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The COMT inhibitors entacapone and tolcapone show similar benefits in relieving levodopa‐induced complications in Parkinson's disease but more data on the safety of tolcapone is required.

As Parkinson's disease progresses the control of the 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. 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. Post‐marketing surveillance identified three cases of fatal hepatic toxicity in patients treated with tolcapone. As a result, tolcapone has been withdrawn from some countries and severe restrictions on its use have been imposed in others.

Cochrane Database of Systematic Reviews: Plain Language Summaries [Internet] - John Wiley & Sons, Ltd.

Version: 2009

Insufficient data are available on the benefits of the COMT inhibitor tolcapone compared with the dopamine agonists bromocriptine and pergolide in relieving the symptoms of later Parkinson's disease.

As Parkinson's disease progresses the control of the 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. However other drugs such as dopamine agonists can also be used at this stage of the disease. This review found that the COMT inhibitor tolcapone as an adjuvant to levodopa treatment had a similar level of benefits as two dopamine agonists, bromocriptine and pergolide. There was no significant difference in efficacy between the adjuvant tolcapone and adjuvant bromocriptine or pergolide in the medium‐term. Tolcapone produced nausea less often than these agonists but there was some evidence of liver function abnormalities with tolcapone. Post‐marketing surveillance identified three cases of fatal hepatic toxicity in patients treated with tolcapone. As a result, tolcapone has been withdrawn from some countries and severe restrictions on its use have been imposed in others.

Cochrane Database of Systematic Reviews: Plain Language Summaries [Internet] - John Wiley & Sons, Ltd.

Version: 2009

Parkinson's Disease: National Clinical Guideline for Diagnosis and Management in Primary and Secondary Care

It is almost 200 years since James Parkinson described the major symptoms of the disease that came to bear his name. Slowly but surely our understanding of the disease has improved and effective treatment has been developed, but Parkinson’s disease remains a huge challenge to those who suffer from it and to those involved in its management. In addition to the difficulties common to other disabling neurological conditions, the management of Parkinson’s disease must take into account the fact that the mainstay of pharmacological treatment, levodopa, can eventually produce dyskinesia and motor fluctuation. Furthermore, there are a number of agents besides levodopa that can help parkinsonian symptoms, and there is the enticing but unconfirmed prospect that other treatments might protect against worsening neurological disability. Thus, a considerable degree of judgement is required in tailoring individual therapy and in timing treatment initiation. It is hoped that this guideline on Parkinson’s disease will be of considerable help to those involved at all levels in these difficult management decisions. The guideline has been produced using standard NICE methodology and is therefore based on a thorough search for best evidence.

NICE Clinical Guidelines - National Collaborating Centre for Chronic Conditions (UK).

Version: 2006
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Drugs for motor complications in people with Parkinson´s disease who are already taking levodopa

One of the complications of long‐term treatment of Parkinson's disease (PD) with levodopa is the development of motor complications e.g. dyskinesia; a jerky, dance‐like movement of the body. Generally clinicians add on drugs (to the levodopa regimen) from one of the other three classes of anti‐Parkinsonian treatments available (e.g. dopamine agonists, catechol‐O‐methyl transferase inhibitors (COMTIs) or monoamine oxidase type B inhibitors (MAOBIs)). However, despite trials having shown that these drugs are beneficial compared to placebo, it remains unclear as to the best way to treat patients experiencing motor complications and, in particular, whether one class of drug may be more effective than another.

Cochrane Database of Systematic Reviews: Plain Language Summaries [Internet] - John Wiley & Sons, Ltd.

Version: 2010

Rotigotine (Neupro) (Transdermal Patch) [Internet]

The objective of this report was to perform a systematic review of the beneficial and harmful effects of rotigotine for the treatment of the signs and symptoms of idiopathic Parkinson disease (PD).

Common Drug Review - Canadian Agency for Drugs and Technologies in Health.

Version: November 2016
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Depression in Adults with a Chronic Physical Health Problem: Treatment and Management

This clinical guideline was commissioned by NICE and developed by the National Collaborating Centre for Mental Health. It sets out clear, evidenceand consensus-based recommendations for healthcare staff on how to treat and manage depression in adults with a chronic physical health problem.

NICE Clinical Guidelines - National Collaborating Centre for Mental Health (UK).

Version: 2010
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Practice parameter: treatment of Parkinson disease with motor fluctuations and dyskinesia (an evidence-based review). Report of the Quality Standards Subcommittee of the American Academy of Neurology

This review evaluated medical and surgical treatments for Parkinson disease with levodopa-induced motor fluctuations and dyskinesia, and found the highest evidence was for the effectiveness of entacapone and rasagiline in reducing off time; treatment recommendations were reported. This is a well-conducted review and the authors' conclusions are likely to be reliable.

Database of Abstracts of Reviews of Effects (DARE): Quality-assessed Reviews [Internet] - Centre for Reviews and Dissemination (UK).

Version: 2006

Pharmacologic treatment of advanced Parkinson's disease: a meta-analysis of COMT inhibitors and MAO-B inhibitors

The authors concluded that catechol-O-methyltransferase or monoamine oxidase type B inhibitors plus levodopa were superior to levodopa alone in reducing symptoms in patients with advanced Parkinson’s disease, but they were associated with increased adverse events. There were some limitations to the review, but overall the authors’ conclusions appeared to be supported by the evidence.

Database of Abstracts of Reviews of Effects (DARE): Quality-assessed Reviews [Internet] - Centre for Reviews and Dissemination (UK).

Version: 2009

Systematic Reviews in PubMed

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