When to Start Levodopa in Parkinson's Disease

Dopamine is a neurotransmitter secreted from the substantia nigra, a small region in the brainstem that withers away in Parkinson's disease. As natural dopamine levels in the brain begin to fall, signs of Parkinson's disease appear. If dopamine is replaced, many of the symptoms improve.

One would think, then, that dopamine should be given as soon as possible. There are other options, though. In addition to given dopamine directly (a drug called carbidopa-levodopa), Parkinson's disease patients may benefit from a class of drugs called dopamine agonists. These are drugs that aren't dopamine but have similar effects on the nervous system. Some physicians have argued that dopamine agonists should be used earlier in the disease's course and that only elderly patients with at least moderate disability should receive levodopa.

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Arguments for Early Use

Levodopa is the most effective medication there is to treat Parkinson's symptoms. That said, it's not without side effects.

One of the fears of levodopa use is that it can cause excessive movement called dyskinesia. People with dyskinesia have a writhing movement that is out of their control. While it looks uncomfortable, however, most with dyskinesia prefer it to parkinsonism, and studies suggest that dyskinesia ultimately doesn't have much an impact on quality of life.

Some researchers have suggested that dopamine may actually accelerate the disease course while patching over the symptoms. More research has not supported this view, however.

Symptoms may fluctuate while on dopamine, meaning there may be times of the day when tremor, rigidity, and slow movements are less well-controlled than others. On the other hand, it's unclear how those fluctuations actually impact quality of life. Furthermore, people on other medications like dopamine agonists may also eventually have fluctuations.

Other arguments in support of the early use of levodopa say that it will improve the quality of life early in the disease's course, the importance of which has not been given sufficient attention. Levodopa is also considerably less expensive than dopamine agonists.

Arguments Against Early Use

Few will argue about the superior effectiveness of levodopa, and all Parkinson's patients will likely eventually need this medication. There are some persuasive arguments for starting it later in the disease's course, though.

Medications need to be titrated throughout the progression of a disease. In other words, someone with mild Parkinson's disease who is started on levodopa will need the medication to be steadily increased as their disease worsens. In general, dopamine's potency will wear off after three years. When maximum doses of levodopa no longer control the symptoms, what else is there to turn to? Without stronger medicinal options, surgery may be the only recourse. Isn't it better to save the "big gun" for later, when symptoms are more severe?

In addition to the side effects of levodopa already discussed, there are additional potential complications including worsening cognitive function, psychosis, and diminished impulse control. It's true, though, that other medications such as dopamine agonists also have side effects, such as swelling, somnolence and psychiatric side effects, such as a gambling addiction.

In short, why would you use your "big gun" early, especially when past researchers (even if they've since been contradicted) have suggested it can make the disease worse? Especially when you can use a milder medication that might actually slow the disease process, in addition to helping with symptoms?

Other Medication Options

Another option would be to start a medication such as a monoamine oxidase inhibitor. An example is rasagiline, which seems to be very helpful when started early. Some studies have even suggested that rasagiline may slow neurological deterioration in addition to controlling symptoms, these studies are very controversial. This is in contrast to dopamine, in which some early studies have suggested disease worsening with the drug. Amantadine is another treatment option for Parkinson's disease, and anticholinergics are used to treat the tremor-predominate form of the disease.

Conflict Resolution

How can these two viewpoints be reconciled? Ultimately, there is no one medication regimen that fits everyone. People are different and need individually tailored medications. One potential approach might be to start with a medication like rasagiline, followed by a lower dose of levodopa. As the disease progresses, a dopamine agonist could be added, followed by a high dose of levodopa. Ultimately, though, the best approach will vary both based on the patient's unique needs and the doctor's preference regarding different medications.

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By Peter Pressman, MD
Peter Pressman, MD, is a board-certified neurologist developing new ways to diagnose and care for people with neurocognitive disorders.