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.