Skip to main content
Log in

A retrospective study of memantine in children and adolescents with pervasive developmental disorders

  • Original Investigation
  • Published:
Psychopharmacology Aims and scope Submit manuscript

Abstract

Rationale

There are no drugs that have been shown to effectively treat the core social impairment of autism.

Objectives

The purpose of this study was to examine the effectiveness and tolerability of memantine for social impairment in children and adolescents with pervasive developmental disorders (PDDs).

Materials and methods

Medical records of 18 patients with PDDs consecutively treated with open-label memantine were retrospectively reviewed. The data reviewed included prospectively obtained assessments of severity (S) and improvement (I) using the Clinical Global Impressions Scale (CGI). Pretrial and follow-up parent ratings were also available on six patients using the Aberrant Behavior Checklist (ABC).

Results

Eighteen patients (15 male, 3 female; mean age=11.4 years, range 6–19 years) received memantine (mean dosage=10.1 mg/day, range 2.5–20 mg/day) over a mean duration of 19.3 weeks (range 1.5–56 weeks). Eleven of 18 (61%) patients were judged responders to memantine based on a rating of “much improved” or “very much improved” on the CGI-I. Significant improvement was also seen on the CGI-S. Improvement was primarily seen clinically in social withdrawal and inattention. Adverse effects occurred in 7 of 18 (39%) patients and led to drug discontinuation in 4 of 18 (22%) patients. Thirteen of 18 (72%) patients received stable doses of concomitant medications during the memantine trial.

Conclusions

In this open-label retrospective study, memantine was effective in a number of patients with PDDs. Controlled studies are warranted to further assess the efficacy and safety of memantine in PDDs.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1

Similar content being viewed by others

References

  • Aldred S, Moore KM, Fitzgerald M, Waring RH (2003) Plasma amino acid levels in children with autism and their families. J Autism Dev Disord 33:93–97

    Article  PubMed  Google Scholar 

  • Aman MG, Singh NN, Stewart AW, Field C (1985) The aberrant behavior checklist: a behavior rating scale for the assessment of treatment effects. Am J Ment Defic 89:485–491

    PubMed  CAS  Google Scholar 

  • American Psychiatric Association (2000) Diagnostic and statistical manual of mental disorder, text revision (DSM IV-TR), 4th edn. American Psychiatric Association, Washington DC

    Google Scholar 

  • Blue ME, Naidu S, Johnston MV (1999) Development of amino acid receptors in frontal cortex from girls with Rett syndrome. Ann Neurol 45:541–545

    Article  PubMed  CAS  Google Scholar 

  • Carlsson ML (1998) Hypothesis: is infantile autism a hypoglutamatergic disorder? Relevance of glutamate-serotonin interactions for pharmacotherapy. J Neural Transm 105:525–535

    Article  PubMed  CAS  Google Scholar 

  • Chakrabarti S, Fombonne E (2001) Pervasive developmental disorders in preschool children. JAMA 285:3093–3099

    Article  PubMed  CAS  Google Scholar 

  • Chakrabarti S, Fombonne E (2005) Pervasive developmental disorders in preschool children: confirmation of high prevalence. Am J Psychiatry 162:1133–1141

    Article  PubMed  Google Scholar 

  • Chez MG, Hung PC, Chin K, Memon S, Kirschner S (2004) Memantine experience in children and adolescents with autistic spectrum disorders. Ann Neurol 56:C–10 (abstract)

    Google Scholar 

  • Collingride GL, Singer W (1990) Excitatory amino acid receptors and synaptic plasticity. Trends Pharmacol Sci 11:290–296

    Article  Google Scholar 

  • Danysz W, Parsons CG (1998) Glycine and N-methyl-D-aspartate receptors: physiological significance and possible therapeutic applications. Pharmacol Rev 50:597–664

    PubMed  CAS  Google Scholar 

  • Erickson CA, Chambers JE (2006) Memantine for disruptive behavior in autistic disorder. J Clin Psychiatry 67(6):1000

    Article  PubMed  Google Scholar 

  • Fatemi SH, Halt AR, Stary JM, Kanodia R, Schulz SC, Realmuto GR (2002) Glutamic acid decarboxylase 65 and 67 kDa proteins are reduced in the autistic parietal and cerebellar cortices. Biol Psychiatry 52:805–810

    Article  PubMed  CAS  Google Scholar 

  • Goff DC, Tsai G, Levitt J, Amico E, Manoach D, Schoenfeld DA, Hayden OL, McCarley R, Coyle JT (1999) A placebo-controlled trial of D-cycloserine added to conventional nueroleptics in patients with schizophrenia. Arch Gen Psychiatry 56:21–27

    Article  PubMed  CAS  Google Scholar 

  • Guy W (1976) ECDEU Assessment manual for psychopharmacology. US Department Health, Education, and Welfare Publication (ADM) 76–338. National Institute of Mental Health, Rockville, MD

    Google Scholar 

  • Jamain S, Betancur C, Quach H, Philippe A, Fellous M, Giros B, Gillberg C, Leboyer M, Bourgeron T, Paris Autism Research International Sibpair (PARIS) Study (2002) Linkage and association of the glutamate receptor 6 gene with autism. Mol Psychiatry 7:302–310

    Article  PubMed  CAS  Google Scholar 

  • King BH, Wright DM, Handen BL, Sikich L, Zimmerman AW, McMahon W et al (2001) Double-blind, placebo-controlled study of amantadine hydrochloride in the treatment of children with autistic disorder. J Am Acad Child Adolesc Psychiatry 40:658–665

    Article  PubMed  CAS  Google Scholar 

  • Kornhuber J, Weller M, Schoppmeyer K, Riederer P (1994) Amantadine and memantine are NMDA receptor antagonists with neuroprotective properties. J Neural Transm Suppl 43:91–104

    PubMed  CAS  Google Scholar 

  • Lord C, Rutter M, LeCouteur AM (1994) Autism Diagnostic Interview-Revised: a revised version of a diagnostic interview for caregivers of individuals with possible pervasive developmental disorder. J Autism Dev Disord 24:659–685

    Article  PubMed  CAS  Google Scholar 

  • McDougle CJ (2002) Current and emerging therapeutics of autistic disorder and related pervasive developmental disorders. In: Daviv KL, Charney D, Coyle JT, Nemeroff C (eds) Psychopharmacology: the fifth generation of progress. Lippincott Williams & Wilkins, Philadelphia, PA, pp 565–576

    Google Scholar 

  • Möbius HJ (2003) Memantine: update on the current evidence. Int J Geriatr Psychiatry 18:S47–S54

    Article  PubMed  Google Scholar 

  • Parsons CG, Gruner R, Rozental J, Millar J, Lodge D (1993) Patch clamp studies on the kinetics and selectivity of the N-methyl-D-aspartate receptor antagonism by memantine (1-amino-3,5-dimethyladamantan). Neuropharmacology 32:1337–1350

    Article  PubMed  CAS  Google Scholar 

  • Parsons CG, Danysz W, Quack G (1999) Memantine is a clinically well tolerated N-methyl-D-aspartate (NMDA) receptor antagonist—a review of preclinical data. Neuropharmacology 38:735–767

    Article  PubMed  CAS  Google Scholar 

  • Posey DJ, Kem DL, Swiezy NB, Sweeten TL, Wiegand RE, McDougle CJ (2004) A pilot study of D-cycloserine in autistic disorder. Am J Psychiatry 161:2115–2117

    Article  PubMed  Google Scholar 

  • Reisberg B, Doody R, Stoffler A, Schmitt F, Ferris S, Mobius HJ, Memantine Study Group (2003) Memantine in moderate-to-severe Alzheimer’s disease. N Engl J Med 348:1333–1341

    Article  PubMed  CAS  Google Scholar 

  • Rolf LH, Haarmann FY, Grotemeyer KH (1993) Serotonin and amino acid content in platelets of autistic children. Acta Psychiatr Scand 87:312–316

    PubMed  CAS  Google Scholar 

  • Shuang M, Liu J, Jia MX, Yang JZ, Wu SP, Gong XH, Ling YS, Ruan Y, Yang XL, Zhang D (2004) Family-based association study between autism and glutamate receptor 6 gene in Chinese Han trios. Am J Med Genet 131B:48–50

    Article  PubMed  Google Scholar 

  • Wenk GL, O’Leary M, Nemeroff CB, Bissett G, Moser H, Naidu S (1993) Neurochemical alterations in Rett syndrome. Dev Brain Res 74:67–72

    Article  CAS  Google Scholar 

Download references

Acknowledgments

The authors would like to thank Jennifer Wilkerson for her assistance in the preparation of this manuscript. This work was supported in part by a grant from the National Institute of Mental Health (K23 MH68627), a Daniel X. Freedman Psychiatric Research Fellowship, and the Department of Housing and Urban Development (B-01-SP-IN-0200).

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to David J. Posey.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Erickson, C.A., Posey, D.J., Stigler, K.A. et al. A retrospective study of memantine in children and adolescents with pervasive developmental disorders. Psychopharmacology 191, 141–147 (2007). https://doi.org/10.1007/s00213-006-0518-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00213-006-0518-9

Keywords

Navigation