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

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

Research output: Contribution to journalArticlepeer-review

12 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)32-42
Number of pages11
JournalAmerican Journal of Geriatric Psychiatry
Issue number1
StatePublished - Jan 2022

ASJC Scopus subject areas

  • Geriatrics and Gerontology
  • Psychiatry and Mental health


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