Levodopa-induced dyskinesia in Parkinson’s disease: clinical features, pathogenesis, prevention and treatment

• Published in: Postgraduate Medical Journal Vol. 83; no. 980; pp. 384 - 388
• Main Authors: Thanvi, Bhomraj, Lo, Nelson, Robinson, Tom
• Format: Journal Article Book Review
• Language: English
• Published: London The Fellowship of Postgraduate Medicine 01.06.2007; BMJ; Oxford University Press; BMJ Group
• Subjects: 1-methyl-4-phenyl-1; 5-HT; 5-hydroxytryptamine; 6-tetrahydropyridine; Age; Antiparkinson Agents - adverse effects; Biological and medical sciences; catechol-O-methyl transferase; Clinical medicine; COMT; D-I-D; Dopamine; Dopamine Agents - adverse effects; Dyskinesia, Drug-Induced - etiology; Dyskinesia, Drug-Induced - prevention & control; Dyskinesia, Drug-Induced - therapy; dyskinesia-improvement-dyskinesia; Fos-related proteins; FRA; GABA; General aspects; Global Primate Dyskinesia Rating Scale; GPDRS; GPi; Humans; internal globus pallidum; Levodopa - adverse effects; levodopa-induced dyskinesias; LID; Medical sciences; MPTP; N-methyl-D-aspartate; Nervous system (semeiology, syndromes); Nervous system as a whole; Neurology; Neurosurgical Procedures - methods; NMDA; Parkinson Disease - complications; Parkinsons disease; Pathogenesis; Primates; Proteins; RAM; rapid alternating movements; Receptors, N-Methyl-D-Aspartate - drug effects; Review; Risk Factors; Rodents; STN; Studies; subthalamic nucleus; Unified Parkinson’s Disease Rating Scale; UPDRS; γ-aminobutyric acid; Agonist; Nervous system diseases; Pathogenesis; Clinical form; Parkinson disease; Antiparkinson agent; Cerebral disorder; Involuntary movement; Medicine; Prevention; Symptomatology; D2 Dopamine receptor; Treatment; Central nervous system disease; Degenerative disease; Levodopa; Neurological disorder; Extrapyramidal syndrome; Dyskinesia
• ISSN: 0032-5473; 1469-0756
• DOI: 10.1136/pgmj.2006.054759

Levodopa is the most effective drug for treating Parkinson’s disease. However, long-term use of levodopa is often complicated by significantly disabling fluctuations and dyskinesias negating its beneficial effects. Younger age of Parkinson’s disease onset, disease severity, and high levodopa dose increase the risk of development of levodopa-induced dyskinesias (LID). The underlying mechanisms for LID are unclear though recent studies indicate the importance of pulsatile stimulation of striatal postsynaptic receptors in their pathogenesis. The non-human primates with MPTP-induced parkinsonism serve as a useful model to study dyskinesia. Once established, LID are difficult to treat and therefore efforts should be made to prevent them. The therapeutic and preventative strategies for LID include using a lower dosage of levodopa, employing dopamine agonists as initial therapy in Parkinson’s disease, amantadine, atypical neuroleptics, and neurosurgery. LID can adversely affect the quality of life and increase the cost of healthcare.