Change in agitation in Alzheimer's disease in the placebo arm of a nine-week controlled trial

Paul B Rosenberg, Lea T. Drye, Anton P. Porsteinsson, Bruce G. Pollock, D. P. Devanand, Constantine Frangakis, Zahinoor Ismail, Christopher Marano, Curtis L Meinert, Jacobo E. Mintzer, Cynthia Munro, Gregory Pelton, Peter V Rabins, Lon S. Schneider, Dave Shade, Daniel Weintraub, Jeffery Newell, Jerome Yesavage, Constantine G Lyketsos

Research output: Contribution to journalArticle

Abstract

Background: Placebo responses raise significant challenges for the design of clinical trials. We report changes in agitation outcomes in the placebo arm of a recent trial of citalopram for agitation in Alzheimer's disease (CitAD). Methods: In the CitAD study, all participants and caregivers received a psychosocial intervention and 92 were assigned to placebo for nine weeks. Outcomes included Neurobehavioral Rating Scale agitation subscale (NBRS-A), modified AD Cooperative Study-Clinical Global Impression of Change (CGIC), Cohen-Mansfield Agitation Inventory (CMAI), the Neuropsychiatric Inventory (NPI) Agitation/Aggression domain (NPI A/A) and Total (NPI-Total) and ADLs. Continuous outcomes were analyzed with mixed-effects modeling and dichotomous outcomes with logistic regression. Results: Agitation outcomes improved over nine weeks: NBRS-A mean (SD) decreased from 7.8 (3.0) at baseline to 5.4 (3.2), CMAI from 28.7 (6.7) to 26.7 (7.4), NPI A/A from 8.0 (2.4) to 4.9 (3.8), and NPI-Total from 37.3 (17.7) to 28.4 (22.1). The proportion of CGI-C agitation responders ranged from 21 to 29% and was significantly different from zero. MMSE improved from 14.4 (6.9) to 15.7 (7.2) and ADLs similarly improved. Most of the improvement was observed by three weeks and was sustained through nine weeks. The major predictor of improvement in each agitation measure was a higher baseline score in that measure. Conclusions: We observed significant placebo response which may be due to regression to the mean, response to a psychosocial intervention, natural course of symptoms, or nonspecific benefits of participation in a trial.

Original languageEnglish (US)
Pages (from-to)2059-2067
Number of pages9
JournalInternational Psychogeriatrics
Volume27
Issue number12
DOIs
StatePublished - Dec 1 2015

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Alzheimer Disease
Placebos
Equipment and Supplies
Citalopram
Activities of Daily Living
Aggression
Caregivers
Logistic Models
Clinical Trials

Keywords

  • agitation
  • Alzheimer's disease
  • neuropsychiatric symptoms
  • randomized clinical trial

ASJC Scopus subject areas

  • Geriatrics and Gerontology
  • Psychiatry and Mental health
  • Gerontology
  • Clinical Psychology

Cite this

Change in agitation in Alzheimer's disease in the placebo arm of a nine-week controlled trial. / Rosenberg, Paul B; Drye, Lea T.; Porsteinsson, Anton P.; Pollock, Bruce G.; Devanand, D. P.; Frangakis, Constantine; Ismail, Zahinoor; Marano, Christopher; Meinert, Curtis L; Mintzer, Jacobo E.; Munro, Cynthia; Pelton, Gregory; Rabins, Peter V; Schneider, Lon S.; Shade, Dave; Weintraub, Daniel; Newell, Jeffery; Yesavage, Jerome; Lyketsos, Constantine G.

In: International Psychogeriatrics, Vol. 27, No. 12, 01.12.2015, p. 2059-2067.

Research output: Contribution to journalArticle

Rosenberg, PB, Drye, LT, Porsteinsson, AP, Pollock, BG, Devanand, DP, Frangakis, C, Ismail, Z, Marano, C, Meinert, CL, Mintzer, JE, Munro, C, Pelton, G, Rabins, PV, Schneider, LS, Shade, D, Weintraub, D, Newell, J, Yesavage, J & Lyketsos, CG 2015, 'Change in agitation in Alzheimer's disease in the placebo arm of a nine-week controlled trial', International Psychogeriatrics, vol. 27, no. 12, pp. 2059-2067. https://doi.org/10.1017/S1041610215001106
Rosenberg, Paul B ; Drye, Lea T. ; Porsteinsson, Anton P. ; Pollock, Bruce G. ; Devanand, D. P. ; Frangakis, Constantine ; Ismail, Zahinoor ; Marano, Christopher ; Meinert, Curtis L ; Mintzer, Jacobo E. ; Munro, Cynthia ; Pelton, Gregory ; Rabins, Peter V ; Schneider, Lon S. ; Shade, Dave ; Weintraub, Daniel ; Newell, Jeffery ; Yesavage, Jerome ; Lyketsos, Constantine G. / Change in agitation in Alzheimer's disease in the placebo arm of a nine-week controlled trial. In: International Psychogeriatrics. 2015 ; Vol. 27, No. 12. pp. 2059-2067.
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AU - Rosenberg, Paul B

AU - Drye, Lea T.

AU - Porsteinsson, Anton P.

AU - Pollock, Bruce G.

AU - Devanand, D. P.

AU - Frangakis, Constantine

AU - Ismail, Zahinoor

AU - Marano, Christopher

AU - Meinert, Curtis L

AU - Mintzer, Jacobo E.

AU - Munro, Cynthia

AU - Pelton, Gregory

AU - Rabins, Peter V

AU - Schneider, Lon S.

AU - Shade, Dave

AU - Weintraub, Daniel

AU - Newell, Jeffery

AU - Yesavage, Jerome

AU - Lyketsos, Constantine G

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N2 - Background: Placebo responses raise significant challenges for the design of clinical trials. We report changes in agitation outcomes in the placebo arm of a recent trial of citalopram for agitation in Alzheimer's disease (CitAD). Methods: In the CitAD study, all participants and caregivers received a psychosocial intervention and 92 were assigned to placebo for nine weeks. Outcomes included Neurobehavioral Rating Scale agitation subscale (NBRS-A), modified AD Cooperative Study-Clinical Global Impression of Change (CGIC), Cohen-Mansfield Agitation Inventory (CMAI), the Neuropsychiatric Inventory (NPI) Agitation/Aggression domain (NPI A/A) and Total (NPI-Total) and ADLs. Continuous outcomes were analyzed with mixed-effects modeling and dichotomous outcomes with logistic regression. Results: Agitation outcomes improved over nine weeks: NBRS-A mean (SD) decreased from 7.8 (3.0) at baseline to 5.4 (3.2), CMAI from 28.7 (6.7) to 26.7 (7.4), NPI A/A from 8.0 (2.4) to 4.9 (3.8), and NPI-Total from 37.3 (17.7) to 28.4 (22.1). The proportion of CGI-C agitation responders ranged from 21 to 29% and was significantly different from zero. MMSE improved from 14.4 (6.9) to 15.7 (7.2) and ADLs similarly improved. Most of the improvement was observed by three weeks and was sustained through nine weeks. The major predictor of improvement in each agitation measure was a higher baseline score in that measure. Conclusions: We observed significant placebo response which may be due to regression to the mean, response to a psychosocial intervention, natural course of symptoms, or nonspecific benefits of participation in a trial.

AB - Background: Placebo responses raise significant challenges for the design of clinical trials. We report changes in agitation outcomes in the placebo arm of a recent trial of citalopram for agitation in Alzheimer's disease (CitAD). Methods: In the CitAD study, all participants and caregivers received a psychosocial intervention and 92 were assigned to placebo for nine weeks. Outcomes included Neurobehavioral Rating Scale agitation subscale (NBRS-A), modified AD Cooperative Study-Clinical Global Impression of Change (CGIC), Cohen-Mansfield Agitation Inventory (CMAI), the Neuropsychiatric Inventory (NPI) Agitation/Aggression domain (NPI A/A) and Total (NPI-Total) and ADLs. Continuous outcomes were analyzed with mixed-effects modeling and dichotomous outcomes with logistic regression. Results: Agitation outcomes improved over nine weeks: NBRS-A mean (SD) decreased from 7.8 (3.0) at baseline to 5.4 (3.2), CMAI from 28.7 (6.7) to 26.7 (7.4), NPI A/A from 8.0 (2.4) to 4.9 (3.8), and NPI-Total from 37.3 (17.7) to 28.4 (22.1). The proportion of CGI-C agitation responders ranged from 21 to 29% and was significantly different from zero. MMSE improved from 14.4 (6.9) to 15.7 (7.2) and ADLs similarly improved. Most of the improvement was observed by three weeks and was sustained through nine weeks. The major predictor of improvement in each agitation measure was a higher baseline score in that measure. Conclusions: We observed significant placebo response which may be due to regression to the mean, response to a psychosocial intervention, natural course of symptoms, or nonspecific benefits of participation in a trial.

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