Low Dose Lithium Treatment of Behavioral Complications in Alzheimer's Disease: Lit-AD Randomized Clinical Trial.

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.

• Authors: D P Devanand, Elizabeth Crocco, Brent P Forester, Mustafa M Husain, Seonjoo Lee, Ipsit V Vahia, Howard Andrews, Laura Simon-Pearson, Nadia Imran, Luminita Luca, Edward D Huey, Deborah A Deliyannides, Gregory H Pelton
• Journal: The American journal of geriatric psychiatry : official journal of the American Association for Geriatric Psychiatry (Am J Geriatr Psychiatry) Vol. 30 Issue 1 Pg. 32-42 (01 2022) ISSN: 1545-7214 [Electronic] England
• PMID: 34059401 (Publication Type: Journal Article, Randomized Controlled Trial, Research Support, N.I.H., Extramural)
• Copyright: Copyright © 2021 American Association for Geriatric Psychiatry. Published by Elsevier Inc. All rights reserved.

Chemical References

• Lithium Compounds
• Lithium

Topics

• Alzheimer Disease (complications, diagnosis, drug therapy)
• Double-Blind Method
• Humans
• Lithium (therapeutic use)
• Lithium Compounds (adverse effects)
• Psychomotor Agitation (drug therapy, etiology, psychology)
• Treatment Outcome