Efficacy of donepezil in reducing a range of BPSD, e.g., agitation, apathy, anxiety, delusions, depression, disinhibition and irritability has been reported in RCTs over 4–24 weeks.[88, 89, 90] Additional evidence suggests that donepezil use is associated with a reduced need for psychotropic medications (e.g., antidepressants) in patients with AD.[91] Acetylcholinesterase inhibitors should be considered for the treatment of BPSD before neuroleptic treatment is instituted in AD patients with low levels of irritability and agitation.[92]. This evidence concerns the gene ACHE and major depressive disorder.