In addition, COMT inhibitors enable a decrease in both the dose and administration frequency of L-DOPA, reducing “off” time (i.e., decreasing periods of time when symptoms are more noticeable and movements are more difficult) and increasing “on” time (i.e., increasing periods when PD patients experience good symptom control), thereby improving and prolonging the clinical response to L-DOPA [149]. This evidence concerns the gene COMT and Parkinson disease.