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All About Selegiline: Medical Uses, Mechanisms, Side-Effects and More

Written by Biljana Novkovic, PhD | Last updated:
Jonathan Ritter
Matt Carland
Puya Yazdi
Medically reviewed by
Jonathan Ritter, PharmD, PhD (Pharmacology), Matt Carland, PhD (Neuroscience), Puya Yazdi, MD | Written by Biljana Novkovic, PhD | Last updated:

Selegiline is a prescription medication that helps reduce symptoms of early-stage Parkinson’s disease and is also effective against depression. It is also sometimes used “off-label” to treat some symptoms of ADHD, and some early research suggests it may have a number of other interesting effects. Read on to learn more about the common uses of this drug and how it works!

Disclaimer: This post is not a recommendation or endorsement for selegiline. This medication is only approved for the treatment of certain specific medical conditions, and can only be taken by prescription and with oversight from a licensed medical professional. We have written this post for informational purposes only, and our goal is solely to inform people about the science behind selegiline’s effects, mechanisms, and current medical uses.

What Is Selegiline?

Selegiline – also known as L-deprenyl – is a drug similar in structure to the neurotransmitter phenylethylamine [1].

It has a wide spectrum of uses, the most common being ones that involve brain health.

Officially, it has been FDA-approved for the treatment of Parkinson’s disease and depression. Selegiline is also sometimes used “off-label” to treat ADHD.

Mechanism of Action

Selegiline primarily blocks the activity of MAO-B and – at higher doses – also MAO-A. These enzymes break down dopamine and other monoamine neurotransmitters (serotonin and noradrenaline). Thus, by blocking the activity of these enzymes, selegiline increases the overall level of these neurotransmitters [2].

Some evidence also suggests that selegiline can be metabolized into by-products that may further increase dopamine levels in the brain, such as [3, 4]:

  • L-desmethylselegiline
  • L-amphetamine
  • L-methamphetamine

While many different specific mechanisms may be involved in its effects, overall it is believed that selegiline’s effects come primarily from higher levels of dopamine, serotonin, and noradrenaline throughout the brain.

Official Medical Uses

Selegiline has a number of primary medical uses that have been fully approved by the FDA. Although this means that the evidence for its efficacy in these conditions is very strong, always keep in mind that this is a prescription medication that must only be used under the direction and supervision of a qualified medical professional.

1) Selegiline and Parkinson’s Disease

One of the primary and most common uses for selegiline is to treat the symptoms and progression of Parkinson’s disease (PD).

This use stems primarily from selegiline’s ability to increase dopamine levels in the brain. This is important because many of the symptoms of Parkinson’s are caused by reduced levels of dopamine as cell death spreads throughout dopamine-related parts of the brain [4, 5].

Relatedly, it is believed that increased dopamine levels may compensate for the loss of dopamine neurons in PD, which may be why dopamine-enhancing drugs such as selegiline have been reported to improve the movement impairments characteristic of Parkinson’s disease (especially slowness of movement, or bradykinesia) [6, 7].

For example, selegiline was reported to improve motor symptoms in 292 patients with early Parkinson’s disease (double-blind randomized controlled trial) [8].

Similarly, in a double-blind randomized controlled trial of 157 Parkinson’s disease patients, selegiline (10 mg/day) delayed the need for levodopa therapy. It was also reported to slow down the progression of Parkinson’s disease symptoms when used in combination with levodopa, compared to just levodopa alone [9, 5, 10].

In addition to increasing dopamine levels, some evidence suggests that selegiline may also block the effects of MPTP, a neurotoxic compound that causes permanent symptoms of Parkinson’s [5].

Unfortunately, while several of the above studies have reported that selegiline may slow down the progression of symptoms in Parkinson’s disease, it may not ultimately increase lifespan in PD patients. For example, one study found that while selegiline delayed the motor impairments of Parkinson’s patients, this effect did not translate into reduced mortality rates [11].

2) Selegiline and Depression

Another common medical use of selegiline is to treat depression.

It is generally believed that selegiline acts as an antidepressant due to its reported ability to increase the levels of dopamine, serotonin, and norepinephrine throughout the brain [12].

A meta-analysis of 5 different clinical studies reported that selegiline helped alleviate several key symptoms of major depression, including [12]:

  • Depressed mood
  • Persistent feelings of guilt and/or anxiety
  • Oversleeping
  • Overeating
  • Poor concentration
  • Lack of sex drive

Another meta-analysis of 5 short-term trials (with a combined total of 352 subjects) concluded that selegiline significantly improved several different symptoms of major depressive disorder [13].

According to one double-blind randomized controlled trial of 322 subjects with major depression, depressed patients who received selegiline were significantly less likely to relapse, or took a longer time to relapse [14].

Selegiline has also been reported to improve symptoms of apathy in 4 patients following severe brain injury [15]. Because apathy is also one of the main symptoms of depression, this could be considered additional evidence for its effectiveness in alleviating depression.

However, not all of the available evidence supports the efficacy of selegiline in depression. For example, in one double-blind randomized controlled trial in 308 adolescents (12-17 years old) with major depressive disorder, selegiline was reported to have the same effect as an inactive placebo treatment [16].

Nonetheless, while not all of the evidence out there unanimously supports selegiline’s effectiveness as an antidepressant, the fact that it has been officially approved by the FDA for the treatment of depression indicates that the overall weight of the evidence is considered by medical experts to be quite strong.

Off-Label Uses of Selegiline

Occasionally, doctors will prescribe medications to help treat conditions that fall outside of the official uses approved by the FDA – also known as “off-label” drug use [17]. Usually this is done because there is actually decent evidence that the drug may help, although this evidence might not be quite strong enough to get full FDA approval (which generally has very strict requirements).

As always, however, always remember that the decision to use medications in this way can only be made by a licensed medical professional.

Selegiline and ADHD

Although selegiline has not been officially FDA-approved for this purpose, it is not uncommon for doctors to prescribe this medication in order to help improve or control the symptoms of ADHD.

The main rationale for using selegiline in this way stems from its potential to increase dopamine levels throughout the brain. One of dopamine’s many important functions is to promote attention and focus. Additionally, low levels of dopamine in certain specific parts of the brain are believed to be responsible for some of the attention problems frequently seen in ADHD [18].

Although the evidence for this use of selegiline is not quite as strong as it is for Parkinson’s and depression, there is still considerable scientific support behind its use in ADHD. For example, in a double-blind randomized controlled trial in 11 children with ADHD, selegiline was reported to improve sustained attention, learning, and peer interactions, while also reducing hyperactivity [19].

Similarly, in different two double-blind randomized controlled trials with 40 and 28 children each, this drug was reported to be as effective as methylphenidate (a central nervous system stimulant, commonly sold as Ritalin) in improving the symptoms of ADHD. Better yet, selegiline was also reported to cause fewer side effects [20, 21].

However, at least one study contradicts some of this evidence: in one study of 24 adults with ADHD, selegiline was reported to be no more effective than placebo in improving ADHD symptoms [22].

Other Possible Effects of Selegiline

Due to its ability to affect many different important biological mechanisms, selegiline may have a number of additional effects on brain and bodily health. However, keep in mind that all of the effects described below are still in a very early stage of research, and much more research will still be needed to fully confirm any of these effects in humans – so take the findings below with a healthy grain of salt!

1) Selegiline and Oxidative Stress

Some early evidence from animal and cell studies suggests that selegiline may have some antioxidant effects, although it’s not yet known for sure exactly how strong these effects are, or how they might work.

For example, selegiline was reported to prevent the death of neurons caused by oxidative stress in animals and cells [23, 24].

Some evidence from cell studies suggests that this potential anti-oxidant effect may stem from selegiline’s ability to increase levels of the antioxidant enzymes superoxide dismutase (SOD), catalase, and glutathione (GSH) in the mitochondria of rat neurons [25, 5, 26].

Nonetheless, much more research will be needed to figure out what the possible mechanisms are, and if they might apply to humans, so it’s still too early to tell for sure.

2) Selegiline and Brain Repair

According to one animal study, selegiline increased brain-derived neurotrophic factor (BDNF) and glial cell-derived neurotrophic factor (GDNF) levels in a mouse model of Parkinson’s disease [27]. BDNF and GDNF are important for brain health and brain repair.

Similarly, one cell study reported that selegiline may increase BDNF, GDNF, and nerve growth factor (NGF) levels in brain cells [28, 29].

In theory, these effects could potentially protect the brain from the effects of aging or disease – but much more research will still be needed to know the full extent of these effects, as well as if they would apply to human users.

3) Selegiline, Memory, and Learning

According to one study in 32 Parkinson’s disease patients, individuals who were treated with selegiline also showed some potential signs of improved memory and cognitive function [30].

Although many more studies in humans would be necessary to fully confirm any cognitive effects of selegiline, there is also some early evidence from a few animal studies that possibly points in this direction as well.

For example, selegiline was reported to enhance memory in mice with amnesia [31].

Selegiline was also reported to improve learning in aging rats [32, 33].

However, until a lot more human work is done, it’s too early to tell how significant these cognitive effects might be, or if they would translate to humans as well.

4) Selegiline and Alzheimer’s

According to a large-scale review of multiple clinical studies, 8 of 11 clinical trials reported 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 disease [34].

Selegiline was also reported to improve memory in 173 subjects with mild-to-moderate Alzheimer’s disease [35].

One animal study also reports that selegiline may have reversed cognitive impairments in mice caused by the buildup of amyloid-beta peptide (one of the main biological mechanisms believed to contribute to the development of Alzheimer’s) [36].

However, the evidence is still mixed: for example, two meta-analyses (of 17 and 13 double-blind randomized controlled trials) concluded that selegiline’s therapeutic effect in Alzheimer’s disease was most likely non-significant, and possibly entirely ineffective [37, 38].

5) Selegiline, Wakefulness, and Narcolepsy

According to two double-blind randomized controlled trials with 30 and 17 narcoleptic patients, selegiline was reported to decrease both the number and duration of daytime sleep episodes [39, 40].

This early finding may be supported up by at least one animal study, which reported that selegiline may increase wakefulness in rats (specifically, by increasing dopamine and noradrenaline levels in the brain) [41].

6) Selegiline and Motivation

Because dopamine is highly involved in motivation – and because one of selegiline’s mechanisms of action is to increase dopamine levels – there has been some speculation that selegiline use could cause increased levels of motivation, similar to how traditional stimulants are commonly abused [42, 43].

Although specific human studies on this effect are generally lacking, the concern over possible misuse of selegiline for its potential stimulant-like effects has led to it being classified as a banned substance for athletes by the world anti-doping agency [44, 45].

7) Selegiline and Schizophrenia

According to one pilot study on 21 schizophrenia patients, selegiline was reported to reduce some of the cognitive and depressive symptoms of schizophrenia [46].

Furthermore, in two double-blind randomized controlled trials of 67 and 40 patients with chronic schizophrenia, the combination of selegiline with antipsychotic medication was reported to be more effective at reducing negative symptoms compared to just antipsychotic medication alone [47, 48].

While this evidence is definitely not yet strong enough to justify the widespread medical use of selegiline for schizophrenia, these early findings might pave the way for more research on this in the future.

8) Selegiline and Stroke Recovery

According to one double-blind randomized control trial in 24 stroke patients, selegiline was reported to have shortened recovery times [49].

Similarly, in one animal study, selegiline was reported to increase resistance to stroke, and even possibly reduce brain damage after stroke in mice [50].

However, if this effect is real, the mechanisms still haven’t been figured out – so a lot more research will still be needed.

9) Selegiline and Chronic Fatigue Syndrome

According to one double-blind randomized controlled trial, selegiline was reported to improve anxiety, vigor, and sexual relations in 25 patients with chronic fatigue syndrome (CFS) [51].

10) Selegiline and Drug Addiction

Some very early evidence suggests that selegiline may have some potential in helping treat drug addiction – although the available research is currently quite mixed.

In 12 cocaine-dependent volunteers, selegiline was reported to decrease the physical (blood pressure and heart rate) and subjective (good effects, stimulated, high, desire for cocaine) effects of cocaine [52]. The idea is that by making the cocaine less “rewarding” to users, it would be easier for them to quit abusing the drug.

However, in a double-blind trial of 300 subjects with cocaine dependence, selegiline was reported to be no more effective at blocking these pleasurable effects than placebo [53].

11) Selegiline and Nicotine Cravings

A handful of studies suggest that selegiline may have potential in helping people quit smoking by reducing nicotine cravings.

The theory behind this is based on the fact that some of nicotine’s effects are to block MAOs and to increase dopamine. Since selegiline has similar mechanisms, the idea is that giving smokers small amounts of selegiline could make them less dependent on nicotine for these effects [54].

However, so far the only evidence on this is for people with specific genetic variants.

For example, selegiline-treated smokers with a specific nicotine-sensitive genotype (CHRNA5 rs680244 GG) experienced [55]:

  • Lower cravings for nicotine after quitting smoking
  • Less depression symptoms after quitting
  • Higher rates of continued abstinence (i.e. more likely to succeed at quitting in the long-term)

One possible explanation for this is that selegiline blocks the breakdown of nicotine by the CYP2A6 enzyme – this would prolong the effects of nicotine when users smoke less, thereby reducing the overall amount that they smoke [56, 57].

12) Selegiline and Seizures

A handful of animal studies suggest that selegiline may have potential in preventing or controlling seizures.

For example, selegiline has been reported to prevent seizures in mice with epilepsy [58, 59, 60].

A similar effect has also been reported in a rat model of epilepsy [61].

Nonetheless, it goes without saying that studies in human patients would be needed to see if this effect holds up.

Selegiline SideEffects

While selegiline has been approved for safety and efficacy when used as directed, like any other drug it still has its share of potential side-effects that it is important to be aware of.

Keep in mind that the best way to minimize your overall risk of experiencing side-effects is to use this medication only as directed by your doctor, and to keep him or her fully informed about any other medications you are taking, other health conditions, and other relevant factors that may impact your treatment.

May Increase Blood Pressure

High doses (> 10 mg/day) of selegiline have been reported to prevent the MAO-A enzyme from breaking down tyramine. Tyramine in the bloodstream is turned into norepinephrine, which causes blood vessels to constrict. This causes blood pressure to rise, which in some cases could potentially lead to elevated blood pressure (hypertension) [62, 63].

Tyramine is a naturally-occurring amino acid found in fermented meat, soy products, and aged cheese. People using selegiline may be at increased risk of experiencing high blood pressure if they consume too much tyramine (>6 mg) – so talk to your doctor about possibly cutting back on these foods if you are taking selegiline [62, 64].

Other SideEffects

Like other MOA blockers, selegiline can have mild-to-severe side effects, such as [4, 65, 66, 67]:

  • Dizziness
  • Mouth sores (tablet only)
  • Nausea
  • Insomnia
  • Indigestion
  • Anxiety/agitation
  • Increased or abnormal sexual desire
  • Depression
  • Severe headache
  • Irregular heartbeat
  • Vomiting
  • Uncontrollable shaking
  • Hallucinations
  • REM behavior disorder, which is characterized by acting out in one’s dreams [68, 69]
  • Serotonin syndrome, which may possibly lead to seizures and coma

Selegiline withdrawal has also been reported to cause low blood pressure in Parkinson’s disease patients, although it’s still unclear whether this is a potential side-effect for people without Parkinson’s [70, 71].

Selegiline Contraindications

As with many medications, there are some other factors that can interfere with taking selegiline, and which could cause potentially severe side-effects if not taken into account. For this reason, there are a few indicators that a person should actively avoid taking selegiline.

As always, the best way to avoid complications from this medication is to use it only as directed by your doctor, who will take these potential factors into account when deciding whether or not to prescribe it for you.

Some of the known contraindications include [72]:

  • Past hypersensitivity reaction to selegiline or any of its components.
  • Those taking or given meperidine (Demerol).

Due to its possible effects on blood pressure, selegiline should not be used within 10 days before surgery [72].

Use During Pregnancy and Breastfeeding

Selegiline was classified as a category “C” risk drug during pregnancy under the old FDA risk classifications. The risks of selegiline use during pregnancy have not been properly investigated. Therefore, make sure you let your doctor know if you are pregnant (or are planning on becoming pregnant while being treated with selegiline).

It also is not yet known if selegiline is found in breast milk, and caution is therefore generally advised during breastfeeding. In general, discontinuation is advised unless the therapy is absolutely necessary – but [73].

Drug Interactions

There are a few known interactions between selegiline and other medications that may potentially cause issues.

As always, the best way to minimize your risk is to keep your doctor up-to-date about any ongoing medications you are taking.

Some of these potential interactions include:

  • Other antidepressants like fluoxetine (Prozac, Sarafem), clomipramine, and selective serotonin reuptake inhibitors (SSRIs) in general [74, 75, 76, 77]
  • MAO inhibitors (MAOIs) like linezolid or moclobemide [78]
  • Opioids or opioid-like drugs such as tramadol, dextromethorphan, methadone, or propoxyphene [78, 79, 80]
  • Phenethylamine [81]

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 [72].

One study reported that women using hormonal birth control had excess levels of selegiline (10-20 times higher than normal) after treatment [82]. For this reason, the study’s authors suggest that the doses of one or both of these medications should be reduced when taken together. As always, make sure your doctor knows about all your current medications so that he- or she can help you avoid these potential issues.

Interactions with non-medical drugs are also possible. For example, due to selegiline’s effects on several major neurotransmitter systems, it should also never be combined with alcohol [72]. If you are prescribed selegiline, talk to your doctor about cutting back (or even completely stopping) alcohol consumption.

Forms and Dosage

Selegiline is only available legally via prescription. It typically comes 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 pills per day [63].

The patch (Emsam) is available in 6, 9, or 12 mg strengths [83].

According to several researchers, selegiline patches may have one major advantage over other forms of this medication, in that they appear to be associated with significantly fewer side-effects than other forms [4, 84, 85, 86]. However, your doctor will work with you to choose the form that makes the most sense for you, based on your particular medical history and needs.

In general, higher doses of selegiline (6 – 20 mg per day) are reported to be more effective at treating depression [87]. However, there are many different factors that go into choosing dose size, and only your doctor has the necessary training to determine which dose size is best for any individual case.

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.

About the Author

Biljana Novkovic

Biljana Novkovic

Biljana received her PhD from Hokkaido University.
Before joining SelfHacked, she was a research scientist with extensive field and laboratory experience. She spent 4 years reviewing the scientific literature on supplements, lab tests and other areas of health sciences. She is passionate about releasing the most accurate science and health information available on topics, and she's meticulous when writing and reviewing articles to make sure the science is sound. She believes that SelfHacked has the best science that is also layperson-friendly on the web.


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