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Amantadine for ADHD


Amantadine for ADHD

Amantadine (1-tricyclo[,7]decylamine) is

  • Dopamine agonist
  • Dopamine reuptake inhibitors
  • Weak NMDA receptor antagonist1
  • OCT reuptake inhibitors
    • Noradrenaline and (weaker) dopamine are taken up by the organic cation transporters (OCT1, OCT2, OCT3) from the extracellular space into glial cells, where they are degraded by COMT to methoxytyramine.2 Another OCT antagonist is memantine.

1. Amantadine for ADHD

The effect of amantadine on ADHD appears to be positive, but has not yet been sufficiently researched. Amantadine can be used off-label for ADHD.

  • One study found a positive effect of amantadine on ADHD3
    • Of 251 ADHD sufferers between the ages of 6 and 18, 64.5% benefited significantly and a further 20.07% benefited at least minimally. 11.4 % were non-responders.
      • 87.5% of stimulant non-responders were amantadine responders
      • 90.3% of guanfacine or atomoxetine non-responders were amantadine responders
    • Symptom improvement (psychiatrically diagnosed) was shown by ADHD sufferers primarily with
      • Impulsiveness: 82 %
      • Irritability/rage: 52 %
      • Concentration: 51 %
      • Aggression: 29 %
      • Thought processing: 21 %
      • 28.0% of those who were previously taking an SSRI were able to discontinue it with amantadine
    • Compliance
      • 91% of responders continued to take Amantadine for at least 6 months
      • 79.7% of responders continued to take Amantadine for at least 12 months
      • 5.7% of those affected discontinued Amantadine due to side effects, mainly due to
        • Irritability
        • States of anxiety
        • Gastrointestinal complaints/weight loss
        • Sedation
    • ADHD sufferers who were taking other ADHD medications in addition to Amantadine discontinued Amantadine
      • 44.9 % when taking non-stimulants (e.g. atomoxetine, guanfacine)
      • 19.2 % when taking stimulants (e.g. methylphenidate, amphetamine)
      • 48.1% of ADHD sufferers who responded to amantadine received combination therapy with a stimulant.
  • Effect size as for 20 - 30 mg methylphenidate with amantadine 100 mg up to 30 kg and 150 mg from 30 kg (randomized controlled trial in children)4
    • Response rate 30% in the teacher rating (compared to 35% for MPH) to 50% in the parent rating (compared to 55% for MPH)
    • Slightly fewer side effects than MPH
  • Moderate improvements in children aged 5 - 13 years with a single morning dose of 50 - 150 mg (open-label study)5
    • Response rate 46 % (teacher rating) to 58 % (parent rating)
  • Effect strength lower than stimulants and better than non-drug treatment6
  • More than 400 children with ADHD are said to have been successfully treated with Amantadine at Harvard University.7
  • An older source reported that amantadine did not significantly improve hypermotor skills, impulsivity or attention.8

2. Contraindications

Individual cases have been reported in which amantadine triggered a manic phase in bipolar disorders.910

  1. Kornhuber, Bormann, Hübers, Rusche, Riederer (1991): Effects of the 1-amino-adamantanes at the MK-801-binding site of the NMDA-receptor-gated ion channel: a human postmortem brain study. Eur J Pharmacol. 1991 Apr 25;206(4):297-300. doi: 10.1016/0922-4106(91)90113-v. PMID: 1717296.

  2. Böhm (2020): Dopaminerge Systeme, in: Freissmuth, Offermanns, Böhm (Herausgeber): Pharmakologie und Toxikologie. Von den molekularen Grundlagen zur Pharmakotherapie.

  3. Morrow, Choi, Young, Haidar, Boduch, Bourgeois (2021): Amantadine for the treatment of childhood and adolescent psychiatric symptoms. Proc (Bayl Univ Med Cent). 2021 Jun 1;34(5):566-570. doi: 10.1080/08998280.2021.1925827. PMID: 34456474; PMCID: PMC8366930. n = 251 AD(H)S-Betroffene

  4. Mohammadi, Kazemi, Zia, Rezazadeh, Tabrizi, Akhondzadeh (2010): Amantadine versus methylphenidate in children and adolescents with attention deficit/hyperactivity disorder: a randomized, double-blind trial. Hum Psychopharmacol. 2010 Nov;25(7-8):560-5. doi: 10.1002/hup.1154. PMID: 21312290. n = 40

  5. Donfrancesco, Calderoni, Vitiello (2007): Open-label amantadine in children with attention-deficit/hyperactivity disorder. J Child Adolesc Psychopharmacol. 2007 Oct;17(5):657-64. doi: 10.1089/cap.2006.0128. PMID: 17979585. n = 24

  6. Mattes (1980): A pilot trial of amantadine in hyperactive children. Psychopharmacol Bull. 1980 Jul;16(3):67-9. PMID: 7403410., zitiert nach Hosenbocus, Chahal (2013) Amantadine: a review of use in child and adolescent psychiatry. J Can Acad Child Adolesc Psychiatry. 2013 Feb;22(1):55-60. PMID: 23390434; PMCID: PMC3565716. REVIEW

  7. Hallowell, Ratey (2005): Delivered from distraction: Getting the most out of life with attention deficit disorder zitiert nach Hosenbocus, Chahal (2013) Amantadine: a review of use in child and adolescent psychiatry. J Can Acad Child Adolesc Psychiatry. 2013 Feb;22(1):55-60. PMID: 23390434; PMCID: PMC3565716. REVIEW

  8. Hässler, Irmisch (2000): Biochemische Störungen bei Kindern mit hyperkinetischen Störungen, Seite 87, 89, in Steinhausen (Hrsg.) (2000): Hyperkinetische Störungen bei Kindern, Jugendlichen und Erwachsenen, 2. Aufl.

  9. Sodré, Bücker, Zortéa, Sulzbach-Vianna, Gama (2010): Mania switch induced by amantadine in bipolar disorder: report of three cases. Braz J Psychiatry. 2010 Dec;32(4):467-9. doi: 10.1590/s1516-44462010000400029. PMID: 21308277.

  10. Rego, Giller (1989): Mania secondary to amantadine treatment of neuroleptic-induced hyperprolactinemia. J Clin Psychiatry. 1989 Apr;50(4):143-4. PMID: 2564388.

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