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Memantine for ADHD


Memantine for ADHD

Memantine is a noncompetitive NMDA glutamate receptor antagonist.

  • Memantine acts by blocking glutamatergic neurotoxicity at NMDA receptors
  • Very low-dose memantine acts NMDA-independently via neuroimmune mechanisms.

Memantine modulates glutamatergic neurotransmission.1

  • In pathologically elevated glutamate release, it blocks NMDA receptors.
    • NMDA receptors are activated by glutamate and are responsible in neurons for controlling calcium ion influx 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.
  • Similarly, memantine also improves cognitive performance in the presence of decreased glutamatergic neurotransmission.

Memantine is used for, among other things:2

  • Autism Spectrum Disorder3
  • Binge Eating Disorder
  • Post-traumatic stress disorder (PTSD) - augmenting
  • Generalized anxiety disorder - augmentative
  • Obsessive-compulsive disorder - monotherapy and augmenting with SSRIs
  • Schizophrenia (negative symptoms only)
  • Bipolar (manic phase)
  • ADHD4

With respect to ADHD, a double-blind study found significant and substantial improvements with memantine monotherapy in adults with respect to:5

  • Inattention
  • Impulsivity
  • Self-esteem issues
  • ADHD Total Index

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

A study of memantine monotherapy in adults with ADHD had similar results, but also found sustained improvements in hyperactivity.6
A small double-blind study of to a 12-week supplemental medication with memantine to stimulants found evidence of benefit in relation to certain executive functions in adults with ADHD.7
One study found beneficial effects of 20 mg memantine/day in children with ADHD with acceptable side effects.8
Another double-blind study in children with ADHD found a weaker effect with slightly higher side effects compared with methylphenidate.9

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

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

  3. 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.

  4. 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

  5. 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

  6. 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

  7. 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

  8. 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.

  9. 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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