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This information is intended for US healthcare professionals to access current scientific information about J&J Innovative Medicine products. It is prepared by Medical Information and is not intended for promotional purposes, nor to provide medical advice.

SPRAVATO® (esketamine)

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Adverse Event of SPRAVATO - Dysgeusia

Last Updated: 10/24/2024

Summary

In the double-blind phases of the phase 2 and 3 clinical trials in treatment-resistant depression (TRD), dysgeusia was reported in 113 patients (19.3%) treated with SPRAVATO+ a newly initiated oral antidepressant (oral AD; SPRAVATO+oral AD; n=587) and 54 patients (11.1%) treated with oral AD+placebo (n=486). These cases of dysgeusia occurred on the dosing day, and ≥90% of cases resolved on the same day.¹
- Dysgeusia is defined as a metallic taste or change in the sense of taste.
According to a case report, drinking a fruit punch-flavored powdered drink mix shortly after SPRAVATO administration helped to resolve the dysgeusia.²

Clinical DATA

Study-specific data on dysgeusia from phase 3 clinical trials of TRD and major depressive disorder and active suicidal ideation with intent are provided below.

Study/Study Design	Rates of Dysgeusia
Short-term Trials in Treatment-Resistant Depression
Fedgchin et al (2019) (TRANSFORM-1)³ Randomized, DB, active-controlled, multicenter study in patients with TRD aged 18-64 years Assessed efficacy and safety of fixed-dose 56 mg or 84 mg SPRAVATO+oral AD vs oral AD+PBO after 4 weeks of treatment	56 mg SPRAVATO+oral AD: 14.8% (n=17/115) 84 mg SPRAVATO+oral AD: 17.2% (n=20/116) Oral AD+PBO: 15.0% (n=17/113)
Popova et al (2019) (TRANSFORM-2)⁴ Randomized, DB, active-controlled, multicenter study in patients with TRD aged 18-64 years Assessed efficacy and safety of flexibly dosed 56 mg or 84 mg SPRAVATO+oral AD vs oral AD+PBO after 4 weeks of treatment	SPRAVATO+oral AD: 24.3% (n=28/114) Oral AD+PBO: 11.9% (n=13/109)
Ochs-Ross et al (2020) (TRANSFORM-3)⁵ Randomized, DB, multicenter study in elderly patients (≥65 years) with TRD Assessed efficacy and safety of flexibly dosed 28 mg, 56 mg, or 84 mg SPRAVATO+oral AD vs oral AD+PBO after 4 weeks	SPRAVATO+oral AD: 5.6% (n=4/72) Oral AD+PBO: 4.6% (n=3/65)
Chen et al (2023)⁶ Randomized, DB, active-controlled, multicenter study in patients with TRD aged 18-64 years in China and the USA Assessed the efficacy and safety of flexibly dosed 56 or 84 mg SPRAVATO+oral AD vs oral AD+PBO after 4 weeks of treatment	SPRAVATO+oral AD: 11.1% (n=14/126) Oral AD+PBO: 4.8% (n=6/126)
Long-term Trials in Treatment-Resistant Depression
Daly et al (2019) (SUSTAIN-1)⁷ Long-term, DB, multicenter, maintenance-of-effect study in patients with TRD Assessed efficacy of flexibly dosed 56 mg or 84 mg SPRAVATO+oral AD vs oral AD+PBO in delaying relapse of depressive symptoms in patients who were stable remitters and stable responders, after an initial 16 weeks of treatment with SPRAVATO+oral AD	During the DB maintenance phase, dysgeusia was reported in: SPRAVATO+oral AD: 27% (n=41/152) Oral AD+PBO: 6.9% (n=10/145)
Wajs et al (2020) (SUSTAIN-2)⁸ Open-label, multicenter study in patients with TRD Evaluated the long-term (up to 1 year of exposure) safety and tolerability of flexibly dosed 56 mg or 84 mg SPRAVATO+oral AD	SPRAVATO+oral AD: 11.8% (n=95/802)⁸ There were 4 events of severe dysgeusia that resolved in the median time of 12.1 hours⁹
Zaki et al (2023) (SUSTAIN-3)¹⁰ Open-label extension study in patients with TRD Evaluated the long-term safety and efficacy of individualized, intermittently dosed (28 mg [patients aged ≥65 years], 56 mg, or 84 mg) SPRAVATO+oral AD	SPRAVATO+oral AD: 20.2% (n=232/1148)
Reif et al (2023)¹¹ Open-label, randomized, phase 3b, multicenter study in patients with TRD Evaluated the efficacy and safety of SPRAVATO vs QUE-XR in combination with ongoing oral AD (SSRI or SNRI) over 32 weeks	SPRAVATO+oral AD: 40/334 (12.0%)¹² QUE-XR+oral AD: 1/336 (0.3%)¹²
Major Depressive Disorder With Suicidal Ideation and Intent
Fu et al (2020) (ASPIRE-1)¹³ Randomized, DB (4-weeks), PBO-controlled, multicenter study in patients with MDD with suicidal ideation and intent Assessed efficacy and safety of 84 mg SPRAVATO+SOC^a vs PBO+SOC	SPRAVATO+SOC: 14.2% (n=16/113) PBO+SOC: 9.8% (n=11/112)
Ionescu et al (2020) (ASPIRE-2)¹⁴ Randomized, DB (4 weeks), PBO-controlled, multicenter study in patients with MDD with suicidal ideation and intent Evaluated efficacy and safety of 84 mg SPRAVATO+SOC vs PBO+SOC	SPRAVATO+SOC: 25.4% (n=29/114) PBO+SOC: 15.9% (n=18/113)
Abbreviations: AD, antidepressant; DB, double-blind; MDD, major depressive disorder; PBO, placebo nasal spray; QUE-XR, quetiapine extended release; SNRI, serotonin-norepinephrine reuptake inhibitor; SOC, standard of care; SSRI, selective serotonin reuptake inhibitor; TRD, treatment-resistant depression. ^aSOC consisted of newly initiated or optimized AD along with ≥5 days of initial hospitalization, enhanced by twice-weekly intensive visits during DB phase.

MANAGEMENT OF DYSGEUSIA

Bossaller et al (2020)² reported a case of dysgeusia associated with the use of SPRAVATO as part of a clinical trial in patients with MDD with suicidal ideation and intent. Dysgeusia followed by intermittent retching occurred almost immediately after the first dose, and the taste disturbance persisted for approximately 3 hours.

Initially, the patient was advised to rinse his mouth with water and spit it out without swallowing. This did not alleviate the taste disturbance, even with a second attempt.

On the second dosing day, the patient was encouraged to take a fruit punch-flavored powdered drink mixed with water to mask the taste. The dysgeusia resolved after the patient had taken the beverage. He continued to take the drink shortly after administration of SPRAVATO and reported only one subsequent case of dysgeusia on the final day of dosing. Time to resolution was within 30 minutes of the reported adverse event each time.

Literature Search

A literature search of MEDLINE^®, Embase^®, BIOSIS Previews^®, and Derwent Drug File (and/or other resources, including internal/external databases) pertaining to this topic was conducted on 26 September 2024.

References

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1	Center for Drug Evaluation and Research. Other Review. NDA 211243 - SPRAVATO (esketamine) - Reference ID: 4398871; 2019. https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211243Orig1s000OtherR.pdf. Accessed September 26, 2024.
2	Bossaller NA, Shelton RC. Real-world approach to managing dysgeusia following the use of esketamine nasal spray: a case report. Ann Gen Psychiatry. 2020;19:13.
3	Fedgchin M, Trivedi M, Daly EJ, et al. Efficacy and safety of fixed-dose esketamine nasal spray combined with a new oral antidepressant in treatment-resistant depression: results of a randomized, double-blind, active-controlled study (TRANSFORM-1). Int J Neuropsychopharmacol. 2019;22(10):616-630.
4	Popova V, Daly EJ, Trivedi M, et al. Efficacy and safety of flexibly dosed esketamine nasal spray combined with a newly initiated oral antidepressant in treatment-resistant depression: a randomized double-blind active-controlled study. Am J Psychiatry. 2019;176(6):428-438.
5	Ochs-Ross R, Daly EJ, Zhang Y, et al. Efficacy and safety of esketamine nasal spray plus an oral antidepressant in elderly patients with treatment-resistant depression-TRANSFORM-3. Am J Geriatr Psychiatry. 2020;28(2):121-141.
6	Chen X, Hou X, Bai D, et al. Efficacy and safety of flexibly dosed esketamine nasal spray plus a newly initiated oral antidepressant in adult patients with treatment-resistant depression: a randomized, double-blind, multicenter, active-controlled study conducted in China and USA. Neuropsychiatr Dis Treat. 2023;19:693-707.
7	Daly EJ, Trivedi MH, Janik A, et al. Supplement to: Efficacy of esketamine nasal spray plus oral antidepressant treatment for relapse prevention in patients with treatment-resistant depression: a randomized clinical trial. JAMA Psychiatry. 2019;76(9):893-903.
8	Wajs E, Aluisio L, Holder R, et al. Esketamine nasal spray plus oral antidepressant in patients with treatment-resistant depression: assessment of long-term safety in a phase 3, open-label study (SUSTAIN-2). J Clin Psychiatry. 2020;81(3):19m12891.
9	Data on File. Esketamine. Clinical Study Report ESKETINTRD3004. Janssen Research & Development, LLC; 2018.
10	Zaki N, Chen LN, Lane R, et al. Long-term safety and maintenance of response with esketamine nasal spray in treatment-resistant depression: final results of the SUSTAIN-3 study. Poster presented at: the Psych Congress; September 6-10, 2023; Nashville, TN.
11	Reif A, Bitter I, Buyze J, et al. Esketamine nasal spray versus quetiapine for treatment-resistant depression. N Engl J Med. 2023;389(14):1298-1309.
12	Reif A, Bitter I, Buyze J, et al. Supplement to: Esketamine nasal spray versus quetiapine for treatment-resistant depression. N Engl J Med. 2023;389(14):1298-1309.
13	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.
14	Ionescu DF, Fu DJ, Qiu X, et al. Esketamine nasal spray for rapid reduction of depressive symptoms in patients with major depressive disorder who have active suicide ideation with intent: results of a phase 3, double-blind, randomized study (ASPIRE II). Int J Neuropsychopharmacol. 2021;24(1):22-31.