Reducing esketamine's adverse effects with oral antidepressant pairings

By Scott Cunningham, MD, PhD
Published September 20, 2022

Key Takeaways

  • When used with an oral antidepressant, the occurrence of mild-to-moderate adverse effects of esketamine nasal spray decreased over time.

Putting It Into Practice

Approximately one-third of patients with major depressive disorder do not respond to > 2 oral antidepressants.

The S-enantiomer of racemic ketamine has been shown to have a greater affinity for the N-methyl-D-aspartate receptor than the R-enantiomer, thus has a rapid onset (within hours) and durable efficacy.

Patients with treatment-resistant depression who are treated with esketamine nasal spray plus a new oral antidepressant have a decreased symptom burden, and improved functional ability and health-related quality of life.

Why this study matters

Esketamine nasal spray plus a new oral antidepressant is effective and well-tolerated among patients with treatment-resistant depression.

Study design

Data were derived from 2 long-term phase 3 trials involving patients with treatment-resistant major depressive disorder who had not responded to > 2 oral antidepressant medications.

The trial participants were treated with a new oral antidepressant plus esketamine nasal spray (56 or 84 mg biw) during the 4-week induction phase, then weekly x 5 w, and weekly or qow during maintenance. The incidence, frequency, and severity of adverse events were the outcomes of interest in the post hoc analysis.

Results and conclusion

Nine hundred twenty-eight patients with treatment-resistant depression were enrolled in the trials.

The following symptoms and incidences occurred after the 1st week of treatment: dizziness, 20.6%; nausea, 14.0%; vertigo, 12.1%; increased blood pressure, 4.3%; and sedation, 3.8%.

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