A systematic review of catechol-0-methyltransferase inhibitors: efficacy and safety in clinical practice.
Catechol-O-methyltransferase (COMT) inhibitors are drugs commonly used in the management of patients with Parkinson disease complicated by motor fluctuations. Among them, entacapone is the most commonly used. Tolcapone has been reintroduced in patients where entacapone has proved to be ineffective after being withdrawn from the market because of sporadic cases of hepatotoxicity. The last COMT inhibitor is nebicapone, which use in clinical practice is still under study.


OBJECTIVE
The objectives of this study were to analyze the clinical efficacy in reducing motor complications and to evaluate their use in clinical practice and the adverse events reported in the literature.


METHODS
Scientific articles of the main previously mentioned drugs have been reviewed.


RESULTS
All these 3 drugs have proved to be effective in improving wearing-off and significantly reduce the daily dose of levodopa at the number of daily intakes. Tolcapone is undoubtedly the most effective drug, although in clinical practice sporadic cases of hepatotoxicity have limited its use in patients unresponsive to entacapone. Nebicapone is effective, and its safety is still under evaluation. Entacapone is generally well tolerated, and no significant adverse events are reported.


CONCLUSIONS
To manage motor fluctuations, the use of COMT inhibitors is now consolidated in the common clinical practice. Tolcapone is used as a second choice in patients with severe motor fluctuations not responsive to entacapone.
Neurologia, Ospedale San Martino, Belluno, Italy. sandro.zambito@ulss.belluno.it
Sandro Zambito
SZ
Marsala
Manuela
M
Gioulis
Roberto
R
Ceravolo
Michele
M
Tinazzi
D000098:Acetophenones / Q000494:pharmacology / Q000627:therapeutic use; D000978:Antiparkinson Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001577:Benzophenones / Q000494:pharmacology / Q000627:therapeutic use; D002394:Catechol O-Methyltransferase / Q000378:metabolism; D065098:Catechol O-Methyltransferase Inhibitors; D002396:Catechols / Q000494:pharmacology / Q000627:therapeutic use; D056486:Chemical and Drug Induced Liver Injury / Q000453:epidemiology; D002986:Clinical Trials as Topic / Q000379:methods; D004791:Enzyme Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D009570:Nitriles / Q000494:pharmacology / Q000627:therapeutic use; D009596:Nitrophenols / Q000494:pharmacology / Q000627:therapeutic use; D010300:Parkinson Disease / Q000188:drug therapy / Q000201:enzymology* / Q000453:epidemiology; D000077867:Tolcapone; D016896:Treatment Outcome
D000098:Acetophenones; D000978:Antiparkinson Agents; D001577:Benzophenones; D065098:Catechol O-Methyltransferase Inhibitors; D002396:Catechols; D004791:Enzyme Inhibitors; D009570:Nitriles; D009596:Nitrophenols; C071192:entacapone; D000077867:Tolcapone; D002394:Catechol O-Methyltransferase; C433466:nebicapone