Esketamine nasal spray monotherapy showed significant and clinically meaningful improvement over placebo in adults with treatment-resistant depression (TRD) starting within 24 hours after initial dosing, according to the results of a study mounted by drugmaker Janssen and published today in JAMA Psychiatry.
Pharmacotherapy for patients with TRD “commonly involves augmentation or combination approaches. However, some of these patients encounter tolerability issues (e.g., weight gain, sexual dysfunction, lethargy, gastrointestinal issues) … which significantly contribute to nonadherence or discontinuation,” wrote Adam Janik, M.D., an investigator with Janssen’s parent company, Johnson & Johnson, and colleagues. “Esketamine monotherapy may expand treatment options for adult patients with TRD by addressing an unmet need of patients experiencing treatment-limiting tolerability concerns and non-response.”
Esketamine was initially approved by the Food and Drug Administration (FDA) in 2019 as an adjunct medication for TRD. Earlier this year, the FDA expanded the indication to allow esketamine as a stand-alone TRD therapy based on the findings of this study.
Janik and colleagues randomized 378 adults with moderate to severe TRD without psychotic features to receive 56 mg esketamine (n= 86), 84 mg esketamine (n = 95), or placebo spray (n = 197) twice weekly. Researchers assessed participants’ changes on the Montgomery-Åsberg Depression Rating Scale (MADRS) over 28 days, after which most participants opted into an open-label study of esketamine (variable dosing) or traditional oral antidepressants for 12 additional weeks.
After 28 days of treatment, the individuals taking either esketamine dose had larger average reductions in their MADRS scores (13 points for the 56 mg group and 14 for the 84 mg group) than those taking placebo (average seven-point reduction). Response and remission rates were also about two to three times as high in the esketamine groups compared with placebo.
In participants who continued esketamine in the 12-week, open-label phase, depressive symptoms remained stable or improved. Adverse events were common among participants given esketamine, most commonly nausea (25%), dissociation (24%), dizziness (22%), and headache (19%).
Limitations of this study include the exclusion of patients with significant psychiatric or medical comorbidities or substance dependence, as well as limited racial and ethnic diversity among participants. Also, the well-known adverse events that are associated with esketamine, such as dissociation and dizziness, led to many participants correctly guessing their treatment, which could have influenced the study results.
For related information, see the Psychiatric News articles “Helping Patients With Treatment-Resistant Depression Reach Remission” and “Disappointing Results for Esketamine as an Add-On After Acute Phase.”
(Image: Getty Images/iStock/CarlosDavid.org)
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