Prolonged blurred vision as a side effect of intranasal esketamine administration in treatment-resistant major depressive disorder: a case report

Introduction

Esketamine is a glutamatergic agent indicated for treatment-resistant depression (TRD) in association with an oral antidepressant, after the lack of clinical response with two different antidepressant treatments. Common side effects of esketamine are typically transient and include dissociative symptoms, sedation, elevation of blood pressure, dizziness, and blurred vision. Therefore, esketamine is generally regarded as having a favorable safety profile.

Objectives

We report the case of a patient with prolonged blurred vision as a side effect of esketamine treatment, which ultimately led to treatment discontinuation and a switch back to oral medication.

Case Report

A 48-year-old male patient with TRD started esketamine treatment in our service in July 2025. According to his medical history, his first depressive episode was diagnosed in 2016, for which he was treated with sertraline 150 mg/day, bupropion 150 mg/day, and olanzapine 5 mg/day and achieved symptomatic remission.

The patient experienced a second depressive episode in 2024, for which he was initially treated with vortioxetine 20 mg/day and olanzapine 5 mg/day, without clinical improvement. Then, his medications were switched to escitalopram 20 mg/day, mirtazapine 15 mg/day, and quetiapine 150 mg/day. Add-on therapies included buspirone 30 mg/day, gabapentin 300 mg/day, lorazepam 1 mg/day PRN, and propranolol 80 mg/day, without improvement in depressive symptoms.

Concomitant with esketamine initiation, the patient was switched to venlafaxine as oral therapy, which was gradually titrated to 375 mg/day. The patient started intranasal esketamine according to the approved schedule, initially with 56 mg/session, then the dose was increased to 84 mg at session 4. The Montgomery-Åsberg Depression Rating Scale (MADRS) was used to assess treatment response. The score gradually decreased from 32 (session 4) to 16 (session 12).

However, after session 10, the patient started to complain of blurred vision that persisted between sessions. On session 12, it was decided to switch back to 56 mg and maintain administration every two weeks. The patient started to miss sessions due to prolonged blurred vision affecting his quality of life. A pharmacovigilance report was submitted to EudraVigilance. After session 15, esketamine treatment was discontinued at the patient’s request and after achieving a 50% reduction in depressive symptoms, based on MADRS scores. The patient continued oral treatment with venlafaxine. During follow-ups, the patient confirmed that his vision improved after esketamine administration was stopped, but his depressive symptoms worsened as the MADRS score increased to 22. Aripiprazole 5 mg/day was added to venlafaxine as oral treatment after the last follow-up. Currently, the patient’s clinical course is showing mild improvement.

Conclusions

This case report presents an unusual adverse effect of esketamine, as blurred vision in our clinical practice typically resolves after one or two hours following its administration. To our knowledge, this is the first time prolonged blurred vision has been reported as a side effect of esketamine. Clinicians may consider baseline ophthalmological evaluation and regular monitoring during esketamine treatment. Despite the benefits of esketamine in this case, the decision to stop the treatment was taken in order to restore the patient’s functional status as much as possible.

References

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