COMT and sleep disorder: Based on robust evidence from randomized controlled clinical trials, a number of medications have been proved to be effective adjuncts to levodopa treatment in managing wearing-off, such as MAO-B inhibitors (e.g. rasagiline), DA (e.g. pramipexole, ropinirole), and catechol-O-methyltransferase (COMT) inhibitors (e.g. entacapone) etc. [29, 30, 33] The current state of managing EMO is also promising with increasingly numerous pharmacologic therapies aimed at improving nocturnal sleep disorders and alleviating early-morning motor dysfunction.