Esketamine Nasal Spray More Likely to Provide Treatment-Resistant Depression Remission than Quetiapine


Extended-release quetiapine is commonly used for treatment-resistant depression, but a new study reveals patients receiving esketamine nasal spray are 54% more likely to reach remission at 8 weeks.

Esketamine nasal spray (SPRAVATO®) is associated with a 54% increased likelihood of patients reaching remission for treatment-resistant depression (TRD) at 8 weeks compared to the commonly-used quetiapine, according to a new study.1

ESCAPE-TRD, a phase 3b, open-label, single-blind, multi-center, randomized, active-control trial led by Andreas Reif, MD, compared esketamine nasal spray with quetiapine augmentation therapy, looking for remission and relapse. Right now, esketamine nasal spray is the only approved treatment in Europe for TRD, while quetiapine augmentation therapy is commonly prescribed in the US.

Reif and colleagues wanted to look for the “efficacy, safety, and side-effect profile” of both esketamine and quetiapine.

"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,” Reina Benabou, MD, PhD, vice president of Janssen Scientific Affairs, said in a statement accompanying the new data. “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 healthcare providers.”2

The study included participants aged 18 – 74 years old with TD. Investigators assigned 336 patients to the esketamine group, and 340 to the quetiapine group. Along with the additional treatment, participants continued to take either a selective serotonin reuptake (SSRI) or a serotonin-norepinephrine reuptake inhibitor (SNRI).1

Remission was defined as a score of ≤10 on the Montgomery-Asberg Depression Rating Scale (MADRS) at week 8. Investigators found remission occurred significantly more in patients in the esketamine group (n = 91 [27.1%]) than the quetiapine group (n = 60[17.6%]) (95%, CI, 1.20 – 2.52, P = .003).

Also, a greater rate of patients in the esketamine group avoided relapse through week 32 once achieving remission by week 8 (21.7% vs 14.1%).

In week 32, 75.5% of patients had a treatment response in the esketamine group, versus 55.5% in the quetiapine group.

While patients in esketamine group were more likely to have remission by week 8 than the quetiapine group, the esketamine nasal spray is associated with certain adverse effects.

According to Janssen, SPRAVATO® may cause sedation, fainting, dizziness, spinning sensation, anxiety, and dissociation. When taking with an antidepressant, other side effects include nausea, decreased feeling of sensitivity, lack of energy, increased blood pressure, vomiting, feeling drunk, and feeling very happy.2

“Although adverse events occurring during the treatment period were more common in the esketamine group than in the quetiapine group, the events in the esketamine group generally appeared to be transient and mild in severity and occurred on the day of dosing,” investigators wrote. “For example, whereas dizziness was more common in the esketamine group, discontinuation of the trial treatment because of dizziness was more common in the quetiapine group.”1


  1. Reif A, Bitter I, Buyze J, et al. Esketamine Nasal Spray versus Quetiapine for Treatment-Resistant Depression. N Engl J Med. 2023;389(14):1298-1309. doi:10.1056/NEJMoa2304145
  2. 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. October 4, 2023. Accessed October 5, 2023.
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