Effect of methylphenidate exposure on glutamate and glutamate-related metabolites in patients with ADHD: a systematic review

Dysfunctional glutamatergic neurotransmission has been implicated in the underlying pathogenesis of Attention Deficit Hyperactivity Disorder (ADHD). The psychostimulant methylphenidate (MPH), which is used as a first line treatment for ADHD, has been shown to have both acute and chronic effects on prefrontal cortex glutamatergic afferents. Animal studies have also identified an effect of MPH and glutamate in prefrontal areas. Despite this there are ongoing questions as to the extent and direction of this effect, as well as its impact on other neurobiological processes.

Citation:
Richards T, Morandini HAE, Rao P. Effect of methylphenidate exposure on glutamate and glutamate-related metabolites in patients with ADHD: a systematic review. J Psychiatr Res. 2025;189:236-43.

Keywords:
ADHD; Attention Deficit Hyperactivity Disorder;

Abstract:
Dysfunctional glutamatergic neurotransmission has been implicated in the underlying pathogenesis of Attention Deficit Hyperactivity Disorder (ADHD). The psychostimulant methylphenidate (MPH), which is used as a first line treatment for ADHD, has been shown to have both acute and chronic effects on prefrontal cortex glutamatergic afferents. Animal studies have also identified an effect of MPH and glutamate in prefrontal areas. Despite this there are ongoing questions as to the extent and direction of this effect, as well as its impact on other neurobiological processes.