Esketamine in Combination with Oral Antidepressant Could Aid Treatment-Resistant Depression


Individuals treated with esketamine were more likely to reach remission and remain relapse-free at 8 weeks of treatment.

Published in the New England Journal of Medicine, a new study found that individuals with treatment-resistant depression (TRD) that were treated with esketamine (Spravato; Janssen) were 1.54 times more likely to be in remission after 8 weeks, compared with individuals treated with quetiapine (Seroquel; AstraZeneca) extended release (XR). Individuals treated with esketamine were also 1.55 times more likely to refrain from relapsing for a period of 32 weeks, at the 8-week period.

Close up view of doctor touching patient hand, showing empty and kindness - Image credit: Bongkarn |

Image credit: Bongkarn |

Esketamine is a CIII nasal spray medication that can only be attained by prescription, and it was investigated in combination with an oral antidepressant. A health care provider administered the dosage and schedule for prescribed individuals.

The study, called ESCAPE-TRD, was a randomized, open-labeled, rater-blinded, active-controlled, ex-United States study. The press release noted that esketamine nasal spray was compared with quetiapine XR paired with an oral antidepressant to treat TRD and major depressive disorder (MDD). The oral antidepressants included a serotonin reuptake inhibitor, serotonin, and norepinephrine reuptake inhibitor.

TRD is defined as a subset of depression. In total, 280 million individuals worldwide are impacted by depression and 21 million adults in the United States have reported to have a major depressive episode. Out of the 21 million individuals, 2.8 million live with MDD and are diagnosed with TRD. The diagnosis comes with a constant emotional and functional burden on the individual and loved ones. To be diagnosed with TRD, individuals with MDD must not have improved after 2 different antidepressants of a suitable dose.

"This large head-to-head trial gives physicians important data to consider in the management of treatment-resistant depression by comparing the short- and long-term effectiveness of Spravato to an oral antipsychotic,” said Reina Benabou, MD, PhD, Vice President of Medical Affairs, Neuroscience, at Janssen Scientific Affairs, LLC. “Spravato offers patients an additional important option. It is critical that those living with this difficult-to-treat condition have choices to consider for their personal treatment plans, in discussion with their health care providers.”

The press release noted that adverse events and treatment discontinuation were reported that followed the safety profile. The researchers reported that 92% of individuals taking esketamine had treatment-emergent adverse events, compared to 78% for individuals taking quetiapine XR. Among those, 4.2% that took esketamine and 11% that took quetiapine XR discontinued the medication because of the adverse events.

The most common adverse events that were reported included feeling disconnected from their selves, thoughts, feelings, and surroundings; dizziness; nausea; feeling sleepy; spinning sensation; decreased feeling of sensitivity; feeling anxious; lack of energy; increased blood pressure; vomiting; feeling drunk; and feeling very happy or excited.

The study concluded that at week 8 of taking esketamine versus taking quetiapine XR, individuals on esketamine were 1.54 more likely to reach remission compared with 17.6% of quetiapine XR-treated individuals. In terms of remaining relapse free, 21.7% of esketamine treated individuals would remain compared with 14.1% of those receiving quetiapine XR.


Large Head-to-Head Study Shows Patients with Treatment-Resistant Depression Receiving SPRAVATO® (esketamine) CIII Nasal Spray Were 1.54 Times as Likely to Reach Remission at 8 Weeks than Patients treated with Quetiapine XR. Johnson & Johnson. News release. October 4, 2023. Accessed October 9, 2023.

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