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Memantine for ADHD


Memantine for ADHD

Memantine is a non-competitive NMDA glutamate receptor antagonist.

  • Memantine acts by blocking glutamatergic neurotoxicity at NMDA receptors
  • Very low-dose memantine acts independently of NMDA via neuroimmune mechanisms.
  • 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.1 Another OCT antagonist is amantadine.

Memantine modulates glutamatergic neurotransmission.2

  • In pathologically increased glutamate release, it blocks NMDA receptors.
    • NMDA receptors are activated by glutamate and are responsible for controlling the influx of calcium ions in neurons and thus for learning and memory processes. In the case of chronic glutamate overstimulation, the receptors cause damage to the cells due to an excess of calcium.
  • Memantine also improves cognitive performance in cases of reduced glutamatergic neurotransmission.

Memantine is used, among other things, for3

  • Autism spectrum disorder4
  • Binge eating disorder
  • Post-traumatic stress disorder (PTSD) - augmenting
  • Generalized anxiety disorder - augmenting
  • Obsessive-compulsive disorder - monotherapy and augmenting SSRIs
  • Schizophrenia (only negative symptoms)
  • Bipolar (manic phase)
  • ADHD5

With regard to ADHD, a double-blind study found significant and substantial improvements with memantine monotherapy in adults in terms of:6

  • Inattention
  • Impulsiveness
  • Self-esteem problems
  • ADHD overall index

With regard to hyperactivity, the initial strong improvements disappeared within 6 weeks.
The side effects were mild.

A study on memantine monotherapy in adults with ADHD came to comparable results, but also found sustained improvements in hyperactivity.7
A small double-blind study of 12 weeks of memantine added to stimulant medication found evidence of benefit on certain executive functions in adults with ADHD.8
One study found positive effects of 20 mg memantine/day in children with ADHD with acceptable side effects.9
Another double-blind study on children with ADHD found a weaker effect compared to methylphenidate with slightly higher side effects.10

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

  2. NMDA-Rezeptorantagonist: Memantin zur Behandlung der Alzheimer-Demenz, DAZ 2002, Nr. 12, S. 44, 17.03.2002

  3. Lu, Nasrallah (2018): The use of memantine in neuropsychiatric disorders: An overview. Ann Clin Psychiatry. 2018 Aug;30(3):234-248. PMID: 30028898. REVIEW

  4. Joshi, Wozniak, Faraone, Fried, Chan, Furtak, Grimsley, Conroy, Kilcullen, Woodworth, Biederman (2016): A Prospective Open-Label Trial of Memantine Hydrochloride for the Treatment of Social Deficits in Intellectually Capable Adults With Autism Spectrum Disorder. J Clin Psychopharmacol. 2016 Jun;36(3):262-71. doi: 10.1097/JCP.0000000000000499. Erratum in: J Clin Psychopharmacol. 2016 Aug;36(4):339. PMID: 27043118.

  5. Aljuwaiser M, Alayadhi N, Ozidu V, Shafik Zakhari SA, Rushdy R, Naguy A (2023): Clinical Indications of Memantine in Psychiatry-Science or Art? Psychopharmacol Bull. 2023 Feb 28;53(1):30-38. PMID: 36873917; PMCID: PMC9981340. REVIEW

  6. Mohammadzadeh, Ahangari, Yousefi (2019): The effect of memantine in adult patients with attention deficit hyperactivity disorder. Hum Psychopharmacol. 2019 Jan;34(1):e2687. doi: 10.1002/hup.2687. PMID: 30663824. n = 40

  7. Surman, Hammerness, Petty, Spencer, Doyle, Napolean, Chu, Yorks, Biederman (2013): A pilot open label prospective study of memantine monotherapy in adults with ADHD. World J Biol Psychiatry. 2013 May;14(4):291-8. doi: 10.3109/15622975.2011.623716. PMID: 22436083. n = 34

  8. Biederman, Fried, Tarko, Surman, Spencer, Pope, Grossman, McDermott, Woodworth, Faraone (2017): Memantine in the Treatment of Executive Function Deficits in Adults With ADHD. J Atten Disord. 2017 Feb;21(4):343-352. doi: 10.1177/1087054714538656. PMID: 24970718. n = 26

  9. Findling, McNamara, Stansbrey, Maxhimer, Periclou, Mann, Graham (2007): A pilot evaluation of the safety, tolerability, pharmacokinetics, and effectiveness of memantine in pediatric patients with attention-deficit/hyperactivity disorder combined type. J Child Adolesc Psychopharmacol. 2007 Feb;17(1):19-33. doi: 10.1089/cap.2006.0044. PMID: 17343551.

  10. Mohammadi, Mohammadzadeh, Akhondzadeh (2015): Memantine versus Methylphenidate in Children and Adolescents with Attention Deficit Hyperactivity Disorder: A Double-Blind, Randomized Clinical Trial. Iran J Psychiatry. 2015 Apr;10(2):106-14. PMID: 26884787; PMCID: PMC4752523. n = 40

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