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Catechol-O-methyltransferase inhibitors for levodopa-induced complications in Parkinson's disease.
Cochrane Database Syst Rev. 2004 Oct 18CD

Abstract

BACKGROUND

As Parkinson's disease progresses the control of motor symptoms often requires the addition of other drugs to levodopa. The principle aim of COMT inhibitor therapy is to increase the duration of effect of each levodopa dose and thus reduce the time patients spend in the relatively immobile 'off' phase.

OBJECTIVES

To compare the efficacy and safety of adjuvant COMT inhibitor therapy versus placebo in patients with Parkinson's disease, already established on levodopa and suffering from motor complications.

SEARCH STRATEGY

Electronic searches of the Cochrane Controlled Trials Register, (The Cochrane Library Issue 1, 2003), MEDLINE (1966-2003), EMBASE (1974-2003), were conducted. Grey literature was hand searched and the reference lists of identified studies and reviews examined. The manufacturers of COMT inhibitors were contacted.

SELECTION CRITERIA

Randomised controlled trials of adjuvant COMT inhibitor therapy versus a placebo in patients with a clinical diagnosis of idiopathic Parkinson's disease and long-term complications of levodopa therapy.

DATA COLLECTION AND ANALYSIS

Data were abstracted independently by the authors and differences settled by discussion. The outcome measures used included Parkinson's disease rating scales, levodopa dosage, 'off' time measurements and the frequency of withdrawals and adverse events.

MAIN RESULTS

Fourteen trials fulfilled the inclusion criteria. 2566 patients with Parkinson's disease and motor fluctuations were included in this review. Eight trials examined entacapone versus placebo in a total of 1560 patients. These trials were between two and twelve months in duration. Six trials examined tolcapone versus placebo in a total of 1006 patients. These trials were between six weeks and twelve months in duration. Both tolcapone and entacapone reduced 'off' time, reduced levodopa dose and modestly improved motor impairments and disability. This was at the expense of increased risk of dyskinesias, nausea, vomiting, and diarrhoea. A few participants taking tolcapone were found to have raised liver enzyme levels.

REVIEWERS' CONCLUSIONS

In the management of the motor complications seen in Parkinson's disease, tolcapone and entacapone can be used to reduce off time, reduce levodopa dose, and modestly improve motor impairment and disability. This is based on, at best, medium term evidence. However some participants on tolcapone had raised liver enzymes. This combined with three cases of fatal hepatic toxicity found during post-marketing surveillance has raised concerns over the safety of tolcapone.

Links

PMC Free PDF

Authors

Deane KH
No affiliation info available
Spieker S
No affiliation info available
Clarke CE
No affiliation info available

MeSH

Antiparkinson AgentsBenzophenonesCatechol O-Methyltransferase InhibitorsCatecholsEnzyme InhibitorsHumansLevodopaNitrilesNitrophenolsParkinson DiseaseTolcapone

Pub Type(s)

Journal Article
Review
Systematic Review

Language

eng

PubMed ID

15495119

Citation

Deane, K H O., et al. "Catechol-O-methyltransferase Inhibitors for Levodopa-induced Complications in Parkinson's Disease." The Cochrane Database of Systematic Reviews, 2004, p. CD004554.
Deane KH, Spieker S, Clarke CE. Catechol-O-methyltransferase inhibitors for levodopa-induced complications in Parkinson's disease. Cochrane Database Syst Rev. 2004.
Deane, K. H., Spieker, S., & Clarke, C. E. (2004). Catechol-O-methyltransferase inhibitors for levodopa-induced complications in Parkinson's disease. The Cochrane Database of Systematic Reviews, (4), CD004554.
Deane KH, Spieker S, Clarke CE. Catechol-O-methyltransferase Inhibitors for Levodopa-induced Complications in Parkinson's Disease. Cochrane Database Syst Rev. 2004 Oct 18;(4)CD004554. PubMed PMID: 15495119.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Catechol-O-methyltransferase inhibitors for levodopa-induced complications in Parkinson's disease. AU - Deane,K H O, AU - Spieker,S, AU - Clarke,C E, Y1 - 2004/10/18/ PY - 2004/10/21/pubmed PY - 2005/3/24/medline PY - 2004/10/21/entrez SP - CD004554 EP - CD004554 JF - The Cochrane database of systematic reviews JO - Cochrane Database Syst Rev IS - 4 N2 - BACKGROUND: As Parkinson's disease progresses the control of motor symptoms often requires the addition of other drugs to levodopa. The principle aim of COMT inhibitor therapy is to increase the duration of effect of each levodopa dose and thus reduce the time patients spend in the relatively immobile 'off' phase. OBJECTIVES: To compare the efficacy and safety of adjuvant COMT inhibitor therapy versus placebo in patients with Parkinson's disease, already established on levodopa and suffering from motor complications. SEARCH STRATEGY: Electronic searches of the Cochrane Controlled Trials Register, (The Cochrane Library Issue 1, 2003), MEDLINE (1966-2003), EMBASE (1974-2003), were conducted. Grey literature was hand searched and the reference lists of identified studies and reviews examined. The manufacturers of COMT inhibitors were contacted. SELECTION CRITERIA: Randomised controlled trials of adjuvant COMT inhibitor therapy versus a placebo in patients with a clinical diagnosis of idiopathic Parkinson's disease and long-term complications of levodopa therapy. DATA COLLECTION AND ANALYSIS: Data were abstracted independently by the authors and differences settled by discussion. The outcome measures used included Parkinson's disease rating scales, levodopa dosage, 'off' time measurements and the frequency of withdrawals and adverse events. MAIN RESULTS: Fourteen trials fulfilled the inclusion criteria. 2566 patients with Parkinson's disease and motor fluctuations were included in this review. Eight trials examined entacapone versus placebo in a total of 1560 patients. These trials were between two and twelve months in duration. Six trials examined tolcapone versus placebo in a total of 1006 patients. These trials were between six weeks and twelve months in duration. Both tolcapone and entacapone reduced 'off' time, reduced levodopa dose and modestly improved motor impairments and disability. This was at the expense of increased risk of dyskinesias, nausea, vomiting, and diarrhoea. A few participants taking tolcapone were found to have raised liver enzyme levels. REVIEWERS' CONCLUSIONS: In the management of the motor complications seen in Parkinson's disease, tolcapone and entacapone can be used to reduce off time, reduce levodopa dose, and modestly improve motor impairment and disability. This is based on, at best, medium term evidence. However some participants on tolcapone had raised liver enzymes. This combined with three cases of fatal hepatic toxicity found during post-marketing surveillance has raised concerns over the safety of tolcapone. SN - 1469-493X UR - https://www.unboundmedicine.com/medline/citation/15495119/Catechol_O_methyltransferase_inhibitors_for_levodopa_induced_complications_in_Parkinson's_disease_ DB - PRIME DP - Unbound Medicine ER -