The various options available to treat depression usually have moderate efficacy at best. Antidepressants are commonly used. The options available when the response to an antidepressant is considered inadequate are of uncertain value, and few head-to-head trials have been conducted to compare them. They include psychotherapy, a higher dose of the antidepressant, switching to an antidepressant of a different pharmacological class, adding a neuroleptic, and so on.

Esketamine nasal spray (Spravato°), in combination with another antidepressant, was authorised in Europe in 2019 for the treatment of patients experiencing a depressive episode considered "resistant" after treatment with two different antidepressants. Esketamine’s efficacy in this situation is very uncertain. Its adverse effects, on the other hand, are well known, as they are similar to those of the closely related drug ketamine. The main ones are: dissociation, observed in 60% to 79% of patients (hallucinations, confusion, distortion of time and space, altered sensory perception, feeling separate from one’s own body); sedation, up to loss of consciousness with respiratory depression; hypertensive crisis, etc. A risk of addiction and misuse is foreseeable. Esketamine is considered a narcotic and has controlled drug status in many countries, including France.

To minimise the risk to patients, each treatment session is supposed to take place in a healthcare establishment under the supervision of a healthcare professional, who monitors the patient for two hours to reassure them, put them in the recovery position if necessary, and so on. One of the main factors to take into account when choosing between antidepressants is their adverse effect profiles; esketamine is a drug to avoid.

©Prescrire 1 January 2021

Source: "Esketamine (Spravato°) and "treatment-resistant" depression. Huge risks for uncertain efficacy" Prescrire International 2021; 30 (222): 5-9. Subscribers only.

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