Blood pressure should be assessed before treatment with esketamine nasal spray in patients with treatment-resistant depression, according to study findings presented at Psych Congress 2019, held October 3 to 6 in San Diego, California.
Researchers sought to evaluate potential cardiovascular effects of esketamine nasal spray in patients with treatment-resistant depression. The safety analysis population was derived from 5 double-blind placebo-controlled phase 2/3 studies and 1 open-label phase 3 study of esketamine nasal spray. A total of 1708 patients received esketamine nasal spray plus an oral antidepressant vs 486 patients who received an oral antidepressant plus placebo.
The patients were aged 18 to 64 years (5 studies) or ≥65 years (2 studies; mean age, 49.1 years across all studies) and had treatment-resistant depression (defined as a nonresponse to adequate trial of ≥2 antidepressants during the current episode of depression). Patients with cardiovascular (CV) disease were excluded from the study.
Vital signs were measured at baseline and during all dosing visits; blood pressure and pulse/heart rate measurements were taken after the patient had rested for ≥5 minutes and were measured supine (with either completely automated device or manual techniques); and single, 12-lead electrocardiograms were performed at prespecified time points after patients had rested in a supine position for ≥5 minutes.
A total of 1708 patients received ≥1 dose of esketamine in the 6 completed phase 2 and 3 studies, with a combined cumulative exposure to esketamine nasal spray of 611 patient-years in the phase 2/3 treatment-resistant depression studies and 601 patient-years in the phase 3 studies. Of the 1601 patients exposed to esketamine nasal spray in the 5 completed phase 3 studies, 479 were exposed for ≥6 months and 178 for ≥12 months.
Increased blood pressure, abnormal heart rate, and CV adverse events of clinical interest in patients treated with esketamine had an onset shortly after dosing and were resolved within 1.5 hours while they were still in the clinic. Approximately 2.0% to 4.9% of patients in the esketamine group experienced an abnormal blood pressure elevation vs 0.0% to 0.9% in the placebo group across all studies. The abnormal blood pressure elevations were generally higher in patients with vs without a history of hypertension and in elderly patients.
Fewer than 2% of all patients across the studies discontinued esketamine due to adverse events of increased blood pressure and tachycardia, and there were no hospitalizations reported for any blood pressure elevation. In addition, the researchers did not observe any clinically relevant effect on electrocardiogram parameters.
The study’s generalizability may be limited by the exclusion of patients with CV disease within the year before the trial start, uncontrolled hypertension, or clinically significant electrocardiogram abnormalities.
“Our findings suggest that blood pressure should be assessed prior to treatment with esketamine and reassessed after dosing at approximately 40 minutes and subsequently as clinically warranted,” the researchers concluded. The blood pressure elevations were generally transient, asymptomatic, self-limiting, without the need for rescue medications, and not associated with serious CV safety sequalae. However, further monitoring is needed to determine long-term CV outcomes of blood pressure changes.
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Disclosure: Studies discussed in this poster presentation were supported by funding from Janssen Research & Development LLC. Several authors declared affiliations with the Janssen. Please see the original reference for a full list of authors’ disclosures.
Doherty T, Wajs E, Melkote R, Weber MA, Miller J, Singh JB. Cardiac safety of esketamine nasal spray in treatment-resistant depression: results from the clinical development program. Presented at: Psych Congress 2019; October 3-6, 2019; San Diego, CA. Poster 127.