Therapeutic Strategies to Treat or Prevent Off Episodes in Adults with Parkinson's Disease.

Parkinson's disease is a chronic, neurodegenerative disease, which manifests with a mixture of motor, cognitive and behavioural symptoms. Levodopa is the most effective antiparkinsonian treatment to date, although chronic use engenders a mixture of complications in a substantial proportion of patients. Amongst these is the occurrence of episodes of worsening symptoms-'off' phenomena. These episodes can manifest with either motor or non-motor symptoms or a combination of these features and have been found to have profound impacts on patients' quality of life. Although preventative measures are poorly evidenced, avoiding excessive total daily levodopa intake in selected populations that are deemed to be of a higher risk for developing these episodes warrants further exploration. Methods to improve levodopa bioavailability and delivery to the brain are currently available and are of value in addressing these episodes once they have become established. These include modifications to levodopa formulations as well as the use of complimentary agents that improve levodopa bioavailability. The deployment of device-assisted approaches is a further dimension that can be considered in addressing these debilitating episodes. This review summarises the clinical manifestations of 'off' phenomena and the current approaches to treat them. Although we briefly discuss clinical advances on the horizon, the predominant focus is on existing, established treatments.