With SPRAVATO®, your adult patients with depressive symptoms of MDSI may find the efficacy they've been seeking

Depressive symptoms in adults with major depressive disorder (MDD) with acute suicidal ideation or behavior.

MDSI=depressive symptoms in adults with MDD with acute suicidal ideation or behavior.

Limitations of Use:

The effectiveness of SPRAVATO® in preventing suicide or in reducing suicidal ideation or behavior has not been demonstrated. Use of SPRAVATO® does not preclude the need for hospitalization if clinically warranted, even if patients experience improvement after an initial dose of SPRAVATO®.
SPRAVATO® is not approved as an anesthetic agent. The safety and effectiveness of SPRAVATO® as an anesthetic agent have not been established.

Person wearing tan coat and dark shirt in orange circle

Actor portrayal.

Representative patient journey chart showing severity of depressive symptoms over time

For patients with MDD, as depressive symptoms increase in severity, patients may quickly progress to acute suicidal ideation or behavior²
These patients may be treated in an outpatient setting if clinically appropriate as an alternative to inpatient care. Patients may be treatment naive or already receiving treatment for MDD

Rapid reduction of depressive symptoms with superior improvement at 24 hours for adults with MDSI compared to placebo plus comprehensive standard of care (SOC)^3,4

LS mean change in MADRS total scores comparison of SPRAVATO® + SOC versus placebo + SOC over 25 days for adults with MDSI

The treatment difference of SPRAVATO® compared to placebo was rapid, appearing as early as 4 hours
Between 4 hours and Day 25, both the SPRAVATO® and placebo groups continued to improve; the difference between the groups generally remained but did not appear to increase over time through Day 25

LS=least squares.

MADRS=Montgomery-Åsberg Depression Rating Scale.

SOC=comprehensive standard of care (initial hospitalization and a newly initiated or optimized oral antidepressant).

MDSI Study Design^3,4

Evaluated in short-term (4-week), randomized, double-blind, multicenter, placebo-controlled studies, Study 3 and Study 4, in adults with moderate-to-severe MDD (MADRS total score >28) who had active suicidal ideation and intent. Primary endpoint was reduction of severity of depression symptoms of MDD as measured by the change from baseline MADRS total score at 24 hours.^3,4

Depressive symptoms of MDSI Study 3 overview of SPRAVATO® & AD treatment + SOC and placebo nasal spray & AD treatment + SOC

See full MDSI Study Design^3,4

Primary Endpoint

Reduction of severity of depressive symptoms of MDD as measured by the change from baseline MADRS total score at 24 hours after first dose (Day 2)

Dosing

Patients received treatment with SPRAVATO® 84 mg or placebo nasal spray twice weekly for 4 weeks
After the first dose, a one-time dose reduction to SPRAVATO® 56 mg was allowed for patients unable to tolerate the 84-mg dose

Demographics and Baseline Characteristics

Median age 40 years; 61% female; 73% Caucasian; 6% Black

Limitations of Use

The effectiveness of SPRAVATO® in preventing suicide or in reducing suicidal ideation or behavior has not been demonstrated. Use of SPRAVATO® does not preclude the need for hospitalization if clinically warranted, even if patients experience improvement after an initial dose of SPRAVATO®
SPRAVATO® is not approved as an anesthetic agent. The safety and effectiveness of SPRAVATO® as an anesthetic agent have not been established

MDSI Safety and Tolerability of SPRAVATO®

MDSI=depressive symptoms in adults with MDD with acute suicidal ideation or behavior.

AE=adverse event.

SPRAVATO® (esketamine) showed overall consistent safety across indications³

Rates of AEs in MDSI clinical trials

Rates of adverse effects in MDSI clinical trials of SPRAVATO® + oral AD and placebo + oral AD

*The following terms were combined:

Dissociation includes: depersonalization/derealization disorder; derealization; diplopia; dissociation; dysesthesia; feeling cold; feeling hot; hallucination; hallucination, auditory; hallucination, visual; hallucinations, mixed; hyperacusis; paresthesia; paresthesia oral; pharyngeal paresthesia; photophobia; time perception altered; tinnitus; vision blurred

Dizziness includes: dizziness; dizziness exertional; dizziness postural

Sedation includes: sedation; somnolence; stupor

Blood pressure increased includes: blood pressure diastolic increased; blood pressure increased; blood pressure systolic increased; hypertension

Hypoesthesia includes: hypoesthesia; hypoesthesia oral; intranasal hypoesthesia; pharyngeal hypoesthesia

Hyperhidrosis includes: cold sweat; hyperhidrosis

Dysgeusia includes: dysgeusia; hypogeusia

Anxiety includes: agitation; anxiety; anxiety disorder; fear; irritability; nervousness; panic attack; psychomotor hyperactivity; tension

Lethargy includes: atigue; lethargy; psychomotor retardation

Tachycardia includes: heart rate increased; sinus tachycardia; tachycardia

Pollakiuria includes: micturition urgency; pollakiuria

AD=antidepressant.

Safety Considerations³

Click to expand each SPRAVATO® safety consideration below

Contraindications

Sedation

Dissociation

Respiratory Depression

Abuse and Misuse

REMS

Suicidal Thoughts and Behaviors in Young Adults

Blood Pressure

SPRAVATO® causes increases in systolic and/or diastolic blood pressure (BP), which peak at approximately 40 minutes after administration and last approximately 4 hours.

Approximately 8%-19% of SPRAVATO®-treated patients experienced an increase of more than 40 mmHg in systolic BP and/or 25 mmHg in diastolic BP in the first 1.5 hours after administration at least once during the first 4 weeks of treatment. A substantial increase in blood pressure could occur after any dose administered even if smaller blood pressure effects were observed with previous administrations. SPRAVATO® is contraindicated in patients for whom an increase in BP or intracranial pressure poses a serious risk (e.g., aneurysmal vascular disease, arteriovenous malformation, history of intracerebral hemorrhage). Before prescribing SPRAVATO®, patients with other cardiovascular and cerebrovascular conditions should be carefully assessed to determine whether the potential benefits of SPRAVATO® outweigh its risk.

Assess BP prior to administration of SPRAVATO®. In patients whose BP is elevated prior to SPRAVATO® administration (as a general guide: >140/90 mmHg), a decision to delay SPRAVATO® therapy should take into account the balance of benefit and risk in individual patients.

BP should be monitored for at least 2 hours after SPRAVATO® administration. Measure blood pressure around 40 minutes post-dose and subsequently as clinically warranted until values decline. If BP remains high, promptly seek assistance from practitioners experienced in BP management. Refer patients experiencing symptoms of a hypertensive crisis (e.g., chest pain, shortness of breath) or hypertensive encephalopathy (e.g., sudden severe headache, visual disturbances, seizures, diminished consciousness, or focal neurological deficits) immediately for emergency care.

Closely monitor blood pressure with concomitant use of SPRAVATO® with psychostimulants or monoamine oxidase inhibitors (MAOIs).

In patients with a history of hypertensive encephalopathy, more intensive monitoring, including more frequent blood pressure and symptom assessment, is warranted because these patients are at increased risk for developing encephalopathy with even small increases in blood pressure.

Cognitive Impairment

Impaired Ability to Drive and Operate Heavy Machinery

Ulcerative or Interstitial Cystitis

Use in Specific Populations

Pregnancy: SPRAVATO® is not recommended during pregnancy. SPRAVATO® may cause fetal harm when administered to pregnant women. Advise pregnant women of the potential risk to an infant exposed to SPRAVATO® in utero. There are risks to the mother associated with untreated depression in pregnancy. If a woman becomes pregnant while being treated with SPRAVATO®, treatment with SPRAVATO® should be discontinued and the patient should be counseled about the potential risk to the fetus.

Pregnancy Exposure Registry: There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to antidepressants, including SPRAVATO®, during pregnancy. Healthcare providers are encouraged to register patients by contacting the National Pregnancy Registry for Antidepressants at 1‑844‑405‑6185 or online at https://womensmentalhealth.org/clinical-and-research-programs/pregnancyregistry/antidepressants/.

Lactation: SPRAVATO® is present in human milk. Because of the potential for neurotoxicity, advise patients that breastfeeding is not recommended during treatment with SPRAVATO®.

Females and Males of Reproductive Potential: SPRAVATO® may cause embryo-fetal harm when administered to a pregnant woman. Consider pregnancy planning and prevention for females of reproductive potential during treatment with SPRAVATO®.

Pediatric Use: The safety and effectiveness of SPRAVATO® in pediatric patients have not been established.

Geriatric Use: Of the total number of patients in Phase 3 clinical studies exposed to SPRAVATO®, 12% were 65 years of age and older, and 2% were 75 years of age and older. No overall differences in the safety profile were observed between patients 65 years of age and older and patients younger than 65 years of age.

The mean esketamine C_max and AUC values were higher in elderly patients compared with younger adult patients.

The efficacy of SPRAVATO® for the treatment of TRD in geriatric patients was evaluated in a 4-week, randomized, double-blind study comparing flexibly-dosed intranasal SPRAVATO® plus a newly initiated oral antidepressant compared to intranasal placebo plus a newly initiated oral antidepressant in patients ≥65 years of age. At the end of four weeks, there was no statistically significant difference between groups on the primary efficacy endpoint of change from baseline to Week 4 on the Montgomery-Åsberg Depression Rating Scale (MADRS).

Hepatic Impairment: SPRAVATO®-treated patients with moderate hepatic impairment may need to be monitored for adverse reactions for a longer period of time. SPRAVATO® has not been studied in patients with severe hepatic impairment (Child-Pugh class C). Use in this population is not recommended.

Drug Interactions

You can have the confidence that SPRAVATO® demonstrated low discontinuation rates:

4-week MDSI short-term studies percentage of discontinued treatment

For patients with MDSI, adverse reactions leading to SPRAVATO® discontinuation in >1 patient included dissociation-related events (2.6%), blood pressure increased (0.9%), dizziness-related events (0.9%), nausea (0.9%), and sedation-related events (0.9%).

For additional information, please see full Prescribing Information, including Boxed WARNINGS.

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SPRAVATO® is administered at certified treatment centers.

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8 doses over 4 weeks to treat depressive symptoms in adults with MDSI³

MDSI=depressive symptoms in adults with MDD with acute suicidal ideation or behavior.

After 4 weeks of treatment with SPRAVATO®, evidence of therapeutic benefit should be evaluated to determine need for continued treatment. Treatment beyond 4 weeks has not been systematically evaluated.

SPRAVATO® must be taken with an oral AD
SPRAVATO® is self-administered, only under the supervision of a healthcare provider
The dose of SPRAVATO® for depressive symptoms in adults with MDSI is 84 mg (3 devices) throughout treatment

Dosage may be reduced to 56 mg twice per week based on tolerability.

Administration for treatment of depressive symptoms in adults with MDSI³

SPRAVATO® should be self-administered by the patient under the supervision of a healthcare provider in a certified SPRAVATO® treatment center.

Please refer to the full Prescribing Information and Instructions for Use included in the SPRAVATO® packaging.

Dosing and administration overview³

Administration

Patient-administered under supervision of a healthcare provider (eg, a psychiatrist, nurse, or nurse practitioner)

Monitoring & Discharge

Observation by a healthcare provider will be required for at least 2 hours until the provider determines the patient is safe to leave
Monitor patients for changes in respiratory status (including pulse oximetry) at each treatment session
Blood pressure should be monitored prior to and 40 minutes after administration and subsequently as clinically warranted until values remain consistent at a safe level and the treatment session ends
Patients should not drive or operate heavy machinery until the next day, following a restful sleep
- Patients should coordinate transportation after treatment

Careful consideration is advised prior to treatment of individuals with a history of substance use disorder, including alcohol. Monitoring for signs of abuse and dependence is recommended.

References:

1. Stanley B, Brown G. The safety planning intervention to reduce suicide risk for people with SMI. SAMHSA (Substance Abuse and Mental Health Services Administration) webinar. Accessed January 20,2023.
https://www.nasmhpd.org/sites/default/files/SAMHSA%20SPI%20SMI%20PPT%20final_2.pdf

2. Sokero T, Melartin T, Rytsälä H, et al. Prospective study of risk factors for attempted suicide among patients with DSM-IV major depressive disorder. Br J Psychiatry. 2005;186:314-318. doi:10.1192/bjp.186.4.314

3. SPRAVATO® [Prescribing Information]. Titusville, NJ: Janssen Pharmaceuticals, Inc. July 2020.

4. Fu DJ, Ionescu DF, Li X, et al. Esketamine nasal spray for rapid reduction of major depressive disorder symptoms in patients who have active suicidal ideation with intent: double-blind, randomized study (ASPIRE I). J Clin Psychiatry. 2020:81(3):19m13191. doi:10.4088/JCP.19m13191

With SPRAVATO®, your adult patients with depressive symptoms of MDSI may find the efficacy they've been seeking

Rapid reduction of depressive symptoms with superior improvement at 24 hours for adults with MDSI compared to placebo plus comprehensive standard of care (SOC)3,4

See full MDSI Study Design3,4

SPRAVATO® (esketamine) showed overall consistent safety across indications3

Rates of AEs in MDSI clinical trials

You can have the confidence that SPRAVATO® demonstrated low discontinuation rates:

Administration for treatment of depressive symptoms in adults with MDSI3

Administration

Monitoring & Discharge

References:

You are leaving the SPRAVATO® (esketamine) CIII website

Rapid reduction of depressive symptoms with superior improvement at 24 hours for adults with MDSI compared to placebo plus comprehensive standard of care (SOC)^3,4

See full MDSI Study Design^3,4

SPRAVATO® (esketamine) showed overall consistent safety across indications³

Administration for treatment of depressive symptoms in adults with MDSI³