2013;38(6):325-328.
10. Goëb JL, Marco S, Duhamel A, et al. Metabolic side effects of risperidone in children and adolescents with early onset schizophrenia. Prim Care Companion J Clin Psychiatry. 2008;10(6):486-487.
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