In a real-world outpatient setting, 21 patients with treatment-resistant depression received intranasal esketamine. Depressive symptoms, measured by clinician and self-report scales, decreased at 3-month and 6-month follow-ups. Suicidal ideation significantly declined between baseline and 6 months, and patients also reported reduced hopelessness over time. The findings suggest intranasal esketamine is associated with improvements in depressive symptoms, hopelessness, and suicidal ideation in treatment-resistant depression.
Major depressive disorder (MDD) is a leading cause of disability globally, with prevalence twice as high in women as in men. Mental pain, distinct from depression, is a crucial framework in MDD that may precipitate suicide risk. According to Panksepp's emotional theory, the opioid system influences feelings tied to grief and separation, making it a renewed target for antidepressant treatment. Antidepressants with partial mu-opioid receptor agonism and kappa-opioid receptor antagonism could address unmet needs. The combination of dextromethorphan and bupropion is a well-tolerated, rapid-acting treatment for adults with MDD. It is hypothesized that this combination reduces mental pain by targeting the opioid system, potentially improving treatment outcomes.