Adjuvant treatment to levodopa therapy in Parkinson´s disease patients with motor complications

Evidence Summaries

Level of Evidence = C
In Parkinson´s disease add-on therapy for levodopa may reduce off-time and required levodopa dose as well as improve overall disability scores on the expense of dyskinesia and other side-effects. Dopamine agonists may provide more effective symptomatic control than catechol-O-methyl transferase inhibitors (COMTI) and monoamine oxidase type B inhibitors (MAOBI) therapy.

A Cochrane review 1 included 44 RCTs with a total of 8436 patients. Trials compared dopamine agonists, catechol-O-methyl transferase inhibitors (COMTI) or monoamine oxidase type B inhibitors (MAOBI) vs placebo on a background of levodopa therapy in Parkinson’s disease (PD) patients experiencing motor complications. The average length of follow-up was 20 weeks. Compared to placebo, adjuvant therapy significantly reduced off-time (-1.05 hours/day, 95% CI -1.19 to -0.90), the required levodopa dose (-55.65 mg/day, CI -62.67 to -48.62) and improved UPDRS scores (UPDRS ADL score: -1.31 points, CI -1.62 to -0.99; UPDRS motor score: -2.84 points, CI -3.36 to -2.32; UPDRS total score: -3.26 points, CI -4.52 to -2.00). However, dyskinesia (OR 2.50, CI 2.21 to 2.84) and side-effects including constipation (OR 3.19, CI 2.17 to 4.68), dizziness (OR 1.57, CI 1.30 to 1.90), dry mouth (OR 2.33, CI 1.22 to 4.47), hallucinations (OR 2.16, CI 1.70 to 2.74), hypotension (OR 1.47, CI 1.18 to 1.83), insomnia (OR 1.38, CI 1.09 to 1.74), nausea (OR 1.78, CI 1.53 to 2.07), somnolence (OR 1.87, CI 1.40 to 2.51) and vomiting (OR 2.56, CI 1.67 to 3.93) were all increased with adjuvant therapy. Indirect comparisons of the 3 drug classes suggested that dopamine agonists were more efficacious in reducing off-time (dopamine agonist: -1.54 hours/day; COMTI: -0.83 hours/day; MAOBI: -0.93 hours/day) and levodopa dose (dopamine agonist: -116 mg/day; COMTI: -52 mg/day; MAOBI: -29 mg/day). UPDRS scores also improved more with dopamine agonists than with COMTI or MAOBI (UPDRS total scores: dopamine agonist: -10.01 points vs COMTI: -1.46 points vs MAOBI: -2.20 points), although more dyskinesia were seen with dopamine agonists (OR 2.70) and COMTI (OR 2.50) than with MAOBI (OR 0.94). The increase in the overall incidence of side-effects was generally more marked with dopamine agonists (OR 1.52) and COMTI (OR 2.0) than with MAOBI (OR 1.32).

Comment: The quality of the evidence is downgraded by study quality (short follow-up) and indirectness of evidence (differences in studied patients).


1. Stowe R, Ives N, Clarke CE, Deane K, van Hilten, Wheatley K, Gray R, Handley K, Furmston A. Evaluation of the efficacy and safety of adjuvant treatment to levodopa therapy in Parkinson s disease patients with motor complications. Cochrane Database Syst Rev 2010 Jul 7;7:CD007166.  [PMID:20614454]

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