Neurometabolite changes in response to antidepressant medication: a systematic review of1H-MRS findings

ABSTRACT Selective serotonin reuptake inhibitors (SSRIs), serotonin and noradrenaline reuptake inhibitors (SNRIs), and (es-)ketamine are used to treat major depressive disorder (MDD). These different types of medication may involve common neural pathways related to glutamatergic and GABAergic neurotransmitter systems, both of which have been implicated in MDD pathology. We conducted a systematic review of pharmacological 1 H-MRS studies in healthy volunteers and MDD patients to explore the potential impact of these medications on glutamatergic and GABAergic systems. Studies on SSRIs and SNRIs were highly variable, generally underpowered, and yielded no consistent findings across brain regions or specific populations. Although studies on (es-)ketamine were also highly variable, some demonstrated an increase in glutamate levels in the anterior cingulate cortex in a time-dependent manner after administration. Our findings highlight the need for standardized study and acquisition protocols. Additionally, measuring metabolites dynamically over time or combining 1 H-MRS with whole brain functional imaging techniques could provide valuable insights into the effects of these medications on glutamate and GABAergic neurometabolism.