Rapid Stabilization of Trauma-Associated Depression and Suicidality via a Novel Oral Pharmacological Strategy: A Retrospective Case Series

Young people with major depressive disorder can present with trauma, paranoia, and active suicidal thoughts, a profile that often resists selective-serotonin re-uptake inhibitors and other monoaminergic drugs whose clinical effects emerge only after several weeks. Interest has therefore turned to the glutamatergic system; intravenous ketamine, for example, blocks N-methyl-D-aspartate (NMDA) receptors and rapidly improves mood, but its cost and monitoring needs limit use. Cheung’s oral strategy—dextromethorphan boosted by a CYP2D6-inhibiting antidepressant plus piracetam to enhance α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) throughput—aims to reproduce ketamine’s neuroplastic cascade with readily available medicines.This retrospective case series reviews three consecutive patients, two adolescents and one young adult, treated with that combination in routine outpatient care after poor response to previous interventions. The regimen was introduced stepwise, beginning with low-dose fluoxetine and bedtime dextromethorphan, followed by daytime piracetam. Depressive severity was tracked with the Patient Health Questionnaire-9, and clinicians noted functional changes and adverse effects. All three patients showed marked improvement: PHQ-9 scores fell into the mild range within two to four weeks, suicidal ideation ceased, and paranoid ruminations resolved. No clinically significant adverse events or signs of serotonin excess occurred. These observations suggest that an inexpensive oral approach directed at the NMDA–AMPA axis may deliver rapid relief in complex, treatment-resistant depression among adolescents and young adults. Although limited to three cases, the favourable tolerability and speed of response support further systematic study of glutamatergic combinations in this population.