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Published Online: 1 April 2014

Treatment of Pathological Crying in Patient With Schizophrenia After Stroke

Publication: The Journal of Neuropsychiatry and Clinical Neurosciences
To the Editor: A 57-year-old woman with past medical history of paranoid schizophrenia (diagnosed during college), hypertension, and diabetes suffered multiple embolic cerebral vascular accidents (CVAs) resulting in right-sided hemiplegia with neglect, was admitted to the long-term care nursing facility for rehabilitation. The patient's vitals and complete blood count were within normal limits. She was fed via a gastrostomy tube. Within a week of her admission, patient started having episodes of restlessness and crying and wailing out loud. The episodes would start within seconds and last for 5 to 15 minutes nearly every hour throughout, without any clear precipitants; she had tears and was inconsolable. For the initial 2 months, she was given lorazepam and fluoxetine to control these episodes without any success. Fluoxetine was later replaced with valproate 750 mg at bedtime for irritability, mood lability, and crying spells, with slight though insufficient improvement. Because of her expressive and receptive aphasia, evaluation for any evidence of delusions or hallucinations was difficult. She was not noted to be responding to any internal stimuli and antipsychotics were not deemed necessary.
After nearly 6 months of involuntary crying episodes, a diagnosis of pseudobulbar affect was considered. Patient was started on dextromethorphan/quinidine (Nuedexta) 20 mg/10 mg b.i.d. The patient's involuntary crying episodes reduced considerably in frequency and duration within the first 2 months of the start of dextromethorphan/quinidine. Patient did not experience any side effects of dextromethorphan: nausea, vomiting, dizziness, and stomach pain while on the medication. Valproate was discontinued over time. After about 6 months of treatment, dextromethorphan/quinidine was discontinued as patient’s symptoms were significantly reduced. In less than 1 week, the patient’s crying episodes resumed. Thereafter, dextromethorphan/quinidine was restarted. After one and a half years on dextromethorphan/quinidine, her crying episodes were reduced in duration some lasting only a few minutes with much reduced frequency (<3–4 episodes per day) or sometimes none over a period of 6–7 hours. The patient is currently doing well with stable vitals and complete blood count. She is showing good improvement in her communication with caretakers for her needs.

Discussion

Pseudobulbar affect (PBA) is characterized by uncontrollable outbursts of laughter and/or crying episodes that lack an appropriate environmental trigger; is either unrelated or out of proportion to the emotions felt by the patient; and is secondary to a neurological disease or injury. PBA is also known as emotional lability, pathological laughing and crying, or intermittent explosive emotional dysregulation and can occur in patients with amyotrophic lateral sclerosis (ALS) and stroke, as well as in diverse neurological conditions such as multiple sclerosis, traumatic brain injury, Alzheimer’s disease, and Parkinson’s disease.1 Dextromethorphan/quinidine 20 mg/10 mg (Nuedexta) twice daily is indicated in the US for the treatment of PBA.
Dextromethorphan, the active agent, is a potent presynaptic sigma−1 receptor agonist and postsynaptic noncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist, and inhibits glutamatergic signaling in brain regions with high sigma−1 receptor expression, primarily the brainstem and cerebellum. Thus, dextromethorphan acts in brain regions believed to be associated with emotion expression disorders, without causing unwanted systemic effects. Quinidine inhibits CYP2D6 liver enzyme metabolism of dextromethorphan, to increase dextromethorphan plasma concentrations.1
Studies have found PBA to be a frequently reported post-stroke behavioral symptom, with a prevalence rate ranging from 11% to 52%, particularly in older patients with a history of prior stroke and subcortical strokes involving internal capsules and neighboring basal ganglia.2
There are case reports of patients with PBA successfully treated with antidepressants.3,4 Lamotrigine has also been reported to be helpful.5 This case report illustrates that dextromethorphan/quinidine was well tolerated in a patient with schizophrenia, that it was more effective than antidepressant and mood stabilizer, that withdrawal of the medication led to return of symptoms, and that long-term treatment may be needed to keep symptoms under control.

References

1.
Miller A, Pratt H, Schiffer RB: Pseudobulbar affect: the spectrum of clinical presentations, etiologies and treatments. Expert Rev Neurother 2011; 11:1077–1088.
2.
Schiffer R, Pope LE: Review of pseudobulbar affect including a novel and potential therapy. J Neuropsychiatry Clin Neurosci 2005; 17:447–454.
3.
McCullagh S, Feinstein A: Treatment of pathological affect: variability of response for laughter and crying. J Neuropsychiatry Clin Neurosci 2000; 12:100–102
4.
Andersen G, Vestergaard K, Riis JO: Citalopram for post-stroke pathological crying. Lancet 1993; 342:837–839.
5.
Ramasubbu R: Lamotrigine treatment for post-stroke pathological laughing and crying. Clin Neuropharmacol 2003; 26:233–235

Information & Authors

Information

Published In

Go to The Journal of Neuropsychiatry and Clinical Neurosciences
Go to The Journal of Neuropsychiatry and Clinical Neurosciences
The Journal of Neuropsychiatry and Clinical Neurosciences
Pages: E28 - E29
PubMed: 24763781

History

Published online: 1 April 2014
Published in print: Spring 2014

Authors

Affiliations

Glen L. Xiong, M.D.
Dept. of Psychiatry and Behavioral Sciences, University of California at Davis, Sacramento, CA
Latika K. Phillips, M.A., M.D.
Dept. of Psychiatry and Behavioral Sciences, University of California at Davis, Sacramento, CA
David J. Patron, B.A., B.S.
Dept. of Psychiatry and Behavioral Sciences, University of California at Davis, Sacramento, CA

Notes

Send correspondence to Dr. Xiong; e-mail: [email protected]

Competing Interests

Dr. Xiong receives compensation for participation on the Medication and Medical Policy Committee for Blue Cross and Blue Shield, Federal Employee Program. All other authors report no financial relationships with commercial interests.

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