Efficacy of Memantine as Adjunct Therapy for Autism Spectrum Disorder in Children Aged <14 Years

Document Type : Original Article


1 Department of Psychiatry, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran

2 Department of Biostatistics and Epidemiology, Faculty of Health, Lorestan University of Medical Sciences, Khorramabad, Iran

3 Department of Psychiatry, Isfahan University of Medical Sciences, Isfahan, Iran

4 Department of Emergency Medicine, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran


Background: Autism spectrum disorder (ASD) is a neurodevelopmental disorder with a recent increase in prevalence. A timely appropriate treatment for the disorder may play a crucial role in improvements in behaviors, interactions, and communications in an individual's life. It appears that evaluation of therapeutic approaches to the patients is essential and of importance. Thus, the aim of this study was to evaluate the efficacy of memantine as adjunct therapy in children with ASD. Materials and Methods: This randomized single-blind clinical trial included 60 children with ASD aged <14. The children undergoing applied behavior analysis (ABA) were divided into two groups of placebo and memantine (5 mg/day: a half of tablet in the morning and a half in the evening). After a 3-month course, improvements in symptoms of ASD were evaluated in both groups based on Gilliam autism rating scale. The collected data were analyzed with SPSS (version 20) using independent samples t-test, paired samples t-test, Chi-squared test and Fisher's exact test. Results: Both groups were similar in baseline characteristics including age, gender, and ASD symptoms (P > 0.05) but post intervention, total scores of ASD symptoms in both groups of memantine (mean score1 =95.20 ± 14.49; mean score2=73.50 ± 9.81) and control group (mean scorebefore = 91.50 ± 14.35; mean scoreafter = 89.63 ± 13.95) showed a decrease which was only significant in intervention group (P < 0.001). Conclusion: Accordingly, memantine administration as adjunct therapy can be more effective in improvement of ASD symptoms in children than ABA alone. Thus, it can be considered as a new selective adjunct therapy.


American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders (DSM-IV). 5th ed. Arlington, VA: American Psychiatric Publishing; 2013.  Back to cited text no. 1
Brignell A, Song H, Zhu J, Suo C, Lu D, Morgan AT. Communication intervention for autism spectrum disorders in minimally verbal children. The Cochrane Library. 2016. Issue 8. Art. No.: CD012324.  Back to cited text no. 2
Jasmin E, Couture M, McKinley P, Reid G, Fombonne E, Gisel E, et al. Sensori-motor and daily living skills of preschool children with autism spectrum disorders. J Autism Dev Disord 2009;39:231-41.  Back to cited text no. 3
Chez MG, Burton Q, Dowling T, Chang M, Khanna P, Kramer C, et al. Memantine as adjunctive therapy in children diagnosed with autistic spectrum disorders: An observation of initial clinical response and maintenance tolerability. J Child Neurol 2007;22:574-9.  Back to cited text no. 4
Kwon S, Kim J, Choe BH, Ko C, Park S. Electrophysiologic assessment of central auditory processing by auditory brainstem responses in children with autism spectrum disorders. J Korean Med Sci 2007;22:656-9.  Back to cited text no. 5
Samadi SA, Mahmoodizadeh A, McConkey R. A national study of the prevalence of autism among five-year-old children in Iran. Autism 2012;16:5-14.  Back to cited text no. 6
Baird G, Simonoff E, Pickles A, Chandler S, Loucas T, Meldrum D, et al. Prevalence of disorders of the autism spectrum in a population cohort of children in South Thames: The special needs and autism project (SNAP). Lancet 2006;368:210-5.  Back to cited text no. 7
Chaste P, Leboyer M. Autism risk factors: Genes, environment, and gene-environment interactions. Dialogues Clin Neurosci 2012;14:281-92.  Back to cited text no. 8
Shimmura C, Suda S, Tsuchiya KJ, Hashimoto K, Ohno K, Matsuzaki H, et al. Alteration of plasma glutamate and glutamine levels in children with high-functioning autism. PLoS One 2011;6:e25340.  Back to cited text no. 9
Jamain S, Betancur C, Quach H, Philippe A, Fellous M, Giros B, et al. Linkage and association of the glutamate receptor 6 gene with autism. Mol Psychiatry 2002;7:302-10.  Back to cited text no. 10
Ramoz N, Reichert JG, Smith CJ, Silverman JM, Bespalova IN, Davis KL, et al. Linkage and association of the mitochondrial aspartate/glutamate carrier SLC25A12 gene with autism. Am J Psychiatry 2004;161:662-9.  Back to cited text no. 11
D'Souza DC, Charney D, Krystal J. Glycine site agonists of the NMDA receptor: A review. CNS Drug Rev 1995;1:227-60.  Back to cited text no. 12
Joshi G, Wozniak J, Faraone SV, Fried R, Chan J, Furtak S, et al. 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;36:262-71.  Back to cited text no. 13
Posey DJ, Kem DL, Swiezy NB, Sweeten TL, Wiegand RE, McDougle CJ, et al. A pilot study of D-cycloserine in subjects with autistic disorder. Am J Psychiatry 2004;161:2115-7.  Back to cited text no. 14
Hosenbocus S, Chahal R. Memantine: A review of possible uses in child and adolescent psychiatry. J Can Acad Child Adolesc Psychiatry 2013;22:166-71.  Back to cited text no. 15
Surman CB, Hammerness PG, Petty C, Spencer T, Doyle R, Napolean S, et al. A pilot open label prospective study of memantine monotherapy in adults with ADHD. World J Biol Psychiatry 2013;14:291-8.  Back to cited text no. 16
Biederman J, Fried R, Tarko L, Surman C, Spencer T, Pope A, et al. Memantine in the treatment of executive function deficits in adults with ADHD. J Atten Disord 2017;21:343-52.  Back to cited text no. 17
Chez AG, Hung PC, Chin K, Memon S, Kirschner S. Memantine experience in children and adolescents with autistic spectrum disorders. In annals of neurology, proceedings of the 33rd annual meeting of the child. Neurol Soc Poster Sess 2004;56:S109.  Back to cited text no. 18
Erickson CA, Posey DJ, Stigler KA, Mullett J, Katschke AR, McDougle CJ, et al. A retrospective study of memantine in children and adolescents with pervasive developmental disorders. Psychopharmacology (Berl) 2007;191:141-7.  Back to cited text no. 19
Ghaleiha A, Asadabadi M, Mohammadi MR, Shahei M, Tabrizi M, Hajiaghaee R, et al. Memantine as adjunctive treatment to risperidone in children with autistic disorder: A randomized, double-blind, placebo-controlled trial. Int J Neuropsychopharmacol 2013;16:783-9.  Back to cited text no. 20
Autism Society of America. Definition of Autism. The Advocate: Newsletter of the Autism Society America. 1994;26(2):3.  Back to cited text no. 21
Vargas DL, Nascimbene C, Krishnan C, Zimmerman AW, Pardo CA. Neuroglial activation and neuroinflammation in the brain of patients with autism. Ann Neurol 2005;57:67-81.  Back to cited text no. 22
Bhat S, Acharya UR, Adeli H, Bairy GM, Adeli A. Autism: Cause factors, early diagnosis and therapies. Rev Neurosci 2014;25:841-50.  Back to cited text no. 23
Weitlauf AS, McPheeters ML, Peters B, Sathe N, Travis R, Aiello R, et al. Therapies for Children With Autism Spectrum Disorder: Behavioral Interventions Update [Internet]. Rockville (MD): Agency for Healthcare Research and Quality (US); 2014. Available from: http://www.ncbi.nlm.nih.gov/books/NBK241444/. [Last access on 2017 May 17].  Back to cited text no. 24
Peters-Scheffer N, Didden R, Korzilius H, Sturmey P. A meta-analytic study on the effectiveness of comprehensive ABA-based early intervention programs for children with autism spectrum disorders. Res Autism Spectr Disord 2011;5:60-9.  Back to cited text no. 25
Ahmadi SJ, Safari T, Hemmatiyan M, Khalili Z. Effectiveness of applied behavioral analysis approach on symptoms of autism. J Res Behav Sci 2012;4:292-300.  Back to cited text no. 26
Dillenburger K, Keenan M. None of the as in ABA stand for autism: Dispelling the myths. J Intellect Dev Disabil 2009;34:193-5.  Back to cited text no. 27
Solomon M, Goodlin-Jones BL, Anders TF. A social adjustment enhancement intervention for high functioning autism, Asperger's syndrome, and pervasive developmental disorder NOS. J Autism Dev Disord 2004;34:649-68.  Back to cited text no. 28
Hutchins TL, Prelock PA. Using social stories and comic strip conversations to promote socially valid outcomes for children with autism. Semin Speech Lang 2006;27:47-59.  Back to cited text no. 29
Chez MG, Aimonovitch M, Buchanan T, Mrazek S, Tremb RJ. Treating autistic spectrum disorders in children: Utility of the cholinesterase inhibitor rivastigmine tartrate. J Child Neurol 2004;19:165-9.  Back to cited text no. 30
Niederhofer H. Glutamate antagonists seem to be slightly effective in psychopharmacologic treatment of autism. J Clin Psychopharmacol 2007;27:317-8.  Back to cited text no. 31
Bernhardt EB, Walsh KH, Posey DJ, McDougle CJ. Memantine for comorbid obsessive-compulsive disorder and asperger disorder suggests a link in glutamatergic dysregulation. J Clin Psychopharmacol 2011;31:673-5.  Back to cited text no. 32
Aman MG, Findling RL, Hardan AY, Hendren RL, Melmed RD, Kehinde-Nelson O, et al. Safety and efficacy of memantine in children with autism: Randomized, placebo-controlled study and open-label extension. J Child Adolesc Psychopharmacol 2017;27:403-12.  Back to cited text no. 33