Jaskaran B. Singh
Some patients with treatment-resistant depression who were assigned esketamine nasal spray in a clinical trial experienced temporary elevated blood pressure, but these elevations were asymptomatic, generally transient and not associated with serious cardiovascular safety sequalae, according to study findings presented at Psych Congress.
“Although blood pressure goes up, for the most part, it's asymptomatic and not troubling,” researcher Jaskaran B. Singh, MD, of Janssen Research & Development LLC, told Healio Psychiatry. “However, to protect the patient, clinicians should measure blood pressure every time. If a patient’s baseline blood pressure is high, then they should defer dosing until blood pressure is well controlled.”
According to Singh and colleagues, approximately 30% of patients with major depressive disorder do not achieve remission, even after receiving multiple antidepressants. These patients are considered to have treatment-resistant depression, for which esketamine was approved. Previous research found that shortly after dosing, ketamine may cause “transient stimulatory effects” on the cardiovascular system, and these could potentially complicate treatment for the 67% of patients with hypertension and 56% of patients with cardiovascular disease who also have treatment-resistant depression, the researchers wrote.
Singh and colleagues analyzed cardiac safety data from five double-blind, placebo-controlled phase 2/3 studies and one open-label phase 3 study of esketamine nasal spray. Of the patients, 1,708 who were treated with esketamine nasal spray received at least one dose of esketamine in the six completed phase 2 and 3 studies. A total of 1,601 patients were exposed to esketamine nasal spray during the five completed phase 3 studies, and 479 underwent exposure for 6 months or longer. A total of 178 patients were exposed for 12 months or longer.
The researchers found that “markedly abnormal blood pressure elevations” occurred among 2% to 4.9% of patients in the esketamine/antidepressant group compared with 0% to 0.9% in the placebo/antidepressant group. However, they reported no discontinuations due to adverse events in either group, and they observed no clinically relevant effect on ECG parameters.
They concluded that clinicians should assess blood pressure prior to esketamine treatment as well as 40 minutes after dosing, and then subsequently as clinically warranted.
“Long term use is pretty safe, but there's going to be groups of patients who have significant heart conditions or high risk for stroke,” Singh said. “Those are the patients who should generally avoid treatment altogether.” – by Joe Gramigna & Savannah Demko
Doherty T, et al. Cardiac safety of esketamine nasal spray in treatment-resistant depression: Results from the Clinical Development Program. Presented at: Psych Congress; Oct. 3-6, 2019; San Diego.
Disclosures: Singh is an employee of Janssen Research and Development. Please see the study for all other authors’ relevant financial disclosures.