Glutamatergic Agents in the Treatment of Compulsivity and Impulsivity in Child and Adolescent Psychiatry: a Systematic Review of the Literature

Z Kinder Jugendpsychiatr Psychother. 2018 May;46(3):246-263. doi: 10.1024/1422-4917/a000546. Epub 2017 Sep 18.


Objective: Research has implicated glutamatergic projections between the various frontal subregions in the pathogenesis of compulsivity and impulsivity. Reducing striatal glutamate release, or antagonising the action of glutamate at its receptors, may therefore represent viable treatment strategies. Several glutamatergic agents with regulatory approval for other indications are available and may be of potential benefit in the treatment of compulsivity/impulsivity in psychiatric disorders in paediatric patients.

Method: This review was performed according to PRISMA guidelines and evaluates available scientific literature concerning the use of glutamatergic agents in these patients, in order to determine their reported effectiveness/efficacy and tolerability/safety.

Results: Out of a total of 1,426 publications, 21 trials examining six glutamatergic substances in patients with obsessive-compulsive disorder, autism spectrum disorders, and attention deficit/hyperactivity disorder were included.

Conclusions: Trial designs as well as results were heterogeneous and thus comparability was limited. Available data support the hypothesis that glutamatergic agents are of potential value in the treatment of compulsivity/impulsivity in children and adolescents. Based on the data reviewed, memantine and N-acetylcysteine suggest the best risk-benefit profile for future trials. Riluzole should primarily be further investigated in adults. Clinical research of this nature is a key element of the TACTICS Consortium project funded by the European Union (FP7).

Keywords: Glutamate; clinical trials; compulsivity; impulsivity; systematic review.

Publication types

  • Review
  • Systematic Review

MeSH terms

  • Acetylcysteine / adverse effects
  • Acetylcysteine / therapeutic use
  • Adolescent
  • Attention Deficit Disorder with Hyperactivity / drug therapy
  • Autism Spectrum Disorder / drug therapy
  • Brain / drug effects*
  • Child
  • Corpus Striatum / drug effects
  • Excitatory Amino Acid Agents / adverse effects
  • Excitatory Amino Acid Agents / therapeutic use*
  • Glutamic Acid / metabolism
  • Humans
  • Memantine / adverse effects
  • Memantine / therapeutic use
  • Obsessive-Compulsive Disorder / drug therapy*
  • Randomized Controlled Trials as Topic
  • Receptors, Glutamate / drug effects
  • Risk Assessment
  • Treatment Outcome


  • Excitatory Amino Acid Agents
  • Receptors, Glutamate
  • Glutamic Acid
  • Memantine
  • Acetylcysteine