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Treatment of pseudobulbar affect with citalopram in a patient with progressive multifocal leukoencephalopthy
Journal of Clinical Neuroscience 19 (2012) 185–186
Contents lists available at SciVerse ScienceDirect
Journal of Clinical Neuroscience journal homepage: www.elsevier.com/locate/jocn
Short Communication
Treatment of pseudobulbar affect with citalopram in a patient with progressive multifocal leukoencephalopthy R.R. King, J.P. Reiss ⇑ Department of Psychiatry, University of Western Ontario, London Health Sciences Centre, Victoria Hospital, 800 Commissioners Road, London, Ontario, Canada N6A 5W9
a r t i c l e
i n f o
Article history: Received 20 December 2010 Accepted 3 July 2011
Keywords: Pseudobulbar affect Pathological crying Treatment SSRI Progressive multifocal leukoencephalopathy
a b s t r a c t Pseudobulbar affect (PBA) manifests in a variety of neurologic illnesses suggesting a heterogeneous pathophysiology with common underpinnings. We report successful treatment of PBA with a selective serotonin reuptake inhibitor (SSRI) in a 54-year-old woman following progressive multifocal leukoencephalopathy (PML). In light of recent focus on dextromethorphan/quinidine (DM/Q) for the treatment of PBA, the clinician is reminded of the effectiveness of SSRIs. Ó 2011 Elsevier Ltd. All rights reserved.
Pseudobulbar affect (PBA) is ‘a disorder of emotional expression and regulation characterized by uncontrollable outbursts of laughing, crying, or both that are inconsistent with, or disproportionate to, the emotions felt by the patient’.1 It manifests in a variety of neurologic diseases.1,2 Possible mechanisms include damage to limbic/paralimbic structures, brainstem, and cerebellum, and relative dysfunction of neurotransmitters including serotonin, norepinephrine, dopamine, and glutamate.2,3 We report a case of PBA following progressive multifocal leukoencephalopathy (PML) in a patient with sarcoidosis. PML is often fatal,4,5 but this patient recovered allowing treatment of PBA with a selective serotonin reuptake inhibitor (SSRI), citalopram. Details of the assessment, and treatment course of this patient are published elsewhere.6 In brief, a 54 year-old woman acquired PML related to sarcoidosis, but recovered after treatment with a novel agent. Sixteen months later, the patient was left with a pseudobulbar palsy, and referred for assessment of PBA. There were symptoms of a mild major depressive episode (MDE), and anxiety about physical impairments. There were no other psychiatric symptoms. However, there were daily periods of sudden crying that were far out of proportion to the patient’s emotional experience. There was a remote history of two MDEs. Otherwise, psychiatric, medical, substance use, and psychosocial history was unremarkable. Medications included mirtazapine 15 mg at night, and ondansetron as needed. On mental status exam, language was intact. Affect was euthymic interspersed with sudden episodes
⇑ Corresponding author. Tel.: +1 519 685 8500x75665; fax: +1 519 667 6564. E-mail address: [email protected] (J.P. Reiss). 0967-5868/$ - see front matter Ó 2011 Elsevier Ltd. All rights reserved. doi:10.1016/j.jocn.2011.07.006
of crying. Mood was described as ‘‘fine’’ during such episodes. Mini Mental State Exam (MMSE) score was 28/28 (writing and drawing items were omitted due to weakness). Hamilton Rating Scale for Depression (HRSD) score was 9. Young Mania Rating Scale (YMRS) score was 0. As no measure of PBA has been validated in PML, no scales were used to measure PBA. Citalopram 10 mg daily was initiated. Within 4 days, there was a decrease in sudden episodes of crying. At one month, HRSD score decreased to 5, YMRS remained at 0, and MMSE remained at 28/28. Citalopram was increased to 20 mg daily. Subsequently, there was a further decrease in sudden episodes of crying. There were no side effects of treatment. Mirtazapine was discontinued, and symptoms and test scores were unchanged at eight and 20 months. Medical status and neuroimaging findings were stable throughout (Fig. 1).
1. Discussion As the only report to date of treatment of PBA in a patient with PML, the reader is reminded of the effectiveness of SSRIs for the treatment of PBA. While it is possible that the patient’s PBA lessened due to improvement in PML, this is unlikely with stable clinical and radiologic findings, and a rapid reduction of PBA symptoms within days of initiating citalopram. Indeed, SSRIs typically take 4–6 weeks to treat MDEs, yet only 3–5 days to treat PBA. This rapid response suggests a different therapeutic action such as immediate serotonin increases in ascending afferents to the ventral paralimbic network or effects via r1-receptor agonism.2 It also speaks to the differential effect that SSRIs may have in disorders of mood (such as depression) versus disorders of affect (such as
186
R.R. King, J.P. Reiss / Journal of Clinical Neuroscience 19 (2012) 185–186
SSRIs. Although randomised controlled trials in patients with PBA have been small,8 agents such as citalopram have minimal CYP450 enzyme interactions and good safety profiles.2 Thus, specific SSRIs should continue to be first-line for treatment of PBA. References
Fig. 1. A comparison of imaging pre- and post-treatment for pseudobulbar affect (PBA). Fluid-attenuated inversion-recovery (FLAIR) magnetic resonance imaging showing stable white matter changes in the brainstem and cerebellum in successfully treated progressive multifocal leukoencephalopathy (PML) (A) prior to initiating citalopram for PBA and (B) after 1 year of treatment with citalopram for PBA. Lesions were nonenhancing with gadolinium administration.
PBA).2 With the recent focus on dextromethorphan/quinidine(DM/ Q) for treatment of PBA,7 clinicians are reminded of the safety of
1. Rosen HJ, Cummings J. A real reason for patients with pseudobulbar affect to smile. Ann Neurol 2007;61:92–6. 2. Wortzel HS, Oster TJ, Anderson CA, et al. Pathological laughing and crying: epidemiology, pathophysiology and treatment. CNS Drugs 2008;22:531–45. 3. Ghaffar O, Chamelian L, Feinstein A. Neuroanatomy of pseudobulbar affect: a quantitative MRI study in multiple sclerosis. J Neurol 2008;255:406–12. 4. Aksamit AJ. Progressive multifocal leukoencephalopathy. Curr Treat Options Neurol 2008;10:178–85. 5. Graham KC, Spiegel DR. Pseudobulbar palsy and affect in a case of progressive multifocal leukoencephalopathy. J Neuropsychiatry Clin Neurosci 2008;20:110–1. 6. Gofton TE, Al-Khotani A, O’Farrell B, et al. Mefloquine in the treatment of progressive multifocal leukoencephalopathy. J Neurol Neurosurg Psychiatry 2011;82:452–5. 7. Olney N, Rosen H. AVP-923, a combination of dextromethorphan hydrobromide and quinidine sulfate for the treatment of pseudobulbar affect and neuropathic pain. IDrugs 2010;13:254–65. 8. Andersen G, Vestergaard K, Riis JO. Citalopram for post-stroke pathological crying. Lancet 1993;342:837–9.
Contents lists available at SciVerse ScienceDirect
Journal of Clinical Neuroscience journal homepage: www.elsevier.com/locate/jocn
Short Communication
Treatment of pseudobulbar affect with citalopram in a patient with progressive multifocal leukoencephalopthy R.R. King, J.P. Reiss ⇑ Department of Psychiatry, University of Western Ontario, London Health Sciences Centre, Victoria Hospital, 800 Commissioners Road, London, Ontario, Canada N6A 5W9
a r t i c l e
i n f o
Article history: Received 20 December 2010 Accepted 3 July 2011
Keywords: Pseudobulbar affect Pathological crying Treatment SSRI Progressive multifocal leukoencephalopathy
a b s t r a c t Pseudobulbar affect (PBA) manifests in a variety of neurologic illnesses suggesting a heterogeneous pathophysiology with common underpinnings. We report successful treatment of PBA with a selective serotonin reuptake inhibitor (SSRI) in a 54-year-old woman following progressive multifocal leukoencephalopathy (PML). In light of recent focus on dextromethorphan/quinidine (DM/Q) for the treatment of PBA, the clinician is reminded of the effectiveness of SSRIs. Ó 2011 Elsevier Ltd. All rights reserved.
Pseudobulbar affect (PBA) is ‘a disorder of emotional expression and regulation characterized by uncontrollable outbursts of laughing, crying, or both that are inconsistent with, or disproportionate to, the emotions felt by the patient’.1 It manifests in a variety of neurologic diseases.1,2 Possible mechanisms include damage to limbic/paralimbic structures, brainstem, and cerebellum, and relative dysfunction of neurotransmitters including serotonin, norepinephrine, dopamine, and glutamate.2,3 We report a case of PBA following progressive multifocal leukoencephalopathy (PML) in a patient with sarcoidosis. PML is often fatal,4,5 but this patient recovered allowing treatment of PBA with a selective serotonin reuptake inhibitor (SSRI), citalopram. Details of the assessment, and treatment course of this patient are published elsewhere.6 In brief, a 54 year-old woman acquired PML related to sarcoidosis, but recovered after treatment with a novel agent. Sixteen months later, the patient was left with a pseudobulbar palsy, and referred for assessment of PBA. There were symptoms of a mild major depressive episode (MDE), and anxiety about physical impairments. There were no other psychiatric symptoms. However, there were daily periods of sudden crying that were far out of proportion to the patient’s emotional experience. There was a remote history of two MDEs. Otherwise, psychiatric, medical, substance use, and psychosocial history was unremarkable. Medications included mirtazapine 15 mg at night, and ondansetron as needed. On mental status exam, language was intact. Affect was euthymic interspersed with sudden episodes
⇑ Corresponding author. Tel.: +1 519 685 8500x75665; fax: +1 519 667 6564. E-mail address: [email protected] (J.P. Reiss). 0967-5868/$ - see front matter Ó 2011 Elsevier Ltd. All rights reserved. doi:10.1016/j.jocn.2011.07.006
of crying. Mood was described as ‘‘fine’’ during such episodes. Mini Mental State Exam (MMSE) score was 28/28 (writing and drawing items were omitted due to weakness). Hamilton Rating Scale for Depression (HRSD) score was 9. Young Mania Rating Scale (YMRS) score was 0. As no measure of PBA has been validated in PML, no scales were used to measure PBA. Citalopram 10 mg daily was initiated. Within 4 days, there was a decrease in sudden episodes of crying. At one month, HRSD score decreased to 5, YMRS remained at 0, and MMSE remained at 28/28. Citalopram was increased to 20 mg daily. Subsequently, there was a further decrease in sudden episodes of crying. There were no side effects of treatment. Mirtazapine was discontinued, and symptoms and test scores were unchanged at eight and 20 months. Medical status and neuroimaging findings were stable throughout (Fig. 1).
1. Discussion As the only report to date of treatment of PBA in a patient with PML, the reader is reminded of the effectiveness of SSRIs for the treatment of PBA. While it is possible that the patient’s PBA lessened due to improvement in PML, this is unlikely with stable clinical and radiologic findings, and a rapid reduction of PBA symptoms within days of initiating citalopram. Indeed, SSRIs typically take 4–6 weeks to treat MDEs, yet only 3–5 days to treat PBA. This rapid response suggests a different therapeutic action such as immediate serotonin increases in ascending afferents to the ventral paralimbic network or effects via r1-receptor agonism.2 It also speaks to the differential effect that SSRIs may have in disorders of mood (such as depression) versus disorders of affect (such as
186
R.R. King, J.P. Reiss / Journal of Clinical Neuroscience 19 (2012) 185–186
SSRIs. Although randomised controlled trials in patients with PBA have been small,8 agents such as citalopram have minimal CYP450 enzyme interactions and good safety profiles.2 Thus, specific SSRIs should continue to be first-line for treatment of PBA. References
Fig. 1. A comparison of imaging pre- and post-treatment for pseudobulbar affect (PBA). Fluid-attenuated inversion-recovery (FLAIR) magnetic resonance imaging showing stable white matter changes in the brainstem and cerebellum in successfully treated progressive multifocal leukoencephalopathy (PML) (A) prior to initiating citalopram for PBA and (B) after 1 year of treatment with citalopram for PBA. Lesions were nonenhancing with gadolinium administration.
PBA).2 With the recent focus on dextromethorphan/quinidine(DM/ Q) for treatment of PBA,7 clinicians are reminded of the safety of
1. Rosen HJ, Cummings J. A real reason for patients with pseudobulbar affect to smile. Ann Neurol 2007;61:92–6. 2. Wortzel HS, Oster TJ, Anderson CA, et al. Pathological laughing and crying: epidemiology, pathophysiology and treatment. CNS Drugs 2008;22:531–45. 3. Ghaffar O, Chamelian L, Feinstein A. Neuroanatomy of pseudobulbar affect: a quantitative MRI study in multiple sclerosis. J Neurol 2008;255:406–12. 4. Aksamit AJ. Progressive multifocal leukoencephalopathy. Curr Treat Options Neurol 2008;10:178–85. 5. Graham KC, Spiegel DR. Pseudobulbar palsy and affect in a case of progressive multifocal leukoencephalopathy. J Neuropsychiatry Clin Neurosci 2008;20:110–1. 6. Gofton TE, Al-Khotani A, O’Farrell B, et al. Mefloquine in the treatment of progressive multifocal leukoencephalopathy. J Neurol Neurosurg Psychiatry 2011;82:452–5. 7. Olney N, Rosen H. AVP-923, a combination of dextromethorphan hydrobromide and quinidine sulfate for the treatment of pseudobulbar affect and neuropathic pain. IDrugs 2010;13:254–65. 8. Andersen G, Vestergaard K, Riis JO. Citalopram for post-stroke pathological crying. Lancet 1993;342:837–9.