Management of non-motor complications of Parkinson's disease: Clozapine and glutamate inhibitors

Abstract

Parkinson's disease is an age-related degenerative brain condition, that affects predominately the dopamine-producing (“dopaminergic”) neurons in a specific area of the brain called substantia nigra. It’s best known for causing several motor symptoms: bradykinesia, tremor, and rigidity. At the same time, the disease also includes non-motor components, such as psychosis and depression, which significantly reduce the patient's quality of life. PD is the second most common neurodegenerative disease after Alzheimer's disease. Dopamine replacement therapies, including levodopa, MAO-B inhibitors, and dopamine agonists, are the mainstay of treatment, although complications such as dyskinesia and psychosis occur as the disease progresses. The use of traditional antipsychotics is limited by their motor side effects. Clozapine at low doses is effective in managing the psychosis of Parkinson's disease without aggravating motor complications. In parallel, glutamate antagonists, especially NMDA receptor blockers, are considered promising agents in the therapy of both dyskinesia and psychosis.