The DOI matches its Crossref record; 40 of the 40 references it cites were found in a registry or an index; 8 of the 23 sources its claims cite were checked for support.
Efficacy and Safety of Flexibly Dosed Esketamine Nasal Spray Combined With a Newly Initiated Oral Antidepressant in Treatment-Resistant Depression: A Randomized Double-Blind Active-Controlled Study
Open accessAbstract
OBJECTIVE About one-third of patients with depression fail to achieve remission despite treatment with multiple antidepressants. This study compared the efficacy and safety of switching patients with treatment-resistant depression from an ineffective antidepressant to flexibly dosed esketamine nasal spray plus a newly initiated antidepressant or to a newly initiated antidepressant (active comparator) plus placebo nasal spray. METHODS This was a phase 3, double-blind, active-controlled, multicenter study conducted at 39 outpatient referral centers. The study enrolled adults with moderate to severe nonpsychotic depression and a history of nonresponse to at least two antidepressants in the current episode, with one antidepressant assessed prospectively. Confirmed nonresponders were randomly assigned to treatment with esketamine nasal spray (56 or 84 mg twice weekly) and an antidepressant or antidepressant and placebo nasal spray. The primary efficacy endpoint, change from baseline to day 28 in Montgomery-Åsberg Depression Rating Scale (MADRS) score, was assessed by a mixed-effects model using repeated measures. RESULTS Of 435 patients screened, 227 underwent randomization and 197 completed the 28-day double-blind treatment phase. Change in MADRS score with esketamine plus antidepressant was significantly greater than with antidepressant plus placebo at day 28 (difference of least square means=-4.0, SE=1.69, 95% CI=-7.31, -0.64); likewise, clinically meaningful improvement was ob…
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Claims the paper makes
8 of 23 cited sources checked · 6 supported · 0 flagged · accuracy not yet measured
Every source the paper cites for this claim was checked and supports it.
In the paper
“Intravenous ketamine administered at subanesthetic doses was found to exhibit robust and rapid onset of efficacy in patients with treatment-resistant depression (9).”
What the sources say
- Supportedcites [9] source
The Study Design describes an intravenous infusion of 0.5 mg/kg ketamine in patients with major depressive disorder. The Comment reports a robust response within hours, and the Efficacy section reports a 71% response rate the day after infusion in the treatment-resistant sample. The supplied passages do not give page numbers. (LLM, conf=0.92)
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passes- Supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“The odds ratio of 2.4 for response at day 28 in the esketamine plus oral antidepressant group was higher compared with odds ratios reported in a recent systematic review of antidepressant efficacy (34).”
§ Efficacy and Safety of Flexibly Dosed Esketamine Nasal Spray Combined With a Newly Initiated Oral Antidepressant in Treatment-Resistant Depression: A Randomized Double-Blind Active-Controlled Study > DISCUSSION
What the sources say
- Supportedcites [34] source
The Results report response-efficacy odds ratios of 1.37–2.13 for antidepressants versus placebo, all below the citing paper’s 2.4. The source does not report the esketamine result; the citation supports the comparison with its review findings. (LLM, conf=0.92)
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passes- 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
“likewise, clinically meaningful improvement was observed in the esketamine plus antidepressant arm at earlier time points.”
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
“Change in MADRS score with esketamine plus antidepressant was significantly greater than with antidepressant plus placebo at day 28 (difference of least square means=24.0,SE=1.69, 95% CI=27.31,20.64); likewise, clinically meaningful improvement was observed in the esketamine plus antidepressant arm at earlier time points.”
- Also stated in: § RESULTS · plain
“The mean MADRS score decreased from baseline to day 28, with greater improvement observed among those in the esketamine plus antidepressant arm as compared with the antidepressant plus placebo arm (difference of least square means=24.0,SE=1.69, 95% CI=27.31,20.64; p=0.020) (Table 2).”
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes- Also stated in: § RESULTS · 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
“attenuated with repeated dosing (the mean change in CADSS score from before dosing to 40 minutes after dosing decreased from 7.8 [SE=0.84] on day 1 to 3.5 [SE=0.55] on day 25)”
- Also stated in: § DISCUSSION · plain
“evidence of attenuation of dissociation after repeated administrations, unlike esketamine's antidepressant efficacy, which was sustained”
§ Efficacy and Safety of Flexibly Dosed Esketamine Nasal Spray Combined With a Newly Initiated Oral Antidepressant in Treatment-Resistant Depression: A Randomized Double-Blind Active-Controlled Study > RESULTS
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes- Also stated in: § DISCUSSION · 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
“A total of 57.4% [66/115] and 10.1% [11/109] of patients in the esketamine and comparator arms, respectively, had a score #4 (moderate or greater sedation) on the Modified Observer's Assessment of Alertness/ Sedation at any postdose time during the double-blind treatment phase.”
§ Efficacy and Safety of Flexibly Dosed Esketamine Nasal Spray Combined With a Newly Initiated Oral Antidepressant in Treatment-Resistant Depression: A Randomized Double-Blind Active-Controlled Study > RESULTS
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
“The number needed to harm for dissociation was 5 for the esketamine plus antidepressant arm compared with the antidepressant plus placebo arm.”
§ Efficacy and Safety of Flexibly Dosed Esketamine Nasal Spray Combined With a Newly Initiated Oral Antidepressant in Treatment-Resistant Depression: A Randomized Double-Blind Active-Controlled Study > RESULTS
Tests✓ 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
“Six of 112 (5.4%) patients in the esketamine plus antidepressant arm and seven of 109 (6.4%) patients in antidepressant plus placebo arm had treatmentemergent postbaseline suicidal ideation.”
§ Efficacy and Safety of Flexibly Dosed Esketamine Nasal Spray Combined With a Newly Initiated Oral Antidepressant in Treatment-Resistant Depression: A Randomized Double-Blind Active-Controlled Study > RESULTS
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
“and for patients in the antidepressant plus placebo arm, insomnia, irritability, and dysphoric mood/depression.”
§ Efficacy and Safety of Flexibly Dosed Esketamine Nasal Spray Combined With a Newly Initiated Oral Antidepressant in Treatment-Resistant Depression: A Randomized Double-Blind Active-Controlled Study > RESULTS
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesThe 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 number of patients meeting the full criterion for onset of clinical response by day 2 with persistence to day 28, a metric not evaluated in previous antidepressant drug or ketamine trials, was lower than anticipated.”
§ Efficacy and Safety of Flexibly Dosed Esketamine Nasal Spray Combined With a Newly Initiated Oral Antidepressant in Treatment-Resistant Depression: A Randomized Double-Blind Active-Controlled Study > DISCUSSION
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passes
- Probably not a substantial claim. 14
- It may state two separate claims as one. 28
- The quote only partly states this claim. 5
Every source the paper cites for this claim was checked and supports it.
In the paper
“Research on mood disorder pathophysiology has implicated abnormalities in glutamatergic transmission, along with disrupted function and structure in neural circuits involved in mood regulation (4), findings that led to further investigation of glutamatergic N-methyl-D-aspartate (NMDA) receptor modulators in treating depression (5,6).”
What the sources say
- Supportedcites [4] source
The “Implications for Neurocircuitry-Based Models of Depression” section describes structural and functional abnormalities in a mood-related network and reports evidence of increased glutamatergic transmission in depression. “Recent Observations in Humans with Mood Disorders” likewise describes structural and functional alterations in implicated circuits. The later claim about investigating NMDA receptor modulators is attached to other citations, not this one. (LLM, conf=0.93)
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesProbably not a substantial claim. It may state two separate claims as one.
- Supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“The sample size planned for this study was calculated assuming a treatment difference for the double-blind treatment phase of 6.5 points in MADRS score between the esketamine plus antidepressant group and the antidepressant plus placebo group and a standard deviation of 12, based on the results of a phase 2 study of esketamine nasal spray for treatment-resistant depression (11) and clinical”
- Also stated in: § Sample size determination. · plain
“Randomization of 98 individuals to each treatment group was required to achieve 90% power.”
§ Efficacy and Safety of Flexibly Dosed Esketamine Nasal Spray Combined With a Newly Initiated Oral Antidepressant in Treatment-Resistant Depression: A Randomized Double-Blind Active-Controlled Study > Sample size determination.
What the sources say
- Supportedcites [11] source
Split into 2 atoms — 2 confirmed, 0 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesProbably not a substantial claim. It may state two separate claims as one.
- Also stated in: § Sample size determination. · plain
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Earlier studies of esketamine in patients with treatmentresistant depression (10,11) and major depression at imminent risk for suicide (12), which demonstrated greater magnitude of early response, applied a less stringent definition for response onset and employed site-based raters for efficacy evaluation.”
§ Efficacy and Safety of Flexibly Dosed Esketamine Nasal Spray Combined With a Newly Initiated Oral Antidepressant in Treatment-Resistant Depression: A Randomized Double-Blind Active-Controlled Study > DISCUSSION
What the sources say
- Supportedcites [10] source
Split into 2 atoms — 2 confirmed, 0 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.
- Partly supportedcites [11] sourceExperimental — accuracy not yet measured
Split into 2 atoms — 1 confirmed, 1 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.
- Partly supportedcites [12] sourceExperimental — accuracy not yet measured
Split into 2 atoms — 0 confirmed, 2 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
- Supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“The magnitude of postdose blood pressure increases was lower compared with the previous phase 2 study of esketamine nasal spray (11), possibly because of the riskmitigation blood pressure guidelines initiated in phase 3 studies (see the online supplement).”
§ Efficacy and Safety of Flexibly Dosed Esketamine Nasal Spray Combined With a Newly Initiated Oral Antidepressant in Treatment-Resistant Depression: A Randomized Double-Blind Active-Controlled Study > DISCUSSION
What the sources say
- Supportedcites [11] source
The cited paper is the earlier intranasal esketamine study, and its Safety section reports transient postdose blood-pressure increases, with maximum mean changes of 19.0 mm Hg systolic and 10.3 mm Hg diastolic. The citation is attached to that earlier study; the proposed explanation involving phase 3 risk-mitigation guidelines is attributed to the citing paper’s online supplement, not to this source. No page number is available in our copy. (LLM, conf=0.90)
Strength:hedged· not yet calibratedCausal:conditional· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
- 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
“Response was rapid in onset and increased over time during repeated dosing, with least square mean between-group differences, favoring esketamine, of 23.3 (95% CI=25.75, 20.85) 24 hours after dosing (i.e., at the day 2 visit), 22.9 (95% CI=25.17,20.59) at day 8, 22.0 (95% CI=24.78,0.82) at day 15, 23.8 (95% CI=26.87,20.65) at day 22, and, as noted above, 24.0 (95% CI=27.31,20.64) at day 28 (p=0.02”
§ Efficacy and Safety of Flexibly Dosed Esketamine Nasal Spray Combined With a Newly Initiated Oral Antidepressant in Treatment-Resistant Depression: A Randomized Double-Blind Active-Controlled Study > RESULTS
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
“Difference of LS | -4.0 | 1.69 | | |”
- Also stated in: § DISCUSSION · plain
“95% CI on difference -7.31, -0.64”
- Also stated in: § DISCUSSION · plain
“2-sided p value | 0.020”
§ Efficacy and Safety of Flexibly Dosed Esketamine Nasal Spray Combined With a Newly Initiated Oral Antidepressant in Treatment-Resistant Depression: A Randomized Double-Blind Active-Controlled Study > DISCUSSION
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesThe quote only partly states this claim.
- Also stated in: § DISCUSSION · 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
“Nine patients experienced one or more adverse events leading to discontinuation of intranasal study drug during the double-blind treatment phase, eight (of 115, 7.0%) in the esketamine plus antidepressant arm (single events of anxiety, depression, depressive symptoms, panic attack, drug intolerance, feeling drunk, dizziness, headache, vertigo, nausea, road traffic accident, and multiple injuries)”
- Also stated in: § Efficacy and Safety of Flexibly Dosed Esketamine Nasal Spray Combined With a Newly Initiated Oral Antidepressant in Treatment-Resistant Depression: A Randomized Double-Blind Active-Controlled Study · plain
“7% and 0.9% of patients in the respective treatment groups discontinued study drug because of an adverse event.”
§ Efficacy and Safety of Flexibly Dosed Esketamine Nasal Spray Combined With a Newly Initiated Oral Antidepressant in Treatment-Resistant Depression: A Randomized Double-Blind Active-Controlled Study > RESULTS
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesThe quote only partly states this claim.
- Also stated in: § Efficacy and Safety of Flexibly Dosed Esketamine Nasal Spray Combined With a Newly Initiated Oral Antidepressant in Treatment-Resistant Depression: A Randomized Double-Blind Active-Controlled Study · 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
“Generally, for patients who experienced sedation, this symptom started around 15 minutes into dosing and peaked at 30 to 45 minutes after dosing, and symptoms of sedation spontaneously resolved by 1 to 1.5 hours after dosing.”
§ Efficacy and Safety of Flexibly Dosed Esketamine Nasal Spray Combined With a Newly Initiated Oral Antidepressant in Treatment-Resistant Depression: A Randomized Double-Blind Active-Controlled Study > RESULTS
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
“Present-state dissociative symptoms and transient perceptual effects measured by the CADSS (see Figure S5 in the online supplement) began shortly after the start of esketamine dosing, peaked at 40 minutes, generally resolved by 1.5 hours, and attenuated with repeated dosing”
§ Efficacy and Safety of Flexibly Dosed Esketamine Nasal Spray Combined With a Newly Initiated Oral Antidepressant in Treatment-Resistant Depression: A Randomized Double-Blind Active-Controlled Study > RESULTS
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 adverse events were of mild or moderate severity and were transient, with onset shortly after dosing and resolution by 1.5 hours after dosing, while patients were in the clinic.”
- Also stated in: § Efficacy and Safety of Flexibly Dosed Esketamine Nasal Spray Combined With a Newly Initiated Oral Antidepressant in Treatment-Resistant Depression: A Randomized Double-Blind Active-Controlled Study · hedged
“Adverse events in the esketamine plus antidepressant arm generally appeared shortly after dosing and resolved by 1.5 hours after dosing.”
§ Efficacy and Safety of Flexibly Dosed Esketamine Nasal Spray Combined With a Newly Initiated Oral Antidepressant in Treatment-Resistant Depression: A Randomized Double-Blind Active-Controlled Study > RESULTS
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
- Also stated in: § Efficacy and Safety of Flexibly Dosed Esketamine Nasal Spray Combined With a Newly Initiated Oral Antidepressant in Treatment-Resistant Depression: A Randomized Double-Blind Active-Controlled Study · hedged
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
“At day 28, 53 of 101 (52.5%) and 31 of 100 (31.0%) patients in the respective treatment groups were in remission, with an NNT of 5 for remission.”
§ Efficacy and Safety of Flexibly Dosed Esketamine Nasal Spray Combined With a Newly Initiated Oral Antidepressant in Treatment-Resistant Depression: A Randomized Double-Blind Active-Controlled Study > RESULTS
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
“In post hoc analyses, the proportion of patients who at a given time point were responders and in remission in both treatment groups generally increased over time during the double-blind treatment phase, with 70 of 101 patients (69.3%) in the esketamine plus antidepressant arm and 52 of 100 patients (52.0%) in the antidepressant plus placebo arm being responders at day 28 (odds ratio=2.4,95% cred”
§ Efficacy and Safety of Flexibly Dosed Esketamine Nasal Spray Combined With a Newly Initiated Oral Antidepressant in Treatment-Resistant Depression: A Randomized Double-Blind Active-Controlled Study > RESULTS
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
“One patient in the esketamine plus antidepressant arm experienced multiple injuries in a road traffic (motorbike) accident (reported as serious adverse events) on day 16 of the double-blind treatment phase (approximately 28 hours after an esketamine dose) and subsequently died on day 55, 40 days after the last dose of esketamine (additional information is provided in the online supplement).The”
§ Efficacy and Safety of Flexibly Dosed Esketamine Nasal Spray Combined With a Newly Initiated Oral Antidepressant in Treatment-Resistant Depression: A Randomized Double-Blind Active-Controlled Study > RESULTS
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
“Transient blood pressure increases occurred after each dose of esketamine; the maximum value was reached at 40 minutes after dosing in most cases and typically returned to or near the predose range by 1.5-2 hours after dosing (see Figure S3 in the online supplement).”
§ Efficacy and Safety of Flexibly Dosed Esketamine Nasal Spray Combined With a Newly Initiated Oral Antidepressant in Treatment-Resistant Depression: A Randomized Double-Blind Active-Controlled Study > RESULTS
Strength:plain· not yet calibratedCausal:direct· 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
“During the double-blind treatment phase, the five most common treatment-emergent adverse events observed among patients in the esketamine plus antidepressant arm were dizziness, dissociation, dysgeusia, vertigo, and nausea (incidences ranging from 20.9% to 26.1%); the incidence of each was two to 10 times lower in the antidepressant plus placebo arm (Table 3).”
- Also stated in: § Efficacy and Safety of Flexibly Dosed Esketamine Nasal Spray Combined With a Newly Initiated Oral Antidepressant in Treatment-Resistant Depression: A Randomized Double-Blind Active-Controlled Study · plain
“The five most common adverse events (dissociation, nausea, vertigo, dysgeusia, and dizziness) all were observed more frequently in the esketamine plus antidepressant arm than in the antidepressant plus placebo arm”
§ Efficacy and Safety of Flexibly Dosed Esketamine Nasal Spray Combined With a Newly Initiated Oral Antidepressant in Treatment-Resistant Depression: A Randomized Double-Blind Active-Controlled Study > RESULTS
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
- Also stated in: § Efficacy and Safety of Flexibly Dosed Esketamine Nasal Spray Combined With a Newly Initiated Oral Antidepressant in Treatment-Resistant Depression: A Randomized Double-Blind Active-Controlled Study · 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
“The proportion of responders at day 28 was comparable for patients who experienced dissociation (maximum CADSS score .4 on day 1) and those who did not (maximum CADSS score #4 on day 1), with response rates of 68.5% and 70.2%, respectively.”
§ Efficacy and Safety of Flexibly Dosed Esketamine Nasal Spray Combined With a Newly Initiated Oral Antidepressant in Treatment-Resistant Depression: A Randomized Double-Blind Active-Controlled Study > RESULTS
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
“No notable differences were observed between patients using concomitant benzodiazepines compared with those not using benzodiazepines.”
§ Efficacy and Safety of Flexibly Dosed Esketamine Nasal Spray Combined With a Newly Initiated Oral Antidepressant in Treatment-Resistant Depression: A Randomized Double-Blind Active-Controlled Study > RESULTS
Strength:plain· 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 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
“Median CGI-S scores improved from baseline to endpoint of the double-blind treatment phase in both groups, with a median change from baseline of 22.0 (range=25 to 1; interquartile range=2) in the esketamine plus antidepressant arm and 22.0 (range=25 to 1; interquartile range=3) in the antidepressant plus placebo arm (see Table S6 in the online supplement).”
- Also stated in: § RESULTS · hedged
“The ANCOVA analysis based on the ranks of change showed a numerical difference favoring the esketamine arm over the comparator arm, with an odds ratio of 2.8 (95% credible interval=1.14, 7.68), suggesting that the odds of an improved CGI-S score at endpoint for patients in the esketamine arm were 2.8 times the odds for patients in the comparator arm.”
§ Efficacy and Safety of Flexibly Dosed Esketamine Nasal Spray Combined With a Newly Initiated Oral Antidepressant in Treatment-Resistant Depression: A Randomized Double-Blind Active-Controlled Study > RESULTS
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one. The quote only partly states this claim.
- Also stated in: § RESULTS · hedged
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
“nocebo response (i.e., adverse effect following an”
§ Efficacy and Safety of Flexibly Dosed Esketamine Nasal Spray Combined With a Newly Initiated Oral Antidepressant in Treatment-Resistant Depression: A Randomized Double-Blind Active-Controlled Study > DISCUSSION
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesThe quote only partly states this claim.
In the paper
“The response and remission rates seen in the antidepressant plus placebo arm were higher than those reported in the Sequenced Treatment Alternatives to Relieve Depression trial for step 3 (response rate, 16.8%; remission rate, 13.7%) and in the olanzapine-fluoxetine study (33)”
§ Efficacy and Safety of Flexibly Dosed Esketamine Nasal Spray Combined With a Newly Initiated Oral Antidepressant in Treatment-Resistant Depression: A Randomized Double-Blind Active-Controlled Study > DISCUSSION
What the sources say
- Not checked — no full text of the sourcecites [33] source
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
“However, in post hoc analyses, the results from both patient-reported outcomes showed consistency with the primary clinicianbased outcome result (see Figure S6 in the online supplement), providing supportive evidence from patients' perspective of improvement in mood and function after 4 weeks of treatment.”
§ Efficacy and Safety of Flexibly Dosed Esketamine Nasal Spray Combined With a Newly Initiated Oral Antidepressant in Treatment-Resistant Depression: A Randomized Double-Blind Active-Controlled Study > DISCUSSION
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.
In the paper
“About 30% of patients with major depression fail to achieve remission despite treatment with multiple antidepressants and are considered to have treatment-resistant depression (2).”
- Also stated in: § Efficacy and Safety of Flexibly Dosed Esketamine Nasal Spray Combined With a Newly Initiated Oral Antidepressant in Treatment-Resistant Depression: A Randomized Double-Blind Active-Controlled Study · plain
“About one-third of patients with depression fail to achieve remission despite treatment with multiple antidepressants.”
What the sources say
- Not checked — no full text of the sourcecites [2] source
Strength:plain· 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.
- Also stated in: § Efficacy and Safety of Flexibly Dosed Esketamine Nasal Spray Combined With a Newly Initiated Oral Antidepressant in Treatment-Resistant Depression: A Randomized Double-Blind Active-Controlled Study · plain
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
“To maintain blinding, a bittering agent was added to the intranasal placebo to simulate the taste of the esketamine solution, and three devices were administered to all patients at all sessions”
§ Efficacy and Safety of Flexibly Dosed Esketamine Nasal Spray Combined With a Newly Initiated Oral Antidepressant in Treatment-Resistant Depression: A Randomized Double-Blind Active-Controlled Study > Intranasal Study Drug and Administration
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. It may state two separate claims as one.
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
“A delta adjustment tipping point sensitivity analysis was performed to evaluate the robustness of the MMRM analysis to increasing deviations from the missing-at-random assumption (results are presented in the online supplement).”
§ Efficacy and Safety of Flexibly Dosed Esketamine Nasal Spray Combined With a Newly Initiated Oral Antidepressant in Treatment-Resistant Depression: A Randomized Double-Blind Active-Controlled Study > Statistical Analysis
Strength:plain· 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.
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
“Of 435 patients screened, nine (randomized at one site in Poland) were excluded from all analyses because of Good Clinical Practices violations (sensitivity analyses including this site confirmed no impact on the overall conclusions of the study), 227 underwent randomization to treatment; of these, three did not receive any study drug and one did not receive a dose of oral study antidepressant.”
- Also stated in: § RESULTS · plain
“Most randomized patients (197/227, 86.8%) completed the 28-day double-blind treatment phase (see Figure S1 in the online supplement).”
§ Efficacy and Safety of Flexibly Dosed Esketamine Nasal Spray Combined With a Newly Initiated Oral Antidepressant in Treatment-Resistant Depression: A Randomized Double-Blind Active-Controlled Study > RESULTS
Strength:plain· not yet calibratedn = 435Tests✓ 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. The quote only partly states this claim.
- Also stated in: § RESULTS · plain
In the paper
“Ketamine (an NMDA receptor antagonist) affects fast excitatory glutamate transmission, increases release of brain-derived neurotrophic factor, and stimulates synaptogenesis (7).”
What the sources say
- Not checked — no full text of the sourcecites [7] 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. It may state two separate claims as one.
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
“A serial gatekeeping (fixed sequence) approach was applied to adjust for multiplicity and to strongly control type I error across the primary and the three key secondary efficacy endpoints-namely, onset of clinical response by day 2, change in Sheehan Disability Scale score, and change in PHQ-9 score.”
§ Efficacy and Safety of Flexibly Dosed Esketamine Nasal Spray Combined With a Newly Initiated Oral Antidepressant in Treatment-Resistant Depression: A Randomized Double-Blind Active-Controlled Study > Statistical Analysis
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesProbably not a substantial claim.
In the paper
“Early clinical evidence suggested a potential role of ketamine in the treatment of depression, with mood-elevating effects observed in challenge studies (8).”
What the sources say
- Not checked — no full text of the sourcecites [8] source
Strength:hedged· not yet calibratedCausal:conditional· 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.
In the paper
“In patients who respond to antidepressants, the time to onset of effect is typically several weeks, during which time patients remain symptomatic and at risk of suicidal behavior and self-harm (3).”
What the sources say
- Not checked — no full text of the sourcecites [3] source
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
In the paper
“In phase 2 studies, esketamine nasal spray demonstrated rapid onset and persistent efficacy in patients with treatment-resistant depression as well as in depressed patients at imminent risk for suicide (10)(11)(12).”
What the sources say
- Not matchedcites (10)(11)(12)
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
Strength:boosted· not yet calibratedCausal:direct· 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 only medication approved for the treatment of treatment-resistant depression is olanzapine plus fluoxetine, which has an NNT of 8 for response and 13 for remission (35).”
§ Efficacy and Safety of Flexibly Dosed Esketamine Nasal Spray Combined With a Newly Initiated Oral Antidepressant in Treatment-Resistant Depression: A Randomized Double-Blind Active-Controlled Study > DISCUSSION
What the sources say
- Not checked — no full text of the sourcecites [35] source
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A claim is checked only against the cited paper’s full text, never its abstract, and none is available for its sources.
In the paper
“which is considered a clinically meaningful treatment difference (26,27) suggesting rapid onset of antidepressant efficacy.”
§ Efficacy and Safety of Flexibly Dosed Esketamine Nasal Spray Combined With a Newly Initiated Oral Antidepressant in Treatment-Resistant Depression: A Randomized Double-Blind Active-Controlled Study > DISCUSSION
What the sources say
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
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
“it is noteworthy that the dissociation ratings (CADSS scores) increased in the control group who received placebo nasal spray, providing evidence of adequate blinding and supporting expectation of benefit as one of the contributing factors of the higher than anticipated placebo response observed in the control group.”
§ Efficacy and Safety of Flexibly Dosed Esketamine Nasal Spray Combined With a Newly Initiated Oral Antidepressant in Treatment-Resistant Depression: A Randomized Double-Blind Active-Controlled Study > DISCUSSION
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
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
“While eventual efficacy bias was mitigated by using independent remote MADRS raters, it is possible that the specific adverse event profile of esketamine affected the blind for the study patients.”
§ Efficacy and Safety of Flexibly Dosed Esketamine Nasal Spray Combined With a Newly Initiated Oral Antidepressant in Treatment-Resistant Depression: A Randomized Double-Blind Active-Controlled Study > DISCUSSION
Strength:hedged· not yet calibratedCausal:conditional· 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
“A number of factors may have contributed to the smaller than anticipated effect size finding, the lower treatment difference compared with our phase 2 work, and the higher response and remission rates observed for the oral antidepressant plus placebo group”
§ Efficacy and Safety of Flexibly Dosed Esketamine Nasal Spray Combined With a Newly Initiated Oral Antidepressant in Treatment-Resistant Depression: A Randomized Double-Blind Active-Controlled Study > DISCUSSION
Strength:hedged· not yet calibratedCausal:conditional· 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.
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
“Because this trial was a flexible-dose study, dose-response relationships were not evaluated.”
§ Efficacy and Safety of Flexibly Dosed Esketamine Nasal Spray Combined With a Newly Initiated Oral Antidepressant in Treatment-Resistant Depression: A Randomized Double-Blind Active-Controlled Study > DISCUSSION
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.
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
“Based on the predefined testing sequence, the other two key secondary endpoints (change in Sheehan Disability Scale and PHQ-9 scores) could not be formally evaluated.”
§ Efficacy and Safety of Flexibly Dosed Esketamine Nasal Spray Combined With a Newly Initiated Oral Antidepressant in Treatment-Resistant Depression: A Randomized Double-Blind Active-Controlled Study > DISCUSSION
Strength:plain· 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.
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
“use of a newly initiated antidepressant (to which the patients had not shown a previous nonresponse) in the comparator arm (i.e., not a true placebo control)”
§ Efficacy and Safety of Flexibly Dosed Esketamine Nasal Spray Combined With a Newly Initiated Oral Antidepressant in Treatment-Resistant Depression: A Randomized Double-Blind Active-Controlled Study > DISCUSSION
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
The paper relies on this without support.
Current treatment options for treatment-resistant depression have considerable limitations in terms of efficacy and patient acceptability.
“Current treatment options for treatmentresistant depression have considerable limitations in terms of efficacy and patient acceptability.”
The paper relies on this without support.
There is a need to develop novel treatments that provide rapid relief of depressive symptoms, especially in patients with treatment-resistant depression.
“There is a need to develop novel treatments that provide rapid relief of depressive symptoms, especially in patients with treatment-resistant depression.”
The paper relies on this without support.
Esketamine has a higher affinity for the NMDA receptor than the R-enantiomer.
“Esketamine, the S-enantiomer of ketamine racemate, with a higher affinity for the NMDA receptor than the R-enantiomer, was recently approved by the U.S. Food and Drug Administration for treatment-resistant depression in adults.”
The authors state this as an assumption.
The missing data are missing at random.
“A delta adjustment tipping point sensitivity analysis was performed to evaluate the robustness of the MMRM analysis to increasing deviations from the missing-at-random assumption (results are presented in the online supplement).”
The paper relies on this without support.
Esketamine exhibits transient dissociative effects that are difficult to blind.
“Because esketamine exhibits transient dissociative effects that are difficult to blind, possibly biasing the site staff supervising the dosing, all MADRS assessments (used for the primary endpoint, the first key secondary endpoint, and calculation of response and remission rates) were performed by independent, remote (by telephone) raters who were blind to the protocol details, including study vis”
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
“Clinical trials found that esketamine, in combination with an oral antidepressant, rapidly reduced suicidal thoughts compared to placebo in adults with TRD who were at imminent risk for suicide [65,88,89].”
From Ketamine in neuropsychiatric disorders: an update (2024) · cites this paper as [65]
Experimental — accuracy not yet measuredThe cited source says what the claim attributes to it.
In the citing paper
“Among the three pivotal trials, one (NCT02418585 [11]) demonstrated positive results on its primary endpoint, while two (NCT02417064 [9] and NCT02422186 [10]) did not meet their primary endpoints.”
The cited source says what the claim attributes to it.
In the citing paper
“Our findings are concordant with the direction and general magnitude of effect reported in pivotal trials of adjunctive intranasal esketamine in TRD and the relapse-prevention study (18–23)”
In the citing paper
“A phase III trial of over 200 patients using esketamine adjunctive to an antidepressant demonstrated significant improvement in depression at 4 weeks compared with those using a placebo nasal spray.70”
From Ketamine as an antidepressant: Overview of its mechanisms of action and potential predictive biomarkers (2020) · cites this paper as [70]
In the citing paper
“Repeated dosing of ketamine is more efficacious in clinical trials than typical antidepressants alone [109, 110].”
From Beyond the serotonin deficit hypothesis: Communicating a neuroplasticity framework of major depressive disorder (2024) · cites this paper as [110]
In the citing paper
“Results from two 28-day phase III RCTs support multi-dose, adjunctive esketamine’s tolerability and AD efficacy in adult and geriatric samples [109,110].”
From Pharmacotherapies Targeting GABA-Glutamate Neurotransmission for Treatment-Resistant Depression (2023) · cites this paper as [110]
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].”
Citations
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Self-citationAntidepressant effects of ketamine in depressed patients
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Items 101–200 of 894
Seshadri, A., Prokop, L. J., & Singh, B. (2024) · Journal of Affective Disorders · doi:10.1016/j.jad.2024.03.137 · Cited by 55
Vekhova, K. A., Namiot, E. D., Jonsson, J., & Schiöth, H. B. (2024) · Clinical Pharmacology & Therapeutics · doi:10.1002/cpt.3478 · Cited by 61
Ross, E. L., & Soeteman, D. I. (2020) · Psychiatric Services · doi:10.1176/appi.ps.201900625 · Cited by 51
Reporting of harms in clinical trials of esketamine in depression: a systematic review
de Laportalière, T. T., Jullien, A., Yrondi, A., Cestac, P., & Montastruc, F. (2023) · Psychological Medicine · doi:10.1017/s0033291723001058 · Cited by 26
“…AEs in the published articles were referring to only a single phase (most often induction) and did not provide any further information on AEs found in the other phases of the trial (Daly et al., 2018, 2019; Fedgchin et al., 2019; Ochs-Ross et al., 2020; Popova et al., 2019; Takahashi et al., 2021).”
BackgroundResultNew and emerging treatments for major depressive disorder
Njenga, C., Ramanuj, P., de Magalhães, F. J. C., & Pincus, H. A. (2024) · BMJ · doi:10.1136/bmj-2022-073823 · Cited by 51
Feeney, A., & Papakostas, G. I. (2023) · Psychiatric Clinics of North America · doi:10.1016/j.psc.2023.02.003 · Cited by 57
Enhanced ERK activity extends ketamine’s antidepressant effects by augmenting synaptic plasticity
Ma, Z., Guzikowski, N. J., Kim, J., Kavalali, E. T., & Monteggia, L. M. (2025) · Science · doi:10.1126/science.abb6748 · Cited by 54
Pharmacotherapies Targeting GABA-Glutamate Neurotransmission for Treatment-Resistant Depression
Vecera, C. M., C. Courtes, A., Jones, G., Soares, J. C., & Machado-Vieira, R. (2023) · Pharmaceuticals · doi:10.3390/ph16111572 · Cited by 48
“Based on positive phase II results, Popova and colleagues hypothesized a far greater effect size than what manifested from their trial, possibly related to unsuccessfully blinding esketamine’s subjective effects, especially in comparison to inactive placebo [110].”
BackgroundApproval of esketamine for treatment-resistant depression
Singh, J. B., Daly, E. J., Mathews, M., Fedgchin, M., Popova, V., Hough, D., & Drevets, W. C. (2020) · The Lancet Psychiatry · doi:10.1016/s2215-0366(19)30533-4 · Cited by 46
Self-citationRodrigues, N. B., McIntyre, R. S., Lipsitz, O., Lee, Y. L., Cha, D. S., Shekotikhina, M., Vinberg, M., Gill, H., Subramaniapillai, M., Kratiuk, K., et al. (2020) · Journal of Affective Disorders · doi:10.1016/j.jad.2020.12.119 · Cited by 48
Daly, E., Turkoz, I., Salvadore, G., Fedgchin, M. M., Ionescu, D. F., Starr, H. L., Borentain, S., Trivedi, M. H., Thase, M. E., & Singh, J. B. (2021) · Depression and Anxiety · doi:10.1002/da.23193 · Cited by 47
Self-citationResearch advances in the clinical application of esketamine
Zhang, X., Zhang, N., Liu, D., Ding, J., Zhang, Y., & Zhu, Z. (2022) · Ibrain · doi:10.1002/ibra.12019 · Cited by 46
“Depressive symptoms have a long‐lasting effect and delay recurrence, so it has attracted the attention of researchers.(1,2) Ketamine has a powerful sedative and analgesic effect and has been used in clinical anesthesia for more than 50 years.”
Genome-wide association study and polygenic risk score analysis of esketamine treatment response
Li, Q. S., Wajs, E., Ochs-Ross, R., Singh, J. B., & Drevets, W. C. (2020) · Scientific Reports · doi:10.1038/s41598-020-69291-6 · Cited by 49
Self-citationShiroma, P. R., THURAS, P. D., Wels, J., Albott, C. S., Erbes, C. R., Tye, S. J., & Lim, K. O. (2020) · Journal of Affective Disorders · doi:10.1016/j.jad.2020.08.058 · Cited by 49
An, D., Wei, C., Wang, J., & Wu, A. (2021) · Frontiers in Psychology · doi:10.3389/fpsyg.2021.648691 · Cited by 45
Darcy, A., Beaudette, A., Chiauzzi, E., Daniels, J., Goodwin, K., Mariano, T. Y., Wicks, P., & Robinson, A. (2022) · Expert Review of Medical Devices · doi:10.1080/17434440.2022.2075726 · Cited by 40
“Pharmacological treatment Oral antidepressant drugs such as selective serotonin reuptake inhibitors (SSRIs) or serotonin-norepinephrine reuptake inhibitors (SNRIs); intravenous brexanolone for postpartum depression (PPD) [25]; intravenous ketamine for treatmentresistant depression (TRD); intranasal esketamine for TRD…”
BackgroundRetractedAn Update on Glutamatergic System in Suicidal Depression and on the Role of Esketamine
Berardis, D. D., Tomasetti, C., Pompili, M., Serafini, G., Vellante, F., Fornaro, M., Valchera, A., Perna, G., Volpe, U., Martinotti, G., et al. (2020) · Current Topics in Medicinal Chemistry · doi:10.2174/1568026620666200131100316 · Cited by 46
Ng, J., Rosenblat, J. D., Lui, L. M. W., Teopiz, K. M., Lee, Y. L., Lipsitz, O., Mansur, R. B., Rodrigues, N. B., Nasri, F., Gill, H., et al. (2021) · Journal of Affective Disorders · doi:10.1016/j.jad.2021.06.032 · Cited by 47
Sapkota, A., Khurshid, H., Qureshi, I. A., Jahan, N., Went, T. R., Sultan, W., & Alfonso, M. (2021) · Cureus · doi:10.7759/cureus.17352 · Cited by 45
“The most commonly reported adverse effects (AE) in short-term clinical trials [17-19] were nausea, dizziness, dissociation, headache, vertigo, and dysgeusia.”
BackgroundMethodInfluentialVan Amsterdam, J., & Van Den Brink, W. (2022) · Expert Opinion on Drug Safety · doi:10.1080/14740338.2021.1949454 · Cited by 44
“In another study, patients with major depressive disorder were repeatedly treated with oral doses of ketamine (25 mg twice daily for 6 weeks) [78], while in a Phase 3 study two treatment groups (n = 116–117) with moderate-to-severe depression were treated twice weekly for 4 weeks with S-ketamine nasal spray (equivalen…”
BackgroundMethodKetamine in Major Depressive Disorder: Mechanisms and Future Perspectives
Shin, C., & Kim, Y. (2020) · Psychiatry Investigation · doi:10.30773/pi.2019.0236 · Cited by 47
Ochs-Ross, R., Wajs, E., Daly, E., Zhang, Y., Lane, R., Lim, P., Drevets, W. C., Steffens, D. C., Sanacora, G., Jamieson, C., et al. (2021) · American Journal of Geriatric Psychiatry · doi:10.1016/j.jagp.2021.09.014 · Cited by 44
Self-citationSafety and effectiveness of NMDA receptor antagonists for depression: A multidisciplinary review
Moore, T. J., Alami, A., Alexander, G. C., & Mattison, D. R. (2022) · Pharmacotherapy The Journal of Human Pharmacology and Drug Therapy · doi:10.1002/phar.2707 · Cited by 46
Subcutaneous Ketamine in Depression: A Systematic Review
Cavenaghi, V. B., da Costa, L. P., Lacerda, A. L. T., Hirata, E. S., Miguel, E. C., & Fráguas, R. (2021) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2021.513068 · Cited by 44
“This led to FDA approval of intranasal (IN) esketamine for treating depression in 2019 (8, 9).”
BackgroundKetamine for Treatment of Mood Disorders and Suicidality: A Narrative Review of Recent Progress
Kritzer, M. D., Mischel, N., Young, J. R., Lai, C. S., Masand, P. S., Szabo, S. T., & Mathew, S. J. (2021) · Annals of Clinical Psychiatry · doi:10.12788/acp.0048 · Cited by 43
“38 Popova et al 46 recently published results from the SUSTAIN-1 trial.”
Araújo-de-Freitas, L., Santos‐Lima, C., Mendonça-Filho, E., Vieira, F., França, R. J. A. F., Magnavita, G. M., Cardoso, T. L., Correia‐Melo, F. S., Leal, G. C.-G., Jesus‐Nunes, A. P., et al. (2021) · Psychiatry Research · doi:10.1016/j.psychres.2021.114058 · Cited by 41
Esketamine for treatment resistant depression
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Safety and efficacy with esketamine in treatment-resistant depression: long-term extension study
Zaki, N., Chen, L., Lane, R., Doherty, T., Drevets, W. C., Morrison, R. L., Sanacora, G., Wilkinson, S. T., Young, A. H., Lacerda, A. L. T., et al. (2025) · The International Journal of Neuropsychopharmacology · doi:10.1093/ijnp/pyaf027 · Cited by 46
“These approvals were based on phase 2/3 short-term studies of TRD patients 7-10 as well as a relapse prevention study 11 and an open-label, 1-year safety study.”
Self-citationUse of ketamine and esketamine for depression: an overview of systematic reviews with meta-analyses
Lima, T. D. M., Visacri, M. B., & Aguiar, P. M. (2021) · European Journal of Clinical Pharmacology · doi:10.1007/s00228-021-03216-8 · Cited by 43
St. Johnʼs wort (Hypericum perforatum) and depression: what happens to the neurotransmitter systems?
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Ketamine and Electroconvulsive Therapy for Treatment-Refractory Depression
Huang, X., & Zheng, W. (2023) · ALPHA PSYCHIATRY · doi:10.5152/alphapsychiatry.2023.231358 · Cited by 38
“In addition to ECT and ketamine, TRD has been treated with novel pharmacological interventions, including esketamine nasal spray 17 and psilocybin.”
BackgroundReconsidering “dissociation” as a predictor of antidepressant efficacy for esketamine
Mathai, D. S., Nayak, S. M., Yaden, D. B., & Garcia‐Romeu, A. (2023) · Psychopharmacology · doi:10.1007/s00213-023-06324-8 · Cited by 37
Correia, A. S., & Vale, N. (2024) · International Journal of Translational Medicine · doi:10.3390/ijtm4010010 · Cited by 43
Vincenzo, M. D., Martiadis, V., Rocca, B. D., Arsenio, E., D’Arpa, A., Volpicelli, A., Luciano, M., Sampogna, G., & Fiorillo, A. (2024) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2024.1394787 · Cited by 39
Benefit–Risk Assessment of Esketamine Nasal Spray vs. Placebo in Treatment‐Resistant Depression
Katz, E. G., Hough, D. W., Doherty, T., Lane, R., Singh, J. B., & Levitan, B. S. (2020) · Clinical Pharmacology & Therapeutics · doi:10.1002/cpt.2024 · Cited by 36
Self-citationLucchese, A. C., Sarin, L. M., Magalhães, E. T. P., Sant, L. C. D., Puertas, C. B., Tuena, M. A., Nakahira, C., Fava, V. A. R., Delfino, R. S., Surjan, J. C., et al. (2021) · Journal of Psychopharmacology · doi:10.1177/0269881120978398 · Cited by 36
“In March 2019, the United States Food and Drug Administration (FDA) had approved intranasal (IN) esketamine in conjunction with an oral antidepressant for TRD after a large number of phase 2 and 3 studies were published (Canuso et al., 2018; Daly et al., 2018, 2019; Doherty et al., 2020; Popova et al., 2019).”
BackgroundMethodInfluentialIntranasal esketamine: From origins to future implications in treatment-resistant depression
Sanders, B. J., & Brula, A. Q. (2021) · Journal of Psychiatric Research · doi:10.1016/j.jpsychires.2021.02.020 · Cited by 37
Chen, X., Hou, X., Bai, D., Lane, R., Zhang, C., Canuso, C., Wang, G., & Fu, D.-J. (2023) · Neuropsychiatric Disease and Treatment · doi:10.2147/ndt.s391096 · Cited by 35
“There were no obvious factors identified to explain the difference in the primary efficacy outcome between China and US subgroups, and global phase 3 TRD studies.(17,33) With respect to PK, esketamine concentrations exhibited the expected dose-dependent differences between the 56 mg and 84 mg doses and were similar to…”
BackgroundResultInfluentialSelf-citationSaad, Z. S., Hibar, D. P., Fedgchin, M. M., Popova, V., Furey, M. L., Singh, J. B., Kolb, H. C., Drevets, W. C., & Chen, G. (2020) · The International Journal of Neuropsychopharmacology · doi:10.1093/ijnp/pyaa030 · Cited by 34
Self-citationKetamine-Assisted Psychotherapy for PTSD Related to Racial Discrimination
Halstead, M., Reed, S., Krause, R., & Williams, M. T. (2021) · Clinical Case Studies · doi:10.1177/1534650121990894 · Cited by 40
“Ketamine is one of the few medications recently granted Breakthrough Therapy designation as an off-label treatment for depression (Popova et al., 2019).”
BackgroundResultScotton, E., Antqueviezc, B., Vasconcelos, M., Dalpiaz, G., Géa, L. P., Goularte, J. F., Colombo, R., & Rosa, A. R. (2022) · Biochemical Pharmacology · doi:10.1016/j.bcp.2022.114963 · Cited by 37
Jones, R., Freeman, M. P., Kornstein, S. G., Cooper, K., Daly, E., Canuso, C. M., & Nicholson, S. (2022) · Archives of Women s Mental Health · doi:10.1007/s00737-021-01185-6 · Cited by 33
Self-citationCalder, C. N., Kwan, A. T. H., Teopiz, K. M., Wong, S., Rosenblat, J. D., Mansur, R. B., Rhee, T. G., Ho, R., Cao, B., & McIntyre, R. S. (2024) · Journal of Affective Disorders · doi:10.1016/j.jad.2024.04.039 · Cited by 37
Repurposing of Drugs–The Ketamine Story
Das, J. (2020) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.0c01193 · Cited by 41
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Ketamine for depression clinical issues
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“However, esketamine has a higher affinity for NMDA receptors compared with that of ketamine [12].”
BackgroundThe therapeutic role of ketamine and esketamine in treating psychopathological domains of depression
Jawad, M. Y., Vincenzo, J. D. D., Badulescu, S., Teopiz, K. M., Tabassum, A., Ceban, F., Mckenzie, A., Meshkat, S., Rosenblat, J. D., Ho, R., et al. (2022) · Neuropharmacology · doi:10.1016/j.neuropharm.2022.109299 · Cited by 32
Antidepressant mechanisms of ketamine’s action: NF-κB in the spotlight
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Esmethadone-HCl (REL-1017): a promising rapid antidepressant
D, M. F. M., Stahl, S. M., Martin, S. D., Mattarei, A., Bettini, E., Comai, S., Alimonti, A., Bifari, F., Pani, L., Folli, F. B., et al. (2023) · European Archives of Psychiatry and Clinical Neuroscience · doi:10.1007/s00406-023-01571-4 · Cited by 32
Pharmacologic approaches to suicide prevention
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Borentain, S., Gogate, J. P., Williamson, D., Carmody, T. J., Trivedi, M. H., Jamieson, C., Cabrera, P., Popova, V., Wajs, E., DiBernardo, A., et al. (2022) · International Journal of Methods in Psychiatric Research · doi:10.1002/mpr.1927 · Cited by 34
Self-citation(R)-(-)-Ketamine: The Promise of a Novel Treatment for Psychiatric and Neurological Disorders
Shafique, H. S., Demers, J. C., Biesiada, J., Golani, L. K., Cerne, R., Smith, J. L., Szostak, M., & Witkin, J. M. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25126804 · Cited by 31
“The most commonly reported side effects of ( S )-ketamine, or esketamine, include dissociation, nausea, vertigo, headache, and dizziness [69,70].”
BackgroundCole, E., Gulser, M., Stimpson, K., Bentzley, B., Hawkins, J., Xiao, X., Schatzberg, A., Sudheimer, K., & Williams, N. (2019) · Brain Stimulation · doi:10.1016/j.brs.2018.12.299 · Cited by 31
Managing dissociative symptoms following the use of esketamine nasal spray: a case report
Pereira, S., Brennan, E. A., Patel, A. B., Moran, M., Wallier, J., & Liebowitz, M. R. (2020) · International Clinical Psychopharmacology · doi:10.1097/yic.0000000000000327 · Cited by 30
Beating pain with psychedelics: Matter over mind?
Elman, I., Pustilnik, A. C., & Borsook, D. (2021) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2021.12.005 · Cited by 30
Jawad, M. Y., Vincenzo, J. D. D., Ceban, F., Jaberi, S., Lui, L. M. W., Gillissie, E. S., Alnefeesi, Y., Rosenblat, J. D., & McIntyre, R. S. (2022) · Expert Opinion on Drug Safety · doi:10.1080/14740338.2022.2058488 · Cited by 29
Anatomy of a Woebot® (WB001): agent guided CBT for women with postpartum depression
Darcy, A. M., Beaudette, A., Chiauzzi, E. J., Daniels, J., Goodwin, K., Mariano, T. Y., Wicks, P. J., & Robinson, A. H. (2023) · Expert Review of Medical Devices · doi:10.1080/17434440.2023.2280686 · Cited by 32
“Pharmacological treatment Oral antidepressant drugs such as selective serotonin reuptake inhibitors (SSRIs) or serotonin-norepinephrine reuptake inhibitors (SNRIs); intravenous brexanolone for postpartum depression (PPD) [25]; intravenous ketamine for treatmentresistant depression (TRD); intranasal esketamine for TRD…”
BackgroundControl Group Outcomes in Trials of Psilocybin, SSRIs, or Esketamine for Depression
Hieronymus, F., López, E., Sjögren, H. W., & Lundberg, J. (2025) · JAMA Network Open · doi:10.1001/jamanetworkopen.2025.24119 · Cited by 32
Repurposing Ketamine in Depression and Related Disorders: Can This Enigmatic Drug Achieve Success?
Carboni, E., Carta, A. R., Carboni, E., & Novelli, A. (2021) · Frontiers in Neuroscience · doi:10.3389/fnins.2021.657714 · Cited by 33
“…nasal spray was evaluated when added to a newly initiated oral antidepressant in TRD patients, in a randomized double-blind active controlled study (Popova et al., 2019); the authors observed a clinically meaningful improvement in the esketamine plus antidepressant group, while the most common…”
MethodBoudieu, L., Mennetrier, M., Llorca, P., & Samalin, L. (2023) · Pharmaceutics · doi:10.3390/pharmaceutics15122773 · Cited by 31
“Two of the six RCTs showed a sig-nificantly higher improvement in MADRS scores in the IN esketamine group than in the placebo group [38,39].”
BackgroundResultBorentain, S., Williamson, D., Turkoz, I., Popova, V., McCall, W. V., Mathews, M., & Wiegand, F. (2021) · Neuropsychiatric Disease and Treatment · doi:10.2147/ndt.s339090 · Cited by 27
“To evaluate the relationship of sleep disturbance to the antidepressant effects of esketamine, and vice versa, we conducted post-hoc analyses of pooled data from these two similarly designed TRANSFORM studies of TRD.(24,25) The aims of these post-hoc analyses were to determine: 1) if baseline severity of reported slee…”
MethodResultInfluentialSelf-citationXue, X., Pan, J., Zhang, H., Lu, Y., Mao, Q., & Ma, K. (2022) · Journal of Ethnopharmacology · doi:10.1016/j.jep.2022.115218 · Cited by 27
Zhu, T., Zhao, X., Sun, M., An, Y., Kong, W., Ji, F., & Wang, G. (2022) · BMC Anesthesiology · doi:10.1186/s12871-022-01889-x · Cited by 28
“We think that the performance of PONV may be related to the side effect of esketamine [22].”
BackgroundThe Patient’s Perspective on the Effects of Intranasal Esketamine in Treatment-Resistant Depression
Pepe, M., Bartolucci, G., Marcelli, I., Pesaresi, F., Brugnami, A., Caso, R., Fischetti, A., Grisoni, F., Mazza, M., Camardese, G., et al. (2023) · Brain Sciences · doi:10.3390/brainsci13101494 · Cited by 27
Fang, S., Yang, X., & Zhang, W. (2024) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2024.1359088 · Cited by 34
Smith-Apeldoorn, S. Y., Veraart, J. K. E., Kamphuis, J., Spijker, J., van der Meij, A., van Asselt, A. D. I., Rot, M. A. H., & Schoevers, R. A. (2024) · Molecular Psychiatry · doi:10.1038/s41380-024-02478-9 · Cited by 32
“Previous research shows that antidepressant responses occur at a range of subcutaneous and IN doses [9, 36], and a recent study shows fl exible, response-guided dosing of subcutaneous ketamine to be ef fi cacious in treating TRD, while fi xed-dosing was not [12].”
Nanocarrier drug delivery system: promising platform for targeted depression therapy
Feng, X., Jia, P., & Zhang, D.-D. (2024) · Frontiers in Pharmacology · doi:10.3389/fphar.2024.1435133 · Cited by 31
Chen, B. K., Luna, V. M., Shannon, M. E., Hunsberger, H. C., Mastrodonato, A., Stackmann, M., McGowan, J. C., Rubinstenn, G., & Denny, C. A. (2021) · Biological Psychiatry · doi:10.1016/j.biopsych.2021.04.024 · Cited by 24
Ketamine and the Disinhibition Hypothesis: Neurotrophic Factor-Mediated Treatment of Depression
Borsellino, P., Krider, R. I., Chea, D., Grinnell, R., & Vida, T. A. (2023) · Pharmaceuticals · doi:10.3390/ph16050742 · Cited by 29
“In a double-blind RCT, intranasal esketamine in conjunction with a traditional oral antidepressant resulted in greater and quicker improvements in treatment-resistant depression [91].”
BackgroundCitrome, L., DiBernardo, A., & Singh, J. B. (2020) · Journal of Affective Disorders · doi:10.1016/j.jad.2020.03.106 · Cited by 27
Self-citationMa, S., Dou, Y., Wang, W., Wei, A., Lan, M., Liu, J., Yang, L., & Yang, M. (2024) · American Journal of Obstetrics & Gynecology MFM · doi:10.1016/j.ajogmf.2023.101241 · Cited by 28
Zhou, Y., Wang, C., Lan, X., Zheng, W., Li, H., Chao, Z., Wu, K., McIntyre, R. S., & Ning, Y. (2021) · Journal of Psychiatric Research · doi:10.1016/j.jpsychires.2021.10.037 · Cited by 25
“The available evidence supporting the efficacy of ketamine/esketamine in the treatment of adults with TRD resulted in the recent US Food and Drug Administration (FDA) approval of nasal esketamine, the S-enantiomer of ketamine, as augmentation therapy in adults with treatment-resistant depression (TRD) or with major de…”
BackgroundSex differences in ketamine's therapeutic effects for mood disorders: A systematic review
Benitah, K. C., Siegel, A. N., Lipsitz, O., Rodrigues, N. B., Meshkat, S., Lee, Y. L., Mansur, R. B., Nasri, F., Lui, L. M. W., McIntyre, R. S., et al. (2022) · Psychiatry Research · doi:10.1016/j.psychres.2022.114579 · Cited by 24
Sant, L. C. D., Sarin, L. M., Magalhães, E. T. P., Lucchese, A. C., Tuena, M. A., Nakahira, C., Fava, V. A. R., Delfino, R. S., Surjan, J. C., Steglich, M. S., et al. (2020) · Journal of Psychopharmacology · doi:10.1177/0269881120922955 · Cited by 25
“) administration of esketamine, which in conjunction with an oral antidepressant was recently approved by the United States Food and Drug Administration for the treatment of TRD in adults (Canuso et al., 2018; Daly et al., 2018, 2019; Popova et al., 2019), has also been associated with transient and self-limiting BP c…”
BackgroundResultRathod, S., Denee, T., Eva, J., Kerr, C., Jacobsen, N., Desai, M., Baldock, L., & Young, A. H. (2022) · Journal of Affective Disorders · doi:10.1016/j.jad.2021.12.090 · Cited by 23
Rosso, G., d’Andrea, G., Barlati, S., Nicola, M. D., Andriola, I., Marcatili, M., Martiadis, V., Olivola, M., Mauro, S. D., Salvo, G. D., et al. (2025) · Current Neuropharmacology · doi:10.2174/011570159x337670241029062524 · Cited by 25
An update on antidepressant pharmacotherapy in late-life depression
Brender, R., Mulsant, B. H., & Blumberger, D. M. (2021) · Expert Opinion on Pharmacotherapy · doi:10.1080/14656566.2021.1921736 · Cited by 25
Baudot, J., Soeiro, T., Tambon, M., Navarro, N., Veyrac, G., Mezaache, S., & Micallef, J. (2021) · Fundamental and Clinical Pharmacology · doi:10.1111/fcp.12745 · Cited by 25
“Adverse event TRANSFORM-1 (NCT02417064) [31] TRANSFORM-2 (NCT02418585) [32] TRANSFORM-3 (NCT02422186) [33] SUSTAIN-1 (NCT02493868) [34] SUSTAIN-2 (NCT02497287) [35]”
Jeon, H. J., Ju, P., Sulaiman, A. H., Aziz, S. A., Paik, J., Tan, W., Bai, D., & Li, C. (2022) · Clinical Psychopharmacology and Neuroscience · doi:10.9758/cpn.2022.20.1.70 · Cited by 25
“[22,23] and elderly patients ≥ 65 years [24], and a long-term maintenance of effect study [25].”
BackgroundMethodResultInfluentialStahl, S. M., Martin, S. D., Mattarei, A., Bettini, E., Pani, L., Guidetti, C., Folli, F. B., de Somer, M., Traversa, S., Inturrisi, C. E., et al. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms232012196 · Cited by 24
“The antidepressant effects of intravenous (IV) ketamine were replicated with intranasal esketamine [22,23], leading to FDA approval of intranasal esketamine as a rapidly acting antidepressant for TRD.”
BackgroundRoles of the monoaminergic system in the antidepressant effects of ketamine and its metabolites
Ago, Y., Yokoyama, R., Asano, S., & Hashimoto, H. (2022) · Neuropharmacology · doi:10.1016/j.neuropharm.2022.109313 · Cited by 24
Halaris, A. E., & Cook, J. T. (2023) · Advances in experimental medicine and biology · doi:10.1007/978-981-19-7376-5_21 · Cited by 27
Agboola, F., Atlas, S. J., Touchette, D. R., Fazioli, K., & Pearson, S. D. (2020) · Journal of Managed Care & Specialty Pharmacy · doi:10.18553/jmcp.2020.26.1.16 · Cited by 24
“01).(9) However, a statistically significant difference was not observed between esketamine and placebo in TRANSFORM-1 and TRANSFORM-3.”
Schuling, R., Huijbers, M. J., van Ravesteijn, H., Donders, R., Cillessen, L., Kuyken, W., & Speckens, A. E. M. (2020) · Journal of Affective Disorders · doi:10.1016/j.jad.2020.03.182 · Cited by 24
Morrens, J., Mathews, M., Popova, V., Borentain, S., Rive, B., Gonzalez Martin Moro, B., Jamieson, C., & Zhang, Q. (2022) · Neuropsychiatric Disease and Treatment · doi:10.2147/ndt.s358367 · Cited by 24
“This post-hoc analysis was based on data from over 200 adult patients with the same diagnosis (and definition) of TRD participating in a phase 3 clinical study from the registration program of esketamine nasal spray, representing a relatively homogenous population for assessment.(17) Furthermore, the analysis included…”
MethodInfluentialSelf-citationAn integrative view on the cell-type-specific mechanisms of ketamine's antidepressant actions
Lewis, V., Rurak, G. M., Salmaso, N., & Aguilar‐Valles, A. (2024) · Trends in Neurosciences · doi:10.1016/j.tins.2023.12.004 · Cited by 31
Colla, M., Offenhammer, B., Scheerer, H., Kronenberg, G., Vetter, S., Mutschler, J., Mikoteit, T., Bankwitz, A., Adank, A., Schaekel, L., et al. (2024) · Journal of Psychiatric Research · doi:10.1016/j.jpsychires.2024.03.002 · Cited by 22
Doty, R. L., Popova, V., Wylie, C., Fedgchin, M. M., Daly, E., Janik, A., Ochs-Ross, R., Lane, R., Lim, P., Cooper, K. L., et al. (2021) · CNS Drugs · doi:10.1007/s40263-021-00826-9 · Cited by 23
“References: SUSTAIN-1 [14]; TRANSFORM-1 [15]; TRANSFORM-2 [16]; TRANSFORM-3 [17]”
BackgroundMethodInfluentialSelf-citationWłodarczyk, A., Cubała, W. J., Gałuszko‐Węgielnik, M., & Szarmach, J. (2021) · Medicine · doi:10.1097/md.0000000000026769 · Cited by 23
Sarasso, P., Billeci, M., Ronga, I., Raffone, F., Martiadis, V., & Petta, G. D. (2024) · Psychopathology · doi:10.1159/000539714 · Cited by 25
“Several studies showed that ketamine/esketamine-induced dissociation might be associated with better antidepressant response [16 – 18], although other studies discon fi rmed this relationship [19 – 21].”
Gałecki, P., & Bliźniewska-Kowalska, K. M. (2019) · Psychiatria Polska · doi:10.12740/pp/onlinefirst/115208 · Cited by 27
“W dwóch badaniach [59, 60] oceniano skuteczność i bezpieczeństwo stosowania donosowej esketaminy w 28-dniowym okresie podawania leku poprzez ocenę poprawy stanu pacjenta z użyciem skali MADRS (Montgomery-Asberg Depression Rating Scale).”
Background
Metadata
- Authors
- Popova, V., Daly, E. J., Trivedi, M., Cooper, K., Lane, R., Lim, P., Mazzucco, C., Hough, D., Thase, M. E., Shelton, R. C., Molero, P., Vieta, E., Bajbouj, M., Manji, H., Drevets, W. C., & Singh, J. B.
- Affiliations
- Janssen (Belgium) (BE)
- ORCID
- Venue
- American Journal of Psychiatry
- Published
- 2019-06-01
- Volume
- 176
- Issue
- 6
- Pages
- 428-438
- ISSN
- 0002-953X (ISSN-L)
- 1535-7228
- OpenAlex
- W2946661342
- Semantic Scholar
- 6b7c3525b179fffd83aabf69c45b1dca607faa4e
- Cited by
- 904
- References
- 32
- Citations by year
- 2026: 88 · 2025: 114 · 2024: 135 · 2023: 94 · 2022: 95 · 2021: 98 · 2020: 251 · 2019: 28
- FWCI
- 73.29
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- American Journal of Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- Funders
- American Psychiatric Foundation
- Bristol-Myers Squibb
- Eli Lilly and Company
- Pfizer
- AstraZeneca
- GlaxoSmithKline
- Sanofi
- Cancer Prevention and Research Institute of Texas
- AcademyHealth
- Yale University
- Patient-Centered Outcomes Research Institute
- Stanley Medical Research Institute
- Sunovion
- ACADIA Pharmaceuticals
- Sage Therapeutics
- Avanir Pharmaceuticals
- Cerecor
- Myriad Genetics
- Otsuka America
- University of Oxford
- Deutsche Forschungsgemeinschaft
- Generalitat de Catalunya (2014_ SGR_398)
- Gedeon Richter
- Universidad de Navarra
- Ministerio de Ciencia e Innovación
- Servier
- H. Lundbeck A/S
- Gobierno de Navarra
- National Institutes of Health
- Agency for Healthcare Research and Quality
- Allergan
- National Institute of Mental Health
- National Institute on Drug Abuse
- National Institute of Diabetes and Digestive and Kidney Diseases
- Janssen Research and Development
- National Center for Advancing Translational Sciences
- Janssen Pharmaceuticals
- 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
- depression, esketamine, nasal spray, antidepressant switching, flexible dosing, rapid-acting antidepressants, antidepressant non-response, dissociation, adverse events, depression remission, treatment-resistant depression, antidepressant efficacy, nausea, vertigo, dysgeusia, dizziness, treatment discontinuation
- MeSH terms
- Duloxetine Hydrochloride, Venlafaxine Hydrochloride, Administration, Intranasal, Administration, Oral, Adult, Antidepressive Agents, Major Depressive Disorder, Double-Blind Method, Drug Therapy, Combination, Female, Humans, Ketamine, Male, Middle Aged, Citalopram, Treatment Outcome, Sertraline, Depressive Disorder, Treatment-Resistant
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