Feasibility and tolerability of low-dose lithium for the treatment of agitation and abnormal motor behaviors in Frontotemporal Dementia

Agitation and abnormal motor behaviors are common, distressing symptoms of Frontotemporal Dementia (FTD). While these symptoms currently lack efficacious and safe pharmacological treatments, case reports in FTD and a clinical trial in Alzheimer's disease suggest that patients may benefit from lithium treatment. We designed a randomized, double-blind, placebo-controlled, 12-week clinical trial to evaluate low-dose lithium for the treatment of agitation and abnormal motor behaviors in FTD. However, the trial did not meet its recruitment target (n = 60). This report assesses the trial's feasibility and tolerability using recruitment, study completion, and safety metrics. Sixteen adults with FTD (median age 59.5 years; 69% female) were enrolled from 2017 to 2021. Fourteen participants (88%) completed the trial. The majority of participants on lithium were taking the maximum daily dose by Week 12 (600 mg), had median (interquartile range) final serum lithium levels of 0.42 (0.37-0.57), and reported minimal side effects, including drowsiness, diarrhea, constipation and insomnia. Preliminary data from intended efficacy outcomes showed no median pre-post changes between treatment groups. Low-dose lithium is feasible and well-tolerated in an FTD population. Further systematic study of lithium and its efficacy to treat agitation and abnormal motor behaviors in FTD is warranted.