Rasagiline is a selective MAO-B inhibitor taken once daily to treat symptoms of early and advanced Parkinson’s.
Rasagiline was first approved for use as a Parkinson’s treatment in 2005 and continues to receive substantial attention from researchers and people living with Parkinson’s. Because of indications from clinical trials that rasagiline had a neuroprotective effect, this ongoing attention often focuses on whether rasagiline slows the progression of Parkinson’s. Additionally, MAO-B inhibition is a more complicated biochemical process than dopamine replacement therapy like levodopa and dopamine agonists, so rasagiline often raises questions for people with Parkinson’s, their families, and even some health professionals.
Rasagiline Overview
Monoamine Oxidase (MAO) is a family of enzymes involved in the metabolism of monoamine chemical messengers like dopamine and other neurotransmitters and other related substances. There are two types of MAO: MAO-A and MAO-B. The main differences between the two types of MAO are where they are most prominent in the body and what substances they primarily metabolize.
The first MAO inhibitor was used in the 1950s to treat tuberculosis and depression. The medication was withdrawn from use in the 1960s in most parts of the world because of its adverse effects on liver function. Early MAO inhibitors were non-selective, which means that they inhibited both MAO-A and MAO-B. This increased the risk of complications, especially concerning interactions with other drugs. Rasagiline is selective for MAO-B at the approved dosage, so it is safer than earlier MAO inhibitors.
How Rasagiline Improves Parkinson’s Symptoms
By inhibiting MAO-B, rasagiline decreases the breaking down of dopamine and thereby increases the amount of dopamine available in the brain. Additionally, a 2021 article reports that MAO-B inhibition may benefit Parkinson’s symptoms by decreasing the production of GABA, a neurotransmitter that decreases neuronal stimulation.
Rasagiline’s Recommended Use in Early and Advanced Parkinson’s
The American Academy of Neurology’s treatment guidelines for early Parkinson’s indicates that clinicians may prescribe MAO-B inhibitors as the initial dopaminergic therapy for people experiencing mild Parkinson’s symptoms. The guidelines also note that improvements in mobility are more significant with levodopa than with MAO-B inhibitors but that “initial treatment with levodopa may be more likely to induce dyskinesia.”
For people living with more advanced Parkinson’s, rasagiline helps to manage motor fluctuations. For example, in the PRESTO study, people who took rasagiline experienced a nearly 30% decrease in OFF time.
The Question of Neuroprotection
In the preclinical stages of development, rasagiline showed neuroprotective effects. Dr. John Finberg, one of the drug’s early researchers, said in an interview that rasagiline could have a neuroprotective effect by slowing dopamine metabolism, which generates reactive oxygen species, or that effect could result from some other cause.
Other methods proposed to explain how rasagiline could have a neuroprotective effect include:
- A 1999 animal-based study suggested that a neuroprotective effect could result from rasagiline’s influence on acetylcholine transmission. In people with Parkinson’s, ongoing imbalance in levels of acetylcholine is associated with multiple symptoms. Another connection between acetylcholine and rasagiline was reported in a 2006 laboratory study that found that rasagiline interrupted chemical reactions involving acetylcholine that resulted in cell death.
- A 2002 article reported that rasagiline can protect cells involved in neuronal growth from oxygen and glucose deprivation.
- A 2007 animal-based study found that rasagiline increased levels of neurotropic growth factors that are also associated with neuroplasticity and exercise.
- A 2019 study involving 44 people showed that those treated with rasagiline had increased blood flow in some areas of the brain.
Rasagiline’s Approval for Use to Treat Parkinson’s: Symptomatic Treatment Only
In the ADAGIO study, researchers found that treatment with 1 mg of rasagiline showed signs of a “possible disease-modifying effect,” while treatment with 2 mg did not show the same signs. Because of this discrepancy, the FDA did not approve rasagiline as a neuroprotective, disease-modifying therapy.
Despite this decision, researchers have continued to investigate whether rasagiline has neuroprotective effects, and at present, there is no consensus. For example, in 2017, analysis of data from a large trial that involved nearly 800 people who took an MAO-B inhibitor found that more prolonged exposure to an MAO-B inhibitor was associated with less progression of Parkinson’s; in contrast, a 2021 study evaluating rasagiline for neuroprotective effect found no signs of disease-modifying effect over one year of treatment with rasagiline.
Rasagiline Risks
While uncertainty around the neuroprotective effects of rasagiline remains, there is important data regarding safety of the medication.
The most common side effects in clinical trials included headache, nausea, lightheadedness, and insomnia. There were also reports of hallucination and orthostatic hypotension. Dyskinesia was also reported in clinical trials for rasagiline that allowed participants also to take levodopa, but it tended to resolve when the levodopa dose was lowered.
Additional risks include:
Serotonin Syndrome
Rasagiline slows serotonin metabolism, so when it is taken concurrently with other medications that have the same effect or increase serotonin levels, there is an elevated risk of serotonin syndrome. Types of drugs associated with this increased risk include:
- Multiple types of antidepressants
- Certain pain medications, like Demerol
- Cold and cough medications, including dextromethorphan
- Multiple recreational drugs
Notably, the risk of serotonin syndrome resulting from drug interactions with rasagiline is low. For example, a 2014 study involving over 1500 people found no cases of serotonin syndrome associated with the concurrent use of rasagiline and antidepressants. Moreover, an Australian government safety report found no incidence of serotonin syndrome during the clinical trial process for rasagiline, which involved thousands of people. However, this report notes that during a periodic review of safety data about rasagiline in 2009-2010, three cases of serotonin syndrome were found. These cases were suspected to involve concurrent use of rasagiline and antidepressants.
Blood Pressure Concerns
Rasagiline can contribute to dangerous blood pressure elevation when taken with certain sympathomimetic medications, including some drugs for weight loss, glaucoma, and urinary incontinence, as well as the common decongestants pseudoephedrine, phenylephrine, and ephedrine. Notably, the FDA reports in the prescribing information for rasagiline that this risk is low but advises caution, particularly with decongestants.
One reason for this advice is that decongestants can break down into substances that raise blood pressure, like norepinephrine. While these substances are not predominantly metabolized by MAO-B, it is possible that rasagiline would slow the process of breaking them down and thereby contribute to blood pressure elevation. Therefore, people taking rasagiline can find safer, non-pharmaceutical relief from nasal congestion by using warm compresses and rinsing.
Another risk factor for blood pressure elevation is eating foods with high levels of tyramine, such as aged meats and cheeses while taking rasagiline. This interaction is possible because tyramine elevates blood pressure, and tyramine can accumulate in the body when MAO is inhibited.
However, the FDA states that tyramine restriction is not generally required when taking rasagiline because MAO-A is prevalent in the digestive system, and MAO-A is not inhibited by rasagiline at the standard dosage. Still, there have been reports of tyramine-induced blood pressure elevation in people taking rasagiline, so the FDA advises that people taking rasagiline should avoid consuming food with high levels (over 150mg) of tyramine.
It is important to note that when rasagiline is taken at higher than recommended doses, it becomes less selective and inhibits both MAO-A and MAO-B. Hence, the risk of blood pressure elevation increases significantly if you take more than the recommended dose.
Other Interactions and Risks
In addition to elevating the risk of serotonin syndrome, using the cough medicine dextromethorphan with rasagiline is also associated with the risk of episodic psychosis. Notably, taking high doses of dextromethorphan in isolation is also a possible side effect.
Ciprofloxacin, a common antibiotic, can problematically increase the effects of rasagiline, so the FDA recommends that people taking both medications take a .5mg dose of rasagiline.
Rasagiline has not been tested in breastfeeding people, but animal studies showed that it interfered with milk production.
Visit the medications to avoid page of our medication guide to view a list of some other specific medications known to have interactions with rasagiline.
Consult Your Care Team
MAO inhibitors have complex risk factors, but rasagiline is considered a safe and well-tolerated medication. Still, because of the significance of the risks described above, you should consult with your medical care team:
- About all medications you take before you start rasagiline
- Before starting any new medication while taking rasagiline
- Before stopping rasagiline because it's important to taper off the use of the medication slowly
Rasagiline’s Benefits
Many studies demonstrate rasagiline’s symptomatic benefits for people with Parkinson’s. While these benefits are more modest than the symptomatic benefits from levodopa or dopamine agonists, there are many reasons why you and your care team might consider including rasagiline as part of your treatment plan to help you live well today and in the future.
Some specific benefits of rasagiline include:
The Ease of One Pill
Especially early in your time living with Parkinson’s, rasagiline can be the only pill you take to manage symptoms and improve your quality of life adequately. In contrast, most people who take levodopa take multiple doses each day, and for maximum efficacy, each dose must be carefully timed relative to meals.
Fewer Side Effects than Dopamine Agonists
The TEMPO study found that the “incidence of adverse experiences, particularly somnolence, peripheral edema, hallucinations, nausea, and constipation, is higher with dopamine agonists than was observed in this trial.”
Extending the Effects of Each Levodopa Dose and Managing Motor Fluctuations/Dyskinesia
Rasagiline can be beneficial as an adjunct to other medications. When paired with levodopa, rasagiline extends how long each dose of levodopa remains effective. This can lower the amount of levodopa you take and help manage motor fluctuations, including dyskinesia.
Improving Sleep
Rasagiline has been found to improve sleep quality when used in conjunction with levodopa. In one trial, participants who took rasagiline and levodopa fell asleep faster, slept longer, and woke up less frequently during the night than those who took only levodopa.
Helping with Gait Disturbances
In 2016, a small European study found that adding rasagiline to a person’s treatment corresponded with improvements in general mobility and freezing of gait. Data analysis from two more extensive studies, PRESTO and LARGO, found similar results.
Lessening Fatigue
Data from the ADAGIO study provides evidence that rasagiline lessens the progression of fatigue in people with Parkinson’s. A 2015 study finds additional evidence of rasagiline’s beneficial effects on fatigue.
Elevating Mood
Another critical but presently uncertain potential benefit of using rasagiline is that it may have mild mood elevation and stabilization effects.
The Possibility of Neuroprotection
The evidence that rasagiline has a neuroprotective effect for people with Parkinson’s is inconclusive at best. Despite this, many researchers and Parkinson’s specialists still think rasagiline may have neuroprotective effects. Especially in the context of the other known benefits of rasagiline, the possibility that rasagiline slows progression of Parkinson’s may be another reason for you and your care team to consider including it as a part of your treatment plan.
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