Exploring seven recently approved Parkinson’s treatments
Remarkably, in the last five years, seven new medications have been approved for the treatment of the motor symptoms of Parkinson’s disease (PD), with two approved in 2020. That’s exciting progress! And while it is great to have so many choices, the various options can be confusing — so today I will describe these new medications and their uses.
Medications already available
The older medications that were used, and continue to be used to treat Parkinson’s, include carbidopa/levodopa formulations, dopamine agonists (available in immediate-release, long-acting, patch form, and injectable form), catechol-O-methyltransferase (COMT) inhibitors, monoamine oxidase B (MAO-B) inhibitors, anticholinergics, and amantadine. Although these medications can bring substantial relief to some motor symptoms of PD, additional therapies were necessary to address other major impediments to quality of life as PD advances, including:
New Treatments for Parkinson’s Disease
Important points about the new medications
With multiple new medications available for the treatment of PD, there is more hope than ever that Parkinson’s symptoms can be successfully managed for many years. A few things to consider:
- For people whose symptoms are difficult to control, these new treatments are welcome additions to what was previously available and many people with PD have been using these new medications with significant benefit.
- On the other hand, many of the newly-approved medications have the same mechanisms of action as older medications (that is, they are very similar drugs to ones already available) so they are not breaking new ground in treating symptoms.
- In addition, for some people, the effect on symptoms may be mild or not substantial.
These caveats may mean that your physician has not suggested a medication change for you. It is also important to note that despite all the new medications, carbidopa/levodopa remains the most potent medication to treat the motor symptoms of PD.
If your doctor does choose to try one of the new options, there may be multiple paths that your doctor can take when contemplating a medication adjustment. Often trial and error is the only way to determine the best medication regimen for you, so you may need to practice some patience as you work together with your doctor to determine what works or doesn’t work.
New Medications for OFF time
A number of new medications approved recently are designed to reduce OFF time. These medications fall into two major categories:
- Medications that lengthen the effect of a carbidopa/levodopa dose
- Medications that are used “as needed” if medication effects wear off
We’ll give specific examples below. In general, new medications that extend the length of a carbidopa/levodopa dose are used if OFF time is somewhat predictable and occurs prior to next dose. New medications that are used “as needed” are most beneficial when OFF time is not predictable.
New medications that lengthen the effect of a dose of carbidopa/levodopa
- Istradefylline (Nourianz®) is an adenosine A2A receptor antagonist which was approved in the US in 2019 as an add-on therapy to levodopa for treatment of OFF time in PD. Unlike many of the other medications, it has a novel mechanism of action and is the first medication in its class to be approved for PD. It acts on the adenosine receptor, which modulates the dopaminergic system, but is not directly dopaminergic. The drug was developed in Japan and underwent clinical trials both in Japan and in the US.
- Opicapone (Ongentys®) is a catechol-O-methyltransferase (COMT) inhibitor that is taken once a day. It was approved in the US in 2020 as an add-on therapy to levodopa for motor fluctuations.
- Safinamide (Xadago®) Safinamide was approved in 2017 as an add-on therapy to carbidopa/ levodopa for the treatment of OFF It is a selective monoamine oxidase B (MAO-B) inhibitor but has other mechanisms of action as well such as inhibition of glutamate release.
Previous restrictions on the intake of foods containing tyramine (for example, aged cheeses, red wine, and draft beers) with selective MAO-B inhibitors have been relaxed by the Food and Drug Administration (FDA). However, MAO-B inhibitors can interact with other medications, such as certain antidepressants, nasal decongestants, and narcotic pain medications. Typically, if a person is undergoing a procedure in the hospital and is taking a selective MAO-B inhibitor, they are advised to stop the medication two weeks prior to the procedure and to restart it 1-2 weeks after the procedure to avoid any unintentional medication interactions.
New formulations of levodopa designed to be used as needed if medication effects wear off
- Levodopa inhalation powder (Inbrija®) Levodopa inhalation powder was approved in 2018 to be used as needed if medication effects wear off between oral doses of carbidopa/levodopa. A breath-activated inhalation device is provided into which capsules of 42 mg of levodopa are inserted. One dose consists of two capsules. Absorption of the medication is through the pulmonary tree which bypasses the GI tract as the location of absorption. One limitation of the system is that the device can’t be pre-loaded, so a capsule needs to be unwrapped and inserted into the inhalation device when needed. A person with PD who is attempting to use the inhalation device while OFF may find this fine motor manipulation difficult. The capsules only contain levodopa without a dopa-decarboxylase inhibitor, which means that the inhalation powder needs to be added to a regimen of carbidopa/levodopa.
Other medications used as needed if medication effects wear off
- Apomorphine HCl sublingual film (Kynmobi®) Apomorphine is a dopamine agonist whose effects have a rapid onset. It can be used as a rescue medication for someone whose dose of levodopa wears off unexpectedly before the next dose is due. Apomorphine is available as an under the skin injection. In 2020, a sublingual film (Kynmobi®) was approved which can be used as needed during the day if medication effects wear off.
This new route of delivery can have some side effects including dry mouth, oral mucosal irritation and swelling, and throat irritation, which may lead to discontinuation of treatment. In addition, apomorphine (both injectable and sublingual) can induce nausea, leading to the recommendation that it be taken with an anti-emetic, typically trimethobenzamide. Often, the anti-emetic is used only as apomorphine is started and does not need to be continued long-term.
Medications for dyskinesias
- Amantadine formulations (Gocovri® and Osmolex ER™) Originally used to prevent or treat influenza, amantadine was observed to ease the tremor of Parkinson’s as well as muscle It has therefore been used as an adjunct medication to other therapies for PD. In addition, it was also observed to be effective at decreasing dyskinesias caused by levodopa.
In 2017, amantadine extended-release capsules ( Gocovri®), was approved. It is taken once daily at night and is indicated for both the treatment of levodopa-induced dyskinesias and for reduction of OFF time. It is designed to provide an initial lag, followed by a slow rise in amantadine concentration during the night, and a high concentration in the morning and through the waking day. In 2018, a second extended-release formulation of amantadine (Osmolex ER™) was approved. It is taken once daily in the morning and is indicated for the treatment of PD motor symptoms as well as drug-induced parkinsonism.
Despite the new treatments discussed above, PD presents significant challenges for many people, especially as the disease advances. Research focused on improvement of motor and non-motor symptoms continues. In addition, discovering treatments that will slow down or halt disease progression is a major emphasis of current PD research, with the hope that soon medications will not only be available to treat symptoms, but to improve the course of PD.
Tips and Takeaways
- Seven new medications have been approved for Parkinson’s motor symptoms since 2017
- Talk with your doctor about whether any of the new medications may benefit you
- It can take time (and patience) to find the best balance of medication for your specific situation. Some trial and error may be required, but don’t give up too quickly – some small adjustments could eventually make a big difference.
- Despite the new treatments, PD continues to present challenges and the research community is focused on a treatment that will not just treat symptoms but will slow down or halt disease progression