Some patients say, “The medication doesn’t work as well as it used to. A single dose used to last 4 hours, but now the medication wears off in 2 hours”. What is this? This is the most common drug complication, also known as the “end-of-dose phenomenon,” which occurs between doses (mostly 3.5 hours after the previous dose) and is characterized by end-of-dose worsening and reappearance of Parkinson’s disease symptoms, and in many patients, off-phase dyskinesia, such as painful foot spasms. Symptom fluctuations are common in patients who are effectively treated with levodopa, and the “end-of-dose phenomenon” appears earlier and earlier as the duration of treatment increases. Should I increase the dose or frequency of dosing in this case? This phenomenon is often associated with an inadequate dose of levodopa and can be predicted. If the original dose of the medication is small, e.g., less than 4 capsules of methyldopa, and each dose is less than one capsule, the dose can be increased first. If half a capsule, it can be changed to three-quarters; three-quarters can be changed to one capsule. If you are already taking one capsule, or if you develop xerostomia after adding the drug, you can change to increasing the number of doses given at the same dose as the original. Adding a long half-life dopamine agonist, COMT inhibitor, or adding MAO-B (Midolpir) may improve symptoms. Are there any adverse consequences of increasing the dosage on your own? If you increase the dosage of medication on your own, you may experience side effects such as allergic reactions, gastrointestinal problems such as nausea and vomiting, constipation, or psychiatric side effects such as euphoria and nighttime hallucinations. Therefore, it is best to do so under the supervision of a specialist. Do I need to use other medications in combination? What effect can it have? Do I need to use the combination for a long time? Combination of medications is possible when end-of-dose phenomenon occurs or symptoms worsen. Combining medications usually prolongs the duration of the prescribed period and reduces the side effects of allodynia. Usually patients with Parkinson’s disease who have been on three or more anti-Parkinson’s drugs and still have drug complications such as end-of-dose phenomenon, on/off phenomenon, and ochronosis, and who have had the disease for more than five years, are recommended to have surgery within three years of the onset of these symptoms, which is currently advocated internationally as early treatment for Parkinson’s disease.