Selegiline

Parkinson's Disease

Selegiline is primarily used to treat the symptoms of Parkinson's disease, including tremors, muscle stiffness, and loss of muscle control. It is typically prescribed as an add-on therapy for individuals who are already taking a combination of levodopa and carbidopa.

In the treatment of Parkinson's, selegiline is often used to help manage "off" episodes. These are periods when the effects of other medications wear off before the next dose is due, leading to a temporary return of symptoms such as difficulty moving or walking.

Major Depressive Disorder

A specific form of selegiline, applied as a transdermal (skin) patch, is used to treat major depressive disorder in adults. This delivery method allows the medication to be absorbed through the skin to help improve mood and emotional symptoms.

Typical Use Cases

• Combination Therapy: Used alongside levodopa and carbidopa to enhance symptom control in Parkinson's disease.
• Symptom Management: Helps reduce the severity of movement-related issues and may allow for a reduction in the required dose of other Parkinson's medications.
• Depression Treatment: Used as a standalone treatment for depression when administered via a skin patch.

Mechanism of Action

Selegiline belongs to a class of medications known as monoamine oxidase inhibitors (MAOIs). It specifically targets and blocks the activity of an enzyme in the brain called monoamine oxidase type B (MAO-B).

The primary role of the MAO-B enzyme is to break down dopamine, a chemical messenger that the brain uses to control muscle movement and coordination. In people with Parkinson's disease, there is a shortage of dopamine in certain areas of the brain. By blocking the enzyme that destroys dopamine, selegiline helps maintain higher levels of this chemical.

Selegiline affects the body in the following ways:

• Dopamine Preservation: It slows the natural breakdown of dopamine already present in the brain.
• Enhancing Other Treatments: When used with other Parkinson's medications like levodopa, selegiline helps those drugs work more effectively and for longer periods by protecting the dopamine they produce.
• Neurotransmitter Regulation: In certain forms, such as the transdermal patch used for depression, selegiline also helps increase the levels of other mood-regulating chemicals, including serotonin and norepinephrine.

Common Side Effects

Some side effects of selegiline may go away as your body adjusts to the medication. Common symptoms include:

• Dizziness, lightheadedness, or fainting
• Nausea, abdominal pain, or dry mouth
• Headache
• Insomnia or trouble sleeping
• Constipation or diarrhea
• Back pain or muscle aches
• Runny or stuffy nose and sore throat

Patients using the orally disintegrating tablet form may experience mouth sores or redness. Those using the transdermal patch may experience skin irritation where the patch is applied.

Serious Side Effects

Contact your doctor immediately or seek emergency care if you experience any of the following:

• Signs of a hypertensive crisis: severe headache, chest pain, nausea, vomiting, stiff neck, sweating, and sensitivity to light
• Hallucinations or confusion
• Unusual changes in behavior or intense urges, such as increased gambling, binge eating, or sexual urges
• Increased involuntary muscle movements or tremors
• Swelling in the hands, ankles, or feet

Drug Interactions and Serotonin Syndrome

Selegiline can cause a life-threatening condition called serotonin syndrome when combined with certain other medications. This risk is highest when taken with antidepressants (such as SSRIs, SNRIs, or tricyclic antidepressants), certain pain medications like meperidine, or other MAO inhibitors. Symptoms of serotonin syndrome may include agitation, hallucinations, rapid heart rate, fever, and muscle stiffness.

Hypertensive Crisis

At standard doses used for Parkinson's disease, selegiline is usually selective; however, at higher doses, it may lose this selectivity. This can lead to a dangerous increase in blood pressure, known as a hypertensive crisis, especially if the medication is taken with foods high in tyramine. Healthcare providers may recommend avoiding aged cheeses, air-dried meats, and fermented products while taking this drug.

Blood Pressure and Dizziness

This medication may cause orthostatic hypotension, which is a sudden drop in blood pressure when standing up from a sitting or lying position. This can lead to dizziness, lightheadedness, or fainting, increasing the risk of falls.

Behavioral and Mental Health Changes

Some individuals taking selegiline have reported intense urges to gamble, increased sexual urges, binge eating, or other compulsive behaviors. Additionally, the medication may cause or worsen hallucinations, confusion, or psychotic-like behavior, particularly in older adults or those also taking levodopa.

Other Precautions

• Dyskinesia: Selegiline may increase the side effects of levodopa, including involuntary movements or twitching (dyskinesia).
• Skin Cancer: People with Parkinson's disease may have a higher risk of developing melanoma. Regular skin examinations by a healthcare professional are often recommended.
• Withdrawal: Stopping selegiline abruptly may cause symptoms to worsen. A healthcare provider typically manages the discontinuation process.

Pregnancy

There are no adequate and well-controlled studies of selegiline use in pregnant women. Research in animals has shown some adverse effects on the fetus when the drug was given at doses much higher than those used in humans. Because the risks to a human pregnancy are unknown, selegiline should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

If you become pregnant or are planning to become pregnant, talk to your doctor about the potential risks and benefits of using this medication.

Breastfeeding

It is not known whether selegiline is excreted in human breast milk. Because many drugs can pass into breast milk and potentially affect a nursing infant, caution is advised. There is also a possibility that selegiline could interfere with milk production by lowering prolactin levels.

Healthcare providers typically recommend weighing the benefits of breastfeeding against the potential risks to the infant before using selegiline while nursing.

Available Forms

Selegiline is produced in the following forms:

• Oral Capsule: A standard capsule taken by mouth.
• Oral Tablet: A conventional tablet taken by mouth.
• Orally Disintegrating Tablet: A tablet designed to dissolve on the tongue.
• Transdermal Patch: A patch applied to the skin that releases medication over a period of time.

FDA-Approved Indications

The FDA has approved selegiline for different uses depending on the formulation:

• Parkinson's Disease: Oral forms, including capsules, tablets, and orally disintegrating tablets, are approved as an add-on treatment for patients with Parkinson's disease who are already taking levodopa and carbidopa and are experiencing a decrease in the effectiveness of those medications.
• Major Depressive Disorder: The transdermal patch formulation is FDA-approved for the treatment of major depressive disorder in adults.

Boxed Warning

The transdermal patch formulation of selegiline carries a boxed warning, which is the FDA's most serious warning. This warning highlights an increased risk of suicidal thoughts and behaviors in children, adolescents, and young adults taking antidepressant medications. This formulation is not approved for use in pediatric patients.

Regulatory Status

Selegiline is a prescription-only medication and is not classified as a controlled substance. While the oral forms were initially approved for Parkinson's disease, the transdermal patch for depression received FDA approval in 2006. Patients must be monitored for clinical worsening and the emergence of suicidal thoughts when using the medication for depression.

Risks of Stopping Selegiline

You should not stop taking selegiline or change your dosage without first consulting your healthcare provider. Abruptly discontinuing this medication can lead to a return of symptoms or specific withdrawal effects depending on the condition being treated.

Withdrawal Symptoms

When selegiline is used for depression, stopping the medication suddenly may lead to withdrawal symptoms. These can include:

• Mood changes
• Irritability
• Sleep problems or insomnia

Worsening of Parkinson's Symptoms

For individuals taking selegiline for Parkinson's disease, stopping the drug suddenly can cause symptoms such as tremors, stiffness, and difficulty moving to become significantly worse. In rare instances, a sudden stop or rapid reduction in medications that affect dopamine levels can lead to a serious condition characterized by high fever, muscle rigidity, and confusion. To avoid these risks, doctors typically recommend a gradual reduction of the dose rather than stopping all at once.