Objective: To review the efficacy and safety of psychostimulants for negative behavioral symptoms (ie, apathy, excessive daytime sedation) and cognition in patients with dementia.
Data sources: Literature was accessed through PubMed and MEDLINE (1966-June 2010), using the terms stimulant, psychostimulant, methylphenidate, dexmethylphenidate, amphetamine, dextroamphetamine, lisdexamfetamine, atomoxetine, modafinil, armodafinil, dementia, Alzheimer disease, vascular dementia, Lewy body dementia, mixed dementia, frontotemporal dementia, therapy, treatment, and therapeutic. Additional references identified from the initial search were reviewed.
Study selection and data extraction: All relevant clinical trials published in English and involving primarily older adults with dementia were included. Case reports, review articles, and other preclinical literature were included as appropriate.
Data synthesis: Psychostimulants have been employed as a treatment for cognitive and behavioral symptoms in dementia for decades, but the literature has lagged behind this practice. Eight reports on use of psychostimulants as a treatment of apathy in dementia were reviewed. Methylphenidate was the most frequently studied medication and improvements in apathy were consistently noted; however, the magnitude and duration of effect remain unclear. Six studies examining the cognitive effects of a variety of psychostimulants in patients with dementia were reviewed; psychostimulants had little to no effect on cognition. A lack of studies exists to draw conclusions about the use of psychostimulants for the treatment of excessive daytime sedation in dementia. The possibility of psychostimulants to increase blood pressure; elevate heart rate; and lead to irritability, agitation, and psychosis makes careful patient selection critical, especially in older adults with severe cardiovascular disease or other underlying cardiac abnormalities.
Conclusions: Based on limited studies, methylphenidate is a possible treatment for apathy in patients with dementia. Psychostimulants, as a group, do not appear to be broadly effective treatments for behavioral or cognitive symptoms of dementia. The potential utility of psychostimulants must be balanced with careful patient selection.