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.
Overview
Integrity signals
Registry
Cites
Statistics
Verification
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
Cites
A new depression scale designed to be sensitive to change
Montgomery, S. A., & Åsberg, M. (1979) · British Journal of Psychiatry · doi:10.1192/bjp.134.4.382 · Cited by 13,962
The Brief Psychiatric Rating Scale.
Overall, J. E., & Gorham, D. R. (1962) · Psychological Reports · doi:10.2466/pr0.1962.10.3.799 · Cited by 11,090
Spitzer, R. L. (1999) · JAMA · doi:10.1001/jama.282.18.1737 · Cited by 9,802
Rush, A. J., Trivedi, M. H., Wisniewski, S. R., Nierenberg, A. A., Stewart, J. W., Warden, D., Niederehe, G., Thase, M. E., Lavori, P. W., Lebowitz, B. D., et al. (2006) · American Journal of Psychiatry · doi:10.1176/ajp.2006.163.11.1905 · Cited by 5,643
Posner, K., Brown, G. K., Stanley, B., Brent, D. A., Yershova, K. V., Oquendo, M. A., Currier, G. W., Melvin, G. A., Greenhill, L., Shen, S., et al. (2011) · American Journal of Psychiatry · doi:10.1176/appi.ajp.2011.10111704 · Cited by 5,157
Benedict, R. H. B., Schretlen, D., Groninger, L., & Brandt, J. (1998) · The Clinical Neuropsychologist · doi:10.1076/clin.12.1.43.1726 · Cited by 1,597
Sheehan, D. V., Harnett-Sheehan, K., & Raj, B. A. (1996) · International Clinical Psychopharmacology · doi:10.1097/00004850-199606003-00015 · Cited by 1,440
Validity and Reliability of the Observer??s
CHERNIK, D. A., Gillings, D. B., LAINE, H., Hendler, J., Silver, J., DAVIDSON, A. B., Schwam, E. M., & Siegel, J. L. (1990) · Journal of Clinical Psychopharmacology · doi:10.1097/00004714-199008000-00003 · Cited by 1,246
Assessing Psychiatric Impairment in Primary Care with the Sheehan Disability Scale
Leon, A. C., Olfson, M., Portera, L., Farber, L., & Sheehan, D. V. (1997) · The International Journal of Psychiatry in Medicine · doi:10.2190/t8em-c8yh-373n-1uwd · Cited by 987
Popova, V., Daly, E. J., Trivedi, M., Cooper, K., Lane, R., Lim, P., Mazzucco, C., Hough, D., Thase, M. E., Shelton, R. C., et al. (2019) · American Journal of Psychiatry · doi:10.1176/appi.ajp.2019.19020172 · Cited by 904
Self-citation
Flagged first, then by citations
Research works printed but not linked: 6
- [7]7. P u b M e d C r o s s R e f 7. Morgan CJ, Curran HV; Independent Scientific Committee on Drugs. Ketamine use: a review. Addiction. 2012;107(1):27-38.
- [9]9. P u M e d C r o s s R e f 9. Sanacora G, Frye MA, McDonald W, et al; American Psychiatric Association (APA) Council of Research Task Force on Novel Biomarkers and Treatments. A consensus statement on the use of ketamine in the treatment of mood disorders. JAMA Psychiatry. 2017;74(4):399-405.
- [28]28. P u b M e d C r o s s R e f 26. Guy W. CGI Clinical Global Impressions. ECDEU Assessment Manual for Psychopharmacology. Rockville, MD: National Institute of Mental Health; 1976:217-222.
- [35]35. Bruce KM, Robinson SR, Smith JA, et al. Validity of a screening tool for detecting subtle cognitive impairment in the middle-aged and elderly. Clin Interv Aging. 2014;9:2165-2176. 35. P u b M e d
- [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.
- [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.
Cited by
Sorted by citations
Items 201–297 of 297
Depression with comorbid borderline personality disorder - could ketamine be a treatment catalyst?
Więdłocha, M., Marcinowicz, P., Komarnicki, J., Tobiaszewska, M., Dębowska, W., Dębowska, M. D., & Szulc, A. (2024) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2024.1398859 · Cited by 8
Moleón-Ruiz, Á., de Toledo, P. Á., Pérez, I. G., Narbona, J., Gutiérrez-Rojas, L., & García, M. M.-B. (2025) · Psychiatry Research Case Reports · doi:10.1016/j.psycr.2025.100250 · Cited by 3
Ketamine for unipolar depression: A systematic review of efficacy and safety
Peiris, T. E., Pokhrel, A., & Paudel, Y. (2025) · Australasian Psychiatry · doi:10.1177/10398562251328805 · Cited by 3
Reif, A., Anıl, Y. A., Bitter, I., Buyze, J., Frey, R., Fu, D. J., Godinov, Y., Haggström, L., Kambarov, Y., Nielsen, R., et al. (2026) · European Neuropsychopharmacology · doi:10.1016/j.euroneuro.2026.112801 · Cited by 4
Ketamine pharmacotherapy for major depressive disorder: A narrative review
Miller, C. H., Hickman, A., Baten, C., Ali, Z., Kahlon, S. K., Klassen, A. M., Zamora, G., Shepherd, J. H., Venegas, G., Miller, J. A., et al. (2026) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2026.111651 · Cited by 3
Moncrieff, J., Jakobsen, J. C., & Bachmann, M. O. (2021) · BMJ Evidence-Based Medicine · doi:10.1136/bmjebm-2021-111743 · Cited by 3
Oliveira-Maia, A. J., Rive, B., Godinov, Y., & Mulhern-Haughey, S. (2024) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2024.1459633 · Cited by 3
Massaneda‐Tuneu, C., Martin, D. M., Glozier, N., Bayes, A. J., Cao, T. V., Thornton, N. L. R., Brettell, L., Antoniou, S., Barreiros, A. R., Flynn, M., et al. (2025) · Journal of Affective Disorders · doi:10.1016/j.jad.2025.120192 · Cited by 4
Floriano, I., Silvinato, A., & Bernardo, W. M. (2023) · Revista da Associação Médica Brasileira · doi:10.1590/1806-9282.2023d696 · Cited by 9
“Vazquez 2021 Does not meet eligibility criteria Wajs 2020 Depression resistant to conventional antidepressants 21 https://doi.org/10.1371/journal.pmed1000097 5 Rev Assoc Med Bras.”
BackgroundInfluentialThe “new wave” of antidepressants: are these agents paradigm-shifters in treating major depression?
Petrescu, B. M., Marinescu, I. P., Marinescu, D., Vasiliu, O., Mangalagiu, A. G., & Cândea, C. A. (2023) · Psihiatru ro · doi:10.26416/psih.75.4.2023.8926 · Cited by 4
Esketamine for treatment-resistant depression
(2020) · Drug and Therapeutics Bulletin · doi:10.1136/dtb.2020.000043 · Cited by 3
Borentain, S., Desai, P., Fu, D., Chen, L. N., Lane, R., Mathews, M., & Canuso, C. M. (2022) · Journal of Psychopharmacology · doi:10.1177/02698811221123046 · Cited by 2
“…among patients who achieved stable remission and 70% (HR = 0.30, 95% CI: 0.16–0.55) among those who achieved stable response, compared with antidepressant plus placebo) and by Wajs et al. (2020) for up to 1 year of treatment (response rate of 76.5% at endpoint of optimization/maintenance phase).”
BackgroundInfluentialSelf-citationAuto-Induction in Oral Esketamine Treatment for Treatment-Resistant Depression: An Exploratory Study
Veraart, J. K. E., Vos, C. F., Punt, N. C., Visser, D., Wessels, A. M. A., Smith-Apeldoorn, S. Y., Kamphuis, J., Schoevers, R. A., & Touw, D. J. (2025) · Pharmaceuticals · doi:10.3390/ph18050627 · Cited by 2
“In addition to the antidepressant effects, multiple studies investigating intranasal and intravenous esketamine for TRD have found that dissociative symptoms and perceptual changes attenuate with repeated dosing [9,12–14].”
Understanding the Experience of Ketamine-Assisted Therapy and the Importance of Context
Stockwell, G., Hoeh, N. R., Fogarty, F. A., Clayden, C., & Reynolds, L. (2025) · Journal of Psychoactive Drugs · doi:10.1080/02791072.2025.2527299 · Cited by 3
Canuso, C. M., Bossie, C. A., Fu, D., Lane, R., Doherty, T., Lignugaris, A., Fagiolini, A. M., Llorca, P., McIntyre, R. S., Reif, A., et al. (2025) · American Journal of Psychiatry · doi:10.1176/appi.ajp.20250250 · Cited by 2
Self-citationAyad, N., Aziz, K. A., Makhoul, S., Abbas, B., & Javaid, S. F. (2026) · BJPsych Open · doi:10.1192/bjo.2025.10950 · Cited by 3
“18,20 However, concerns about long-term safety and abuse potential remain, especially regarding urological side-effects with chronic use, especially in patients with high cumulative doses.”
Ketamine as an NMDA-modulating therapy in bipolar disorder: rationale and evidence
Queissner, R., Fellendorf, F. T., & Reininghaus, E. (2026) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2026.1777402 · Cited by 2
Mathai, D. S., Cluck, M., Aslam, A. M., Amato, E., Azam, A., Banov, M., Barrett, K. A., Bonnett, C. J., Feifel, D., Grundmann, N., et al. (2026) · Journal of Affective Disorders · doi:10.1016/j.jad.2026.121970 · Cited by 6
An Update on Somatic Treatments for Suicide Risk
Rizk, M., & Mann, J. J. (2026) · American Journal of Psychiatry · doi:10.1176/appi.ajp.20260287 · Cited by 2
New drug: Esketamine hydrochloride for treatment-resistant depression
(2021) · Australian Prescriber · doi:10.18773/austprescr.2021.061 · Cited by 2
Increasing the bioavailability of oral esketamine by a single dose of cobicistat: A case study
Vos, C. F., Hemminga, W. L., Aarnoutse, R. E., & Ruhé, H. G. (2024) · Pharmacotherapy The Journal of Human Pharmacology and Drug Therapy · doi:10.1002/phar.2942 · Cited by 2
Jiang, W., Peng, Y., Chen, X., et al. (2024) · BMJ Open · doi:10.1136/bmjopen-2024-088177 · Cited by 2
Chen, B. K., Whye, A., Matthews, L. C., Moniz, T., Mendez‐David, I., Gardier, A. M., David, D. J. P., Johns, S., Weisblum, E., & Denny, C. A. (2025) · Neuropsychopharmacology · doi:10.1038/s41386-025-02107-1 · Cited by 3
Williamson, D., Williamson, L. E., Vaccarino, V., & Bremner, J. D. (2025) · Journal of Affective Disorders · doi:10.1016/j.jad.2025.119632 · Cited by 2
Letter to BJPsych in response to Horowitz and Moncrieff
Kasper, S. F., Young, A. H., Vieta, E., Goodwin, G., & Meyer‐Lindenberg, A. (2021) · The British Journal of Psychiatry · doi:10.1192/bjp.2021.161 · Cited by 2
Self-citationFritz, B. A., Pennington, B. R. T., Palanca, B. J. A., Schweiger, J. A., Willie, J. T., & Farber, N. B. (2022) · F1000Research · doi:10.12688/f1000research.121529.1 · Cited by 2
Recent Advances in Psychopharmacology
Poznanski, A. J., & Akinyemi, E. (2022) · Advances in Psychiatry and Behavioral Health · doi:10.1016/j.ypsc.2022.03.009 · Cited by 2
Grabski, M., & Morgan, C. J. A. (2022) · Elsevier eBooks · doi:10.1016/b978-0-323-91497-0.00236-8 · Cited by 2
Xie, J., Pu, C., & Sun, M. (2026) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2026.1774549 · Cited by 1
“Intranasal esketamine has been evaluated primarily as an adjunct to a newly initiated oral antidepressant (typically an SSRI or SNRI) in short-term induction trials, followed by continuation/ maintenance regimens in longer-term designs (18 – 25).”
Samalin, L., Boudieu, L., & Llorca, P. (2025) · Neuromethods · doi:10.1007/978-1-0716-4599-4_14 · Cited by 1
Choi, W.-S., Woo, Y. S., Bahk, W., Kim, N.-Y., Park, S., Kim, W., Lee, J. G., Yang, C.-M., Sung, H. M., Wang, S., et al. (2025) · 신경정신의학 · doi:10.4306/jknpa.2025.64.3.178 · Cited by 1
Hopwood, M., Codyre, D., Barton, D., Scott, E. M., Puig, A., King, J., & Hickie, I. B. (2025) · Research Directions Depression · doi:10.1017/dep.2025.10001 · Cited by 1
Ketamine for Late-Life Depression: Where Do We Stand?
Oughli, H. A., Gebara, M. A., & Flint, A. J. (2025) · American Journal of Geriatric Psychiatry · doi:10.1016/j.jagp.2025.09.008 · Cited by 1
Ketamine dosing formula in treatment-resistant bipolar depression
Kwaśny, A., Cubała, W. J., & Wilkowska, A. (2025) · Therapeutic Advances in Psychopharmacology · doi:10.1177/20451253251392817 · Cited by 1
“9,10 Despite encouraging efficacy data, there is no consensus on the optimal ketamine dosing strategy for TRBD.”
Lemeshova, A., Patel, K. A., Bloom, A. J., Golan, L., Haidari, H., Limbada, A., Zhao, C., & Honeycutt, J. A. (2025) · Pharmacology Biochemistry and Behavior · doi:10.1016/j.pbb.2025.174144 · Cited by 2
Qutishat, M., Al‐Huseini, S., & Albalushi, M. (2026) · International Journal of Mental Health · doi:10.1080/00207411.2025.2610783 · Cited by 1
“Wajs et al. (2020) and Daly et al. (2018) noted that early improvements can occur as soon as 4 hours.”
Advances in antidepressant pharmacotherapy: phase 3 evidence and clinical perspectives
Cuomo, A., Pinzi, M., & Fagiolini, A. M. (2026) · Expert Opinion on Pharmacotherapy · doi:10.1080/14656566.2026.2634195 · Cited by 1
Almadani, A. H., Alghamdi, A. H., Almazyad, G. M., Alfawaz, S. I., Ghaith, M. A.-A., Alshehri, A. A., Aljaffer, M. A., & Alghamdi, S. A. (2026) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2026.1726411 · Cited by 1
“However, esketamine has demonstrated a good safety and tolerability pro fi le, and real-world data con fi rm it does not appear to initiate substance abuse in at-risk populations (28).”
Prato, M., Carminati, M., Frizzi, F., Verri, G., Tondello, M., Barbini, B., Colombo, C., & Raffaella, Z. (2026) · International Journal of Psychiatry in Clinical Practice · doi:10.1080/13651501.2026.2642680 · Cited by 1
Ketamine for negative and depressive symptoms in schizophrenia: the evidence so far
Diendorfer, C., Bum, C., Weidenauer, A., Sauerzopf, U., Bartova, L., Dajic, I., Müller, L., Rujescu, D., Praschak-Rieder, N., & Willeit, M. (2026) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2026.1766485 · Cited by 1
“Considering its bene fi cial effects in affective disorders (63), and along the idea that it might help to rebalance the blunted DA transmission associated with negative symptoms, S-ketamine could thus hold therapeutic potential in depressive and negative symptoms of SCZ.”
García-Jiménez, J., Núñez-Arias, D., Merelo, G. C., Miller, A., Romero, A. M., Gutiérrez-Rojas, L., & Mesones-Peral, J. E. (2026) · Journal of Psychopharmacology · doi:10.1177/02698811261430495 · Cited by 1
“Data from phase 3 extension studies and post hoc analyses demonstrate continued gains during the optimization and early maintenance phases following symp-tom-driven adjustments in dosing and administration intervals (Nijs et al., 2020; Wajs et al., 2020).”
Liu, T.-H., Shen, H.-S., Wu, J., Huang, P., Shih, Y.-J., & Lai, C.-C. (2026) · Translational Psychiatry · doi:10.1038/s41398-026-04032-3 · Cited by 2
“These fi ndings extend evidence from RCTs to broader clinical populations, supporting the long-term effectiveness, safety, and potential survival bene fi t of esketamine in routine psychiatric practice.”
An, J., Li, X., Li, Z., Wang, J., & Pan, Y. (2026) · Journal of Nanobiotechnology · doi:10.1186/s12951-026-04417-y · Cited by 3
“For treatment-resistant depression, approved doses range from 56 mg to 84 mg, with elderly patients (≥ 65 years) initiating at 28 mg [98, 119].”
InfluentialEvaluating the abuse liability of ketamine in the treatment of mood disorders: A systematic review
Vasudeva, S., Lovell, G. F. M., Wong, S., Le, G. H., Orsini, D. K., Luch, S. D. D., McIntyre, R. S., & Rosenblat, J. D. (2026) · Journal of Psychopharmacology · doi:10.1177/02698811261453814 · Cited by 2
Postránecká, Z., Lucký, M., Mravčík, V., & Páleníček, T. (2026) · Journal of Psychedelic Studies · doi:10.1556/2054.2026.00514 · Cited by 1
Martiadis, V., Raffone, F., Atripaldi, D., Pessina, E., Cattaneo, C. I., Testa, S., Iaccarino, C., d’Andrea, G., Cavallotto, C., Olivola, M., et al. (2026) · European Archives of Psychiatry and Clinical Neuroscience · doi:10.1007/s00406-026-02361-4 · Cited by 1
Pompili, M., Sarubbi, S., Biase, G. D., Roberto, P., Fascetti, W., Trocchia, M. A., Erbuto, D., & Berardelli, I. (2026) · Journal of Psychiatric Research · doi:10.1016/j.jpsychires.2026.09.005 · Cited by 1
González-Pinto, A. M. (2020) · Psiquiatría Biológica · doi:10.1016/j.psiq.2020.01.001 · Cited by 1
Kowalski, L., Delanogare, E., & de Oliveira, T. B. (2021) · VITTALLE - Revista de Ciências da Saúde · doi:10.14295/vittalle.v33i3.13224 · Cited by 1
“Ainda, 76 pacientes (9,5% da amostra) interromperam o uso de escetamina pelos efeitos adversos (tontura, dissociação, náusea e cefaleia), e 55 pacientes (6,9%) experenciaram sérios efeitos adversos (ideação suicida, tentativa de suicídio, ansiedade e delírio) (68).”
InfluentialIt is ethical to publish successful case reports about patient with treatment-resistant depression
Sauvaget, A., Bulteau, S., & Laurin, A. (2024) · International Clinical Psychopharmacology · doi:10.1097/yic.0000000000000525 · Cited by 1
Xu, J., Jian, J., Zhang, Y., Wu, J., & Qiu, Y. (2024) · Frontiers in Medicine · doi:10.3389/fmed.2024.1344160 · Cited by 1
“The intranasal spray of esketamine has been approved by FDA in treatment-resistant depression (9, 10), but the analgesic feature of the intranasal spray of esketamine on acute pain has yet to be clarified.”
BackgroundAntón, B. U., Colmenares, M. O., & Aparicio, J. F. (2024) · Psiquiatría Biológica · doi:10.1016/j.psiq.2024.100488 · Cited by 1
Neurocognitive changes in a patient receiving esketamine for treatment-resistant depression
Kundert, C. F., Sobule, R., & Ithman, M. (2024) · JAAPA · doi:10.1097/01.jaa.0000000000000036 · Cited by 1
Shan, G., Lu, X., Zhang, Y., & Wu, S. S. (2024) · Statistical Papers · doi:10.1007/s00362-024-01606-5 · Cited by 1
Research trends in esketamine for depression over the past decade: a bibliometric analysis
Zhang, B., Liu, Y., Zheng, J., & Chen, J. (2025) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2025.1621830 · Cited by 2
González, C. Á., Zaragozá, C., & Lopez-Munoz, F. J. (2020) · Revista de Investigación y Educación en Ciencias de la Salud (RIECS) · doi:10.37536/riecs.2020.5.2.214 · Cited by 2
Spravato oder die Frage: „Wie viel darf ein Antidepressivum kosten?“
Spießl, H. (2021) · Psychiatrische Praxis · doi:10.1055/a-1500-9805 · Cited by 1
“Die Langzeitsicherheitsstudie SUSTAIN-2 [5] mit etwas mehr als 800 Patienten über 52 Wochen erbrachte eine gegenüber der Kontrollgruppe schlechtere Verträglichkeit, die häufigsten Nebenwirkungen waren Schwindelgefühle (33%), Dissoziationen (28%), Übelkeit Spravato oder die Frage: „Wie viel darf ein Antidepressivum kos…”
BackgroundInfluentialEvers, A. G., Klein, M. E., Aloysi, A. S., Murrough, J., & Jha, M. K. (2022) · Annals of Clinical Psychiatry · doi:10.12788/acp.0055 · Cited by 1
Loo, C. K. A., Glozier, N., Barton, D., Baune, B. T., Mills, N. T., Fitzgerald, P. B., Glue, P., Sarma, S., Gálvez, V., Hadži-Pavlović, D., et al. (2022) · SSRN Electronic Journal · doi:10.2139/ssrn.4107711 · Cited by 1
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. (2021) · medRxiv · doi:10.1101/2021.02.21.21252178
“For example, Esketamine for TRD is not recommended by The National Institute for Health and Care Excellence (NICE) in UK (69).”
BackgroundInfluentialAre we repeating mistakes of the past? A review of the evidence for esketamine – CORRIGENDUM
Horowitz, M. A., & Moncrieff, J. (2021) · The British Journal of Psychiatry · doi:10.1192/bjp.2021.40
Janski, A. M., Hristidis, V. C., Zorumski, C. F., & Conway, C. R. (2023) · Elsevier eBooks · doi:10.1016/b978-0-323-95702-1.00064-6
Kavakbasi, E., Bauermeister, H., Lemcke, L., & Baune, B. T. (2024) · Brain Sciences · doi:10.3390/brainsci14020159
“To preserve the improvement after the acute phase, the patients are offered a maintenance treatment [11].”
BackgroundEffects of Ketamine and Esketamine on Cognitive Functions in Treatment-Resistant Depression
Mutlu, M., Öven, Ç., Kurt, B. S., & SUNAY, E. (2024) · Psikiyatride Guncel Yaklasimlar - Current Approaches in Psychiatry · doi:10.18863/pgy.1524106
Anhedonia: a unifying symptom and a transdiagnostic therapeutic target
Rosso, G., Pesci, N. R., PERACCHIA, S., Garrone, C., Salvo, G. D., & Maina, G. (2025) · Minerva Psychiatry · doi:10.23736/s2724-6612.24.02572-7
Dutra, R. N., Nascimento, M. V. F., Gontijo, J. P. S., LISBOA, K. S., Viana, G. F., Coelho, N. C., Dutra, S. M., & Alves, B. D. M. L. (2025) · STUDIES IN HEALTH SCIENCES · doi:10.54022/shsv6n1-037
Stereotactic Radiosurgery for Treatment Resistant Depression: Systematic Review
Vanleuven, J., Hori, Y. S., Osama, T., Harary, P., Lui, A., Persad, A. R. L., Tayag, A., Emrich, S., Ustrzynski, L., Purger, D., et al. (2025) · World Neurosurgery: X · doi:10.1016/j.wnsx.2025.100451
Busz, A., Schmidt, E. (. J. )., van den Brink, R., Foeken, K., de Jong, M., Mertens, J. (. B. C. )., van Noorden, M. S., Olivier, E. (. J. F. L. )., Schruers, K. R. J., Schutters, S. I. J., et al. (2025) · Journal of Affective Disorders Reports · doi:10.1016/j.jadr.2025.100905 · Cited by 1
Challenges in management of treatment-resistant depression
Piech, G. M., & Lis, I. (2024) · Biuletyn Głównej Biblioteki Lekarskiej · doi:10.2478/bgbl-2024-0032
Chen, B. K., Hunsberger, H. C., Whye, A., Matthews, L. C., Yook, A., Willner, M. J., Logan, R., Johns, S., Weisblum, E., & Denny, C. (2025) · Alzheimer's Research & Therapy · doi:10.1186/s13195-025-01804-9 · Cited by 2
Ketamine/esketamine for treatment-resistant depression
Nikayin, S., & Sanacora, G. (2022) · Elsevier eBooks · doi:10.1016/b978-0-12-824067-0.00013-x · Cited by 3
Self-citationKetamine’s Multifaceted Neuropharmacological and Neurobiological Actions
Kohtala, S., & Annala, I. (2025) · Neuromethods · doi:10.1007/978-1-0716-4603-8_2
Benhaddouch, Y., & Ammouri, A. E. (2025) · General Hospital Psychiatry · doi:10.1016/j.genhosppsych.2025.10.005
Ketamine for depression and other psychiatric diseases
Roth, W. (2025) · Elsevier eBooks · doi:10.1016/b978-0-443-29930-8.00005-9
Almadani, A. H., Alghamdi, A. H., Alfahad, F., Alibrahim, A. S., Binbakhit, A. I., Alenazi, Z. B., Alruwaili, L. M., Alshahwan, A. A., Muhnna, A. K., & Aljaffer, M. A. (2025) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2025.1678119
Xie, J.-X., & Zhou, L.-W. (2025) · Molecular Biology Reports · doi:10.1007/s11033-025-11357-7
“At the same time, clinical applications must consider the transient neuropsychiatric disturbances associated with ketamine derivatives, including dissociative symptoms, vertigo, and cephalgia, which occur in 40–60% of recipients according to phase III trial data [ 30 , 31 ].”
Eckert, D., & Kasper, S. F. (2026) · The World Journal of Biological Psychiatry · doi:10.1080/15622975.2026.2617195 · Cited by 1
“Its antidepressant effects come into play very rapidly, with measurable changes in rating scales within hours (Daly et al. 2019; Popova et al. 2019; Wajs et al. 2020; McIntyre and Jain 2024).”
Self-citationLejman, A., Bednarczyk, R., Bednarczyk, N., Binkowski, R. K., Kurek, A., Krajewska, N., Mazurkiewicz, A., Sidor, H., & Wołosik, M. (2026) · International Journal of Innovative Technologies in Social Science · doi:10.31435/ijitss.1(49).2026.4697
Samalin, L., Rothärmel, M., Mékaoui, L., Sauvaget, A., Wicart, C., Gaudre-Wattinne, E., Cohignac, V., Malatesta, A., & Dupin, J. (2026) · Journal of Psychiatric Research · doi:10.1016/j.jpsychires.2026.03.011
Guffanti, A., Leonardi, M., Brondino, N., Dell’Osso, B. M., Martiadis, V., & Olivola, M. (2026) · Clinics and Practice · doi:10.3390/clinpract16030061
“Reported results indicate a similar response to esketamine at six-month follow-up [23].”
Cognitive Effects of Esketamine in Treatment-Resistant Depression
Guglielmo, R., Facchinetti, E. L., Cioci, D., Olivola, M., da Silva, B. P., Mazzocchi, A., Dell’Osso, B. M., Amore, M., & Serafini, G. (2026) · Journal of Clinical Psychopharmacology · doi:10.1097/jcp.0000000000002165 · Cited by 2
“26 Taken together, the available evidence suggests that esketamine does not impair memory in adults with TRD and may, in some cases, enhance memory performance, particularly over longer treatment durations.”
Psychedelics: Future Therapeutics in Major Depression?
Olivier, B., & Olivier, J. D. A. (2026) · Advances in experimental medicine and biology · doi:10.1007/978-981-95-6872-7_25
Eckert, D., & Kasper, S. F. (2026) · International Journal of Psychiatry in Clinical Practice · doi:10.1080/13651501.2026.2663307
“More recently, esketamine has emerged as an evidence-based option for patients with TRD, demonstrating rapid and sustained clinical effects (Daly et al., 2019; Kasper et al., 2021; McIntyre & Jain, 2024; Popova et al., 2019; Wajs et al., 2020).”
Self-citationESKETAMINE AND DEEP BRAIN STIMULATION IN TREATMENT-RESISTANT DEPRESSION: A LITERATURE REVIEW
Wiśniewska, J., Wiśniewski, M., Buczek, W., Bartnik, P., Barzyk, K., & Pietrzak, M. (2026) · International Journal of Innovative Technologies in Social Science · doi:10.31435/ijitss.1(49).2026.5003
Shrestha, N., Liu, M. M., 牛少宁, Cheng, H., Sun, Y., Mei, S., & Luo, F. (2026) · Journal of Pain Research · doi:10.2147/jpr.s598907 · Cited by 1
“16,20,22 These pharmacological properties make ESK an attractive candidate for the treatment of chronic pain conditions characterized by central sensitization, such as FM.”
Martínez‐Gras, I., Molina, J. D. D., Sánchez-Pastor, L., Llamas, S., Espejo-Saavedra, J. M., Compaired, A., Leza, J. C., & Rubio, G. (2026) · Psychiatry Research Case Reports · doi:10.1016/j.psycr.2026.100332
Westenhöfer, S., Ehrt‐Schäfer, Y., Provaznikova, B., Prinz, S., Spies, M., Akhmetova, L., Nadesalingam, N., Strickler, E., Krähenmann, R., Seifritz, E., et al. (2026) · Research Square · doi:10.21203/rs.3.rs-10250654/v1
Gould, T. D., Mathew, S. J., D, M. F. M., & Shekhar, A. (2026) · Journal of Psychopharmacology · doi:10.1177/02698811261456206 · Cited by 1
“The sustained antidepressant effects appear to be independent of ODP, as most standard effective ketamine treatment paradigms include treatments separated by several days (McIntyre et al., 2021; Wajs et al., 2020).”
Young, A., Baune, B., Benatti, B., Bennabi, D., Estercam, S., Gorwood, P., Gutiérrez-Rojas, L., Martiadis, V., Molero, P., Normann, C., et al. (2026) · European Neuropsychopharmacology · doi:10.1016/j.euroneuro.2026.112907 · Cited by 1
Self-citationWu, Q., Li, W., Luo, Z., Wang, C., Lan, X., Shen, J., Chen, Z. X., Pan, J., Liu, X., Zhu, H., et al. (2026) · BMC Psychiatry · doi:10.21203/rs.3.rs-10020524/v1
Hopwood, M., Codyre, D., Barton, D., Scott, E. M., Puig, A., King, J., & Hickie, I. B. (2026) · Journal of Psychiatric Research · doi:10.1016/j.jpsychires.2026.07.011
Intranasal esketamine for ECT-refractory bipolar depression: a case report
Abbas, M., Kallas, B., & Garris, M. (2026) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2026.1890002
“Results from phase III trials have shown esketamine ’ s effectiveness in improving depressive symptoms in patients with unipolar depression (15, 16).”
Moreira, R., Frade, P., Campeão, N., Gomes, S., Lopes, A. D. M., Lapa, G., Vian, J., Fonseca, A., Polido, F., Barata, B. C., et al. (2026) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2026.1749006
Kelly, C., Cooley, B. J., Zeng, L., Hurzeler, T. P., Manning, V., McNally, G. P., Watt, J., Haber, P., & Morley, K. C. (2026) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2026.106911
Kallarackal, J., Dyer, B. J., & Huang, J. (2026) · Springer eBooks · doi:10.1007/978-3-032-25214-2_36
Pinzi, M., Cuomo, A., Rescalli, M. B., Pierini, C., & Fagiolini, A. M. (2026) · Expert Review of Neurotherapeutics · doi:10.1080/14737175.2026.2714839
“Long-term open-label data have not identified progressive cognitive deterioration with supervised use, although continued pharmacovigilance is required [40].”
Llorca, P., Sauvaget, A., Olié, É., Mékaoui, L., Samalin, L., Rothärmel, M., Boitez, A.-L., Dupin, J., Wicart, C., Gaudre-Wattinne, E., et al. (2026) · Therapeutic Advances in Psychopharmacology · doi:10.1177/20451253261463652
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 ›
Are you an author, or do you see a problem with this page? Request a review
