Esketamine (Spravato): what the evidence shows

Since 2020, the US label covers depressive symptoms in adults with major depression who have acute suicidal ideation or behaviour, alongside an oral antidepressant. The EU authorises a short-term use in psychiatric emergencies.¹²

In the two trials behind this approval, depression improved faster than with placebo within 24 hours, but the drug didn't separate from placebo on the suicidality measure.³⁴

The FDA approved esketamine nasal spray for treatment-resistant depression in March 2019, and the EU followed in December 2019 — in both cases alongside an oral antidepressant.⁵²

In January 2025 the FDA also approved it as a monotherapy, without a daily antidepressant.⁶

The benefit is real but moderate: about 4 points more improvement on the MADRS than placebo at four weeks.⁷

Staying on it helps: people who continued were much less likely to relapse (26.7% versus 45.3%).⁸

Head-to-head against quetiapine, more people reached remission with esketamine at week 8 (27.1% versus 17.6%).⁹