vertigo positional
Sedation
Sedation was eva luated by adverse event reports and using the Modified Observer’sAlertness/Sedation scale (MOAA/s). In the MOAA/s scale, 5 means “responds readily to namespoken in normal tone” and 0 means “no response after painful trapezius squeeze.” Any decreasein MOAA/s from pre-dose is considered to indicate presence of sedation, and such a decreaseoccurred in a higher number of patients on esketamine than placebo during the short-term trials(Table 4). Dose-related increases in the incidence of sedation were observed in a fixed-dosestudy [see Warnings and Precautions (5.1)].
Table 4: Incidence of Sedation (MOAA/s <5) in Double-Blind, Randomized, Placebo-Controlled FixedDoseStudy with Patients < 65 Years of Age and Double-Blind, Randomized, Placebo-ControlledFlexible-Dose Study with Patients ≥65 yearsPatients <65 years Patients ≥65 years
Placebo +
Oral AD
SPRAVATO
+ Oral AD
Placebo +
Oral AD
SPRAVATO
+ Oral AD
56 mg 84 mg 28 to 84 mg
Number of patients* N=112 N=114 N=114 N=63 N=72
Sedation (MOAA/s <5) 11% 50% 61% 19% 49%
*Patients who were eva luated with MOAA/s
Dissociation/Perceptual Changes
SPRAVATO can cause dissociative symptoms (including derealization and depersonalization)and perceptual changes (including distortion of time and space, and illusions). In clinical trials,dissociation was transient and occurred on the day of dosing. Dissociation was eva luated byadverse event reports and the Clinician-Administered Dissociative States Scale (CADSS)questionnaire. A CADSS total score of more than 4 indicates presence of dissociative symptoms,and such an increase to a score of 4 or more occurred in a higher number of patients onesketamine compared to placebo during the short-term trials (see Table 5). Dose-relatedincreases in the incidence of dissociative symptoms (CADSS total score >4) were observed in afixed-dose study. Table 5 shows the incidence of dissociation (CADSS total score >4) in adouble-blind, randomized, placebo-controlled, fixed-dose study in adults <65 years of age and adouble-blind, randomized, placebo-controlled, flexible-dose study with patients ≥ 65 years ofage.
Table 5: Incidence of Dissociation (CADSS Total Score >4) in Double-Blind, Randomized, PlaceboControlledStudies (Fixed-Dose Study with Patients <65 Years and Flexible-Dose Study with
Patients ≥65 Years)
Patients <65 years Patients ≥65 years
Placebo + Oral
AD
SPRAVATO
+ Oral AD Placebo +
Oral AD
SPRAVATO
+ Oral AD
56 mg 84 mg 28 to 84 mg
Number of patients N=113 N=113 N=116 N=65 N=72
CADSS total score >4
and change >0 5% 61% 69% 12% 75% * Number of patients who were eva luated with CADSSIncrease in Blood PressureThe mean placebo-adjusted increases in systolic and diastolic blood pressure (SBP and DBP)over time were about 7 to 9 mmHg in SBP and 4 to 6 mmHg in DBP at 40 minutes post-dose and2 to 5 mmHg in SBP and 1 to 3 mmHg in DBP at 1.5 hours post-dose in patients receivingSPRAVATO plus oral antidepressants (Table 6).
Table 6: Increases in Blood Pressure in Double-blind, Randomized-controlled, Short-term Trials ofSPRAVATO + Oral AD Compared to Placebo Nasal Spray + Oral AD in the Treatment of TRDPatients <65 years Patients ≥65 years
SPRAVATO
+ Oral AD
N=346
Placebo +
Oral AD
N=222
SPRAVATO
+ Oral AD
N =72
Placebo + Oral
AD
N=65
Systolic blood pressure
≥180 mmHg |
