The DOI matches its Crossref record; 34 of the 34 references it cites were found in a registry or an index; 3 of the 19 sources its claims cite were checked for support.
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)
Open accessAbstract
OBJECTIVE: To evaluate long-term safety and efficacy of esketamine nasal spray plus a new oral antidepressant (OAD) in patients with treatment-resistant depression (TRD). METHODS: This phase 3, open-label, multicenter, long-term (up to 1 year) study was conducted between October 2015 and October 2017. Patients (≥ 18 years) with TRD (DSM-5 diagnosis of major depressive disorder and nonresponse to ≥ 2 OAD treatments) were enrolled directly or transferred from a short-term study (patients aged ≥ 65 years). Esketamine nasal spray (28-mg, 56-mg, or 84-mg) plus new OAD was administered twice a week in a 4-week induction (IND) phase and weekly or every-other-week for patients who were responders and entered a 48-week optimization/maintenance (OP/MAINT) phase. RESULTS: Of 802 enrolled patients, 86.2% were direct-entry and 13.8% were transferred-entry; 580 (74.5%) of 779 patients who entered the IND phase completed the phase, and 150 (24.9%) of 603 who entered the OP/MAINT phase completed the phase. Common treatment-emergent adverse events (TEAEs) were dizziness (32.9%), dissociation (27.6%), nausea (25.1%), and headache (24.9%). Seventy-six patients (9.5%) discontinued esketamine due to TEAEs. Fifty-five patients (6.9%) experienced serious TEAEs. Most TEAEs occurred on dosing days, were mild or moderate in severity, and resolved on the same day. Two deaths were reported; neither was considered related to esketamine. Cognitive performance generally either improved or remained stable postbaseline. There was no case of interstitial cystitis or respiratory depression. Treatment-emergent dissociative symptoms were transient and generally resolved within 1.5 hours postdose. Montgomery-Åsberg Depression Rating Scale total score decreased during the IND phase, and this reduction persisted during the OP/MAINT phase (mean [SD] change from baseline of respective phase to endpoint: IND, -16.4 [8.76]; OP/MAINT, 0.3 [8.12]). CONCLUSIONS: Long-term esketamine nasal spray plus new OAD therapy had a manageable safety profile, and improvements in depression appeared to be sustained in patients with TRD. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT02497287.
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Claims the paper makes
3 of 19 cited sources checked · 1 supported · 0 flagged · accuracy not yet measured
Every source the paper cites for this claim was checked and supports it.
In the paper
“Finally, alternate forms (HVLT-R: Forms 1-6; Cogstate: playing-cards-based tests [DET, IDN, OCL, and ONB tasks] and 18 parallel maze forms for the GMLT) were used for all cognitive tests to attenuate practice effects.36”
§ 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) > DISCUSSION
What the sources say
- Supportedcites [36] 36. Goldberg TE, Harvey PD, Wesnes KA, et al. Practice effects due to serial cognitive assessment: Implications for preclinical Alzheimer's disease randomized controlled trials. Alzheimers Dement (Amst). 2015;1(1):103-111. 36. P u b M e d source
The Results and Recommendations identify well-matched alternate forms as a way to attenuate practice effects. The statement that forms were used for all the listed tests describes the citing authors’ own methods; the source supports the rationale for that choice, not those study-specific details. (LLM, conf=0.90)
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passes- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“The incidence of UTI (8.1%) in the present study was analogous to rates observed in a general adult female population (over 10%) over a 1-year period.31”
§ 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) > DISCUSSION
What the sources say
- Partly supportedcites [31] 31. P u b M e d C r o s s R e f 30. Rowe TA, Juthani-Mehta M. Urinary tract infection in older adults. Aging Health. 2013;9(5):ahe.13.38. P u b M e d C r o s s R e f 31. Foxman B, Barlow R, D'Arcy H, et al. Urinary tract infection: self-reported incidence and associated costs. Ann Epidemiol. 2000;10(8):509-515. sourceExperimental — accuracy not yet measured
The 'Urinary tract infection' subsection reports that over 10% of women older than 65 had a UTI in the past 12 months. It does not give that rate for the general adult female population. The 8.1% figure is identified as the citing authors' own finding, not a result attributed to this source. (LLM, conf=0.88)
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passes- Partly supported
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In patients who discontinued from the OP/MAINT phase, the most common (> 20%) new or worsening”
§ 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) > Withdrawal Symptoms
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Cognitive performance generally either improved or remained stable postbaseline.”
§ 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) > Abstract
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In the present study, preservation or improvement in all clinically significant cognitive domains on the Cogstate and HLVT-R was observed, except in patients aged ≥ 65 years, who had slowing of performance only on simple (DET) and choice reaction-time (IDN) tests of the Cogstate.”
§ 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) > DISCUSSION
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In addition, there was no significant change in the more complex cognitive domains (verbal, visual, working memory, and executive function), suggesting that the slowing in reaction times may be an isolated observation, not implicating attentional deficit.35”
§ 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) > DISCUSSION
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Treatment-emergent dissociative symptoms were transient and generally resolved within 1.5 hours postdose.”
§ 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) > Abstract
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Seventysix patients (9.5%) had TEAEs that led to discontinuation of esketamine.”
§ 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) > Safety
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In the present study, 14.5% of patients who did not have suicidal ideation at baseline reported new suicidal ideation, 6 patients (0.7%) attempted suicide (1.571 per 100 patient years), and 1 patient completed suicide (0.262 per 100 patient years).”
§ 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) > DISCUSSION
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The improvement in MADRS total score appeared to be sustained in patients who were responders (direct and transfer entry) and who continued treatment for up to 1 year of exposure (mean [SD] change from OP/ MAINT baseline to endpoint: 0.3 [8.12])”
§ 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) > Efficacy
Load-bearingStrength:hedged· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes
- It may state two separate claims as one. 35
- The quote only partly states this claim. 1
- Probably not a substantial claim. 9
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Furthermore, the high retention rates (75% of patients from the IND phase entered the OP/MAINT phase) and attainment of adequate exposure requirements (as outlined in the International Council for Harmonisation [ICH] E1 guideline) 40 adds to the comprehensiveness of the data collected during this longitudinal study.41,42”
§ 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) > DISCUSSION
What the sources say
- Not matchedcites [40] 40. P u b M e d C r o s s R e f 40. ICH Harmonised tripartite guideline-The Extent Of Population Exposure To Assess Clinical Safety For Drugs Intended For Long-Term Treatment Of Non-Life-Threatening Conditions E1. International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use; 1994.
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- Partly supportedcites [41] 41. Abshire M, Dinglas VD, Cajita MI, et al. Participant retention practices in longitudinal clinical research studies with high retention rates. BMC Med Res Methodol. 2017;17(1):30. P u b M e d C r o s s R e f sourceExperimental — accuracy not yet measured
The Background (page unavailable) says participant retention is vital to the power and internal validity of longitudinal research, supporting the general point that retention strengthens the data. The Results (page unavailable) concern studies with at least 80% retention; this paper does not establish the citing study’s 75% transition from IND to OP/MAINT or its exposure requirements. The ICH guideline is cited separately as reference 40. (LLM, conf=0.85)
- Not checked — no full text of the sourcecites [42] 42. Simmonds B, Turner N, Thomas L, et al. Patients' experiences of participating in a large-scale trial of cognitive behavioural therapy for depression: a mixed methods study. Fam Pract. 2013;30(6):705-711. 42. P u M e d C r o s s R e f See supplementary material for this article at . source
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
- Not matched
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Montgomery-Åsberg Depression Rating Scale total score decreased during the IND phase, and this reduction persisted during the OP/MAINT phase (mean [SD] change from baseline of respective phase to endpoint: IND, -16.4 [8.76]; OP/MAINT, 0.3 [8.12]).”
§ 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) > Abstract
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Dizziness (32.9%), dissociation (27.6%), nausea (25.1%), and headache (24.9%) were reported frequently (≥ 20% patients) during the IND and OP/MAINT phases”
§ 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) > Safety
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesThe quote only partly states this claim.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The mean (SD) PWC-20 total scores (range 0-60; 0-3-point scale [not present = 0, mild = 1, moderate = 2, severe = 3]) were 8.0 (7.61) (at end of treatment) and 7.9 (6.91) (week 1), 8.0 (7.42) (week 2), and 7.7 (7.07) (week 4) during follow-up.”
§ 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) > Withdrawal Symptoms
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Most esketamine-related TEAEs were mild or moderate in intensity, occurred shortly after esketamine nasal spray administration, and resolved the same day.”
§ 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) > Safety
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Of 802 enrolled patients, 86.2% were direct-entry and 13.8% were transferred-entry”
§ 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) > Abstract
Strength:plain· not yet calibratedn = 802Tests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“No case of interstitial/ ulcerative cystitis was reported, and TEAEs of cystitis were mostly of mild severity, transient and self-limiting, and considered to be suggestive of an infectious etiology (ie, UTI).”
§ 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) > DISCUSSION
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Two deaths, assessed as doubtful or unrelated to esketamine by the investigator, were reported”
§ 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) > Safety
Strength:hedged· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
In the paper
“This study involved difficult-to-treat patients with a long-term history of TRD, moderate to severe depression at baseline, and a mean duration of the current depressive episode of about 3 years, and approximately a quarter of the sample had a prior history of suicidal ideation.39”
§ 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) > DISCUSSION
What the sources say
- Not matchedcites [39] 39. P u b M e d C r o s s R e f 39. Al-Harbi KS. Treatment-resistant depression: therapeutic trends, challenges, and future directions. Patient Prefer Adherence. 2012;6:369-388.
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
- Not matched
In the paper
“The mean (SD) PWC-20 total score 2 weeks after discontinuation of esketamine (8.0 [7.42]) was similar to that observed at end of treatment (8.0 [7.61]) and was approximately 2-to 3-times lower than the total scores reported in patients after successful (17.2 [11.6]) and unsuccessful (24.6 [12.6]) tapering-off of their benzodiazepines.19”
§ 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) > DISCUSSION
What the sources say
- Not matchedcites [19] 19. P u b M e d
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
- Not matched
In the paper
“Similar to that in earlier reports of esketamine, [1][2][3][4][5]10 severity of dissociative symptoms in this study attenuated over time in most cases, although in rare instances transient reemergence of higher intensity dissociative symptoms at a later dosing session was observed.”
§ 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) > DISCUSSION
What the sources say
- Not matchedcites [1][2][3][4][5]10
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
Strength:plain· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
- Not matched
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“580 (74.5%) of 779 patients who entered the IND phase completed the phase, and 150 (24.9%) of 603 who entered the OP/MAINT phase completed the phase.”
§ 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) > Abstract
Strength:plain· not yet calibratedn = 779Tests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“The serious TEAEs related to renal and urinary tract disorders were assessed as not related to esketamine and resolved while the treatment was ongoing.”
§ 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) > DISCUSSION
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The percentage of responders and remitters at the OP/MAINT phase endpoint was 76.5% and 58.2%, respectively (Table 3).”
§ 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) > Efficacy
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In the present study, 14.5% of patients who did not have suicidal ideation at baseline reported new suicidal ideation, 6 patients (0.7%) attempted suicide (1.571 per 100 patient years), and 1 patient completed suicide (0.262 per 100 patient years).”
§ 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) > DISCUSSION
Strength:plain· not yet calibratedn = 6Tests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“There was no case of interstitial cystitis or respiratory depression.”
§ 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) > Abstract
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In patients with low cardiovascular risk at baseline, increases in BP observed after esketamine administration were generally transient and led to discontinuation in 0.7% of patients.”
§ 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) > DISCUSSION
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Maximum post-dose CADSS total scores generally declined over time, with the steepest decline in the 4-week induction phase.”
§ 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) > Additional information
Strength:plain· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Responders c at endpoint, n (%) 461 (62.0) d 449 (74.6) e”
§ 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) > Additional information
Strength:plain· not yet calibratedn = 744Tests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The events of anxiety and delusions were reported together with the serious TEAE of alcohol abuse (not esketaminerelated), 5 days after administration of the first dose of esketamine.”
§ 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) > Additional information
Strength:plain· not yet calibratedSingle caseTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“One patient with marked ALT and bilirubin elevations was discontinued due to hepatitis B and ovarian cancer.”
§ 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) > Additional information
Strength:plain· not yet calibratedSingle caseTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“The event was not considered related to esketamine treatment by the investigator.”
§ 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) > Additional information
Strength:plain· not yet calibratedSingle caseTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“During the IND and OP/MAINT phases, 13 (1.7%)patients had elevations of alanine aminotransferase (ALT) >3 times the upper limit of normal; in 11 patients these elevations returned to baseline or near baseline levels while treatment with esketamine was ongoing.”
§ 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) > Additional information
Strength:plain· not yet calibratedn = 13Tests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Of the two deaths reported, one patient, a 60-year-old man, with a medical history of hypertension and right lower limb vein surgery, died on day 113 of the study (last dose of esketamine: day 108) due to acute cardiac and respiratory failure that were assessed as doubtfully related to esketamine treatment by the investigator.”
§ 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) > Additional information
Strength:plain· not yet calibratedSingle caseTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Remitters f at endpoint, n (%) 201 (26.9) b 286 (47.4)”
§ 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) > Additional information
Strength:plain· not yet calibratedn = 286Tests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“| Remitters j at endpoint, n (%) | 137 (21.1) d | 220 (39.5) g |”
§ 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) > Additional information
Strength:plain· not yet calibratedn = 648Tests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“| (%) | 310 (47.8) d | 351 (63.0) g |”
§ 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) > Additional information
Strength:plain· not yet calibratedn = 648Tests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The mean (SD) PHQ-9 total scores decreased from IND baseline to endpoint and this improvement appeared to be maintained from OP/MAINT baseline to endpoint”
§ 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) > Additional information
Strength:hedged· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Baseline b , mean (SD) | 22.2 (5.45) c | 11.3 (7.27) f |”
- Also stated in: § Additional information · plain
“Endpoint, mean (SD) | 12.8 (7.89) d | 9.5 (7.89) g |”
§ 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) > Additional information
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
- Also stated in: § Additional information · plain
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Delirium occurred 35 minutes after esketamine dosing on day 127 in a patient with prior history of alcohol use.”
§ 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) > Additional information
Strength:plain· not yet calibratedSingle caseTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“In the landmark Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study, 38 remission rates assessed by a different instrument and more strict criteria (Quick Inventory of Depressive Symptomatology-Self-Report [QIDS-SR] ≤ 5) were 30.6% after 2, 13.7% after 3, and 13.0% after 4 failed AD trials.”
§ 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) > DISCUSSION
What the sources say
- Not checked — no full text of the sourcecites [38] 38. Rush AJ, Trivedi MH, Wisniewski SR, et al. Acute and longer-term outcomes in depressed outpatients requiring one or several treatment steps: a STAR*D report. Am J Psychiatry. 2006;163(11):1905-1917. source
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
In the paper
“Suicidal ideation and behavior are associated with TRD with estimated incidence rates of 0.47 completed and 4.66 attempted suicides per 100 patient years.”
§ 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) > DISCUSSION
What the sources say
- Not checked — no full text of the sourcecites [32] 32. P u b M e d C r o s s R e f 32. Bergfeld IO, Mantione M, Figee M, et al. Treatment-resistant depression and suicidality. J Affect Disord. 2018;235:362-367. source
Strength:hedged· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Long-term (up to 1 year) treatment with esketamine nasal spray demonstrated acceptable tolerability and an adverse event profile comparable with that of the shortterm studies in patients with TRD.”
§ 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) > Clinical Points
Load-bearingStrength:boosted· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
- Rests on an assumption: The open-label design did not materially affect the safety findings.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“The definition of remission as a MADRS score ≤ 12 was selected taking into account that the patients manifested TRD prior to entry and thus had higher MADRS scores at baseline than those typically included for studies assessing the efficacy of new treatments in the general MDD population.”
§ 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) > DISCUSSION
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesProbably not a substantial claim.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“This study had several limitations including its openlabel study design, the simultaneous initiation of a new OAD, and the absence of a control group; however, the high response and remission rates suggest that long-term (up to 1 year) esketamine treatment appears to provide sustained symptom improvement.”
§ 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) > DISCUSSION
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Reductions in depressive symptoms were observed during the first 4 weeks of treatment (IND phase) and appeared to be sustained through the 1-year exposure period.”
§ 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) > DISCUSSION
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
In the paper
“Another study 33 reported that in TRD patients, the life-time risk of suicide attempts is assessed to be close to 30%.”
§ 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) > DISCUSSION
What the sources say
- Not checked — no full text of the sourcecites [33] 33. P u b M e d C r o s s R e f 33. Dunner DL, Rush AJ, Russell JM, et al. Prospective, long-term, multicenter study of the naturalistic outcomes of patients with treatment-resistant depression. J Clin Psychiatry. 2006;67(5):688-695. source
Strength:hedged· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Collectively, these findings and discontinuation-related symptoms from the PWC-20 assessment suggest that withdrawal symptoms were infrequent, mild, and in quality appeared generally indistinguishable from early return in MDD symptoms.”
§ 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) > DISCUSSION
Load-bearingStrength:hedged· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“As dosing frequency was based on treatment response together with tolerability, for most patients, the findings suggested consistent benefits and acceptable tolerability of esketamine nasal spray treatment over a period of up to 1 year.”
§ 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) > DISCUSSION
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
In the paper
“Although a single subanesthetic dose (0.2 and 0.5-mg/kg) of ketamine showed no cognitive impairment (working memory and go/no-go tasks on days 3 and 14 postketamine infusion) in patients with TRD, effects on cognitive performance with repeated use of ketamine over longer periods remains elusive.34”
§ 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) > DISCUSSION
What the sources say
- Not checked — no full text of the sourcecites [34] 34. P u b M e d C r o s s R e f 34. Chen MH, Li CT, Lin WC, et al. Cognitive function of patients with treatment-resistant depression after a single low dose of ketamine infusion. J Affect Disord. 2018;241:1-7. P u b M e d C r o s s R e f source
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
In the paper
“These rates are substantially higher than those in the general MDD population and similar to those found before and after treatments such as electroconvulsive therapy.32”
§ 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) > DISCUSSION
What the sources say
- Not checked — no full text of the sourcecites [32] 32. P u b M e d C r o s s R e f 32. Bergfeld IO, Mantione M, Figee M, et al. Treatment-resistant depression and suicidality. J Affect Disord. 2018;235:362-367. source
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
In the paper
“Cognitive deficits, impairments in working memory, and decrements in episodic memory have been documented following acute and repeated recreational abuse of ketamine.8”
§ 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) > DISCUSSION
What the sources say
- Not checked — no full text of the sourcecites [8] 8. P u b M e d C r o s s R e f 8. Morgan CJ, Muetzelfeldt L, Curran HV. Consequences of chronic ketamine self- administration upon neurocognitive function and psychological wellbeing: a 1-year longitudinal study. Addiction. 2010;105(1):121-133. source
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
The paper relies on this without support.
Long-term safety data for esketamine in treatment-resistant depression were lacking before this study.
“data on its long-term safety have been lacking prior to the current study.”
The paper relies on this without support.
Esketamine has shown favorable efficacy and tolerability in short-term studies of treatment-resistant depression.
“Esketamine has shown favorable efficacy and tolerability in short-term studies of patients with treatment-resistant depression (TRD)”
The paper relies on this without support.
The open-label design did not materially affect the safety findings.
“This open-label (OL), multicenter study was conducted between October 2015 and October 2017 at 114 sites in 21 countries.”
The paper relies on this without support.
Esketamine's rapid plasma clearance, short half-life, and low dosing frequency prevent steady-state accumulation in patients.
“Notably, the rapid clearance from plasma, short half-life, and low frequency of dosing (weekly or everyother-week) did not allow esketamine to reach steady-state in patients dosed in this study.”
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Intranasal esketamine spray co- initi ated with an antidepressant has also demonstrated rapid clinically meaningful efficacy in patients with TRD.”
From Treatment‐resistant depression: definition, prevalence, detection, management, and investigational interventions (2023) · cites this paper as [195]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Unlike IV ketamine, there are also data demonstrating long- term (i.e., greater than 3- year) safety and tolerability for esketamine 194,195 .”
From Treatment‐resistant depression: definition, prevalence, detection, management, and investigational interventions (2023) · cites this paper as [195]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“The absence of long- term data with SGAs is a point of differentiation with esketamine, which has long- term multi- year establishment of efficacy and safety 195 .”
From Treatment‐resistant depression: definition, prevalence, detection, management, and investigational interventions (2023) · cites this paper as [195]
Experimental — accuracy not yet measuredIn the citing paper
“No deaths were reported in the placebo group.”
From Pharmacotherapies Targeting GABA-Glutamate Neurotransmission for Treatment-Resistant Depression (2023) · cites this paper as [113]
In the citing paper
“The approvals of esketamine nasal spray were based on efficacy and safety findings from phase 2/3 studies of TRD treatment for 4 weeks to 1 year [9–14].”
In the citing paper
“The safety profile of esketamine, with continuous intermittent dosing for up to 4.5 years in SUSTAIN-3 (2,769 cumulative patient-years), is consistent with its established safety profile in participants with TRD treated for up to 1 year [7, 8, 14].”
In the citing paper
“The incidence of clinically-relevant sedation (MOAA/S score ≤ 3) in SUSTAIN-3 (6.1% in the induction phase and 6.9% in the optimization/maintenance phase) is similar to that observed in the prior long-term SUSTAIN-2 study (8.4% and 7.0% in the respective phases) [14].”
In the citing paper
“Our findings extend those of Wajs et al. [14], who reported a 47.2% remission rate at 12 months.”
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
Each contradiction between two passages listed here was confirmed by an independent check.
Reported absence of impaired reaction time conflicts with patient data
MajorThe paper says no patient had impaired reaction time at endpoints, using a z-score threshold below −1.5. In the simple-reaction-time table, patient 15 had a baseline score of 0.52 and an OP/MAINT endpoint score of −2.68.
“no patient manifested impaired reaction time (z score < -1.5 on detection or identification tasks) at study endpoints and follow-up”
“15 71 0.52 -2.01 -1.38 -1.59 -0.43 -2.68 -0.83”
Citations
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Items 101–200 of 297
Mapping consent practices for outpatient psychiatric use of ketamine
Mathai, D. S., Lee, S. M., Mora, V., O’Donnell, K. C., Garcia‐Romeu, A., & Storch, E. A. (2022) · Journal of Affective Disorders · doi:10.1016/j.jad.2022.06.036 · Cited by 16
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“27,47 In contrast, esketamine has been found to augment serotonin release in a dose-dependent manner, particularly within the prefrontal cortex of the brain.”
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Role of group II metabotropic glutamate receptors in ketamine's antidepressant actions
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Early effects predict trajectories of response to esketamine in treatment-resistant depression
Estrade, I., Petit, A., Sylvestre, V., Danon, M., Leroy, S., Perrain, R., Vinckier, F., Mékaoui, L., Gaillard, R., Advenier-Iakovlev, E., et al. (2023) · Journal of Affective Disorders · doi:10.1016/j.jad.2023.09.030 · Cited by 16
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Kumari, S., Chaudhry, H. A., Sagot, A. J., Doumas, S. J., Abdullah, H. M., Alcera, E. C., Solhkhah, R., & Afzal, S. (2024) · Cureus · doi:10.7759/cureus.53987 · Cited by 15
“The three TRANSFORM trials were to determine short-term efficacy, while SUSTAIN-1 was a withdrawal study to examine the maintenance of effect, and SUSTAIN-2 was a long-term study aimed at determining ESK's safety parameters [10-14 , 25].”
BackgroundInfluentialSingh, J. B., Fedgchin, M. M., Daly, E., & Drevets, W. C. (2020) · Advances in pharmacology · doi:10.1016/bs.apha.2020.05.002 · Cited by 18
Self-citationFairchild, A. O., Katz, E. G., Reed, S. D., Johnson, F. R., DiBernardo, A., Hough, D. W., Sing, J., & Levitan, B. S. (2020) · Neurology Psychiatry and Brain Research · doi:10.1016/j.npbr.2020.05.003 · Cited by 15
Self-citationChen, B. K., Pen, G. L., Eckmier, A., Rubinstenn, G., Jay, T. M., & Denny, C. A. (2021) · The International Journal of Neuropsychopharmacology · doi:10.1093/ijnp/pyab007 · Cited by 14
Craving and addictive potential of esketamine as side effects?
Orsolini, L., Salvi, V., & Volpe, U. (2022) · Expert Opinion on Drug Safety · doi:10.1080/14740338.2022.2071422 · Cited by 16
“[23] describing the occurrence of dizziness, dissociation, and somnolence as frequent adverse events (>10% of patients), occurred on the day of ESK-NS administration.”
BackgroundTargeting the dysfunction of glutamate receptors for the development of novel antidepressants
Xia, C., He, J., Du, L., Yan, Y., Lian, W., Xu, J., & Zhang, W. (2021) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2021.107875 · Cited by 15
Siebert, M., Gaba, J. F., Renault, A., Laviolle, B., Locher, C., Moher, D., & Naudet, F. (2022) · BMC Medicine · doi:10.1186/s12916-022-02377-2 · Cited by 15
“One study did not specify primary endpoints in its protocol but only objectives [44].”
BackgroundJiang, Q., Qi, Y., Zhou, M., Dong, Y., Zheng, W., Zhu, L., Li, Y., Zhou, H., & Wang, L. (2024) · BMC Anesthesiology · doi:10.1186/s12871-024-02681-9 · Cited by 14
“Additionally, literature reports that repeated administration of ketamine nasal spray can rapidly treat refractory depression in the short term, and its antidepressant effects persist for several weeks after discontinuation of treatment [32].”
BackgroundGibuła‐Tarłowska, E., Wiszniewska, A., Turyk, M., Szymczyk, P., Kotlinska, J. H., & Kędzierska, E. (2025) · Molecules · doi:10.3390/molecules30132824 · Cited by 18
“Two patients died during the study; however, this was found to be unrelated to the treatment [201].”
Li, S. W., Kumpf, K. T., Urrutia, J., Krystal, J. H., Sanacora, G., & Wilkinson, S. T. (2025) · American Journal of Psychiatry · doi:10.1176/appi.ajp.20250276 · Cited by 16
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Pepe, M., Bartolucci, G., Marcelli, I., Simonetti, A., Camardese, G., Nicola, M. D., & Sani, G. (2023) · Journal of Psychiatric Practice · doi:10.1097/pra.0000000000000723 · Cited by 13
Cognitive outcomes from the randomised, active-controlled Ketamine for Adult Depression Study (KADS)
Martin, D. M., Harvey, A. J., Baune, B., Berk, M., Carter, G. L., Dong, V., Glozier, N., Glue, P., Hood, S. D., Hadži-Pavlović, D., et al. (2024) · Journal of Affective Disorders · doi:10.1016/j.jad.2024.02.052 · Cited by 13
Gandolfo, P., Soeiro, T., Jouve, É., Revol, B., Daveluy, A., Bertin, C., Eiden, C., Gibaja, V., Chaouachi, L., Pérault‐Pochat, M., et al. (2024) · Fundamental and Clinical Pharmacology · doi:10.1111/fcp.12995 · Cited by 13
“[ 25] A recent review that assessed the quality of reporting of adverse events in clinical trials studying esketamine suggests that an assessment of the benefits/risks balance of esketamine based on the results reported in trial publications is flawed due to the poor accuracy and completeness of…”
Chiappini, S., Guirguis, A., Schifano, N., Corkery, J., Semeraro, F., Mosca, A., D’Andrea, G., Papanti, G. D., Arillotta, D., Floresta, G., et al. (2024) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2024.111213 · Cited by 13
“Further extending the scope of safety assessment, the SUSTAIN-1 (Daly et al., 2019) and SUSTAIN-2 trials (Wajs et al., 2020) focused on the maintenance phase of esketamine treatment: SUSTAIN-1 demonstrated that esketamine nasal spray plus an oral antidepressant significantly delayed relapse in…”
Katz, E. G., McNulty, P., Levitan, B. S., Treichler, P., Martynowicz, J., & Jamieson, C. (2021) · Therapeutic Innovation & Regulatory Science · doi:10.1007/s43441-021-00340-6 · Cited by 13
“SUSTAIN-2 (NCT02497287) was an open-label phase 3 trial that assessed long-term safety and efficacy of esketamine + AD in patients with TRD [15].”
BackgroundChen, G., Mannens, G., Boeck, M. D., Daly, E., Canuso, C. M., Teuns, G., Manji, H. K., & Drevets, W. C. (2022) · Molecular Psychiatry · doi:10.1038/s41380-022-01447-4 · Cited by 13
“, respiratory depression) in RCTs of patients with depression receiving (S)-ketamine [11], the absence of withdrawal effects observed following discontinuation of (S)-ketamine [12], and the absence of an effect of functional MOR gene polymorphisms on (S)-ketamine’s antidepressant effect [8].”
BackgroundSelf-citationMoccia, L., Lanzotti, P., Pepe, M., Palumbo, L., Janiri, D., Camardese, G., Bentivoglio, A. R., Nicola, M. D., Calabresi, P., & Sani, G. (2021) · International Clinical Psychopharmacology · doi:10.1097/yic.0000000000000378 · Cited by 12
“Besides, preliminary evidence is available on long-term efficacy of continuation of esketamine nasal spray in addition to oral antidepressants for patients with TRD who do not experience complete remission of depressive symptoms after the first month of treatment (Daly et al., 2019; Wajs et al., 2020; Turkoz et al., 2…”
BackgroundIntravenous ketamine versus esketamine for depression: a systematic review and meta-analysis
Elmosalamy, A., Tarikogullari, I., Patarroyo-Rodríguez, L., Wilson, G., Voort, J. L. V., Kung, S., Frye, M. A., & Singh, B. (2025) · Therapeutic Advances in Psychopharmacology · doi:10.1177/20451253251394127 · Cited by 14
Treatment-Resistant Depression in Portugal: Perspective From Psychiatry Experts
Bessa, J. M., Carvalho, S., Cunha, I. B., Fernandes, M., Matos-Pires, A., Neves, R., Oliveira-Maia, A. J., Santos, S. G., & Santos, V. (2022) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2022.824919 · Cited by 13
“sustained responses, as well as development of novel therapeutic options for the future (17, 51).”
BackgroundTherapeutic Protocols Using Ketamine and Esketamine for Depressive Disorders: A Systematic Review
FREIND, J. M. K., Beserra, F. R., Menezes, B. S., & Mograbi, D. C. (2023) · Journal of Psychoactive Drugs · doi:10.1080/02791072.2023.2248989 · Cited by 12
Efficacy, Safety, and Tolerability of Psychedelics in Treatment-Resistant Depression (TRD)
Olivier, B., & Olivier, J. D. A. (2024) · Advances in experimental medicine and biology · doi:10.1007/978-981-97-4402-2_3 · Cited by 12
Is there a risk of esketamine misuse in clinical practice?
Roncero, C., Torres, M. M., Szerman, N., Torrens, M., Vega, P., Andrés-Olivera, P., & Alvarez, E. (2025) · Therapeutic Advances in Drug Safety · doi:10.1177/20420986241310685 · Cited by 16
General Anesthetics: Aspects of Chirality, Pharmacodynamics, and Pharmacokinetics
Cizmáriková, R., Habala, L., & Valentová, J. (2025) · Pharmaceuticals · doi:10.3390/ph18020250 · Cited by 14
“In 2019, it was approved in the United States for use with other antidepressants for the treatment of depression in adults, provided it is administered in a clinical setting [170].”
New and emerging pharmacologic treatments for MDD
Uyar, A., & Gönül, A. S. (2025) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2025.1621887 · Cited by 16
Hovda, N., Gerrish, W. G., Frizzell, W., & Shackelford, R. (2023) · Journal of Affective Disorders · doi:10.1016/j.jad.2023.10.120 · Cited by 13
Major challenges in youth psychopathology: treatment-resistant depression. A narrative review
Menculini, G., Cinesi, G., Scopetta, F., Cardelli, M., Caramanico, G., Balducci, P. M., Giorgi, F. D., Moretti, P., & Tortorella, A. A. V. (2024) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2024.1417977 · Cited by 13
Morrison, R. L., Singh, J. B., Daly, E., Fedgchin, M. M., Ochs-Ross, R., Karcher, K., Lane, R., Cooper, K. L., Sanacora, G., Maruff, P. T., et al. (2024) · The International Journal of Neuropsychopharmacology · doi:10.1093/ijnp/pyae046 · Cited by 12
Self-citationEsketamine: uncertain safety and efficacy data in depression
Horowitz, M. A., & Moncrieff, J. (2021) · The British Journal of Psychiatry · doi:10.1192/bjp.2021.163 · Cited by 11
Hou, L., Miao, J., Meng, H., Liu, X., Wang, D., Tan, Y., & Li, C. (2022) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2022.855810 · Cited by 12
Self-citationWilliamson, D., Turkoz, I., Wajs, E., Singh, J. B., Borentain, S., & Drevets, W. C. (2022) · The International Journal of Neuropsychopharmacology · doi:10.1093/ijnp/pyac081 · Cited by 12
Self-citationFloriano, I., Silvinato, A., & Bernardo, W. M. (2023) · Revista da Associação Médica Brasileira · doi:10.1590/1806-9282.2023d694 · Cited by 12
Mukhaizeem, S. A., Nasa, A., Waldron, D., McDaid, A., Gorman, P., Featherstone, M., Barry, M., Murphy, P. M., Gallagher, H., Nair, S., et al. (2023) · Frontiers in Pain Research · doi:10.3389/fpain.2023.1268985 · Cited by 12
Kojic, M., Saelens, J., Kadriu, B., Zarate, C. A., & Kraus, C. (2022) · Current topics in behavioral neurosciences · doi:10.1007/7854_2022_313 · Cited by 12
Molero, P., Ibáñez, Á., de Diego-Adeliño, J., Ramos‐Quiroga, J. A., Dorado, M. G., Rengel, P. M. L., & Sáiz, P. A. (2025) · Advances in Therapy · doi:10.1007/s12325-025-03149-z · Cited by 13
“Two long‑ term trials (SUSTAIN trials) reported a signifi‑ cant reduction in the risk of relapse in patients who previously achieved stable remission or stable response after short‑term treatment with ESK‑NS [26] and a long‑term manageable safety profile [27].”
Hussain, S., Gale, C. K., Sarma, S., Smith, J. P., Bayes, A. J., & Loo, C. K. A. (2025) · Australian & New Zealand Journal of Psychiatry · doi:10.1177/00048674251333577 · Cited by 10
“…the KSET-Revised (KSET-R) (Bayes et al., 2025) and frequencies of side effects from naturalistic settings as well as the Janssen 2 and 3 year data (Wajs et al., 2020; Zaki et al., 2023) Prescribers should be aware that frequent and long-term ketamine use in non-medical circumstances has been…”
The why, when, where, how, and so what of so-called rapidly acting antidepressants
Schatzberg, A. F., & Mathew, S. J. (2023) · Neuropsychopharmacology · doi:10.1038/s41386-023-01647-8 · Cited by 11
“In the SUSTAIN-2 study [58] esketamine was evaluated in 802 patients with a median drug exposure of 22.9 weeks.”
MethodInfluentialWhat clinicians need to know about intranasal esketamine for treatment-resistant depression?
Hope, J., Copolov, D., Tiller, J. W. G., Galbally, M., Hopwood, M., Newton, R., & Keks, N. A. (2023) · Australasian Psychiatry · doi:10.1177/10398562231211171 · Cited by 10
“In the fi ve pivotal studies (including two long-term 12,13 ) of intranasal esketamine plus antidepressant, the most common adverse effects were dissociation, dizziness, nausea, sedation and headache (Table 2).”
BackgroundYoung, A. H., Abdelghani, M., Juruena, M. F., Nikolova, V. L., & Nilforooshan, R. (2023) · Neuropsychiatric Disease and Treatment · doi:10.2147/ndt.s388392 · Cited by 10
“In the SUSTAIN-2 trial (patients aged ≥18, N=806), which examined the long-term safety of esketamine nasal spray, less than 4% of dissociative/perceptual changes were reported as severe in intensity.(15) Across the registrational trials as a whole, the onset of dissociative symptoms and perceptual changes (as measured…”
BackgroundSelf-citationOlivola, M., Mazzoni, F., Tarantino, B., Guffanti, A., Marcatili, M., Macellaro, M., Girone, N., Martiadis, V., Raffone, F., Prodi, T., et al. (2026) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2025.1736114 · Cited by 10
Cost-Utility Analysis of Esketamine for Patients with Treatment-Resistant Depression in Italy
Rognoni, C., Falivena, C., Costa, F., & Armeni, P. (2023) · PharmacoEconomics · doi:10.1007/s40273-022-01220-z · Cited by 10
“A longer time horizon study [18] reported that common (involving ≥ 10% of patients) treatment-emergent adverse events (TEAEs) for esketamine were dizziness (32.”
BackgroundChepke, C., Shelton, R. C., Sanacora, G., Doherty, T., Tsytsik, P., & Parker, N. (2024) · The International Journal of Neuropsychopharmacology · doi:10.1093/ijnp/pyae058 · Cited by 9
“…clinically relevant; therefore, they were not reported as adverse events (AEs) by the investigators in the majority of cases (Daly et al., 2019; Fedgchin et al., 2019; Popova et al., 2019; Fu et al., 2020; Ionescu et al., 2020; Ochs-Ross et al., 2020; Wajs et al., 2020; Reif et al., 2023).”
Self-citationEsketamine Nasal Spray in Major Depressive Disorder: A Meta‐Analysis of Randomized Controlled Trials
Wang, Z., Jiang, L., Ma, W., Li, X., Gao, Q., Lian, S., & Yu, W. (2025) · Clinical Pharmacology & Therapeutics · doi:10.1002/cpt.3555 · Cited by 12
Sukhdeo, R., Tamura, J. K., Dri, C. E., & McIntyre, R. S. (2025) · American Journal of Geriatric Psychiatry · doi:10.1016/j.jagp.2025.08.001 · Cited by 12
Olivola, M., Mazzoni, F., Tarantino, B., Guffanti, A., Marcatili, M., Motta, F. L., Cornaggia, R. D., Martiadis, V., Prodi, T., Politi, P., et al. (2025) · Journal of Affective Disorders · doi:10.1016/j.jad.2025.120231 · Cited by 9
Kitay, B. M., Murphy, E., Macaluso, M., Corlett, P. R., Hershenberg, R., Joormann, J., Martinez‐Kaigi, V., Nikayin, S., Rhee, T. G., Sanacora, G., et al. (2023) · Psychiatry Research · doi:10.1016/j.psychres.2023.115585 · Cited by 13
Self-citationThe effects of esketamine on the intestinal microenvironment and intestinal microbiota in mice
Zhang, Y., Ma, W., Lin, H., Gu, X., & Xie, H. (2023) · Human & Experimental Toxicology · doi:10.1177/09603271231211894 · Cited by 9
“…suggests that the use of ketamine or esketamine may induce many side effects, for example, dizziness, dissociation, nausea, and head-ache; 11 – 13 rapid intravenous injection can cause transient apnoea and increase the incidence of laryngospasm, 14 and drug abuse may also trigger cystitis and…”
BackgroundKetamine in depression and electroconvulsive therapy
Rozet, I. (2021) · Current Opinion in Anaesthesiology · doi:10.1097/aco.0000000000001039 · Cited by 10
Widespread reductions in cortical thickness following ketamine abuse
Tang, J.-S., Wu, Q.-X., Qi, C., Xie, A., Liu, J., Sun, Y.-K., Yuan, T.-F., Chen, W., Liu, T.-Q., Hao, W., et al. (2024) · Journal of Psychiatry & Neuroscience · doi:10.1503/jpn.230111 · Cited by 7
“63 !”
Gutiérrez-Rojas, L., Vendrell-Serres, J., Ramos‐Quiroga, J. A., Etxeandia-Pradera, J.-I., Aguilar, E. J., de Santiago-Díaz, A. I., Hernández-Huerta, D., Tordera, V., Ventoso, C. V., Bolívar, M., et al. (2024) · Journal of Psychopharmacology · doi:10.1177/02698811241267837 · Cited by 12
“For example, Day et al. (2019) had a loss of around 64% of the sample, while Wajs et al. (2020) reported discontinuation rates of 50% during the same timeframe (180 days).”
Gutiérrez, G., Vázquez, G. H., Ravindran, N., Lam, R. W. M., Giacobbe, P., Ganapathy, K., Kowara, A., Do, A., Baskaran, A., Nestor, S. M., et al. (2025) · Therapeutic Advances in Drug Safety · doi:10.1177/20420986251347360 · Cited by 8
“For instance, in agreement with the results of this study, a study by Wajs et al. 52 looking into the effectiveness of IN esketamine treatment in addition to an oral antidepressant for the treatment of patients with MDD-TRD, reported that none of their participants sought to use, abused, or…”
Urological symptoms following ketamine treatment for psychiatric disorders: A systematic review
Kerr‐Gaffney, J., Tröger, A., Caulfield, A., Ritter, P. S., Rucker, J., & Young, A. H. (2025) · Journal of Psychopharmacology · doi:10.1177/02698811251350267 · Cited by 8
“Dosage in studies using intranasal routes ranged from 28 mg (d’Andrea et al., 2024; Daly et al., 2018; Ochs-Ross et al., 2020; Wajs et al., 2020; Zaki et al., 2023) to 100 mg (Gálvez et al., 2018).”
InfluentialSelf-citationKetamine in Clinical Practice: Transitioning from Anesthetic Agent to Psychiatric Therapeutic
Quintero, J.-M., Bustos, R., Lechtig, S., Beltran, S., & Zarate, C. A. (2025) · Cambridge University Press eBooks · doi:10.1017/9781009585330.007 · Cited by 12
Singanwad, P., Tatode, A., Qutub, M., Taksande, B. G., Umekar, M. J., Trivedi, R., & Premchandani, T. (2025) · Neuropeptides · doi:10.1016/j.npep.2025.102538 · Cited by 9
Treatment-resistant depression and intranasal esketamine: Spanish consensus on theoretical aspects
Mora, F., Ramos‐Quiroga, J. A., Baca‐García, E., Crespo, J. M., Gutiérrez-Rojas, L., Madrazo, A., Pérez-Costillas, L., Sáiz, P. A., Tordera, V., & Vieta, E. (2025) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2025.1623659 · Cited by 11
Haikazian, S., McIntyre, R. S., Meshkat, S., Kratiuk, K., Llach, C.-D., Orsini, D. K., Luch, S. D. D., & Rosenblat, J. D. (2025) · Psychiatry Research · doi:10.1016/j.psychres.2025.116691 · Cited by 9
Lapa, C. D. O., Viola, T. W., Delfino, R. S., Dutra, L., Rubira, G., Rodrigues, R. J. K., Castro, S. C. C., Ramos‐Quiroga, J. A., & Spanemberg, L. (2026) · Journal of Affective Disorders · doi:10.1016/j.jad.2026.121257 · Cited by 10
Hopwood, M., Scott, E. M., Codyre, D., Barton, D., Puig, A., King, J., Joks, G., & Hickie, I. B. (2024) · Psychiatry Research Communications · doi:10.1016/j.psycom.2024.100177 · Cited by 9
Guidelines for ketamine use in clinical psychiatry practice
Jelen, L. A., McShane, R. H., & Young, A. H. (2024) · BJPsych Open · doi:10.1192/bjo.2024.62 · Cited by 8
“12 Both ketamine and esketamine give rise to safety concerns encompassing psychiatric (dissociation, psychotomimetic and increased suicidality), neurological/cognitive, genitourinary and hemodynamic effects that require monitoring.”
BackgroundSelf-citationComment to Drs Gastaldon, Papola, Ostuzzi and Barbui
Mathews, M., Daly, E. J., Popova, V., Heerlein, K., Canuso, C., & Drevets, W. C. (2020) · Epidemiology and Psychiatric Sciences · doi:10.1017/s2045796020000268 · Cited by 7
“The two phase 3 registration trials [SUSTAIN-1 (Daly et al ., 2019); SUSTAIN-2 (Wajs et al ., 2020)] assessed the maintenance of anti-depressant effects beyond the initial acute treatment period with esketamine nasal spray in adult patients with treatment-resistant MDD (Food and Drug…”
InfluentialSelf-citationBremner, J. D., Williamson, D., & Vaccarino, V. (2024) · Journal of Affective Disorders · doi:10.1016/j.jad.2024.08.050 · Cited by 8
Sobreiro, M. D. F. M., Silveira, P. S. P., Cavenaghi, V. B., da Costa, L. P., de Souza, B. P. F., Takahashi, R. E. S., Starek, R. V. M., Siqueira, J. D. O., & Fráguas, R. (2025) · Pharmaceuticals · doi:10.3390/ph18020173 · Cited by 7
“In the SUSTAIN-2 study, a slowing reaction time, as assessed by the Detection–Attention (simple) and Identification–Attention (choice) reaction time of the CogState Computerized Test Battery, was found after week 20, particularly among patients over 65 years of age [19].”
InfluentialVeraart, J. K. E., Smith-Apeldoorn, S. Y., van der Meij, A., Spijker, J., Schoevers, R. A., & Kamphuis, J. (2025) · Journal of Psychopharmacology · doi:10.1177/02698811251332831 · Cited by 9
Liu, T., Wu, J., Huang, P., Cheng, W.-L., & Lai, C. (2025) · European Neuropsychopharmacology · doi:10.1016/j.euroneuro.2025.07.006 · Cited by 8
Spravato for Treatment-Resistant Depression: Efficacy and Sexual Side Effect Profile
Raza, A., Ahmed, G. U., Zafar, H., Akhtar, S. O., Mobin, M. B., & Samadi, A. (2025) · Neuropsychiatric Disease and Treatment · doi:10.2147/ndt.s548944 · Cited by 6
“48 These results were supported by the long-term SUSTAIN-3 study, 65 with no sex differences noted.”
Raffone, F., Mazzoni, F., Ciechi, A. D., Girone, N., Macellaro, M., Martinotti, G., Dell’Osso, B. M., Olivola, M., & Martiadis, V. (2026) · Asian Journal of Psychiatry · doi:10.1016/j.ajp.2026.104983 · Cited by 8
Efficacy of ketamine versus esketamine in the treatment of perioperative depression: A review
Wen, W., Zhao, W., Xia, X., Duan, X., Zhang, L., Lin, D., Qi, Z., Wang, S., Gao, M., Liu, C., et al. (2024) · Pharmacology Biochemistry and Behavior · doi:10.1016/j.pbb.2024.173773 · Cited by 9
Bayes, A. J., Cao, T. V., Barreiros, A. R., Massaneda‐Tuneu, C., Dong, V., Thornton, N. L. R., Glozier, N., Beesley, L., Moreno, D., Gálvez, V., et al. (2024) · Psychiatry Research · doi:10.1016/j.psychres.2024.116334 · Cited by 7
Ketamine and Esketamine for Treatment-Resistant Depression: Response to Reus, Mattes, and Schatzberg
McIntyre, R. S. (2021) · American Journal of Psychiatry · doi:10.1176/appi.ajp.2021.21060653r · Cited by 7
Ayub, J. G. M., Tosta, C. L., Macedo, B. L., Barreto, T. F., Lopes, L. M., Fracalossi, M. P. D. S., Andreatini, R., & Beijamini, V. (2022) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2022.175382 · Cited by 6
Li, H., Xu, W.-J., Wang, Y., Xie, S., & Wang, H. (2025) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2025.1476449 · Cited by 8
Pompili, M., Trocchia, M. A., Longhini, L., Dispenza, E., Legge, C. D., Sarubbi, S., Erbuto, D., & Berardelli, I. (2025) · Human Psychopharmacology Clinical and Experimental · doi:10.1002/hup.70008 · Cited by 7
“In SUSTAIN‐2, flexible doses of intranasal esketamine along with SSRI/SNRI antidepressants were given continuously in an open‐label setting for up to 1 year, showing good safety and tolerability over the medium to long term (Wajs et al. 2020).”
Perspectives in treatment-resistant depression: esketamine and electroconvulsive therapy
Baldinger, P., Spies, M., Bozic, I., Kasper, S. F., Rujescu, D., & Frey, R. (2024) · Wiener klinische Wochenschrift · doi:10.1007/s00508-024-02358-w · Cited by 8
“A phase 3 safety trial over 1 year showed that the most common side effects were mild and self-limiting within 90min and include dissociation (as a characteristic phenomenon), dizziness, headache and nausea [80].”
Self-citationBozzatello, P., Novelli, R., Schisano, R., Brasso, C., Rocca, P., & Bellino, S. (2025) · Pharmaceuticals · doi:10.3390/ph18050665 · Cited by 7
“This is further confirmed by the SUSTAIN-2 study, in which no manic symptoms were reported among adverse events [80].”
Oliveira-Maia, A., Rive, B., Morrens, J., Godinov, Y., Cabrieto, J., Perualila, N., & Mulhern-Haughey, S. (2023) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2023.1250987 · Cited by 7
Carmellini, P., Pinzi, M., Rescalli, M. B., & Cuomo, A. (2025) · Brain Sciences · doi:10.3390/brainsci16010018 · Cited by 7
“Long-term esketamine data are likewise limited, with existing extensions (e.g., SUS-TAIN trials) spanning 1–2 years but lacking robust longitudinal neurocognitive or urological monitoring [94,95].”
Le, G. H., Wong, S., Johnson, D. E., Lu, A., Orsini, D. K., Chisamore, N., Luch, S. D. D., Rosenblat, J. D., & McIntyre, R. S. (2025) · Journal of Affective Disorders · doi:10.1016/j.jad.2025.121081 · Cited by 6
Harvey, A. J., Nikolin, S., Chand, N., Flanney, W., Tan, L., Moffa, A. H., Loo, C. K. A., & Martin, D. M. (2023) · Depression and Anxiety · doi:10.1155/2023/3371272 · Cited by 7
“, [10, 14, 15]) resulted in its approval for the treatment of TRD by the Food and Drug Administration (FDA) in 2019.”
Ahmed, N. N., Albishi, F., Khan, S. A., Alsayegh, A., Stip, É., & Makhoul, S. (2023) · Middle East Current Psychiatry · doi:10.1186/s43045-023-00369-3 · Cited by 5
“…mmHg and/or diastolic blood pressure [DBP] ≥ 110 mmHg) were more frequent in patients ≥ 65 years old and in those with a history of hypertension, reinforcing the importance of ensuring hypertension is adequately controlled before initiating treatment with esketa-mine nasal spray [11, 36, 39, 45].”
BackgroundMethodInfluentialKavakbasi, E., & Baune, B. T. (2024) · Neuromodulation Technology at the Neural Interface · doi:10.1016/j.neurom.2023.12.004 · Cited by 5
Research Progress on NMDA Receptor Enhancement Drugs for the Treatment of Depressive Disorder
Liu, R., Liu, N., Ma, L., Liu, Y., Huang, Z., Peng, X., Zhuang, C., Niu, J., Yu, J., & Du, J. (2024) · CNS Drugs · doi:10.1007/s40263-024-01123-x · Cited by 5
“Additionally, it carries a risk of dependence and potential for misuse [42, 43].”
Tamman, A. J. F., Anand, A., & Mathew, S. J. (2022) · Expert Opinion on Drug Safety · doi:10.1080/14740338.2022.2049754 · Cited by 6
Thornton, N. L. R., Black, W., Bognar, A., Dagge, D., Gitau, T., Hua, B., Joks, G., King, J., Lord, A., Scott, E. M., et al. (2023) · Asia-Pacific Psychiatry · doi:10.1111/appy.12550 · Cited by 5
“…efficacy and tolerability of esketamine in this indication has been shown in three short-term studies (the TRANSFORM series), and two long-term studies (the SUSTAIN series) (Daly et al., 2019; Dold et al., 2020; Fedgchin et al., 2019; Ochs-Ross et al., 2020; Popova et al., 2019; Wajs et al., 2020).”
BackgroundLiu, R., Liu, C., Feng, D., Guo, T., & Wang, Y. (2024) · Frontiers in Pharmacology · doi:10.3389/fphar.2024.1414703 · Cited by 5
Qiu, L., Chen, X., Fu, J., Chen, X., & Wang, X. (2024) · BMC Psychiatry · doi:10.1186/s12888-024-06035-0 · Cited by 9
Praktische Aspekte der Ketaminbehandlung – Sicherheit, Kombinationstherapien und Komorbiditäten
Findeis, H., Ludwig, V. M., Mikoláš, P., Graff, J., Bauer, M., & Ritter, P. S. (2022) · Der Nervenarzt · doi:10.1007/s00115-021-01260-4 · Cited by 5
“In den Zulassungsstudien für Ketamin intranasal zur Behandlung depressiver Episoden wurden als Kombinationspräparate selektive Serotoninwiederaufnahmehemmer oder selektive SerotoninNoradrenalin-Wiederaufnahmehemmer verwendet [8, 34].”
BackgroundInfluentialRamos‐Quiroga, J. A., Mora, F., Arostegui, S., Cardoner, N., Etxeandia-Pradera, J.-I., Gómez-Juanes, R., Gómez‐Revuelta, M., Montes, J. M. G., & Vieta, E. (2025) · The European Journal of Psychiatry · doi:10.1016/j.ejpsy.2025.100313 · Cited by 4
The cognitive neuroscience of ketamine in major depression
Costi, S., Wigg, C., Pulcu, E., Murphy, S. E., & Harmer, C. J. (2025) · Brain · doi:10.1093/brain/awaf242 · Cited by 6
“23,24 The largest study on i.v. ketamine to date was a non-inferiority trial comparing ketamine with electroconvulsive therapy (ECT) for treatment-resistant depression (TRD), which included a 6-month follow-up period.”
General intravenous anesthetics - pharmacodynamics, pharmacokinetics and chiral properties
Cizmáriková, R., Habala, L., & Markuliak, M. (2023) · Česká a slovenská farmacie · doi:10.5817/csf2023-4-155 · Cited by 4
Tomy, M., Alexander, W., Gupta, S., Schaefer, D., & Case, A. A. (2024) · Journal of Palliative Medicine · doi:10.1089/jpm.2024.0040 · Cited by 4
Learning how to make use of dissociative therapies
Mathai, D. S. (2024) · International Review of Psychiatry · doi:10.1080/09540261.2024.2406329 · Cited by 5
“There is relatively more evidence to guide maintenance treatment with esket-amine, administered approximately weekly to biweekly after a four-week induction phase (Daly et al., 2019; Wajs et al., 2020).”
Clemens, K., Zhdanava, M., Teeple, A., Voegel, A., Joshi, K., Shah, A., Chen, C., & Pilon, D. (2024) · Journal of Managed Care & Specialty Pharmacy · doi:10.18553/jmcp.2025.24240 · Cited by 5
Oliveira-Maia, A. J., Morrens, J., Rive, B., Godinov, Y., Cabrieto, J., Perualila, N. J., Barbreau, S., & Mulhern-Haughey, S. (2023) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2023.1250980 · Cited by 4
Metadata
- Authors
- Wajs, E., Aluisio, L., Holder, R., Daly, E. J., Lane, R., Lim, P., George, J. E., Morrison, R. L., Sanacora, G., Young, A. H., Kasper, S., Sulaiman, A. H., Li, C.-T., Paik, J.-W., Manji, H., Hough, D., Grunfeld, J., Jeon, H. J., Wilkinson, S. T., Drevets, W. C., & Singh, J. B.
- Affiliations
- Janssen (Belgium) (BE)
- Janssen Research & Development (United States) (US)
- Janssen Canada (Canada) (CA)
- Yale University (US)
- King's College London (GB)
- Medical University of Vienna (AT)
- University of Malaya (MY)
- Taipei Veterans General Hospital (TW)
- Kyung Hee University (KR)
- Peninsula Health (AU)
- Samsung Medical Center (KR)
- Corresponding author
- Wajs, Ewa
- ORCID
- Venue
- The Journal of Clinical Psychiatry
- Publisher
- Physicians Postgraduate Press, Inc
- Published
- 2020-04-28
- Volume
- 81
- Issue
- 3
- ISSN
- 0160-6689 (ISSN-L)
- 1555-2101
- OpenAlex
- W3017383621
- Cited by
- 308
- References
- 3
- Citations by year
- 2026: 50 · 2025: 61 · 2024: 48 · 2023: 44 · 2022: 47 · 2021: 38 · 2020: 19
- FWCI
- 20.16
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- The Journal of Clinical Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- The University of Malaya Research Repository (University of Malaya) (submittedVersion)
- Funders
- National Institute for Health and Care Research (NF-SI-0616-10091)
- Topics
- Health Sciences › Medicine › Pharmacology (medical) › Treatment of Major Depression
- Health Sciences › Medicine › Psychiatry and Mental health › Electroconvulsive Therapy Studies
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Keywords
- esketamine, nasal spray, treatment-resistant depression, major depressive disorder, oral antidepressant, long-term safety, treatment-emergent adverse events, dissociation, cognitive performance, maintenance therapy, induction phase, interstitial cystitis, respiratory depression, antidepressant non-response, elderly patients, mood stabilizers, antipsychotic drugs, antiepileptic drugs
- MeSH terms
- Administration, Intranasal, Administration, Oral, Adolescent, Adult, Aged, Antidepressive Agents, Cognition, Drug Therapy, Combination, Female, Humans, Ketamine, Male, Middle Aged, Young Adult, Nasal Sprays, Depressive Disorder, Treatment-Resistant
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
A language model drew the claims from the paper on 2026-09-28, under version 3 of the claim definition (prompt extract-v3).
A second model labelled each claim on 2026-09-28 (model jev-1.13-20260917, definition revision gold-guideline-v0.2).
Cited sources are checked with a language model’s help (gpt-6-sol).
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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