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Selegiline for ADHD


Selegiline for ADHD

Selegiline: L-deprenyl; C13H17N

Brand names: Movergan, Antiparkin, Xilopar as well as generic

1. Mechanisms of action of selegiline

Selegiline is an MAO inhibitor used primarily in Parkinson’s disease. At low doses, it is a selective MAO-B inhibitor.
Selegiline irreversibly inhibits MAO-B, reducing dopamine degradation. In the process, selegiline itself is metabolized to amphetamines or methamphetamines.
In higher doses (above 20 mg/day), selegiline additionally inhibits MAO-A, which increases serotonin and norepinephrine levels in the brain.

Dopamine is degraded by both isoenzymes of MAO, MAO-A and MAO-B. In humans, the degradation by MAO-A predominates in vivo (within the degradation by MAO), because hardly any dopamine reaches astrocytes, where it could be degraded by MAO-B.

More about this under Dopamine degradation by monoamine oxidase (MAO-A, MAO-B) in the article Dopamine degradation in the chapter Neurological aspects

Furthermore, selegiline acts as a dopamine reuptake inhibitor.

2. Selegiline for ADHD

One study comparing 20 mg and 60 mg selegiline versus placebo found no improvement in self-report ADHD symptomatology in the subjects.1 Another study of 24 children with ADHD and comorbid Tourette’s found only modest improvements in ADHD symptomatology while maintaining a high dropout rate among participants2

An older study found good improvement in ADHD symptoms with selegiline in children with ADHD and comorbid tic disorder over a test period of more than 6 months. Only 2 of the 29 subjects reported worsening of tics. Side effects were mild.3
Three smaller studies found no difference in effect between selegiline and methylphenidate in parent report in 15 families,4 in parent and teacher report in 28 children,5 and in parent and teacher report in 40 children.6
In another small placebo-controlled study, selegiline improved only inattention but not hyperactivity/impulsivity.7 In animal studies, a significant reduction in impulsivity was found in SHR (animal model of ADHD-C) at as little as 0.25 mg/kg8

Selegiline appears to be used at times off-label for ADHD.9

3. Selegiline side effects

  • Dizziness
  • Nausea
  • Vomiting
  • Dry mouth
  • Movement disorders
  • Psychoses
  • Blood pressure drop
  • moderate elevation of liver enzymes

The side effects of

  • Loss of appetite
  • Sleep problems
  • Headache

were slightly less frequent with selegiline than with methylphenidate, with otherwise comparable amounts of side effects.5

4. Contraindications of selegiline

  • Extrapyramidal syndromes not due to dopamine deficiency
  • Impaired kidney or liver function
  • Stomach or intestinal ulcers
  • Pregnancy and lactation

Selegiline must not be combined with:

  • SSRI
  • SNRI
  • tricyclic antidepressants
  • Sympathomimetics
  • Pethidine
  • Opioids
  • Serotonin agonists
  • Bupropion

A study of comedication of stimulants and MAO inhibitors in depression found no problems arising.10 Another study reported successful comedication of selegiline and lisdexamfetamine (Vyvanse) in ADHD and comorbid depression11
Thus, combination medication of selegiline with stimulants may also be considered for ADHD.

  1. Ernst, Liebenauer, Jons, Tebeka, Cohen, Zametkin (1996): Selegiline in adults with attention deficit hyperactivity disorder: clinical efficacy and safety. Psychopharmacol Bull. 1996;32(3):327-34. PMID: 8961775.

  2. Feigin, Kurlan, McDermott, Beach, Dimitsopulos, Brower, Chapieski, Trinidad, Como, Jankovic (1996): A controlled trial of deprenyl in children with Tourette’s syndrome and attention deficit hyperactivity disorder. Neurology. 1996 Apr;46(4):965-8. doi: 10.1212/wnl.46.4.965. PMID: 8780073.

  3. Jankovic J. Deprenyl in attention deficit associated with Tourette’s syndrome. Arch Neurol. 1993 Mar;50(3):286-8. doi: 10.1001/archneur.1993.00540030052014. PMID: 8442708. n = 29

  4. Niederhofer (2003): Selegiline and methylphenidate in treatment of ADHD. Psychiatr Danub. 2003 Jun;15(1-2):3-6. PMID: 19112366. n = 15

  5. Akhondzadeh, Tavakolian, Davari-Ashtiani, Arabgol, Amini (2003): Selegiline in the treatment of attention deficit hyperactivity disorder in children: a double blind and randomized trial. Prog Neuropsychopharmacol Biol Psychiatry. 2003 Aug;27(5):841-5. doi: 10.1016/S0278-5846(03)00117-9. PMID: 12921918. n = 28

  6. Mohammadi MR, Ghanizadeh A, Alaghband-Rad J, Tehranidoost M, Mesgarpour B, Soori H. Selegiline in comparison with methylphenidate in attention deficit hyperactivity disorder children and adolescents in a double-blind, randomized clinical trial. J Child Adolesc Psychopharmacol. 2004 Fall;14(3):418-25. doi: 10.1089/cap.2004.14.418. PMID: 15650498. n = 40

  7. Rubinstein, Malone, Roberts, Logan (2006): Placebo-controlled study examining effects of selegiline in children with attention-deficit/hyperactivity disorder. J Child Adolesc Psychopharmacol. 2006 Aug;16(4):404-15. doi: 10.1089/cap.2006.16.404. PMID: 16958566. n = 11

  8. Boix, Qiao, Kolpus, Sagvolden (1998): Chronic L-deprenyl treatment alters brain monoamine levels and reduces impulsiveness in an animal model of Attention-Deficit/Hyperactivity Disorder. Behav Brain Res. 1998 Jul;94(1):153-62. doi: 10.1016/s0166-4328(97)00176-9. PMID: 9708846.

  9. Moore, Saadabadi (2018): Selegiline. SourceStatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2018-2018 Aug 30.

  10. Feinberg (2004): Combining stimulants with monoamine oxidase inhibitors: a review of uses and one possible additional indication. J Clin Psychiatry. 2004 Nov;65(11):1520-4. doi: 10.4088/jcp.v65n1113. PMID: 15554766.

  11. Israel (2015): Combining Stimulants and Monoamine Oxidase Inhibitors: A Reexamination of the Literature and a Report of a New Treatment Combination. Prim Care Companion CNS Disord. 2015 Dec 10;17(6):10.4088/PCC.15br01836. doi: 10.4088/PCC.15br01836. PMID: 27057401; PMCID: PMC4805402., REVIEW