Intranasal esketamine leading to rapid remission in treatment-resistant major depressive disorder after multiple treatment failures

Background

Treatment‑resistant depression (TRD) affects approximately one‑third of patients with major depressive disorder (MDD) and remains a major therapeutic challenge. Esketamine, the S‑enantiomer of ketamine and a non‑competitive NMDA receptor antagonist, has emerged as a rapid‑acting antidepressant approved for TRD in combination with an oral antidepressant. Intranasal administration enables rapid systemic absorption and clinically meaningful reductions in depressive symptoms. Treatment is delivered under medical supervision due to possible transient adverse effects such as dissociation and blood pressure elevation.

Objective

To describe clinical remission following guideline‑consistent intranasal esketamine treatment in a patient with severe treatment‑resistant depression after failure of multiple pharmacological and somatic interventions including electroconvulsive therapy.

Case Description / Methods

A 59‑year‑old female physician presented with severe chronic major depressive disorder resulting in profound occupational impairment. Symptoms began in 1999 following the death of her mother and evolved into persistent anhedonia, avolition, impaired concentration, and marked functional decline. Previous treatments in Denmark included multiple antidepressants, lithium and lamotrigine augmentation, antipsychotic augmentation strategies, inpatient hospitalizations, and approximately 12 sessions of electroconvulsive therapy without adequate clinical response.

After comprehensive evaluation confirming treatment‑resistant depression, intranasal esketamine therapy was initiated in Türkiye. Each administration consisted of 28 mg esketamine (2×2 intranasal sprays) under medical supervision. Vital signs were monitored before dosing, at 15 minutes, and every 30 minutes for two hours post‑administration.

The treatment followed guideline‑based dosing phases: an induction phase during the first four weeks with twice‑weekly administrations, followed by a maintenance phase between weeks 5–8 with once‑weekly dosing, and then extended maintenance with dosing every two weeks until week 12, after which treatment was discontinued. Concomitant pharmacotherapy with duloxetine 90 mg/day and quetiapine 100 mg/day was maintained. Transient dissociative symptoms occurred during the first hour after some administrations but resolved spontaneously within the observation period without clinically significant adverse events.

Results

Depression severity was assessed using the Montgomery–Åsberg Depression Rating Scale (MADRS). Baseline MADRS score was 42 indicating severe depression. MADRS scores decreased to 37 at week 2, 18 at week 4, and 7 at week 6, indicating full remission. Functional recovery occurred alongside symptom improvement, and the patient regained the capacity to resume professional activities.

Following remission, esketamine treatment was discontinued after week 12 while maintenance pharmacotherapy was optimized to duloxetine 120 mg/day and quetiapine 100 mg/day.

Conclusions

This case demonstrates that intranasal esketamine administered according to recommended induction and maintenance schedules can produce rapid and sustained remission in severe treatment‑resistant depression even after failure of multiple pharmacological strategies and electroconvulsive therapy. The case also highlights the potential of esketamine treatment to restore occupational functioning and quality of life.

Keywords

Treatment‑resistant depression; Esketamine; Intranasal ketamine; Rapid‑acting antidepressant; MADRS

Poster Take‑Home Message

Guideline‑based intranasal esketamine treatment may produce rapid remission and restore functional capacity in severe treatment‑resistant depression even after extensive treatment failures including ECT.

References

Daly EJ et al. Efficacy and Safety of Intranasal Esketamine Adjunctive to Oral Antidepressant Therapy in Treatment‑Resistant Depression. JAMA Psychiatry. Wajs E et al. Long‑term Safety of Esketamine Nasal Spray in Treatment‑Resistant Depression. Neuropsychopharmacology. European Medicines Agency. Spravato (Esketamine) European Public Assessment Report. Rothärmel M et al. Real‑World Effectiveness of Intranasal Esketamine in Treatment‑Resistant Depression. Frontiers in Psychiatry. Chen G et al. Dissociation and Antidepressant Effects of Esketamine in Treatment‑Resistant Depression. Neuropsychopharmacology.