Pharmacological treatment of apathy in neurodegenerative diseases: a systematic review.

OBJECTIVE To evaluate the efficacy of pharmacological treatment of apathy in patients with neurodegenerative diseases. METHODS Systematic review of studies assessing the effects of pharmacological treatment on apathy in neurodegenerative diseases. RESULTS Thirty-five studies were included: 2 meta-analyses, 13 randomized controlled trials (RCTs), 14 open-label studies, 5 case series, and 1 single case study. Eight studies included apathy as a primary outcome. A cholinesterase inhibitor was investigated in 24 studies, methylphenidate in 5, and other medications in 6 studies. Most RCTs of cholinesterase inhibitors reported a small but statistically significant improvement of apathetic symptoms. CONCLUSIONS Although some medications are promising candidates for further study, there is as yet insufficient evidence that pharmacological treatment improves apathetic symptoms in patients with neurodegenerative disease. Large-scale, placebo-controlled RCTs with apathy as a primary outcome measure are needed to establish the potential benefit of pharmacological treatment of apathy.