Selegiline is a prescription medication that helps reduce symptoms of early-stage Parkinson’s disease and is also effective against depression. In addition, it increases wakefulness and motivation, may improve cognitive function, and may even increase longevity.
Disclaimer: By writing this post, we are not recommending this drug. Some of our readers who were already taking the drug requested that we commission a post on it, and we are simply providing information that is available in the clinical and scientific literature. Please discuss your medications with your doctor.
What Is Selegiline?
Selegiline, also known as L-deprenyl, is a drug similar in structure to the neurotransmitter phenylethylamine .
It has a wide spectrum of uses, the most common being ones that involve brain health.
Selegiline Mechanism of Action
As a result, there are higher levels of dopamine, serotonin, and noradrenaline in the brain.
Uses of Selegiline
1) Helps with Parkinson’s Disease
Selegiline improved symptoms in 292 patients with early Parkinson’s (double-blind randomized controlled trial) .
In a study of 157 Parkinson’s disease patients (double-blind randomized controlled trial), selegiline (10 mg/day) delayed the need for levodopa therapy. It also slowed down the progression of disease symptoms when used in addition to levodopa, compared to levodopa alone [8, 4, 9].
Selegiline blocks the effects of MPTP, a brain toxin that causes permanent symptoms of Parkinson’s disease .
However, it likely does not affect lifespan in Parkinson’s disease patients .
2) Helps Combat Depression
A meta-analysis of 5 clinical studies showed that selegiline patches successfully treated symptoms of major depression such as :
- Depressed mood
- Poor concentration
- Lack of sex drive
Another meta-analysis of 5 short-term trials with 352 subjects concluded that this drug improved symptoms in major depressive disorder .
In 322 subjects with major depression (double-blind randomized controlled trial), those who received the drug were less likely to relapse or took a longer time to relapse .
However, in 308 adolescents (12 to 17 years old) with major depressive disorder (double-blind randomized controlled trial), both selegiline and placebo decreased depression symptoms to a similar extent .
This drug also improved apathy in 4 patients following severe brain injury .
An important benefit of selegiline patches is that they produce fewer side effects than oral treatments, and they don’t require the same dietary restrictions as other drugs of the same type [3, 16, 17, 18, 17].
3) Is an Antioxidant
4) May Assist in Brain Repair
This drug increased brain-derived neurotrophic factor (BDNF) and glial cell-derived neurotrophic factor (GDNF) levels in a mouse model of Parkinson’s disease . BDNF and GDNF are important for brain health and brain repair.
5) May Improve Memory and Learning
In a study with 32 Parkinson’s disease patients, those who received selegiline had improved memory and cognitive function .
This drug enhanced memory in mice with amnesia .
6) May Improve Alzheimer’s Symptoms
In a review of clinical studies, 8 of 11 trials showed that selegiline improved cognitive function (word fluency and total recall), and 2 of 5 trials showed it improved behavior (anxiety and depression) associated with Alzheimer’s .
Selegiline improved memory in 173 subjects with mild to moderate Alzheimer’s disease .
7) May Increase Wakefulness and Improves Narcolepsy
8) May Increase Motivation
9) May Improve ADHD
In 11 children with ADHD (double-blind randomized controlled trial), selegiline improved sustained attention, learning, and peer interactions, and reduced hyperactivity .
In two double-blind randomized controlled trials with 40 and 28 children each, this drug was as effective as methylphenidate (a central nervous system stimulant, commonly sold as Ritalin) in improving ADHD, with fewer side effects [44, 45].
However, it was not more effective than placebo in 24 adults with ADHD .
10) May Be Beneficial for Schizophrenia
In a pilot study with 21 patients, selegiline reduced negative and depressive symptoms of schizophrenia .
Furthermore, in two double-blind randomized controlled trials of 67 and 40 patients with chronic schizophrenia, the combination of selegiline with antipsychotic medication showed superiority over antipsychotic medication alone in decreasing negative symptoms [48, 49].
11) May Help with Stroke Recovery
Selegiline improved recovery after stroke in 24 patients (double-blind randomized controlled trial) .
This drug seems to be beneficial after a brain infarction, by speeding up the recovery process.
It increased resistance to stroke and decreased brain damage after stroke in mice .
This drug improved anxiety, vigor, and sexual relations in 25 patients with chronic fatigue syndrome (double-blind randomized controlled trial) .
13) May Help with Drug Withdrawal
However, in a double-blind trial of 300 subjects with cocaine dependence, it was no more efficient than placebo .
14) May Reduce Nicotine Cravings
This drug may help people quit smoking by reducing nicotine cravings. Nicotine blocks MAOs and increases dopamine (hence the rewarding effect). Selegiline mimics the effects of nicotine on MAOs .
- Lower post-quit craving
- Less post-quit depression
- Higher rates of abstinence
15) May Prevent Seizures
16) May Increase Longevity
Selegiline may prevent physical decline. Hamsters treated with selegiline show less age-related decline in both mind and body .
However, a later study showed that this drug lengthened the lifespan of female but not male hamsters .
However, it prolonged lifespan in female rats only when they lacked sex organs .
Finally, selegiline also increased the lifespan of elderly dogs .
Side Effects of Selegiline
1) Can Cause High Blood Pressure
High doses (> 10 mg/day) of the drug stop MAO-A from breaking down tyramine. Tyramine in the bloodstream is turned into norepinephrine, which causes blood vessels to constrict, causing blood pressure to rise [71, 72].
Tyramine is a naturally-occurring amino acid found in fermented meat, soy products, and aged cheese. People using selegiline may experience high blood pressure due to excess tyramine after eating > 6 mg [71, 73].
2) May Cause Birth Defects
High-dose selegiline decreased fetal body weight in rats and caused a postimplantation loss in rabbits .
However, a pregnant woman with Parkinson’s disease was treated with selegiline and levodopa and gave birth to a healthy child .
3) Other Side Effects
Like other MOA blockers, selegiline can have mild to severe side effects.
- Mouth sores (tablet only)
- Increased or abnormal sexual desire
- Severe headache
- Irregular heartbeat
- Uncontrollable shaking
- REM behavior disorder, which is characterized by acting out in one’s dreams [79, 80]
- Serotonin syndrome (patch) that may lead to seizures and coma
It may worsen symptoms associated with involuntary movement (tardive dyskinesia) in Parkinson’s .
Contraindications of Selegiline
They include the following :
- Past hypersensitivity reaction to selegiline or any of its components.
- Those taking or given meperidine (Demerol).
- Selegiline should not be used within 10 days before surgery.
Selegiline Use During Pregnancy and Breastfeeding
Selegiline was a category C risk drug in pregnancy under the old FDA risk classifications. The risks of selegiline use during pregnancy have not been properly investigated. Therefore, if the potential benefits outweigh the potential risks, selegiline could be used during pregnancy.
It is not known if selegiline is found in breast milk, therefore caution is advised in its use during breastfeeding. Discontinuation is advised unless the therapy is absolutely necessary .
Drug Interactions of Selegiline
Selegiline should not be used together with these drugs because it can cause serious adverse effects:
- Other antidepressants like fluoxetine (Prozac, Sarafem), clomipramine, and selective serotonin reuptake inhibitors (SSRIs) [86, 87, 88, 89]
- MAO inhibitors (MAOIs) like linezolid or moclobemide 
- Opioids or opioid-like drugs such as tramadol, dextromethorphan, methadone, or propoxyphene [90, 91, 92]
- Phenethylamine 
The major enzyme in the body that metabolized selegiline is CYP2B6. Therefore caution is advised when patients are taking other medications metabolized by this enzyme .
Women using birth control had excess levels of selegiline (10-20 times higher than normal) after treatment .
Forms and Dosage of Selegiline
Selegiline is available via prescription in the form of capsules, tablets, orally disintegrating tablets (ODTs), or the transdermal patch.
Selegiline capsules or tablets (Eldepryl) are normally taken twice per day, with meals. However, dosages vary, with the most common being two 5 mg per day pills .
The patch (Emsam) is available in 6, 9, or 12 mg strengths .
Higher doses (6 to 20 mg per day) treat depression more effectively .
Limitations and Caveats
Potential benefits of this drug are based on a few clinical studies and need to be supported by larger clinical trials.
Some of the benefits have not been studied in humans.
It is always advised to be cautious when using this drug. All MAOIs should be obtained through a prescription, and only after consulting a physician.
Selegiline is a drug that affects your neurotransmitters. Want to understand your variants in these genes and how they affect your mood and tendency to respond to such drugs? Check out the Mood DNA Wellness Report here.