Management of Apathy in Major Neurocognitive Disorders

Pharmacotherapy for apathy depends primarily upon the underlying etiology and disease background. In terms of treatment strategies for apathy in Alzheimer’s disease, Rea et al.’s [80] systematic review emphasized that four categories of drugs were used: cholinesterase inhibitors, monoaminergic agents (methylphenidate and modafinil), the selective serotonin reuptake inhibitor (SSRI) citalopram, and various other drugs (such as Ginkgo biloba extract Egb 761). Cholinesterase inhibitors have been evaluated in randomized controlled trials in which behavioral disturbances were secondary outcome measures. Some trials reported positive effects on behavior in Alzheimer’s disease [81,82], Lewy body dementia [83], and Alzheimer’s disease and mixed dementia [84], including a reduction in apathy in few trials [83, 84]. The randomized, controlled trial of methylphenidate for the treatment of apathy (the primary outcome) was positive [85]. Ginkgo biloba extract Egb 761 did not prove to be beneficial in cognitive disorders but reportedly improved apathy in a mixed population with various major neurocognitive disorders [86]. A trial of the SSRI citalopram was negative [87]. In a randomized, controlled study in patients with a variety of major neurocognitive disorders [88], memantine was found reduce apathy (evaluated as a secondary outcome). In terms of behavioral disturbances due to frontotemporal degeneration, the benefits reported with trazodone and with paroxetine in one trial did not include apathy. Rivastigmine [89] and memantine [90] failed to relieve apathy. Interestingly, a recent Phase II study suggests that oxytocin relieves apathy in frontotemporal dementia [91], and Phase III trials are now eagerly awaited. Lastly, the ongoing development of non-pharmacological approaches may improve the management of apathy in major neurocognitive disorders.

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