Purpose: This multicenter randomized controlled trial investigates the efficacy of sustained-release oxycodone/naloxone on severe pain in patients with Parkinson’s disease.
Background
Pain is a common phenomenon in patients with PD. To date, few studies have examined drug effects in Parkinson’s-associated pain. Opiates may be effective here, but they also have peripheral side effects that can lead to further impairment, so a combination with naloxone is likely to be better tolerated.
Patients and methods
The randomized controlled multicenter phase II trial enrolled 202 patients with advanced PD and a pain score of at least 6 (0-10) on the numeric rating scale (NRS) in 47 European centers. The primary outcome criterion was the mean score on the NRS over one week after 16 weeks of treatment. The combination medication of sustained-release oxycodone/naloxone could be increased from 5/2.5 mg to 20/10 mg 2×/d.
Results
Eighty-eight patients were evaluated in the verum group and 106 patients in the placebo group. Pain ratings did not differ significantly at a difference of 0.6 in favor of the verum (p=0.058). This difference became significant in patients who completed the protocol and at the study time points of four, eight, and 12 weeks (exploratory testing). In particular, patients with nocturnal or musculoskeletal pain showed a good response. Adverse events occurred equally infrequently in both groups. However, the rate of patients experiencing nausea and constipation was significantly higher in the verum group (17% vs. 9% and 17% vs. 6%, respectively). Here, total discontinuation rates were also higher, whereas in the placebo group, discontinuation rates were higher due to the lack of treatment effect.
Conclusions of the authors
The primary endpoint was missed. However, at the other time points collected and in the group of patients who completed the study, the study found a positive effect of combination therapy of an opiate with an opiate antagonist on pain in PD – this with good tolerability. Exclusion of patients with high dopaminergic demand medication (>300 mg L-dopa) and milder pain affected the study results. In addition, only a daily dose of 40/20 mg was approved. The authors emphasize the importance of this first larger study and hold out the prospect of further research.
Comment
Before starting the therapy of pain in PD, the correct diagnosis of the pain and especially the question whether an improvement can be achieved by optimizing motor complications are important. With regard to central pain, a study on duloxetine is already available. The agonist rotigotine has also been shown to have pain therapeutic effects by influencing sleep and motor function. Oxycodone in combination with naloxone is a complementary therapeutic option for the treatment of musculoskeletal and nocturnal severe pain with overall satisfactory tolerability in Parkinson’s disease (PD) when better medication control of motor symptoms is not possible. Because the therapeutic effect was relatively small at this low dose, further studies are needed at higher doses and in patients with low pain and in patients with optimized therapy.
InFo NEUROLOGY & PSYCHIATRY 2016; 14(1): 19.
