Amantadine improves gait in PD patients with STN stimulation

In advanced Parkinson's disease (PD), axial symptoms such as speech, gait, and balance impairment often become levodopa-unresponsive and they are difficult to manage, even in patients with subthalamic nucleus deep brain stimulation (STN-DBS). We anecdotally observed that oral administration of amantadine was very effective in treating both residual and stimulation-induced axial symptoms after bilateral STN-DBS in one PD patient. Therefore, we conducted a prospective multicenter observational study to evaluate the effects of amantadine on speech, gait and balance in PD patients with STN-DBS and incomplete axial benefit. Primary outcomes were changes in speech (UPDRS III, item 18), gait (item 29) and postural stability (item 30) with amantadine treatment compared to baseline. Secondary outcome was the patients' subjective scoring of axial symptoms with amantadine compared to baseline. Forty-six PD patients with STN-DBS were enrolled in the study and followed for 10.35 ± 8.21 months (median: 9.00; range: 1-31). The mean daily dose of amantadine was 273.44 ± 47.49 mg. Gait scores significantly improved (from 1.51 ± 0.89 to 1.11 ± 0.92, P = 0.015) with amantadine treatment, whereas postural stability and speech scores were similar before and after treatment. Thirty-five (76.1%) patients reported subjective improvement in speech, gait or balance with amantadine, whereas thirty (65.2%) patients reported improvement in gait and balance. In conclusion, our data suggest that amantadine may have new beneficial effects on axial symptoms in PD patients with STN-DBS.