Categories & Effectiveness

Brain Health

Dopamine Support

10/10

Strong evidence of effectiveness

Brain Antioxidant Shield

7/10

Strong evidence of effectiveness

Neuro-Repair Support

7/10

Strong evidence of effectiveness

Neurogenesis (BDNF/NGF)

7/10

Strong evidence of effectiveness

Mood & Stress

Mood Elevation

7/10

Strong evidence of effectiveness

Systemic Health

Cellular Repair

7/10

Strong evidence of effectiveness

Systemic Antioxidant

4/10

Moderate evidence of effectiveness

Dosage & Side Effects

Recommended Dosage

The typical oral dosage for Parkinson's disease is 5 mg taken twice daily, often alongside L-dopa therapy, though doses up to 60 mg/day have been studied for psychiatric conditions. Transdermal patches delivering 6 mg to 12 mg per 24 hours are approved for major depressive disorder, bypassing initial metabolism and potentially leading to greater MAO-A inhibition alongside MAO-B. Due to the irreversible nature of its MAO-B inhibition and the enzyme's slow recovery (half-time around 40 days), some research suggests standard clinical doses might be higher than necessary for sustained MAO-B inhibition alone.

Potential Side Effects

Common mild side effects can include insomnia, dizziness, dry mouth (xerostomia, especially with oral forms), and application site reactions with the transdermal patch. Higher doses that lose selectivity for MAO-B and inhibit MAO-A increase the risk of hypertensive crisis if tyramine-rich foods are consumed (the "cheese effect"), although this is less common with selective MAO-B inhibition or the low-dose transdermal patch used without dietary restrictions. Potential severe risks, though rare, can involve interactions with other medications (like SSRIs leading to serotonin syndrome) or stimulant-like effects from its metabolites (amphetamine/methamphetamine with oral forms).

Bioavailability & Half-Life

Oral Selegiline has low bioavailability (less than 10%) due to extensive first-pass metabolism in the liver primarily by CYP2B6, CYP2A6, and CYP3A4 enzymes, producing metabolites like L-methamphetamine and L-amphetamine. Formulations like the orally disintegrating tablet (Zydis) or the transdermal patch bypass this initial metabolism, resulting in higher bioavailability (patch ~73%) and different metabolite profiles. Peak plasma levels (Tmax) occur roughly 0.5-0.9 hours after oral intake, with a plasma elimination half-life (T1/2) around 1.2-2 hours. However, because Selegiline irreversibly inhibits MAO-B, its pharmacodynamic effect lasts much longer, with enzyme activity recovery having a half-time of approximately 40 days.

Interactions & Stacks

Selegiline is commonly used synergistically with L-dopa for managing Parkinson's disease symptoms. Caution is strongly advised when combining Selegiline with SSRIs, SNRIs, tricyclic antidepressants, certain pain medications (like tramadol or meperidine), stimulants, and sympathomimetics due to risks of serotonin syndrome or hypertensive crisis, especially at doses inhibiting MAO-A. User consensus and clinical guidelines emphasize careful medication review before starting Selegiline.

Benefits by Use Case

Parkinson's Symptom Management

Improves motor control and may delay the need for L-dopa in early stages by boosting dopamine. Primarily offers symptomatic relief, not proven to halt disease progression.

Depression Treatment

Reduces depressive symptoms, particularly effective for atypical depression via transdermal patch or higher oral doses (which inhibit MAO-A). Requires careful monitoring for side effects and interactions.

Cognitive Support Post-Stroke

May enhance attention and executive functions during recovery after a stroke, as shown in one explorative study. Further research is needed to confirm this benefit.

Neuroprotection (Potential)

Shows antioxidant and anti-apoptotic properties in preclinical models, suggesting potential to protect neurons. Clinical evidence for disease modification in humans is currently lacking.

Mechanism of Action

Selegiline primarily acts as an irreversible inhibitor of monoamine oxidase B (MAO-B), an enzyme that breaks down dopamine. By inhibiting MAO-B, particularly in the brain's basal ganglia, Selegiline increases dopamine levels, which helps alleviate motor symptoms in Parkinson's disease. At higher doses or with formulations bypassing first-pass metabolism (transdermal, Zydis), Selegiline also inhibits MAO-A, increasing levels of serotonin and norepinephrine, contributing to its antidepressant effects. Additional proposed mechanisms, often independent of MAO-B inhibition, include enhancing dopamine release, blocking dopamine reuptake, upregulating antioxidant enzymes (like SOD and catalase), modulating mitochondrial function (preventing mPTP opening), inducing anti-apoptotic proteins (Bcl-2 family), increasing neurotrophic factors (BDNF, GDNF), and potentially altering α-synuclein aggregation pathways.

Frequently Asked Questions

Is Selegiline addictive?

When should I take Selegiline?

Can Selegiline improve focus or cognition?

Is Selegiline safe?

What's the difference between oral and transdermal Selegiline?

Does Selegiline slow Parkinson's progression?

Do I need dietary restrictions with Selegiline?

Summary & Expert Opinion

Selegiline is a well-established irreversible MAO-B inhibitor with significant clinical use, primarily offering symptomatic relief for Parkinson's disease and demonstrating efficacy as an antidepressant, especially in its transdermal form. Its strengths lie in improving dopamine-related functions and mood, backed by considerable research, while preclinical studies highlight intriguing neuroprotective potential through antioxidant and anti-apoptotic mechanisms. However, limitations include potential side effects (insomnia, dry mouth), the production of stimulant metabolites with oral forms, and the lack of conclusive clinical evidence for slowing neurodegenerative disease progression in humans. Selegiline is appropriate for individuals diagnosed with Parkinson's disease or specific types of depression, always under the guidance of a healthcare professional aware of its interaction profile. It should generally be avoided by those taking contraindicated medications (like SSRIs or certain stimulants) or those highly sensitive to its potential side effects, unless carefully managed by a physician.

Research Studies

Showing 5 of 10 studies

Efficacy and safety of selegiline across different psychiatric disorders: A systematic review and meta-analysis of oral and transdermal formulations (2023)

ADHD atypical depression depression +3 more

Authors:

Alessandro Vellucci, Andrea Sobrino, Andrea de Bartolomeis, Carlo Ignazio Cattaneo, Claudio Caiazza, Felice Iasevoli, Flavia Rossano, Henricus G. Ruhé, Ken Gillman, Michele Fornaro, Niccolò Solini, Nicolas Zotti, Stephen Stahl, Tom K. Birkenhager, Vincent Van den Eynde

Findings:

Selegiline (oral and transdermal) significantly outperformed placebo in reducing depressive symptoms (SMD=-0.96) and improving depression response rates (RR=1.61), particularly for atypical depression (RR=2.23). However, it did not show significant efficacy over placebo for negative or positive symptoms of schizophrenia, ADHD symptoms reduction, or smoking abstinence rates. Selegiline showed comparable acceptability (all-cause discontinuation) to placebo but was associated with significantly higher rates of insomnia and application site reactions (transdermal) and xerostomia (oral).

Participants:

Systematic review (42 studies) and meta-analysis (23 studies) involving human participants (any age) with primary psychiatric disorders, including depression (MDD, atypical, bipolar; k=10, n=1308 for symptoms; k=9, n=1238 for response; k=3, n=136 for atypical response), schizophrenia (k=4, n=191 for negative symptoms), ADHD (children, adolescents, adults; k=2, n=68 vs methylphenidate; k=2, n=48 vs placebo), smoking addiction (k=4, n=402 for abstinence), cocaine addiction (1 study included in SR), and social phobia (1 study included in SR).

Dosage:

Systematic review covered various oral (e.g., 5mg BID/TID, 10-60mg/day) and transdermal (STS 6mg/24h, 6-12mg/24h, 10-20mg/24h) formulations and dosages. Oral doses ≥20 mg/day mentioned for non-selective MAOI activity. STS 6-12 mg/24h approved for MDD.

Study Quality Assessment:

Systematic review and meta-analysis following PRISMA guidelines (PROSPERO registered: CRD42022359815). Searched multiple databases (PubMed/MEDLINE/Cochrane-Central/WHO-ICTRP/Clarivate-WebOfScience, Chinese-Electronic-Journal Database) up to 10/26/2022. Included interventional controlled studies (randomized and non-randomized). Used random-effects meta-analyses, assessed heterogeneity (I², τ², Q-test, GOSH), publication bias (funnel plot, Egger's test), and risk of bias (RoB2 for RCTs, ROBINS-I for non-randomized studies). Conducted sensitivity, subgroup, and meta-regression analyses. Confidence assessed using GRADE. 21/23 meta-analyzed studies were RCTs (RoB: 13 low, 3 unclear, 5 high). Confidence rated low/very-low for most outcomes, moderate for transdermal selegiline in depression symptom reduction. Acknowledged limitations include high heterogeneity for specific outcomes.

All Effects:

ADHD atypical depression depression schizophrenia side effects smoking cessation

Neuroprotective Function of Rasagiline and Selegiline ... (2022)

apoptosis inhibition gene induction mitochondrial function +2 more

Authors:

M Naoi

Findings:

This review indicates preclinical studies show neuroprotective functions for MAO-B inhibitors rasagiline and selegiline, including preventing mitochondrial apoptosis, inducing anti-apoptotic (Bcl-2) and pro-survival neurotrophic factors (BDNF, GDNF), and mitigating α-synuclein toxicity. MAO-A is also implicated in rasagiline's neuroprotective signaling. Despite preclinical promise, clinical trials have largely failed to demonstrate clear disease-modifying effects in synucleinopathies, highlighting the need for improved clinical trial strategies.

Participants:

Review summarizing studies involving cellular models (e.g., SH-SY5Y, U118MG, iPSCs), animal models (rats, mice, non-human primates), healthy human subjects, and patients with synucleinopathies (Parkinson's disease (PD), dementia with Lewy body (DLB), multiple system atrophy (MSA)) or mild cognitive impairment (MCI).

Dosage:

Selegiline: 10 mg/day (oral trials/pharmacokinetics), 5 mg/day (CSF study), 6 mg/24h (transdermal). Rasagiline: 1 mg/day or 2 mg/day (oral trials/pharmacokinetics), 0.1-0.25 mg/day (non-human primate study), 1 mg/day (MSA trial). In vitro concentrations mentioned (e.g., rasagiline 10⁻⁷–10⁻¹⁰ M for GDNF induction, selegiline 10⁻⁷–10⁻⁹ M for BDNF induction).

Study Quality Assessment:

Review mentions preclinical studies and clinical trials. Specific trials cited include: DATATOP (double-blind placebo-controlled), ADAGIO (controlled, randomized, delayed-start), TEMPO (controlled trial), PRESTO, LARGO, PROUD (delayed-start), LEAP (delayed-start), a phase III selegiline trial (randomized double-blind placebo-controlled), a phase 2 ladostigil trial (randomized, double-blind, placebo-controlled), an MSA trial (randomized, placebo-controlled), depression trials (double-blind, placebo-controlled). Assessment methods mentioned: Unified Parkinson’s Disease Rating Scale (UPDRS), PET imaging (β-CIT SPECT, [18F]fluorodopa PET, [11C]clorgyline PET). Acknowledges limitations of clinical trials (difficulty differentiating disease-modifying vs symptomatic effects, need for better trial design/markers).

All Effects:

apoptosis inhibition gene induction mitochondrial function neuroprotection α-synuclein modulation

An explorative study regarding the effect of l-deprenyl on cognitive and functional recovery in patients after stroke (2015)

attention cognitive functioning executive functions +1 more

Authors:

Annarita Capone, Chiara Zucchella, Francesco Pierelli, Giorgio Sandrini, Michelangelo Bartolo

Findings:

Selegiline (10 mg/day for 6 weeks) significantly improved performance on most neuropsychological tests after 2 and 6 weeks compared to placebo in stroke patients. Attention and executive functions benefited most. Both groups showed significant functional status improvement, but there was no significant difference between the selegiline and placebo groups regarding functional status.

Participants:

N=47 patients enrolled within two weeks of first-ever ischaemic or haemorrhagic stroke, with MMSE score 10-23 and FIM score ≤ 60. Randomly assigned to Study Group (n=23) or Control Group (n=24).

Dosage:

Selegiline 10 mg/day once a day for six weeks.

Study Quality Assessment:

Randomized controlled study; placebo-controlled (matched placebo); N=47 (23 treatment, 24 control); specific inclusion/exclusion criteria detailed; statistical methods mentioned (Student's t-test, Mann–Whitney U-test, chi-square test, Friedman test); conflict of interest declared none; funding source mentioned (donation from CHIESI Farmaceutici S.p.a.); study design suggestions acknowledged.

All Effects:

attention cognitive functioning executive functions stroke recovery

... trials in Parkinson's disease: systematic review

Authors:

Hart

Participants:

Studies involving Parkinson's Disease (PD)

Study Quality Assessment:

Study type: Synthesis of studies (likely systematic review or meta-analysis)

Efficacy and safety of selegiline across different psychiatric disorders: A systematic review and meta-analysis of oral and transdermal formulations

ADHD atypical depression depression +2 more

Findings:

Selegiline (oral and transdermal) significantly outperformed placebo in reducing depressive symptoms (SMD = -0.96) and improving depression response rates (RR = 1.61), particularly for atypical depression (RR = 2.23). However, selegiline failed to show significant superiority over placebo for negative or positive symptoms of schizophrenia, ADHD symptom reduction, or smoking abstinence rates. Selegiline acceptability (all-cause discontinuation) did not significantly differ from placebo, but it was associated with higher rates of xerostomia (RR = 1.58), insomnia (RR = 1.61), and application-site reactions for the transdermal formulation (RR = 1.81).

Participants:

Systematic review included studies on humans (any age) with primary psychiatric disorders (depression, schizophrenia, ADHD, smoking addiction, cocaine addiction, social phobia). Meta-analysis included N=23 studies involving patients with depression (N=1308 for symptoms, N=1238 for response), schizophrenia (N=191), ADHD (N=68 vs methylphenidate, N=48 vs placebo), and smoking addiction (N=402 endpoint, N=572 follow-up). Specific studies included adults, adolescents (12-17y), and children (4-16y).

Dosage:

Oral formulations studied ranged from 5mg BID (twice daily) or TID (thrice daily) up to 60mg/day (with doses ≥20mg/day noted for non-selective MAOI activity). Transdermal Selegiline System (STS) doses studied included 6mg/24h, 6-12mg/24h, and up to 20mg/24h patches.

Study Quality Assessment:

Systematic review and meta-analysis following PRISMA guidelines (PROSPERO registered: CRD42022359815). Searched multiple databases (PubMed, MEDLINE, Cochrane Central, ClinicalTrials.gov, WHO-ICTRP, Chinese Electronic Journal Database, Clarivate WebOfScience) until October 26th, 2022. Included 42 studies (SR), 23 (MA) - randomized (parallel, crossover) and non-randomized controlled trials (placebo-controlled, active comparator). Used random-effects meta-analysis models, assessed heterogeneity (I², τ², GOSH plots), publication bias (funnel plots, Egger's test), and risk of bias (RoB2, ROBINS-I tools). Conducted sensitivity, subgroup, and meta-regression analyses. GRADE framework used for evidence confidence (rated low/very-low for most outcomes, moderate for transdermal depression symptom reduction). High heterogeneity noted for some outcomes (e.g., depressive symptoms I²=97.9%). Significant publication bias detected for depression outcomes via Egger's test.

All Effects:

ADHD atypical depression depression schizophrenia side effects

Evidence that formulations of the selective MAO-B ...

MAO-A inhibition PET imaging brain enzyme activity +2 more

Findings:

Zydis selegiline (10 mg/day for 28 days) significantly inhibited brain MAO-A (mean 36.9%) but not DAT in healthy men. Transdermal selegiline (Emsam patch, 6 mg/day) also inhibited MAO-A (mean 33.2%), though not significantly in the small sample tested (N=3). This provides the first direct evidence that selegiline formulations bypassing first-pass metabolism inhibit brain MAO-A in humans.

Participants:

18 healthy men; 3 subjects receiving the selegiline transdermal system.

Dosage:

Zydis selegiline (orally disintegrating formulation): 2.5, 5.0, or 10 mg/day for 28 days. Selegiline transdermal system (Emsam patch): 6 mg/day.

Study Quality Assessment:

Clinical Trial; Measured brain MAO-A using positron emission tomography (PET) and [(11)C]clorgyline radiotracer; Measured dopamine transporter (DAT) availability; Sample size N=18 for Zydis group, N=3 for Emsam group; Acknowledged limitation: small sample size for Emsam group analysis; Funding sources mentioned (NIH, Non-U.S. Gov't, U.S. Gov't Non-P.H.S.).

All Effects:

MAO-A inhibition PET imaging brain enzyme activity pharmacodynamics selegiline

Neuroprotective actions of selegiline

anti-apoptosis antioxidant dopamine modulation +2 more

Authors:

Ebadi

Findings:

A retrospective analysis indicated increased survival in Parkinson's patients using selegiline plus L-dopa versus L-dopa alone. Selegiline exhibits neuroprotective effects against various neurotoxins affecting different neuron types. Its complex mechanism involves MAO-B inhibition, dopamine modulation (release enhancement, reuptake blockade), antioxidant actions (radical reduction, enzyme up-regulation, autooxidation suppression), and anti-apoptotic effects, many of which are independent of MAO-B inhibition.

Participants:

Patients with Parkinson's disease (mentioned in context of a retrospective analysis). The text also mentions effects on dopaminergic, adrenergic, cholinergic, and sertoninergic neurons, suggesting cellular or animal models were likely involved in mechanism studies, but doesn't explicitly state the subjects for those experiments.

Study Quality Assessment:

Mentions a 'retrospective analysis' of data from patients with Parkinson's disease.

All Effects:

anti-apoptosis antioxidant dopamine modulation neuroprotection survival increase (Parkinson's)

Pharmacological actions of l-deprenyl (selegiline) and other selective monoamine oxidase B inhibitors

Parkinson's disease adjuvant therapy antiParkinson action +1 more

Findings:

l-deprenyl (l-selegiline) is a useful adjuvant to L-dopa therapy and monotherapy for Parkinson's disease, although not all aspects of its antiParkinson action are fully understood.

Study Quality Assessment:

Mentions studies using brains obtained at autopsy.

All Effects:

Parkinson's disease adjuvant therapy antiParkinson action monotherapy

Selegiline (l-deprenyl) mitigated oxidative stress, …

Parkinson's disease treatment antiapoptotic neurotrophic

Slow recovery of human brain MAO B after L-deprenyl ...

L-deprenyl withdrawal MAO B recovery Parkinson's disease +2 more

Findings:

Following withdrawal from L-deprenyl (Selegeline), the half-time for human brain MAO B synthesis was measured to be 40 days in both Parkinson's disease patients and normal subjects. This slow recovery suggests the standard clinical dose may be excessive, warranting evaluation of reduced dosing. This study provided the first measurement of a specific protein synthesis rate in the living human brain.

Participants:

Humans, including individuals with Parkinson's disease and normal subjects. MeSH terms indicate participants included Aged, Middle Aged, Male, and Female individuals.

Dosage:

The standard clinical dose for Parkinson's disease is mentioned as 5 mg twice a day.

Study Quality Assessment:

Designated as a 'Clinical Trial'. Methods included Tomography, Emission-Computed (as per MeSH terms). Funding sources mentioned: Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.; Research Support, U.S. Gov't, P.H.S.; NS 15638/NS/NINDS NIH HHS/United States.

All Effects:

L-deprenyl withdrawal MAO B recovery Parkinson's disease dosing enzyme synthesis

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Categories & Effectiveness

Brain Health

Dopamine Support

Brain Antioxidant Shield

Neuro-Repair Support

Neurogenesis (BDNF/NGF)

Mood & Stress

Mood Elevation

Systemic Health

Cellular Repair

Systemic Antioxidant

Dosage & Side Effects

Recommended Dosage

Potential Side Effects

Bioavailability & Half-Life

Interactions & Stacks

Benefits by Use Case

Parkinson's Symptom Management

Depression Treatment

Cognitive Support Post-Stroke

Neuroprotection (Potential)

Mechanism of Action

Frequently Asked Questions

Summary & Expert Opinion

Research Studies

Efficacy and safety of selegiline across different psychiatric disorders: A systematic review and meta-analysis of oral and transdermal formulations (2023)

Authors:

Findings:

Participants:

Dosage:

Study Quality Assessment:

All Effects:

Neuroprotective Function of Rasagiline and Selegiline ... (2022)

Authors:

Findings:

Participants:

Dosage:

Study Quality Assessment:

All Effects:

An explorative study regarding the effect of l-deprenyl on cognitive and functional recovery in patients after stroke (2015)

Authors:

Findings:

Participants:

Dosage:

Study Quality Assessment:

All Effects:

... trials in Parkinson's disease: systematic review

Authors:

Participants:

Study Quality Assessment:

Efficacy and safety of selegiline across different psychiatric disorders: A systematic review and meta-analysis of oral and transdermal formulations

Findings:

Participants:

Dosage:

Study Quality Assessment:

All Effects:

Evidence that formulations of the selective MAO-B ...

Findings:

Participants:

Dosage:

Study Quality Assessment:

All Effects:

Neuroprotective actions of selegiline

Authors:

Findings:

Participants:

Study Quality Assessment:

All Effects:

Pharmacological actions of l-deprenyl (selegiline) and other selective monoamine oxidase B inhibitors

Findings:

Study Quality Assessment:

All Effects:

Selegiline (l-deprenyl) mitigated oxidative stress, …

Authors:

Findings:

Slow recovery of human brain MAO B after L-deprenyl ...

Findings:

Participants:

Dosage: