How long before levodopa stops working in Parkinson’s disease?

Carbidopa-levodopa is a drug combination that works to reduce symptoms in Parkinson's disease for as long as a patient takes it. Put simply, levodopa converts into dopamine in the brain, helping to control movement, while carbidopa prevents the breakdown of levodopa in the bloodstream so more levodopa can enter the brain. Carbidopa can also reduce nausea and vomiting, common levodopa side effects. As the underlying disease progresses and symptoms get worse, patients may need to increase their dose or take levodopa more frequently to experience the same reduction in symptoms.

After taking levodopa for some time, typically a few years, patients may begin to experience a wearing off period, when symptoms return before it's time for their next dose of levodopa. This is also referred to as "off time.” Off time is common, and according to patient surveys, around half of patients who take levodopa report experiencing wearing off periods. Of those patients, 25% experience it 3 to 6 hours per day, and 52% have symptoms for 1 to 3 hours a day.

Some patients notice the return of motor symptoms during "off" time — that's why the phenomenon is sometimes referred to as "motor fluctuations." You may also notice non-motor symptoms onset, such as a drop in energy levels or an increase in muscle stiffness, depending on your individual experience with Parkinson’s disease.

"Off" time can last anywhere from 15 minutes to several hours, depending on your current medication dosage. Talk to your doctor if you've noticed that your symptoms, such as tremors, return before it's time for your next dose. There are a few adjustments that can help, including increasing your dosage, changing medications, and adjusting protein intake.

Levodopa side effects

One reason patients sometimes delay levodopa treatment is because of its side effects — particularly dyskinesia, or uncontrolled movements that can look like fidgeting, writhing, wriggling, head bobbing, or body swaying. Dyskinesia is a side effect of long-term use of levodopa, not a symptom itself. Other levodopa side effects include low blood pressure, nausea, and confusion. 

If you're experiencing dyskinesia, talk with your doctor. Adjusting your dose or using an extended-release form of levodopa can help reduce dyskinesia. Your doctor may also prescribe extended-release amantadine, which is approved to treat dyskinesia. Some patients who experience severe dyskinesia also consider deep brain stimulation (DBS) surgery.

Should I avoid taking levodopa for Parkinson's disease?

Some people with Parkinson's disease put off taking levodopa to delay its eventual side effects. Parkinson's disease is different for everyone, and it's important to talk about your treatment options with a doctor before making a decision on your treatment course.

Other medication options for Parkinson's disease treatment include: 

  • Dopamine agonists, such as pramipexole (Mirapex), ropinirole (Requip), rotigotine (Neupro, given as a patch), and apomorphine (Apokyn)
  • MAO-B inhibitors, such as selegiline (Zelapar), rasagiline (Azilect), and safinamide (Xadago), which can be taken alone or along with levodopa 
  • Catechol O-methyltransferase (COMT) inhibitors, such as entacapone (Comtan) and opicapone (Ongentys)
  • Anticholinergics, including benztropine (Cogentin) or trihexyphenidyl
  • Amantadine
  • DBS can also help Parkinson's motor symptoms

Since Parkinson's disease is an individual disease, it can take time to find the best treatment plan that works for you. It's important to note that no treatment has been found to be superior to levodopa, so many doctors advise against avoiding levodopa. Your healthcare team can help you make the right decision for your particular case.

Parkinson's clinical trials are currently researching potential new options for treating a range of Parkinson's symptoms and side effects, including "off" time. If you're interested in volunteering, answer a few questions to see if you may qualify for clinical trials near you.