Carbidopa/levodopa/entacapone: the evidence for its place in the treatment of Parkinson’s disease

Markos Poulopoulos, Cheryl Waters

Department of Neurology, Division of Movement Disorders, Columbia University Medical Center, Neurological Institute of New York, Center of Parkinson’s Disease and Other Movement Disorders, New York, NY, USA

Introduction: Parkinson’s disease (PD) is a common neurodegenerative disease. In the 1960s, it was shown that the degeneration of dopamine producing neurons in the substantia nigra (SN) caused the motor features of PD. Dopamine replacement with levodopa, a dopamine precursor, resulted in remarkable benefit. Yet, the intermittent administration of levodopa is a major cause of motor complications, such as “wearing-off ” of levodopa’s benefit and involuntary movements, known as dyskinesia. Therefore, agents that prolong levodopa’s half-life were employed, such as carbidopa, an aromatic amino acid decarboxylase (AADC) inhibitor, and entacapone, a catechol-O-methyltransferase (COMT) inhibitor. The combination product carbidopa/levodopa/entacapone (CLE) was approved in 2003 for the treatment of PD patients.

Aims: To assess the evidence for the place of CLE in the treatment of PD.

Evidence review: CLE has a good efficacy, safety and tolerability profile, similar to that of entacapone taken separately with carbidopa/levodopa (CL). Compared to CL alone, it prolongs levodopa’s benefit, and improves the quality of life but not the motor performance in PD patients with nondebilitating “wearing-off ” or dyskinesia. However, it increases the dyskinesia rate in early PD patients, and has adverse events in advanced patients with significant motor complications. There is insufficient evidence regarding cost-effectiveness.

Place in therapy: CLE is an attractive alternative for patients with nondisabling “wearing-off ” or dyskinesia taking CL with or without entacapone. It cannot be recommended for early PD patients, as it can induce more dyskinesia than CL alone, or in any patients who seem to have more adverse events.

Keywords: Parkinson’s disease, levodopa, entacapone, carbidopa, treatment