Pharmacists are no strangers to neurodegenerative disease. However, Parkinson’s cases present great difficulty to patients and clinicians, as our medical world lacks a solid understanding of the disease in comparison to other conditions. After Alzheimer’s disease, Parkinson’s is the second most prevalent neurodegenerative disease. It is estimated at least 1 million people in the U.S. suffer from Parkinson’s and up to 6 million worldwide. Parkinson’s has a large opportunity to negatively impact quality of life, therefore it is our responsibility to remain informed of all medication therapies to make individualized decisions with our patients. In this article, we will provide a breakdown of MAOIs in Parkinson’s
Parkinson’s is characterized by the loss of dopamine resulting in motor disturbances such as bradykinesia, rigidity, and resting tremor. There are a variety of medications that aim to replenish dopamine levels in the brain to help with motor symptoms depending on the state of progression. Monoamine oxidase type B (MAO-B) inhibitors are some of the earliest tried therapies for Parkinson’s, although they may not be seen as common as they once were. MAO-B is an enzyme that breaks down dopamine, therefore inhibiting MAO-B can help maintain higher levels of dopamine.
The three available MAO-B inhibitors include the following:
- Selegiline (Eldepryl/Deprenyl) 5 mg twice daily
- Rasagiline (Azilect) 0.5 mg or 1 mg once daily
- Safinamide (Xadago) 50 mg or 100 mg once daily
MAOIs in Parkinson’s (type B) are used as adjunct therapy in the early stages of the dieseae in combination with other medications (i.e., levodopa). Longitudinal studies have shown daily selegiline use resulted in 30-40% reduction of levodopa total daily dose, which may help reduce the “on” vs. “off” times (good vs. bad symptom response) that have been associated with levodopa use. They may be helpful in later stages as well, however, a functional benefit may be difficult to notice. The benefits are typically mild in comparison to levodopa and other dopamine agonists (i.e., pramipexole, ropinirole). They are considered to have low dopaminergic activity and carry few side effects such as nausea, dry mouth, lightheadedness, constipation, and insomnia. MAO inhibitors are also notorious for having multiple drug interactions, including contraindications with concomitant opioids and various antidepressants, so it is important to remain aware of this and double-check for wash-out periods when considering them for Parkinson’s treatment. Most drug-drug interactions result in an increased risk of serotonin syndrome (MAO-B breaks down serotonin along with dopamine) and hypertensive crisis.
MAOIs in Parkinson’s – Should we worry about the Tyramine interaction?
You may be curious about the so-called “cheese effect” that is a well-known concern with MAO inhibitors. MAO occurs in two isoforms, A and B. MAO-A is responsible for deaminating tyramine in the gut. Tyramine is an amino acid found in high amounts in many kinds of cheese, cured meats, and beer. When this process is blocked by MAO-A inhibitors (i.e., isocarboxazid, phenelzine), tyramine gets absorbed into the central nervous system and displaces stored norepinephrine, potentially resulting in a hypertensive crisis upon release. MAO-B is not involved in tyramine deamination in the gut, therefore inhibitors with high selectivity for MAO-B (i.e., selegiline) carry a lower risk of the “cheese effect” and can generally be used safely in Parkinson’s without worry for a low-tyramine diet. That being said, MAO-B inhibitors have a dose-dependent nature of selectivity, and it is recommended to consider diet restrictions when using above the recommended dose (i.e., 10 mg/day for selegiline).
There have not been any head-to-head comparisons between the three current MAO-B inhibitors available. Safinamide (Xadago) is the newest therapy (approved for use in 2017) and may be more expensive than selegiline and rasagiline. Unfortunately, we have not had many revolutionary ideas for decades when it comes to Parkinson’s progression and management. Treatment has remained fairly consistent with levodopa as the mainstay in therapy since the late 1960s. MAO-B inhibitors, specifically selegiline, had some evidence to support slowed progression of disease if used early on in therapy, however, we have been unable to confirm it as a disease-modifying agent based on FDA requirements. The time for new therapies to slow progression of Parkinson’s is long overdue and highly sought after by medical researchers. Until then, please remain diligent as a pharmacist to individualize medication therapy and encourage non-pharmacologic therapies such as physical therapy, occupational therapy, exercise (yoga, boxing, and tai chi have evidence to support benefits in PD), and social support when needed to optimize quality of life in Parkinson’s.
This article on MAOIs in Parkinson’s was written by Hannah Wetter, PharmD Candidate in collaboration with Eric Christianson, PharmD, BCGP, BCPS
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