Nasal esketamine (Spravato°) has been authorised since 2019 as an add-on to antidepressant therapy in patients with so-called "treatment-resistant" depression, despite its uncertain efficacy and its frequent, and sometimes serious, neuropsychiatric adverse effects. In addition to dissociative symptoms (e.g. hallucinations, distortion of time and space, and altered sensory perception), nasal esketamine’s known adverse effect profile includes sedation, dizziness, nausea, vomiting, urinary tract disorders and increased blood pressure. A risk of addiction and misuse has been suggested.

Esketamine has now also been approved as an acute short-term treatment for "psychiatric emergencies" in patients with depression, in combination with an antidepressant. The clinical evaluation data, mainly obtained in two trials in urgently hospitalised adults, show an uncertain effect on depressive symptoms, more self-harming behaviour, and more suicide attempts in the weeks following treatment. A pharmacovigilance study conducted one year after the market introduction of esketamine in the United States confirmed a worrying risk of suicidal ideation and suicide.

When a patient appears to be at high risk of suicide, one of the first goals is to establish a trusting relationship in a safe and secure environment. Urgent hospitalisation is often necessary. Antidepressants are of limited value. A benzodiazepine or a sedating neuroleptic sometimes appears to help alleviate the patient’s psychological distress.

©Prescrire 1 June 2022

Source: "Esketamine (Spravato°) in depression with a high risk of suicide" Prescrire International 2022; 31 (238): 150-151. Subscribers only.

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