Parkinson's disease (PD), a consequence of death of neurons in the brain area known as the substantia nigra, is the second most common neurodegenerative disease in the world, after Alzheimer's disease. This movement disorder affects about 7 million people worldwide and 1 million in the US alone currently, with more to come as many more of us age into our 80s and older since PD occurs more often as people age. Now for the good news: in what's known as a 'pragmatic' trial undertaken in the UK and reported in the Lancet, as Rick and I discuss on PodMed this week, an old drug known as L-DOPA or levodopa seems the best choice for most when it comes to initial medical management.
Pragmatic trials attempt to assess interventions as they are implemented in the real world rather than the rarified air of a clinical trial. In this case 1620 people newly diagnosed with PD were randomly assigned to either levodopa, another type of drug known as a dopamine agonist, or yet another class called monoamine oxidase type B inhibitors. Each of these three types of drugs works by a different mechanism in an attempt to overcome loss of the neurotransmitter called dopamine, normally produced by the neurons that die. People entering the trial were diagnosed by movement disorder experts, were either untreated previously or treated for less than six months with levodopa. Both subjects and clinicians were aware of which drug was selected.
Data from 7 years of follow-up is presented in this study. One outcome measure was the mobility subscale of a questionnaire known as the PDQ-39. This self-report data is sensitive to items regarded as important to people with PD but that may not be represented on clinical rating scales. Quality-adjusted life-years were determined along with a host of other outcomes such as changes in the mini-mental state examination, hospitalizations, and mortality. The study determined that for those assigned to the levodopa arm, small but persistent benefits in mobility scores by self-report were seen. Moreover, with regard to compliance, "179 (28%) of 632 patients allocated dopamine agonists and 104 (23%) of 460 patients allocated MAOBI discontinued allocated treatment because of side-effects compared with 11 (2%) of 528 patients allocated levodopa (p<0·0001)." As Rick and I opine in the podcast, this may be regarded as good news since levodopa is off-patent, we have an abundant track record regarding its use, and more sensitive titration of the drug clinically may preclude some of the side effects or at least delay them.
The authors have done a cost analysis that is forthcoming, but predict that the economic analysis will also favor use of L-DOPA. Since we have so many people who will undoubtedly develop PD in the near term, this is of public health benefit as well. Finally, Rick and I do mention other strategies such as electrode implantation as promising, but agree that for now, knowing which medication is likely to be most beneficial is very helpful for all concerned.
Other topics this week include two studies from NEJM on managing another common condition, obstructive sleep apnea. We also look at statins and physical activity in older men in JAMA Internal Medicine, and what happens when insulin is added to metformin for the management of type 2 diabetes in JAMA. Until next week, y'all live well.