We used ShinyGO18 with the MATADOR19 database to identify overlap between top MAGMA genes and drugs of interest (Figure S3). Riluzole, an NMDA antagonist currently used to treat amyotrophic lateral sclerosis, was one of our top findings. This drug is currently in trials for combination therapy for treatment resistant depression.28 Another drug, cyclothiazide, is an allosteric modulator of AMPA (glutamatergic) receptors. Allosteric modulation of glutamatergic receptors has been considered a mechanistic treatment target for depression.29 This screen also identified an anti-seizure medication, felbamate, which has side effects including increasing depressive symptoms, suicidal ideation, and attempts. These three identified drugs, riluzole, felbamate and cyclothiazide, have been shown to modulate glutamatergic activity.30 Although the exact mechanisms underlying the drugs’ effects on the system remain to be elucidated, it is especially interesting that they were identified in this study considering the emerging evidence of glutamate’s role in the pathophysiology and treatment of mood disorders and the recent US FDA approval of ketamine for treatment-resistant depression. Riluzole has already been identified as a potential antidepressant treatment, with support for its antidepressant properties found in
