Conjecture 16 most PwP can be better medicated with existing drugs than they are now.
Is the drug cocktail that you're on optimal?
To the extent that Parkinson's is a disease characterized by a shortage of dopamine in the brain, it seems reasonable to suppose that the aim of any dopamine replacement therapy (DRT) should not just be to supply the missing amount, but to supply it just when it is needed.
The consequences of getting it wrong include:
- under-medicated: slowness, stiffness;
- over-medicated: dyskinesia;
- peaks and troughs in DRT levels [1]:
"Evidence from preclinical and clinical studies indicates that pulsatile stimulation of striatal dopamine receptors is a key factor in the development of levodopa-associated motor complications."
Many of us are chronically under-medicated, so as to avoid complications, but this leads to a lower quality of life than that needed.
I would estimate that in the ideal world, where dopamine/agonist levels could be monitored continuously and could be controlled dynamically, doses could be doubled without any increase in complications. This estimate is based on evidence about Rytary and Duodopa.
Regarding Rytary [2]:
"The final total daily dose of levodopa from RYTARY was approximately double that of the final total daily dose of levodopa from immediate-release tablets." However, we also need to take into account: "The bioavailability of levodopa from RYTARY in patients was approximately 70% relative to immediate-release carbidopa-levodopa."
Regarding Duodopa, doctors in Denmark report the following percentage changes in levodopa equivalent consumption on being introduced to Duodopa on 14 patients [3]:
+64, +281, +261, -18, +222, -53, +477, +25, -29, +19, +438, +6
Some of these changes are due to the differences in the technology involved, some will be due to the sub-optimality of the dosing regeme before taking levodopa.
As I see it, many PwP live, metaphorically speaking, in a house with a central boiler and a supply of wood, that once was adequate, but with no way to adapt, other than through interventions by a heating engineer every 6 months, to changes of weather or changes of need in different rooms or changes in the efficiency of the boiler.
Clearly it should be an expectation that the DRT is monitored frequently (every week, perhaps), and changes made with smaller granularity than at present. If the health system does not provide this regular updating, we should deliver it ourselves.
References:
[1] "Continuous dopaminergic stimulation in early and advanced Parkinson’s disease"
Fabrizio Stocchi, MD PhD and C. Warren Olanow, MD FRCPC
Neurology January 13, 2004 vol. 62 no. 1 suppl 1 S56-S63
http://www.neurology.org/content/62/...1/S56.abstract
[2] Rotary Full Prescribing Information
http://www.accessdata.fda.gov/drugsa...312s000lbl.pdf
[3] "Duodopa pump treatment in patients with advanced Parkinson‘s disease"
Merete Karlsborg, Lise Korbo, Lisbeth Regeur & Arne Glad
Dan Med Bull, June 2010
http://www.danmedj.dk/portal/pls/por...me=5274860.PDF
John