Abstract
Objectives
Neuropsychiatric symptoms (NPS) are a core and troubling feature among patients with
Alzheimer disease (AD). Because of growing safety warnings against antipsychotics,
the use of antidepressants (ATD) in AD has increased extensively. We investigated
the potential long-term associations between ATD exposure and functional and cognitive
progression in patients with mild to moderate AD.
Design
Two-year prospective multicenter cohort ICTUS (Impact of Cholinergic Treatment USe)
study with biannual assessments.
Setting
Twenty-nine memory clinics from 12 European countries.
Participants
Community-dwelling patients with mild to moderate AD.
Methods
Global cognitive function was measured using the Mini Mental State Examination (MMSE)
and the Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog). Functional
impairment was measured using the Activities of Daily Living (ADL). Assessments were
performed biannually for 2 years. Antidepressant exposure was defined by an ATD prescription
for a minimum period of 6 months. Linear mixed models were used to study the associations
between ATD exposure and cognitive and functional progression.
Results
Antidepressant exposure was not associated with cognitive decline [MMSE: β-coefficients
of the linear mixed models (Coef) = 0.06, 95% confidence interval (CI) −0.65 to 0.76,
P = .87; ADAS-Cog: Coef = −13.9, 95% CI −34.80 to 7.03, P = .19] or with functional decline (ADL: Coef = −0.05, 95% CI −0.21 to 0.09, P = .48) at 2-year follow-up. Antipsychotic exposure at baseline was associated with
a greater functional decline in the ADL score (Coef = −0.39, 95% CI − 0.68 to 0.10,
P < .01).
Conclusions and Implications
Antidepressant exposure was not associated with a faster rate of cognitive or functional
decline in patients with mild to moderate AD. Antidepressants might be appropriate
alternatives to antipsychotics in the management of NPS in mild to moderate AD.
Keywords
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Article info
Publication history
Published online: July 28, 2020
Footnotes
ICTUS/DSA (Impact of Cholinergic Treatment Use/Data Sharing Alzheimer cohort) Study Group refers to the following: ICTUS Study Group: Vellas B., Reynish E., Ousset PJ., Andrieu S. (Toulouse), Burns A. (Manchester), Pasquier F. (Lille), Frisoni G.(Brescia), Salmon E. (Liège), Michel J.P., Zekry D.S. (Geneva), Boada M. (Barcelona), Dartigues J.F. (Bordeaux), Olde-Rikkert M.G.M. (Nijmejen), Rigaud A.S. (Paris), Winblad B. (Huddinge), Malick A., Sinclair A. (Warwick), Frölich L. (Mannheim), Scheltens P. (Amsterdam), Ribera C.(Madrid), Touchon J. (Montpellier), Robert P. (Nice), Salva A. (Barcelona), Waldmar G. (Copenhagen), Bullock R. (Swindon), Costa-Tsolaki M. (Thesaloniki), Rodriguez G. (Genoa), Spiru L. (Bucharest), Jones R.W. (Bath), Stiens G., Stoppe G. (Goettingen), Eriksdotter Jönhagen M. (Stockholm), Cherubini A. (Perugia), Lage P.M., Gomez-Isla T. (Pamplona), Camus V. (Tours), Agüera-Morales E., Lopez F. (Cordoba).
DSA Group: Andrieu S., Cantet C., Coley N.
The authors declare no conflicts of interest.
The ICTUS study was supported by the European Commission within the 5th framework programme (grant: QLK6-CT-2002–02645) and by unrestricted equal grants from each of Eisai, Janssen, Lundbeck, and Novartis Pharmaceuticals Corporation. The pharmaceutical companies had no role in study design, data collection, data analysis, data interpretation. Promotion of the ICTUS study was supported by the University Hospital Center of Toulouse. The data sharing activity was supported by the “Association Monegasque pour la recherche sur la maladie d’Alzheimer” (AMPA) and the UMR 1027 Unit INSERM – University of Toulouse III.
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