Highlights
- •What is the primary question addressed by this study?The main goal was to evaluate the efficacy and side effects of low-dose lithium to treat agitation in Alzheimer's disease (AD).
- •What is the main finding of this study?In 77 patients with AD and agitation randomized to lithium or placebo in a four-site study, lithium was not significantly superior to placebo in treating agitation/aggression but demonstrated excellent safety. Compared to patients who received placebo, patients who received lithium showed greater improvement in Clinical Global Impression scores and greater improvement in patients with high Young Mania Rating Scale scores.
- •What is the meaning of the finding?Low-dose lithium was not efficacious in treating agitation in AD but was associated with global clinical improvement, reduction in behavioral symptoms that overlap with mania, and excellent safety.
ABSTRACT
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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Article info
Publication history
Published online: May 12, 2021
Accepted:
April 22,
2021
Received in revised form:
April 21,
2021
Received:
April 8,
2021
Footnotes
Trial registration: ClinicalTrials.gov Identifier NCT02129348
Identification
Copyright
© 2021 American Association for Geriatric Psychiatry. Published by Elsevier Inc. All rights reserved.
