ketamine + riluzole

Ketamine + riluzole is an investigational combination therapy involving two small molecule drugs, ketamine and riluzole, both of which modulate glutamatergic neurotransmission. Ketamine is a non-competitive N-methyl-D-aspartate (NMDA) receptor antagonist known for its rapid antidepressant effects in treatment-resistant depression (TRD). Riluzole acts as a glutamate modulator with neuroprotective and synaptic plasticity-enhancing properties, approved for amyotrophic lateral sclerosis but also studied for potential antidepressant effects. The rationale behind combining these agents is to determine whether riluzole can prolong or enhance the antidepressant response initiated by ketamine. Clinical studies have shown that while ketamine produces rapid and robust improvement in depressive symptoms, the addition of riluzole does not significantly alter the course or duration of this effect compared to placebo[1][2][3].