Freezing of gait (FOG) is frequently considered as one of the
dopamine-resistant motor symptoms of
Parkinsonism. Recent studies have clearly demonstrated that the Off-related FOG is improved by
levodopa (
L-dopa) or
entacapone treatment.
L-dopa can decrease duration of each FOG episode as well as its frequency. On-related FOGs are not common and difficult to diagnose. Only in the most advanced stages of the disease, FOGs are resistant to treatment as many other symptoms. Off-related FOGs are likely to be improved by
dopamine agonists (
DAs), but this has never been looked at systematically. In contrast, DA treatment might provoke FOG, and in two pivotal studies when
DAs were compared to
L-dopa in early stages of
Parkinson's disease, the DA-treated arms experienced more FOGs.
MAO-B inhibitors (
selegiline and
rasagiline) can decrease FOG frequency or severity, but its clinical significance is still unknown. L-
Threo-DOPS has been reported to have a symptomatic beneficial effect in patients with pure freezing syndrome, but small-scale, controlled trials in
Parkinson's disease could not support those early observations.
Botulinum toxin injected into the calf muscles has been suggested to have a symptomatic benefit. However, double-blind, prospective studies could not support that early observation and increased fall risk in the injected patients has put this direction of treatment on hold. The potential benefit of
amantadine, antidepressive drugs,
acetylcholine esterase inhibitors, and
methylphenidate on FOG has been studied in small-scale studies, and there is a need for prospective studies to understand the future role of those drugs.