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 - 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.
UR - http://www.scopus.com/inward/record.url?scp=85107037879&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85107037879&partnerID=8YFLogxK
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 -