Mibampator (LY451395) randomized clinical trial for agitation/aggression in Alzheimer's disease

International Psychogeriatrics

Volumn 25, Issue 5, 2013, Pages 707-719

  Trzepacz, Paula T ^a   Cummings, Jeffrey ^b   Konechnik, Thomas ^a   Forrester, Tammy D ^a   Chang, Curtis ^a   Dennehy, Ellen B ^a   Willis, Brian A ^a   Shuler, Catherine ^a   Tabas, Linda B ^a   Lyketsos, Constantine ^c  

^a ELI LILLY AND COMPANY   (United States)

^b LERNER RESEARCH INSTITUTE   (United States)

^c JOHNS HOPKINS UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

aggression; agitation; Alzheimer's disease; AMPA; glutamate; mibampator; Neuropsychiatric Inventory; neuropsychiatric symptoms

Indexed keywords

CHOLINESTERASE INHIBITOR; CITALOPRAM; ESCITALOPRAM; FLUOXETINE; LORAZEPAM; MEMANTINE; MIBAMPATOR; PLACEBO; SERTRALINE;

AGED; AGGRESSION; AGITATION; ALZHEIMER DISEASE; ALZHEIMER DISEASE ASSESSMENT SCALE; ARTICLE; BACKACHE; BRAIN HEMORRHAGE; COHEN MANSFIELD AGITATION INVENTORY; CONTROLLED STUDY; CORNELL SCALE FOR DEPRESSION IN DEMENTIA; DEPRESSION; DIZZINESS; DOUBLE BLIND PROCEDURE; DRUG ABSORPTION; DRUG CLEARANCE; DRUG EFFICACY; DRUG TOLERABILITY; DRUG WITHDRAWAL; ELECTROCARDIOGRAPHY; FEMALE; FRONTAL SYSTEMS BEHAVIOR INVENTORY; HUMAN; LABORATORY TEST; MAJOR CLINICAL STUDY; MALE; MYALGIA; NAMED INVENTORIES, QUESTIONNAIRES AND RATING SCALES; NEUROPSYCHIATRIC INVENTORY; OUTCOME ASSESSMENT; OUTPATIENT; PANCREAS PSEUDOCYST; PATIENT MONITORING; PNEUMONIA; PSYCHOSIS; RANDOMIZED CONTROLLED TRIAL; STEADY STATE; THORAX PAIN; TRANSIENT ISCHEMIC ATTACK; VITAL SIGN;

AGED; AGED, 80 AND OVER; AGGRESSION; ALZHEIMER DISEASE; BIPHENYL COMPOUNDS; DOUBLE-BLIND METHOD; FEMALE; HUMANS; MALE; MIDDLE AGED; NEUROPSYCHOLOGICAL TESTS; OUTPATIENTS; PSYCHOMOTOR AGITATION; QUESTIONNAIRES; SULFONAMIDES; TREATMENT OUTCOME;

EID: 84875475732     PISSN: 10416102     EISSN: 1741203X     Source Type: Journal    
DOI: 10.1017/S1041610212002141     Document Type: Article

References (52)

1. Aalten, P. et al. (2007). Neuropsychiatric syndromes in dementia. Results from the European Alzheimer Disease Consortium: part I. Dementia and Geriatric Cognitive Disorders, 24, 457-463. doi:10.1159/000110738.
2. Alexopoulos, G. S., Abrams, R. C., Young, R. C. and Shamoian, C. A. (1988). Cornell Scale for Depression in Dementia. Biological Psychiatry, 23, 271-284.
3. Ballard, C., Corbett, A., Chitramohan, R. and Aarsland, D. (2009). Management of agitation and aggression associated with Alzheimer's disease: controversies and possible solutions. Current Opinion in Psychiatry, 22, 532-540. doi:10.1097/YCO.0b013e32833111f9.
4. Blanchard, B. J., Chen, A., Rozeboom, L. M., Stafford, K. A., Weigele, P. and Ingram, V. M. (2004). Efficient reversal of Alzheimer's disease fibril formation and elimination of neurotoxicity by a small molecule. Proceedings of the National Academy of Sciences USA, 101, 14326-14332. doi:10.1073/pnas. 0405941101.
5. Chappell, A. S., Gonzales, C., Williams, J., Witte, M. M., Mohs, R. C. and Sperling, R. (2007). AMPA potentiator treatment of cognitive deficits in Alzheimer disease. Neurology, 68, 1008-1012. doi:10.1212/ 01.wnl.0000260240. 46070.7c.
6. Cohen-Mansfield, J., Werner, P., Watson, V. and Pasis, S. (1995). Agitation among elderly persons at adult day-care centers: the experiences of relatives and staff members. International Psychogeriatrics, 7, 447-458.
7. Cummings, J. L., Mega, M., Gray, K., Rosenberg-Thompson, S., Carusi, D. A. and Gornbein, J. (1994). The Neuropsychiatric Inventory: comprehensive assessment of psychopathology in dementia. Neurology, 44, 2308-2314.
8. Davis, J. D. and Tremont, G. (2007). Impact of frontal systems behavioral functioning in dementia on caregiver burden. The Journal of Neuropsychiatry and Clinical Neurosciences, 19, 43-49. doi:10.1176/appi.neuropsych. 19.1.43.
9. Dennehy, E. B., Kahle-Wrobleski, K., Sarsour, K. and Milton, D. R. (2012). Derivation of a brief measure of agitation and aggression in Alzheimer's disease. International Journal of Geriatric Psychiatry. doi:10.1002/ gps.3807.
10. Doody, R. S. et al. (2001). Practice parameter: management of dementia (an evidence-based review). Report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology, 56, 1154-1166.
11. Folstein, M. F., Folstein, S. E. andMcHugh, P. R. (1975). "Mini-mental state." A practical method for grading the cognitive state of patients for the clinician. Journal of Psychiatric Research, 12, 189-198.
12. Fox, C. et al. (2012). Efficacy of memantine for agitation in Alzheimer's dementia: a randomised double-blind placebo-controlled trial. PLoS One, 7: e35185 (Epub May 2). doi:10.1371%2Fjournal.pone.0035185.
13. Galasko, D., Kershaw, P. R., Schneider, L., Zhu, Y. and Tariot, P. N. (2004). Galantamine maintains ability to perform activities of daily living in patients with Alzheimer's disease. Journal of American Geriatrics Society, 52, 1070-1076. doi:10.1111/j.1532-5415.2004.52303.x.
14. Gates, M., Ogden, A. and Bleakman, D. (2001). Pharmacological effects of AMPA receptor potentiators LY392098 and LY404187 on rat neuronal AMPA receptors in vitro. Neuropharmacology, 40, 984-991. doi:10.1016/S0028-3908(01)00040-5.
15. Gilley, D. W., Bienias, J. L., Wilson, R. S., Bennett, D. A., Beck, T. L. and Evans, D. A. (2004). Influence of behavioral symptoms on rates of institutionalization for persons with Alzheimer's disease. Psychological Medicine, 34, 1129-1135. doi:10.1017/S0033291703001831.
16. Grace, J. and Malloy, P. F. (2001). Frontal Systems Behavior Scale (FrSBe): Professional Manual. Lutz, FL: Psychological Assessment Resources.
17. Guy, W. (1976). ECDEU Assessment Manual for Psychopharmacology, revised. Bethesda, MD: US Department of Health, Education, and Welfare.
18. Herrmann, N. and Lanctôt, K. L. (2007). Pharmacologic management of neuropsychiatric symptoms of Alzheimer's disease. Canadian Journal of Psychiatry, 52, 630-646.
19. Herrmann, N., Lanctôt, K. L. and Khan, L. R. (2004). The role of norepinephrine in the behavioral and psychological symptoms of dementia. Journal of Neuropsychiatry and Clinical Neurosciences, 16, 261-276. doi:10.1176/appi.neuropsych.16.3.261.
20. Hirono, N., Mega, M. S., Dinov, I. D., Mishkin, F. and Cummings, J. L. (2000). Left frontotemporal hypoperfusion is associated with aggression in patients with dementia. Archives of Neurology, 57, 861-866. doi:10-1001/pubs. Arch Neurol.-ISSN-0003-9942-57-6-noc90037.
21. Holmes, C. et al. (2001). Psychosis and aggression in Alzheimer's disease: the effect of dopamine receptor gene variation. Journal of Neurology, Neurosurgery, and Psychiatry, 71, 777-779. doi:10.1136/jnnp.71.6.777.
22. Jeste, D. V. et al. (2008). ACNP White Paper: update on use of antipsychotic drugs in elderly persons with dementia. Neuropsychopharmacology, 33, 957-970. doi:10.1038/ sj.npp.1301492.
23. Jhee, S. S. et al. (2006). Multiple-dose plasma pharmacokinetic and safety study of LY450108 and LY451395 (AMPA receptor potentiators) and their concentration in cerebrospinal fluid in healthy human subjects. Journal of Clinical Pharmacology, 46, 424-432. doi:10.1177/0091270006286899.
24. Lopez, O. L., Kaufer, D., Reiter, C. T., Carra, J., DeKosky, S. T. and Palmer, A. M. (1996). Relationship between CSF neurotransmitter metabolites and aggressive behavior in Alzheimer's disease. European Journal of Neurology, 3, 153-155.
25. Lyketsos, C. G. et al. (2011). Neuropsychiatric symptoms in Alzheimer's disease. Alzheimers & Dementia, 7, 532-539. doi:10.1016/j.jalz.2011.05.2410.
26. Lynch, G. (2004). AMPA receptor modulators as cognitive enhancers. Current Opinion in Pharmacology, 4, 4-11. doi:10.1016/j.coph.2003.09.009.
27. Mackowiak, M., O'Neill, M. J., Hicks, C. A., Bleakman, D. and Skolnick, P. (2002). An AMPA receptor potentiator modulates hippocampal expression of BDNF: an in vivo study. Neuropharmacology, 43, 1-10. doi:10.1016/S0028-3908(02) 00066-7.
28. Madsen, U., Ebert, B. and Krogsgaard-Larsen, P. (1994). Modulation of AMPA receptor function in relation to glutamatergic abnormalities in Alzheimer's disease. Biomedicine & Pharmacotherapy, 48, 305-311.
29. Malloy, P., Tremont, G., Grace, J. and Frakey, L. (2007). The Frontal Systems Behavior Scale discriminates frontotemporal dementia from Alzheimer's disease. Alzheimers & Dementia, 3, 200-203. doi:10.1016/ j.jalz.2007.04.374.
30. Murman, D. L., Chen, Q., Powell, M. C., Kuo, S. B., Bradley, C. J. and Colenda, C. C. (2002). The incremental direct costs associated with behavioral symptoms in AD. Neurology, 59, 1721-1729.
31. O'Neill, M. J. (2004). SMi 4th Annual Conference on Neurodegenerative Disorders: a focus on Alzheimer's and Parkinson's disease. Expert Opinion on Investigational Drugs, 13, 1369-1373. http://informahealthcare.com/doi/pdf/10. 1517/13543784.13.10.1369.
32. Reinikainen, K. J., Soininen, H. and Riekkinen, P. J. (1990). Neurotransmitter changes in Alzheimer's disease: implications to diagnostics and therapy. Journal of Neuroscience Research, 27, 576-586. doi:10.1002/ jnr.490270419.
33. Robinson, A., Spencer, B. and White, L. (2007). Understanding Difficult Behaviors: Practical Suggestions for Coping with Alzheimer's Disease and Related Illnesses. Eastern Michigan University Alzheimer's Education Program Ypsilanti, MI: Eastern Michigan University. Available at: http://www.amazon.com/ Understanding-Difficult-Behaviors-suggestionsAlzheimers/dp/0978902009.
34. Rosen, W. G., Mohs, R. C. and Davis, K. L. (1984). A new rating scale for Alzheimer's disease. American Journal of Psychiatry, 141, 1356-1364.
35. Rosenheck, R. A. et al. (2007). Cost-benefit analysis of second-generation antipsychotics and placebo in a randomized trial of the treatment of psychosis and aggression in Alzheimer's disease. Archives of General Psychiatry, 64, 1259-1268. doi: 10.1001/archpsyc.64.11.1259.
36. Shin, I. S., Carter, M.,Masterman,D., Fairbanks, L. and Cummings, J. L. (2005). Neuropsychiatric symptoms and quality of life in Alzheimer's disease. American Journal of Geriatric Psychiatry, 13, 469-474. doi:10.1176/appi.ajgp.13. 6.469.
37. doi:10.1176/appi.ajgp.13.6.469. Sperling, R. A., Jack, C. R. Jr. and Aisen, P. S. (2011). Testing the right target and right drug at the right stage. Science Translational Medicine, 3, 1-5. doi:10.1126/ scitranslmed.3002609.
38. Sukonick, D. L. et al. (2001). The 5-HTTPR*S/*L polymorphism and aggressive behavior in Alzheimer's disease. Archives of Neurology, 58, 1425-1428. doi:10-1001/pubs.Arch Neurol.-ISSN-0003-9942-58-9-noc00319.
39. Sultzer, D. L. et al. (2008). Clinical symptom responses to atypical antipsychotic medications in Alzheimer's disease: phase 1 outcomes from the CATIE-AD effectiveness trial. American Journal of Psychiatry, 165, 844-854. doi:10.1176/appi.ajp.2008.07111779.
40. Sweet, R. A. et al. (2001). The 5-HTTPR polymorphism confers liability to a combined phenotype of psychotic and aggressive behavior in Alzheimer's disease. International Psychogeriatrics, 13, 401-409. doi:10.1017/ S1041610201007827.
41. Tekin, S. (2001). Orbitofrontal and anterior cingulate cortex neurofibrillary tangle burden is associated with agitation in Alzheimer's disease. Annals of Neurology, 49, 355-361. doi:10.1002/ana.72.
42. Trinh, N. H., Hoblyn, J., Mohanty, S. and Yaffe, K. (2003). Efficacy of cholinesterase inhibitors in the treatment of neuropsychiatric symptoms and functional impairment in Alzheimer disease: a meta-analysis. Journal of the American Medical Association, 289, 210-216. doi:10.1001/jama.289.2.210.
43. Trzepacz, P. T., Mittal, D., Torres, R., Kanary, K., Norton, J. and Jimerson, N. (2001). Validation of the Delirium Rating Scale-revised-98: comparison with the delirium rating scale and the cognitive test for delirium. The Journal of Neuropsychiatry and Clinical Neurosciences, 13, 229-242. doi:10.1176/appi.neuropsych.13.2.229.
44. Vandergriff, J., Huff, K., Bond, A. and Lodge, D. (2001). Potentiation of responses to AMPA on central neurones by LY392098 and LY404187 in vivo. Neuropharmacology, 40, 1003-1009. doi:10.1016/S0028-3908(01)00031-4.
45. Walton, H. S. andDodd, P. R. (2007). Glutamateglutamine cycling in Alzheimer's disease. Neurochemistry International, 50, 1052-1066. doi:10.1016/j. neuint.2006.10.007.
46. Weiner, M. F. et al. (2000). Quantifying behavioral disturbance in Alzheimer's disease patients. Journal of Psychiatric Research, 34, 163-167. doi:10.1016/ S0022-3956(99)00042-4.
47. Wilcock, G. K., Ballard, C. G., Cooper, J. A. and Loft, H. (2008). Memantine for agitation/aggression and psychosis in moderately severe to severe Alzheimer's disease: a pooled analysis of 3 studies. Journal of Clinical Pharmacology, 69, 341-348.
48. Wood, S. et al. (2000). The use of the neuropsychiatric inventory in nursing home residents. Characterization and measurement. American Journal of Geriatric Psychiatry, 8, 75-83.
49. Woodward, M., Jacova, C., Black, S. E., Kertesz, A., Mackenzie, I. R., Feldman, H. and the ACCORD investigator group (2010). Differentiating the frontal variant of Alzheimer's disease. International Journal of Geriatric Psychiatry, 25, 732-738. doi:10.1002/gps.2415.
50. Wu, X. et al. (2004). AMPA protects cultured neurons against glutamate excitotoxicity through a phosphatidylinositol 3-kinase-dependent activation in extracellular signal-regulated kinase to upregulate BDNF gene expression. Journal of Neurochemistry, 90, 807-818. doi:10.1111/j.1471-4159.2004.02526.x.
51. Yamada, K. A. (2000). Therapeutic potential of positive AMPA receptor modulators in the treatment of neurological disease. Expert Opinion on Investigational Drugs, 9, 765-778. doi:10.1517/13543784.9.4.765.
52. Zhao, P., Ignacio, S., Beattie, E. C. and Abood, M. E. (2008). Altered presymptomatic AMPA and cannabinoid receptor trafficking in motor neurons of ALS model mice: implications for excitotoxicity. European Journal of Neuroscience, 27, 572-579. doi:10.1111/ j.1460-9568.2008.06041.x.