Dopamine agonists provide symptomatic benefit when taken with levodopa, or as taken alone (monotherapy) in early stages of Parkinson's disease. This is the current recommended approach for many people newly diagnosed with the disease (especially those under age 60) because it can delay the need for levodopa and thus postpone the motor fluctuations that may occur with long-term levodopa therapy.
There is interest as to whether their early and sustained use can forestall long-term levodopa-associated complications. Monotherapy with dopamine agonists is generally as effective as levodopa/PDI when a patient first requires symptomatic therapy. After one to three years of disease progression, monotherapy with a dopamine agonist often becomes inadequate and levodopa therapy must be added. In moderate and advanced disease, patients with motor fluctuations on levodopa may benefit from the addition of a dopamine agonist to smooth motor fluctuations and improve symptom control.
A dopamine agonist may be added to treatment with levodopa for advanced Parkinson's disease when:
When used alone in early Parkinson's disease, dopamine agonists may reduce symptoms of the disease, especially those affecting motor function, such as stiffness and slowness.
When taken in combination with levodopa, dopamine agonists may:
Dopamine agonists can be taken with or without food. Patients with nausea should take their medication after a meal. For patients on combination therapy with levodopa, the dopamine agonist is usually scheduled to be taken when levodopa is administered as a matter of convenience.
The most common side effects of dopamine agonists include:
Dopamine's oxidative metabolism may lead to free radical formation and cause or accelerate neuronal degeneration, and Rapidly fluctuating levels of levodopa-derived dopamine may sensitize dopamine receptors and lead to dyskinesia. Unlike levodopa, dopamine agonists directly stimulate post-synaptic dopamine receptors. They do not undergo oxidative metabolism and there is no concern that they might accelerate the disease process. In fact, animals fed a diet including pergolide were found to experience less age-related loss of dopamine neurons. Bromocriptine, pergolide, ropinirole, pramipexole, and cabergoline all have significantly longer half-lives than levodopa and do not expose receptors to rapidly fluctuating levels of stimulation. Animal studies have demonstrated that dopamine agonists are associated with a lower incidence of dyskinesia than levodopa. Several investigators have examined the possibility that dopamine agonists, alone or in combination with levodopa, could delay motor fluctuations and dyskinesia. A series of retrospective studies found fewer motor complications in patients treated with agonists rather than levodopa. Initial treatment with a dopamine agonist followed by the addition of levodopa, when necessary, is associated with a lower prevalence of dyskinesia.
The main limitation of dopamine agonist monotherapy is that symptoms are adequately controlled for a period of only one to three years. One study found that after three years of bromocriptine monotherapy only 28%, and after 5 years only 7%, of patients were still adequately maintained on monotherapy alone. After a few years, most patients require levodopa to sustain good benefit.
In moderate and advanced disease, dopamine agonists provide benefit for patients with motor fluctuations on levodopa therapy. When an agonist is added, off time is reduced, motor function is improved and levodopa doses may be reduced. Only rarely can a patient with fluctuations and dyskinesia be adequately managed with dopamine agonists alone.
When used alone, the dopamine agonists are less effective in controlling symptoms than levodopa and often need to be increased slowly over time. These medications can cause side effects, especially sleepiness and hallucinations. Dopamine agonists tend to cause more side effects than levodopa does.
Increasing numbers of doctors are using dopamine agonists as initial therapy in people with newly diagnosed Parkinson's disease in order to delay treatment with levodopa. The American Academy of Neurology now recommends this approach for most people with the disease. In theory, the purpose behind delaying treatment with levodopa, especially in younger people with Parkinson's, is to delay the motor fluctuations that eventually occur with long-term levodopa therapy. However, these motor fluctuations may also occur with the dopamine agonists alone. If a dopamine agonist is used as initial therapy, levodopa may be added when the dopamine agonist is no longer able to control symptoms adequately on its own.
Pramipexole (Mirapex) and ropinirole (Requip) are the newest dopamine agonists and may cause fewer side effects than the older dopamine agonists (bromocriptine and pergolide). These newer medications are also more expensive.
