Nelotanserin
The Food and Drug Administration (FDA) has granted fast track designation to nelotanserin, a novel 5-HT2A inverse agonist, for the treatment of visual hallucinations disorder in DLB. One small, double-blind randomized study demonstrated no difference in behaviors associated with rapid eye movement sleep behavior disorder between patients (with either DLB or Parkinson disease dementia) taking nelotanserin compared with placebo.[71]Stefani A, Santamaria J, Iranzo A, et al. Nelotanserin as symptomatic treatment for rapid eye movement sleep behavior disorder: a double-blind randomized study using video analysis in patients with dementia with Lewy bodies or Parkinson's disease dementia. Sleep Med. 2021 May;81:180-7.
https://www.sciencedirect.com/science/article/pii/S1389945721001374?via%3Dihub
http://www.ncbi.nlm.nih.gov/pubmed/33714847?tool=bestpractice.com
Intepirdine
A selective 5-HT6 receptor antagonist that increases extracellular acetylcholine and glutamate. One randomized, placebo-controlled, phase 2b clinical trial reported that intepirdine did not lead to improvements compared with placebo in patients with DLB.[72]Lang FM, Kwon DY, Aarsland D, et al. An international, randomized, placebo-controlled, phase 2b clinical trial of intepirdine for dementia with Lewy bodies (HEADWAY-DLB). Alzheimers Dement (NY). 2021;7(1):e12171.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8215076
http://www.ncbi.nlm.nih.gov/pubmed/34189249?tool=bestpractice.com
Mevidalen
A selective positive allosteric modulator of the dopamine D1 receptor subtype. In one randomized, placebo-controlled phase 2 trial, mevidalen was associated with improvement in the motor symptoms of DLB while improving or not worsening nonmotor symptoms - including cognition - that are associated with classic dopaminergic therapy.[73]Biglan K, Munsie L, Svensson KA, et al. Safety and efficacy of mevidalen in Lewy body dementia: a phase 2, randomized, placebo-controlled trial. Mov Disord. 2022 Mar;37(3):513-24.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9300146
http://www.ncbi.nlm.nih.gov/pubmed/34859493?tool=bestpractice.com
Neflamapimod
An oral p38 alpha kinase inhibitor that has shown promising results in one phase 2 clinical trial investigating effects on cognitive function in patients with DLB.[74]ClinicalTrials.gov. Cognitive effects of oral p38 alpha kinase inhibitor neflamapimod in dementia with Lewy bodies (AscenD-LB). NCT04001517. 2 November 2021 [internet publication].
https://clinicaltrials.gov/ct2/show/NCT04001517
Dextromethorphan quinidine
This drug combination is FDA-approved for pseudobulbar affect and is being investigated for agitation in dementia.[75]Cummings JL, Lyketsos CG, Peskind ER, et al. Effect of dextromethorphan-quinidine on agitation in patients with Alzheimer disease dementia: a randomized clinical trial. JAMA. 2015 Sep 22-29;314(12):1242-54.
https://jamanetwork.com/journals/jama/fullarticle/2442936
http://www.ncbi.nlm.nih.gov/pubmed/26393847?tool=bestpractice.com
Cannabinoids
Under investigation for dementia-related agitation and aggression.[76]Magierski R, Sobow T, Schwertner E, et al. Pharmacotherapy of behavioral and psychological symptoms of dementia: state of the art and future progress. Front Pharmacol. 2020 Jul 31;11:1168.
https://www.frontiersin.org/articles/10.3389/fphar.2020.01168/full
http://www.ncbi.nlm.nih.gov/pubmed/32848775?tool=bestpractice.com
[77]ClinicalTrials.gov. The effect of cannabis on dementia related agitation and aggression. NCT03328676. 8 March 2022 [internet publication].
https://clinicaltrials.gov/ct2/show/NCT03328676