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Memantine may affect pseudobulbar affect in patients with Alzheimer's disease

Published online by Cambridge University Press:  24 April 2013

Tatjana Prokšelj ,
Aleš Jerin  and
Aleš Kogoj
Tatjana Prokšelj
Affiliation:
General Hospital Novo mesto, Neuropsychiatric Department, Novo mesto, Slovenia
Aleš Jerin
Affiliation:
Institute of Clinical Chemistry and Biochemistry, University Medical Center Ljubljana, Slovenia
Aleš Kogoj*
Affiliation:
University Psychiatric Hospital Ljubljana, Gerontopsychiatric Department, Ljubljana, Slovenia
*
Aleš Kogoj, University Psychiatric Hospital Ljubljana, Gerontopsychiatric Department, Studenec 48, 1260 Ljubljana, Slovenia. Tel: +386 1 5872 506; +386 1 5872 487; Fax: +386 1 5872 590; E-mail: ales.kogoj@psih-klinika.si
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Abstract

Objective

Behavioural symptoms are common in moderate to severe Alzheimer's disease (AD) and are improved by memantine with the most pronounced effect on agitation/aggression. Dextromethorphan in combination with quinidine is the only drug approved by US Food and Drug Administration for the treatment of pseudobulbar affect (PBA) on the basis of efficacy in patients with multiple sclerosis or amyotrophic lateral sclerosis. The aim of our study was to evaluate the efficacy of memantine on PBA in patients with AD.

Methods

In a prospective, double-blind, case-control study to assess PBA with pathological laughter and crying scale patients were administered memantine (final dose of 20 mg daily) or citalopram (20 mg once daily), each for 10 weeks. The number of episodes of involuntary emotional expression, Neuropsychiatric Inventory (NPI) and Overt Aggression Scale-Modified (OAS-M) total scores were also recorded. Furthermore, the platelet serotonin (5-HT) concentration was measured.

Results

Although memantine had beneficial effects on PBA, it also had a crucial impact on behavioural symptoms, especially aggression and agitation (to an average of 3.5 times higher end-point scores on OAS-M and increase of NPI total scores for an average of 114% of initial value). Therefore, the study was prematurely stopped. In addition, we had evidenced a drop of platelet 5-HT concentration (to an average of 73% of initial value).

Conclusion

Surprisingly, our research showed the opposite action of memantine on neuropsychiatric symptoms as expected. In a limited number of AD patients with PBA, memantine had a beneficial effect on involuntary emotional expression, but it potentiated agitation/aggression, irritability and caused a crucial drop of the platelet 5-HT concentration.

Keywords

affective symptomsaggressionemotional disturbancesmemantineserotonin
Type
Original Articles
Information
Acta Neuropsychiatrica , Volume 25 , Issue 6 , December 2013 , pp. 361 - 366
Copyright
Copyright © Scandinavian College of Neuropsychopharmacology 2013 

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References

1.Cummings, JL, Cole, G. Alzheimer disease. JAMA 2002;287:2335–2338.CrossRefGoogle ScholarPubMed
2.Mega, MS, Cummings, JL, Fiorello, T, Gornbein, J. The spectrum of behavioral changes in Alzheimer's disease. Neurology 1996;46:130–135.CrossRefGoogle ScholarPubMed
3.Cummings, JL, Arciniegas, DB, Brooks, BRet al. Defining and diagnosing involuntary emotional expression disorder. CNS Spectr 2006;11:1–7.CrossRefGoogle ScholarPubMed
4.Lieberman, A, Benson, F. Control of emotional expression in pseudobulbar palsy. Arch Neurol 1977;34:717–719.CrossRefGoogle ScholarPubMed
5.Tanaka, M, Sumitsuji, N. Electromyographic study of facial expression during pathological laughing and crying. Electromyogr Clin Neurophysiol 1991;31:399–406.Google ScholarPubMed
6.Starkstein, SE, Migliorelli, R, Tesón, Aet al. Prevalence and clinical correlates of pathological affective display in Alzheimer's disease. J Neurol Neurosurg Psychiatry 1995;59:55–60.CrossRefGoogle ScholarPubMed
7.Selkoe, DJ. The molecular pathology of Alzheimer's disease. Neuron 1991;6:487–498.CrossRefGoogle ScholarPubMed
8.Lanctôt, KL, Herrmann, N, Mazzotta, P. Role of serotonin in the behavioral and psychological symptoms of dementia. J Neuropsychiatry Clin Neurosci 2001;13:5–21.CrossRefGoogle ScholarPubMed
9.Camacho, A, Dimsdale, JE. Platelets and psychiatry: lessons learned from old and new studies. Psychosom Med 2000;62:326–336.CrossRefGoogle ScholarPubMed
10.Meszaros, Z, Borsiczky, D, Mate, Met al. Platelet MAO-B activity and serotonin content in patients with dementia: effect of age, medication and disease. Neurochem Res 1998;23:863–868.CrossRefGoogle ScholarPubMed
11.Kumar, AM, Sevush, S, Kumar, M, Ruiz, J, Eisdorfer, C. Peripheral serotonin in Alzheimer's disease. Neuropsychobiology 1995;32:9–12.CrossRefGoogle ScholarPubMed
12.Mimica, N, Muck-Seler, D, Pivac, N, Mustapic, M, Folnegovic-Smalc, V. Platelet serotonin and monoamine oxidase activity in patients with early-onset and late-onset of Alzheimer's disease. Period Biol 2005;107:211–215.Google Scholar
13.Mimica, N, Muck-Šeler, D, Pivac, Net al. Platelet serotonin and monoamine oxidase in Alzheimer's disease with psychotic features. Coll Antropol 2008;32:119–122.Google ScholarPubMed
14.Siddique, H, Hynan, LS, Weiner, MF. Effect of a serotonin reuptake inhibitor on irritability, apathy and psychotic symptoms in patients with Alzheimer's disease. J Clin Psychiatry 2009;70:915–918.CrossRefGoogle ScholarPubMed
15.Andersen, G, Vestergaard, K, Riis, JO. Citalopram for post-stroke pathological crying. Lancet 1993;342:837–839.CrossRefGoogle ScholarPubMed
16.Parsons, CG, Danysz, W, Quack, G. Memantine is clinically well tolerated N-methyl-D-aspartate (NMDA) receptor antagonist – a review of preclinical data. Neuropharmacology 1999;38:735–767.CrossRefGoogle ScholarPubMed
17.Van Dyke, CH, Tariot, PN, Meyers, B, Malca Resnick, E. A 24-week randomized controlled trial of memantine in patients with moderate-to-severe Alzheimer disease. Alzheimer Dis Assoc Disord 2007;21:136–143.CrossRefGoogle Scholar
18.Gauthier, S, Loft, H, Cummings, J. Improvement in behavioral symptoms in patients with moderate to severe Alzheimer's disease by memantine: a pooled data analysis. Int J Geriatr Psychiatry 2008;23:537–545.CrossRefGoogle ScholarPubMed
19.Brooks, BR, Thirsted, RA, Appel, SHet al. Treatment of pseudobulbar affect in ALS with dextromethorphan/quinidine: a randomized trial. Neurology 2004;63:1364–1370.CrossRefGoogle ScholarPubMed
20.Panitch, HS, Thisted, RA, Smith, RAet al. Randomized, controlled trial of dextromethorphan/quinidine for pseudobulbar affect in multiple sclerosis. Ann Neurol 2006;59:780–787.CrossRefGoogle ScholarPubMed
21.Torella, FC, Pellicano, M, Bowery, NG. Dextromethorphan and neuromodulation: old drug coughs up new activities. Trends Pharmacol Sci 1989;10:501–507.CrossRefGoogle Scholar
22.Rogawski, MA. Low affinity channel blocking (uncompetitive) NMDA receptor antagonists as therapeutic agents toward an understanding of their favorable tolerability. Amino Acids 2000;19:133–149.CrossRefGoogle ScholarPubMed
23.American Psychiatric Association. Diagnostic and statistical manual of mental disorders, 4th edition. Washington, DC: American Psychiatric Association, 2000.Google Scholar
24.Mckhann, G, Drachman, D, Folstein, M, Katzman, R, Price, D, Stadlan, EM. Clinical diagnosis of Alzheimer's disease: report of the NINCDS-ADRDA work group under the auspices of Department of Health & Human Services Task Force on Alzheimer's disease. Neurology 1984;34:939–944.CrossRefGoogle ScholarPubMed
25.Robinson, RG, Parikh, RM, Lipsley, JR, Starkstein, SE, Price, TR. Pathological laughing and crying following stroke: validation of a measurement scale and a double-blind treatment study. Am J Psychiatry 1993;150:286–293.Google Scholar
26.Cummings, JL, Mega, M, Gray, K, Rosenberg-Tompson, S, Carusi, DA, Gornbein, J. The Neuropsychiatric Inventory: comprehensive assessment of psychopathology in dementia. Neurology 1994;44:2308–2314.CrossRefGoogle ScholarPubMed
27.Coccaro, EF, Harvey, PD, Kupsaw-Lawrence, E, Herbert, JL, Bernstein, DP. Development of Neuropharmacologically based behavioral assessments of impulsive aggressive behaviour. J Neuropsych Clin Neurosci 1991;3:S44–S51.Google Scholar
28.Rakusa, M, Granda, G, Kogoj, A, Mlakar, J, Vodusek, DB. Mini-mental state examination: standardization and validation for the elderly Slovenian population. Eur J Neurol 2006;13:141–145.CrossRefGoogle ScholarPubMed
29.Rammes, G, Rupprecht, R, Ferrari, U, Zieglgänsberger, W, Parsons, CG. The N-methyl-D-aspartate receptor channel blockers memantine, MRZ 2/579 and other amino-alkyl-cyclohexanes antagonize 5-HT(3) receptor currents in cultured HEK-293 and N1E-115 cell systems in a non-competitive manner. Neurosci Lett 2001;306:81–84.CrossRefGoogle Scholar
30.Onogi, H, Ishigaki, S, Nakagawasai, Oet al. Influence of memantine on brain monoaminergic neurotransmission parameters in mice: neurochemical and behavioral study. Biol Pharm Bull 2009;32:850–855.CrossRefGoogle ScholarPubMed
31.Muhonen, LH, Lönnqvist, J, Juva, K, Alho, H. Double-blind, randomized comparison of memantine and escitalopram for the treatment of major depressive disorder comorbid with alcohol dependence. J Clin Psychiatry 2008;69:392–399.CrossRefGoogle ScholarPubMed
32.Bermack, JE, Debonnel, G. The role of sigma receptors in depression. J Pharmacol Sci 2005;97:317–336.CrossRefGoogle ScholarPubMed
33.Stahl, SM. Stahl's essential psychopharmacology: neuroscientific basis and practical applications. New York: Cambridge University Press, 2008.Google Scholar
34.Narita, N, Hashimoto, K, Tomitaka, S, Minabe, Y. Interactions of selective serotonin reuptake inhibitors with subtypes of sigma receptors in rat brain. Eur J Pharmacol 1996;307:117–119.CrossRefGoogle ScholarPubMed
35.Van Watum, PJ. Rapid response to low dose citalopram in pathological crying. Gen Hosp Psychiatry 2001;23:166–170.CrossRefGoogle Scholar
36.King, RR, Reiss, JP. Treatment of pseudobulbar affect with citalopram in a patient with progressive multifocal leukoencephalopathy. J Clin Neurosci 2012;19:185–186.CrossRefGoogle Scholar