Understanding Selegiline and Its Mechanism
Selegiline is a medication primarily used as an adjunct therapy in managing Parkinson's disease for patients treated with levodopa/carbidopa who experience a decline in response [1.8.3]. It is also used to treat major depressive disorder, particularly in its transdermal patch form (Emsam) [1.8.2]. Selegiline belongs to a class of drugs called monoamine oxidase inhibitors (MAOIs). Specifically, at recommended doses for Parkinson's (10 mg/day), it is a selective, irreversible inhibitor of monoamine oxidase type B (MAO-B) [1.8.3].
MAO-B is an enzyme that breaks down neurotransmitters like dopamine in the brain [1.8.3]. By inhibiting this enzyme, selegiline increases the amount of available dopamine, which helps alleviate the motor symptoms of Parkinson's disease caused by dopamine deficiency [1.8.3]. At higher doses, or with the transdermal system used for depression, selegiline loses its selectivity and also inhibits MAO-A, which can lead to more significant interactions and side effects [1.8.2, 1.8.3].
Common Adverse Effects of Selegiline
Many patients taking selegiline experience mild to moderate side effects. The frequency and type can vary depending on the dosage form (oral tablet, orally disintegrating tablet, or transdermal patch) and whether it's used alone or with other medications like levodopa [1.3.2, 1.4.3].
Common side effects include:
- Neurological: Dizziness, lightheadedness, headache, and insomnia are very common [1.4.3, 1.3.2]. Some patients may experience vivid dreams or difficulty sleeping [1.3.2].
- Gastrointestinal: Nausea is a leading side effect, occurring in up to 20% of patients using tablets [1.3.2]. Dry mouth, stomach pain, and constipation are also frequently reported [1.3.2, 1.4.2].
- Application Site Reactions (Transdermal Patch): For those using the Emsam patch, skin reactions at the application site are the most common adverse event, affecting about a third of patients [1.7.2, 1.7.4].
- Oral Irritation (Orally Disintegrating Tablets): The orally disintegrating form (Zelapar) can cause mouth sores, pain, and irritation of the buccal mucosa [1.4.1, 1.4.2].
- Cardiovascular: Orthostatic hypotension (a drop in blood pressure upon standing) can cause dizziness and fainting and is a significant risk, especially in elderly patients [1.4.2, 1.9.3].
Serious Adverse Effects and Medical Emergencies
While less common, selegiline is associated with several potentially life-threatening adverse effects that require immediate medical attention.
Hypertensive Crisis
This is a rapid, severe increase in blood pressure that can be fatal [1.11.4]. It is a classic risk associated with MAOIs when taken with tyramine-rich foods or certain medications [1.11.1, 1.11.2]. At standard Parkinson's doses (10mg/day), selegiline is selective for MAO-B, which minimizes this risk [1.4.4]. However, the risk increases significantly at higher doses or with non-selective forms like the higher-strength transdermal patches [1.8.3].
Foods high in tyramine to avoid include:
- Aged cheeses (cheddar, blue cheese, swiss) [1.11.2]
- Aged, cured, or fermented meats and fish (salami, pepperoni, pickled herring) [1.5.2]
- Fermented soybean products (soy sauce, miso) and fava beans [1.5.2]
- Sauerkraut [1.11.2]
- Tap beer and some wines [1.11.2]
Symptoms of a hypertensive crisis include a severe headache, stiff neck, chest pain, rapid heartbeat, nausea, vomiting, and sweating [1.11.4].
Serotonin Syndrome
This potentially fatal condition occurs when there is an excess of serotonin in the body [1.10.3]. The risk is highest when selegiline is combined with other medications that increase serotonin levels, such as SSRI and tricyclic antidepressants, certain opioids (like meperidine and tramadol), and the cough suppressant dextromethorphan [1.10.1, 1.10.3, 1.12.4]. Symptoms include agitation, confusion, hallucinations, high fever, rapid heart rate, muscle twitching or stiffness, and shivering [1.10.3]. A washout period of at least 14 days is required when switching between selegiline and these medications [1.8.3].
Other Serious Risks
- Impulse Control Disorders: Patients may experience intense urges to gamble, binge eat, shop compulsively, or have increased sexual urges [1.4.1].
- Hallucinations and Psychosis: Selegiline can cause or worsen hallucinations (seeing or hearing things that aren't there) and trigger psychotic-like behavior [1.3.2, 1.12.4].
- Sudden Onset of Sleep: Some individuals have reported falling asleep suddenly during daily activities like driving or talking, sometimes without prior warning of drowsiness [1.3.4, 1.4.1].
- Neuroleptic Malignant Syndrome (NMS)-like Symptoms: Abruptly stopping or rapidly reducing the dose of selegiline can lead to a serious condition with symptoms like high fever, muscle rigidity, and altered consciousness [1.4.1, 1.5.5].
Comparison of Adverse Effects: Oral vs. Transdermal
The route of administration affects the side effect profile of selegiline.
| Adverse Effect Category | Oral Selegiline (Tablets/ODT) | Transdermal Selegiline (Emsam Patch) |
|---|---|---|
| Primary Indication | Parkinson's Disease (adjunct) [1.8.3] | Major Depressive Disorder [1.8.2] |
| Tyramine Interaction | Low risk at 10 mg/day dose; dietary restrictions often not needed [1.8.3]. Risk increases at higher doses [1.4.1]. | No dietary restrictions needed at the lowest dose (6 mg/24h) [1.11.4]. Restrictions required for 9 mg and 12 mg doses [1.8.4]. |
| Common GI Effects | Nausea (up to 20%), dry mouth, constipation are more prominent [1.3.2]. | Diarrhea and dry mouth occur, but generally fewer GI side effects than oral MAOIs [1.7.3, 1.7.4]. |
| Local Site Effects | Irritation, sores, and pain in the mouth (with ODT form) [1.4.1]. | Application site reactions (rash, itching, redness) are very common (up to 24%) [1.7.4]. |
| Other Common Effects | Dizziness, insomnia, confusion, hallucinations [1.3.2]. | Headache, insomnia, and diarrhea are most common [1.7.4]. |
Conclusion
An adverse effect of selegiline can range from manageable symptoms like nausea and dizziness to severe, life-threatening emergencies such as hypertensive crisis and serotonin syndrome. The risk profile is heavily influenced by the dose, the formulation (oral vs. transdermal), and interactions with other medications and tyramine-containing foods [1.4.3, 1.8.3]. Close monitoring by a healthcare provider, adherence to dosage, and patient education on critical warning signs and necessary dietary or medication restrictions are essential for the safe and effective use of selegiline [1.8.1, 1.12.4].
Authoritative Link: For more detailed information from a trusted source, please visit the Mayo Clinic's page on Selegiline (Oral Route). [1.3.3]
