TY - JOUR
T1 - Low Dose Lithium Treatment of Behavioral Complications in Alzheimer's Disease
T2 - Lit-AD Randomized Clinical Trial
AU - Devanand, D. P.
AU - Crocco, Elizabeth
AU - Forester, Brent P.
AU - Husain, Mustafa M.
AU - Lee, Seonjoo
AU - Vahia, Ipsit V.
AU - Andrews, Howard
AU - Simon-Pearson, Laura
AU - Imran, Nadia
AU - Luca, Luminita
AU - Huey, Edward D.
AU - Deliyannides, Deborah A.
AU - Pelton, Gregory H.
N1 - Funding Information:
Dr. Devanand reports receipt of grants to his institution from the National Institute on Aging and the Alzheimer's Association; paid consultancy for Acadia, Biogen, BXCel, Eisai, Genentech, Sunovion, and Green Valley. Dr. Crocco reports receipt of grants to her institution from the National Institute on Aging, Novartis, Avanir, and Neurim. Dr. Forester reports receipt of grants to his institution from the National Institute on Aging, Rogers Family Foundation, Eisai, and Eli Lilly; paid consultancy for Biogen. Dr. Husain reports receipt of grants to his institution from the National Institute of Mental Health, National Institute on Drug Abuse, National Institute of Neurological Disorders and Stroke, National Institute on Aging, Stanley Medical Research Institute. Dr. Lee reports receipt of grants to her institution from the National Institute on Aging. Dr. Huey reports receipt of grants to his institution from the National Institute on Aging. Dr. Vahia reports receipt of grants to his institution from the National Institute on Aging, Once upon a time Foundation, NASA, and paid honorarium from the American Journal of Geriatric Psychiatry. Drs. Andrews, Deliyannides, Pelton, Luca, and Ms. Simon-Pearson and Ms. Imran report receipt of grants to the institution from the National Institute on Aging.
Funding Information:
The study was supported by grant R01AG047146 from the National Institute on Aging, NIH, Bethesda, MD, USA .
Publisher Copyright:
© 2021 American Association for Geriatric Psychiatry
PY - 2022/1
Y1 - 2022/1
N2 - Background: A case series suggested efficacy for lithium to treat agitation in dementia, but no placebo-controlled trials have been conducted. Objectives: To evaluate low-dose lithium treatment of agitation in Alzheimer's disease (AD). Method: In a four-site trial, patients with AD and agitation/aggression score ≥4 on the Neuropsychiatric Inventory (NPI) were randomized, double-blind, to lithium carbonate 150–600 mg daily or placebo for 12 weeks. Primary efficacy outcome was change in NPI agitation/aggression; secondary efficacy outcome was treatment response (30% reduction in NPI score for agitation/aggression plus psychosis and a Clinical Global Impression (CGI) score of much or very much improved). Safety profile of lithium was assessed. Results: Fifty-eight of 77 patients (75.3%) completed the trial. In linear mixed effects model analyses, lithium was not significantly superior to placebo for agitation/aggression. Proportion of responders was 31.6% on lithium and 17.9% on placebo (χ2=1.26, p = 0.26). Moderate or marked improvement (CGI) was greater on lithium (10/38=36.8%) than placebo (0/39=0%, Fisher's exact test p <0.001). In exploratory analyses, improvement on lithium was greater than placebo on NPI delusions and irritability/lability (p's<0.05). Lithium showed greater reduction than placebo in patients with high Young Mania Rating Scale scores (β=5.06; 95%CI,1.18 to 8.94, p = 0.01). Oral dose and serum levels demonstrated similar associations with efficacy outcomes. Lithium did not differ significantly from placebo on safety outcomes. Conclusions: Low-dose lithium was not efficacious in treating agitation but was associated with global clinical improvement and excellent safety. A larger trial may be warranted of likely lithium-responsive behavioral symptoms that overlap with mania.
AB - Background: A case series suggested efficacy for lithium to treat agitation in dementia, but no placebo-controlled trials have been conducted. Objectives: To evaluate low-dose lithium treatment of agitation in Alzheimer's disease (AD). Method: In a four-site trial, patients with AD and agitation/aggression score ≥4 on the Neuropsychiatric Inventory (NPI) were randomized, double-blind, to lithium carbonate 150–600 mg daily or placebo for 12 weeks. Primary efficacy outcome was change in NPI agitation/aggression; secondary efficacy outcome was treatment response (30% reduction in NPI score for agitation/aggression plus psychosis and a Clinical Global Impression (CGI) score of much or very much improved). Safety profile of lithium was assessed. Results: Fifty-eight of 77 patients (75.3%) completed the trial. In linear mixed effects model analyses, lithium was not significantly superior to placebo for agitation/aggression. Proportion of responders was 31.6% on lithium and 17.9% on placebo (χ2=1.26, p = 0.26). Moderate or marked improvement (CGI) was greater on lithium (10/38=36.8%) than placebo (0/39=0%, Fisher's exact test p <0.001). In exploratory analyses, improvement on lithium was greater than placebo on NPI delusions and irritability/lability (p's<0.05). Lithium showed greater reduction than placebo in patients with high Young Mania Rating Scale scores (β=5.06; 95%CI,1.18 to 8.94, p = 0.01). Oral dose and serum levels demonstrated similar associations with efficacy outcomes. Lithium did not differ significantly from placebo on safety outcomes. Conclusions: Low-dose lithium was not efficacious in treating agitation but was associated with global clinical improvement and excellent safety. A larger trial may be warranted of likely lithium-responsive behavioral symptoms that overlap with mania.
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U2 - 10.1016/j.jagp.2021.04.014
DO - 10.1016/j.jagp.2021.04.014
M3 - Article
C2 - 34059401
AN - SCOPUS:85107037879
SN - 1064-7481
VL - 30
SP - 32
EP - 42
JO - American Journal of Geriatric Psychiatry
JF - American Journal of Geriatric Psychiatry
IS - 1
ER -