This is a common scenario. The problem is that L-dopa monotherapy (i.e. L-dopa preparations alone) has a short duration of action. In the blood, this is called the half-life, but it is the concentration in the brain and the metabolism and storage capacity in the brain that give rise to different effects. The longer you have had the disease, the shorter the effect of L-dopa and the more likely you are to experience dose gaps. This varies throughout the day depending on storage capacity, which deteriorates the longer the disease has been present. The stores are depleted during the day, and dose gaps become progressively more pronounced as the day goes on. Storage takes place in other nerve endings (synapses) than those affected by the disease, and in the remaining dopamine nerve endings, turnover increases several-fold as the disease progresses; other types of nerve endings can also partially store and release dopamine, but less precisely than in the nerve endings intended for this purpose.
Treatment for dose gaps involves many different possible measures that must be tailored to the individual.
You can (further) fractionate the L-dopa medication by adding or staggering different individual doses of L-dopa in the way that has been done.
Another approach is to add so-called enzyme inhibitors, which in various ways prolong the effect of L-dopa and the dopamine it produces by slowing down the rapid breakdown of the dopamine formed. There are several different agents/types (MAO-B inhibitors – rasagiline, or safinamine (Xadago), as well as COMT inhibitors, primarily entacapone or oticapone (the latter is not subsidised, but may be suitable for those who have experienced side effects in the form of diarrhoea from entacapone).
If this isn’t enough, you could possibly switch to other L-dopa treatments administered via a pump (subcutaneously, ProDuodopa) or via PEG/intra-intestinal to the small intestine (Duodopa or Lecigon, which also contains the COMT inhibitor entacapone).
Another option, if you can tolerate them, is to prolong the therapeutic effect with a dopamine agonist, via tablets, patches or a pump. Another option is DBS (deep brain stimulation) at either the Gpi (globus pallidum) or STN (subthalamic nucleus) target sites.
You should discuss all these options with your treating doctor to see if any of them might be suitable.
//Håkan Widner