Esketamine in a Patient With Major Depressive Disorder and Polysubstance Use: A Case Report.
Cureus October 1, 2025 Abdelazim Ali, Nahida Ahmed, Sona Varghese
A 41-year-old man with treatment-resistant depression and polysubstance use (daily opioids and intermittent methamphetamine) received intranasal esketamine alongside his existing antidepressant. Depressive symptoms and craving markedly improved within one month. By two months he had stopped using opioids and methamphetamine. At six months he remained in remission and abstinent, with PHQ-9 scores dropping from 24 to 4. Side effects were transient dizziness and mild dissociation. The authors suggest esketamine may reduce craving through glutamatergic modulation and synaptic plasticity, offering dual benefits for depression and substance use, but note that controlled studies are needed.