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
41 Own result · 13 Own method · 9 No full text of the sources · 6 Own interpretation · 5 Supported · 4 No basis given · 2 Sources not found · 1 Partly supported · 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)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- 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)
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- 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.”
plain- Asserted: passes — The authors put it forward as true.
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- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
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
“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).”
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- 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
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- 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
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
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 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
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
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
“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
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
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
“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
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
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 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
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- 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)
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably 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.
plainn = 98- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably 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.
boostedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
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 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)
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It 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
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
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
“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
plainn = 201 ·- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
The 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
plainn = 9- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
The 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
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
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
“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
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
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
“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
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It 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
plaindirectn = 101- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
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
“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
plaincorrelationaln = 101- Asserted: passes — The authors put it forward as true.
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- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
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 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
plainSingle case- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
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
“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
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
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
“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
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It 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
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
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 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
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably 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
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It 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
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
The 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
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
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
“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
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It 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
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably 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
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably 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
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably 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
plainn = 435- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably 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
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably 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
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably 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
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably 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
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It 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.
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It 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
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It 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
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
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
“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
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
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
“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
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably 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
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably 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
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably 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
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably 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
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It 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
Cites
A Brief Measure for Assessing Generalized Anxiety Disorder: The GAD-7
Spitzer, R. L., Kroenke, K., Williams, J. B. W., & Löwe, B. (2006) · Archives of Internal Medicine · doi:10.1001/archinte.166.10.1092 · Cited by 31,765
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
Self-citationAntidepressant effects of ketamine in depressed patients
Berman, R. M., Cappiello, A., Anand, A., Oren, D. A., Heninger, G. R., Charney, D. S., & Krystal, J. H. (2000) · Biological Psychiatry · doi:10.1016/s0006-3223(99)00230-9 · Cited by 3,856
A randomized trial of an N-methyl-D-aspartate antagonist in treatment-resistant major depression.
Zarate, C. A., Singh, J. B., Carlson, P. J., Brutsche, N. E., Ameli, R., Luckenbaugh, D. A., Charney, D. S., & Manji, H. K. (2006) · Archives of General Psychiatry · doi:10.1001/archpsyc.63.8.856 · Cited by 3,766
Self-citationCipriani, A., Furukawa, T. A., Salanti, G., Chaimani, A., Atkinson, L. Z., Ogawa, Y., Leucht, S., Ruhe, H. G., Turner, E. H., Higgins, J. P. T., et al. (2018) · The Lancet · doi:10.1016/s0140-6736(17)32802-7 · Cited by 3,541
Sheehan, D., Lecrubier, Y., Harnett Sheehan, K., Janavs, J., Weiller, E., Keskiner, A., Schinka, J., Knapp, E., Sheehan, M., & Dunbar, G. (1997) · European Psychiatry · doi:10.1016/s0924-9338(97)83297-x · Cited by 2,149
ECDEU Assessment Manual: (591322011-001)
Guy, W. (1976) · PsycEXTRA Dataset · doi:10.1037/e591322011-001 · Cited by 1,896
Synaptic plasticity and depression: new insights from stress and rapid-acting antidepressants
Duman, R. S., Aghajanian, G. K., Sanacora, G., & Krystal, J. H. (2016) · Nature Medicine · doi:10.1038/nm.4050 · Cited by 1,750
Cited by
Sorted by citations
Items 501–600 of 894
Huang, C.-J., Yang, Y., Wang, X., & Liao, C. (2026) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.5c03086 · Cited by 3
Ayad, N., Aziz, K. A., Makhoul, S., Abbas, B., & Javaid, S. F. (2026) · BJPsych Open · doi:10.1192/bjo.2025.10950 · Cited by 3
López-Rodríguez, S., de Arriba‐Arnau, A., Menchón, J. M., Alonso, P., & Urretavizcaya, M. (2026) · Journal of Ect · doi:10.1097/yct.0000000000001233 · Cited by 2
Baune, B., Rosemann, K., Hefter, D., Tonkul, M., & Kavakbasi, E. (2026) · BMC Psychiatry · doi:10.1186/s12888-026-07980-8 · Cited by 2
“…phase 3 program in adult TRD, adding intranasal esketamine to an oral AD produced clinically meaningful symptom reductions by day 2 and sustained benefits through day 28 in short-term trials (e.g., TRANSFORM-2), with mixed results in specific populations (e.g., older adults in TRANSFORM-3) [8–10].”
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
Oral Prolonged-Release Ketamine for Treatment-Resistant Depression
Walter, M., zu Eulenburg, C., Damyanova, A., Schmid, K., Schwienbacher, I., Papanastasiou, E., Maiboe, K., Arvastson, L., Strote, C., Gehrlach, D., et al. (2026) · JAMA Network Open · doi:10.1001/jamanetworkopen.2026.19121 · Cited by 3
Role of the Pharmacist in Managing Treatment-Resistant Depression: A Focus on Ketamine
Liu, L. X. Y., Golts, M., & Fernandes, V. (2021) · Pharmacy · doi:10.3390/pharmacy9030118 · Cited by 2
“The third trial, TRANSFORM2, showed a difference of four points between esketamine and placebo at four weeks on the Montgomery-Åsberg Depression Rating Scale, favoring esketamine [38].”
BackgroundMungo, A., & Hein, M. (2022) · L Encéphale · doi:10.1016/j.encep.2021.12.002 · Cited by 2
The Modulation of Glutamatergic Signaling as a Potential Therapeutic Strategy for Major Depression
Molero, P., Aubá, E., Unceta, M. D. M., & Pedreño, F. O. S. (2022) · Springer eBooks · doi:10.1007/978-3-030-87480-3_11 · Cited by 2
Self-citationLi, Y., Zhou, J., Zheng, W., He, X., Liang, L., & Sunzi, K. (2024) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2023.1331780 · Cited by 3
Kheirabadi, G., & Golkar, S. (2023) · Iranian Journal of Psychiatry and Behavioral Sciences · doi:10.5812/ijpbs-137879 · Cited by 3
Pharmacological treatment of treatment-resistant depression: Towards evidence-based recommendations
Jerotić, S., & Ivković, M. (2024) · Medicinska istrazivanja · doi:10.5937/medi57-48086 · Cited by 2
“Intravenous infusion of ketamine (0.5 mg/kg over 40 minutes) is considered the gold standard, but the efficacy of intranasal spray has been confirmed in multiple randomized controlled studies (39,40).”
BackgroundInfluentialHarding, L., Zhdanava, M., Shah, A., Pesa, J. A., Totev, T. I., Tardif‐Samson, A., Pilon, D., & Joshi, K. (2024) · Current Medical Research and Opinion · doi:10.1080/03007995.2024.2380743 · Cited by 2
Fang, Y., Cao, G., Hu, S., Cheng, J., & Wang, Y. (2024) · Journal of Orthopaedic Surgery and Research · doi:10.1186/s13018-024-05388-2 · 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
Ding, J., Yang, Y., Cao, D., Wang, T., & Yu, Q. (2025) · Journal of obstetrics and gynaecology research · doi:10.1111/jog.16311 · Cited by 2
“16 Esketamine noncompetitively antagonizes NMDA receptors and exerts an inhibitory effect on the opening of their receptor channels, thereby avoiding nociceptive hyperalgesia and the formation of central sensitization.”
Chatterton, M. L., Perez, J. K., Thai, T. T. H., Faller, J., Loo, C. K. A., Glozier, N., Barton, D., Baune, B. T., Mills, N. T., Fitzgerald, P. B., et al. (2025) · Journal of Affective Disorders · doi:10.1016/j.jad.2025.119502 · Cited by 3
Chen, B. K., Jin, M., Turi, G. F., Luna, V. M., Shah, A., Moniz, T., Shannon, M. E., Pauers, M. M., Williams, B. L., Pham, V., et al. (2025) · Biological Psychiatry · doi:10.1016/j.biopsych.2025.09.011 · Cited by 2
Marci, C. D., Joshi, K., Severtson, S. G., Breeze, J. L., & Jha, M. K. (2025) · BMC Psychiatry · doi:10.1186/s12888-025-07485-w · Cited by 2
“Results from several randomized clinical trials (RCTs) and a recent meta-analysis have demonstrated the efficacy of esketamine in patients with TRD reducing depressive symptoms, achieving remission and reducing the risk of relapse [10–13].”
Translational Neuropsychopharmacology for Major Depression: Targeting Neurotransmitter Systems
Kim, H., Kim, Y., & Jeon, H. J. (2022) · Neuromethods · doi:10.1007/978-1-0716-2083-0_15 · Cited by 2
New drugs in psychiatry - cariprazine, lurasidone, esketamine
Pożarowska, K., Rusinek, A., Rudziński, G., Soroka, E., & Masiak, J. (2021) · Current Problems of Psychiatry · doi:10.2478/cpp-2021-0010 · Cited by 2
“However, no clinically relevant effects on the liver or ulcerative cystitis have been observed with esketamine use [32].”
BackgroundInfluentialP.0391 Ultra-resistant major depression: treatment with in-esketamine on compassionate use
de Santiago-Díaz, A. I., Gómez‐Revuelta, M., Sastre-Yañez, J., Gómez-Ruíz, E., & Artal, J. (2021) · European Neuropsychopharmacology · doi:10.1016/j.euroneuro.2021.10.364 · Cited by 2
Intranasal esketamine: A primer
Price, M. Z. (2023) · Current Psychiatry · doi:10.12788/cp.0352 · Cited by 2
Recent advances and challenges in major depressive disorder
Kim, Y. (2021) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2021.110403 · Cited by 2
Fritz, 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
Stahl, S. M. (2020) · Cambridge University Press eBooks · doi:10.1017/9781108921275.024 · 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
Xie, J., Pu, C., & Sun, M. (2026) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2026.1774549 · Cited by 1
Ketamine - precursor of a new generation antidepressant drugs
Zawilska, J. B., & Zwierzyńska, E. (2024) · Farmacja Polska · doi:10.32383/farmpol/186596 · Cited by 1
Gil, T., & Bonetti, T. C. (2024) · Journal of Affective Disorders Reports · doi:10.1016/j.jadr.2024.100809 · Cited by 1
Use of intranasal esketamine in the treatment of treatment-resistant depression: A case report
Jerotić, S., Poleksić, J., Ivković, M., & Latas, M. B. (2024) · Srpski medicinski casopis Lekarske komore · doi:10.5937/smclk5-51004 · Cited by 1
Esketamine-Induced Dissociation: A Case Report
Scarcella, J., MacDaniels, J. S., Coffin, L., & Schwartz, T. L. (2024) · Journal of Psychoactive Drugs · doi:10.1080/02791072.2024.2424283 · Cited by 1
“To a lesser extent, significant transient moderate to severe dissociative phenomena can occur, similar to the events described above with high dose ketamine, requiring caution in its administration (Fedgchin et al. 2019; Ochs-Ross et al. 2020; Popova et al. 2019).”
Progress of Clinical Application of Esketamine in Abdominal Tumor Surgery in Elderly Patients
Xie, J.-X., & Zhou, L.-W. (2025) · Current anesthesiology reports · doi:10.1007/s40140-025-00694-9 · Cited by 1
Zhang, L., Bao, D., & Wang, C. (2025) · Psychiatry Research · doi:10.1016/j.psychres.2025.116490 · Cited by 1
Dormegny-Jeanjean, L. C., Lenoir, S., Humbert, I., Mainberger, O., Lozere, C., Meyer, C., Gény, B., Michel, B., Foucher, J., & de Billy, C. D. C. (2025) · Pharmacopsychiatry · doi:10.1055/a-2590-3469 · Cited by 1
“All 13 patients (median age 56.3 [39.8, 66.5] years) who received intranasal ESK were included in the analysis.”
InfluentialSamalin, L., Boudieu, L., & Llorca, P. (2025) · Neuromethods · doi:10.1007/978-1-0716-4599-4_14 · Cited by 1
Mechanism of antidepressant action of ketamine and differences between its two enantiomers
Zhan, J., Zhang, Y., Tian, H., Zhu, X., Guo, M., Qiu, Z., & Xia, Z. (2025) · Journal of Anesthesia and Translational Medicine · doi:10.1016/j.jatmed.2025.06.001 · Cited by 1
“27–29 A recent clinical trial also demonstrated the acute response to S-keta-mine, with patients showing significant improvement in depressive symptoms 1 day after using S-ketamine nasal spray.”
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
Smith, G., Piatkowski, T. M., Ferris, J., Bonenti, B., Davies, E., Barratt, M. J., Morgan, C. J. A., WINSTOCK, A. R., & Puljević, C. (2025) · Journal of Psychopharmacology · doi:10.1177/02698811251378509 · Cited by 1
“Overall, we found that more respondents experienced positive outcomes from therapeutic ketamine use than negative ones, aligning with existing evidence of ketamine’s efficacy as a rapid-acting antidepressant (Daly et al., 2019; Hopwood et al., 2024; Popova et al., 2019; Reif et al., 2023).”
Fountoulakis, K. Ν., Tatsiopoulou, P., Saitis, A., Fountoulakis, N. K., & Schatzberg, A. F. (2025) · European Child & Adolescent Psychiatry · doi:10.1007/s00787-025-02897-1 · Cited by 2
“Concerning suicidality, it seems that the data are positive at 2–4 h (2/2), equivocal at 24 h (1/4), and negative at week 4 (0/6) [9, 10, 12, 23, 26, 27, 32, 52, 62, 70, 73].”
Antidepressant medications: a comprehensive review of efficacy, safety, and future directions
Shah, N., Parmar, J., Shandilya, S., Parmar, D., & Singhal, P. K. (2025) · International Journal of Community Medicine and Public Health · doi:10.18203/2394-6040.ijcmph20253726 · Cited by 2
Neurobiological mechanisms and recent advances in drug-based therapeutics in depression
Ahmadnia, H., Abdollahzadeh, R., Hatami, H., Masoumi, S., Moezzi, S. M. I., Shahsavari, K., Khanavi, M., Yazarlu, O., Majd, M. T., & Hasanpour, M. (2025) · Neuroscience · doi:10.1016/j.neuroscience.2025.11.002 · Cited by 1
Savica, V., Sīle, L., & Taube, M. (2025) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2025.1666781 · Cited by 1
Sarlon, J., Thomi, D., Brühl, A. B., Liwinski, T., & Lang, U. E. (2026) · Journal of Affective Disorders · doi:10.1016/j.jad.2026.121208 · Cited by 1
Anderson, B., Winokur, A., & Chan, G. (2026) · Psychopharmacology · doi:10.1007/s00213-026-07016-9 · Cited by 2
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
Huc, M., Siddiqi, S., Myers, M., Colman, I., Salmaso, N., Jaworska, N., & Aguilar‐Valles, A. (2026) · Molecular Psychiatry · doi:10.1038/s41380-026-03493-8 · Cited by 3
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
“These concerns align with actual reported side effects in patients from various international studies (35, 40, 41).”
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
“…et al. 2006). among the rapid-acting interventions developed for tRD, intranasal esketamine has emerged as a pharmacological option, with evidence supporting its rapid antidepressant effects when used adjunctively with oral antidepressants (Daly et al. 2018; Kryst et al. 2020; Popova et al. 2019).”
InfluentialEsketamine Nasal Spray: Mechanism of Action, Clinical, and Translational Science
van Hoogdalem, M. W., Fu, D., Drevets, W. C., & Zannikos, P. (2026) · Clinical and Translational Science · doi:10.1111/cts.70527 · Cited by 2
Self-citationAn, J., Li, X., Li, Z., Wang, J., & Pan, Y. (2026) · Journal of Nanobiotechnology · doi:10.1186/s12951-026-04417-y · Cited by 3
Cuomo, A., McIntyre, R. S., Koukouna, D., Pinzi, M., Pardossi, S., Firenzuoli, B., Barillà, G., Carmellini, P., Alamia, A., & Fagiolini, A. M. (2026) · Therapeutic Advances in Psychopharmacology · doi:10.1177/20451253261437597 · Cited by 1
“Results were mixed: TRANSFORM-1 did not achieve statistical significance for the primary endpoint ( p = 0.088 15 ), TRANSFORM-2 demonstrated statistically significant but modest superiority over placebo ( p = 0.020 for 56 mg 16 ), and TRANSFORM-3 showed a non-significant trend ( p = 0.059 17 ).”
InfluentialFigueiredo, I., Bicker, J., Vitorino, C., & Fortuna, A. C. (2026) · Expert Opinion on Drug Delivery · doi:10.1080/17425247.2026.2668677 · Cited by 2
“Dissociation and sedation occurred transiently after administration [13].”
Ketamin und Esketamin bei der therapieresistenten Depression
Schüle, C., Sobieraj, A., & Rogg, H. V. (2026) · Fortschritte der Neurologie · Psychiatrie · doi:10.1055/a-2742-4611 · Cited by 2
“Bei depressiven Patienten mit einer TRD wurden 3 Zulassungs-studien (TRANSFORM 1–3) durchgeführt, wobei nur die Studie TRANSFORM-2 [5] eine signifikante Überlegenheit von intranasalem Esketamin gegenüber dem Placebo-Nasenspray zeigen konnte, während in TRANSFORM-1 [2] und TRANS - FORM-3 [6] zwar…”
Syed, O. A., Sobolenko, V., Nestor, S. M., Husain, M. I., Lipsman, N., Alam, F., & Giacobbe, P. (2026) · CNS Drugs · doi:10.1007/s40263-026-01296-7 · Cited by 1
“The strength of dissociation during treatments, measured by the Clinician-Administered Dissociative States Scale (CADSS), was largely found to have no association with the antidepressant effects [10, 34, 39, 41, 50, 54, 59, 62, 74, 77, 98, 113, 121, 133, 139].”
Inflammation in treatment-resistant depression: From mechanisms to therapeutics
Wu, S., Gao, X., Zhou, Y., Lin, Z., Chen, C. H., Luo, J., Liu, X., Lin, L., 邵红伟, & Liu, S. (2026) · Brain Research Bulletin · doi:10.1016/j.brainresbull.2026.111953 · Cited by 3
Mazzoni, F., Raffone, F., Ciechi, A. D., Girone, N., Macellaro, M., Martinotti, G., Dell’Osso, B. M., Martiadis, V., & Olivola, M. (2026) · Psychiatry Research · doi:10.1016/j.psychres.2026.117288 · Cited by 2
Kršák, M., Sparrow, D., ROSNER, B. A., DeMolles, D. A., & Shannon, S. (2026) · Therapeutic Advances in Psychopharmacology · doi:10.1177/20451253261470523 · Cited by 2
“11,12 Both groups in the study by Lii et al. experienced a significant decrease in their respective depression scales, though they did not diverge, and the effect was lower compared to unmasked ketamine trials.”
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
Esketamine: the first glutamatergic drug for the management of treatment- resistant depression
Musazzi, L. (2020) · doi:10.36118/pharmadvances.03.2020.02 · Cited by 1
[A review of the antidepressant properties of ketamine].
Desfossés, C. Y., & Blier, P. (2021) · Medecine sciences : M/S · doi:10.1051/medsci/2020256 · Cited by 1
Adverse Drug Events on the Use of Sertraline in Clinical Studies: A Review
Hidayat, S., & Puspitasari, I. M. (2021) · JURNAL MANAJEMEN DAN PELAYANAN FARMASI (Journal of Management and Pharmacy Practice) · doi:10.22146/jmpf.56558 · 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
“Assim como o estudo anterior (64), a pontuação total de MADRS diminuiu significativamente nos primeiros 28 dias de tratamento com antidepressivos orais associados a escetamina 56 mg (19,0 ± 13,86) e escetamina 84 mg (18,8 ± 14,12) em comparação ao grupo placebo associado a antidepressivo (14,8 ± 15,07).”
InfluentialEsketamine for treatment-resistant depression in adults
Gastaldon, C., Laurenzi, P. F., Schoretsanitis, G., Papola, D., Cristea, I. A., Naudet, F., Ostuzzi, G., & Barbui, C. (2022) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd015071 · Cited by 1
Depression management and pharmacoepigenetics
Walker, S. A., Su, A., & Kamath, J. (2022) · Elsevier eBooks · doi:10.1016/b978-0-12-823039-8.00002-2 · Cited by 1
“Drugs of Abuse” as “New Antidepressants”: - Medical and Philosophical Considerations in Treatment
Park, S.-Y., An, Y., & Kang, U. G. (2022) · 신경정신의학 · doi:10.4306/jknpa.2022.61.4.254 · Cited by 1
Anzolin, A. P., Cordova, V. H. S., Goularte, J. F., Belmonte-de-Abreu, P. S., Ceresér, K. M. M., Lacerda, A. L. T., & Kauer‐Sant’Anna, M. (2022) · Psychiatry Research Case Reports · doi:10.1016/j.psycr.2022.100097 · Cited by 1
A Pain Physician and Anesthesiologist’s Perspective on Ketamine for Treatment-Resistant Depression
Gatewood, L. E., Gorlin, A. W., Bailey, C. H., Barsoum, G., & Porter, S. B. (2023) · SN Comprehensive Clinical Medicine · doi:10.1007/s42399-023-01439-7 · Cited by 1
“…have since demonstrated the short-term efficacy of ketamine for people with treatment-refractory unipolar or bipolar major depression who have failed to respond to multiple therapeutic trials of traditional antidepressants, mood sta-bilizers, and even electroconvulsive therapy in some cases [5–7].”
Pereira, M. S., Anzolin, A. P., Londero, M. D. B., Zegarra, N. R. M., Pranke, M. A., & Cruz, L. N. (2023) · Psychiatry Research Case Reports · doi:10.1016/j.psycr.2023.100116 · Cited by 1
Cetkovich, M., Abadi, A. F., Camino, S., Bonetto, G. G., Herbst, L., Marengo, E., Torrente, F. M., Maresca, T., Bustin, J., Morra, C. A., et al. (2023) · Vertex Revista Argentina de Psiquiatría · doi:10.53680/vertex.v34i161.488 · Cited by 1
“Sin embargo, en los cuatro ensayos que sustentan su aprobación, padecer TB ha sido utilizado como criterio de exclusión (Popova et al., 2019; Daly et al., 2019; Fu et al., 2020; Ionescu et al., 2021).”
BackgroundXu, J., Jian, J., Zhang, Y., Wu, J., & Qiu, Y. (2024) · Frontiers in Medicine · doi:10.3389/fmed.2024.1344160 · Cited by 1
Schüle, C., Koller, G., & Herwig, U. (2024) · Nervenheilkunde · doi:10.1055/a-2309-6457 · Cited by 1
García, J. M., Lasala, M. T. P., Trancón, M. B., Mellado, R. J. L., Caballero, A. J. U., Villalobos, R. F., & Baca, J. E. R. (2024) · Psiquiatría Biológica · doi:10.1016/j.psiq.2024.100547 · Cited by 1
Zhu, M., Lv, S., Zhu, F., & Zhang, Y. (2025) · Journal of Clinical Psychopharmacology · doi:10.1097/jcp.0000000000001966 · Cited by 1
Zhang, Y., Zhou, Q., Chen, R., et al. (2025) · Scientific Reports · doi:10.1038/s41598-025-03297-w · Cited by 1
“As reported in adult patients with treatment-resistant depression, blood pressure increase began shortly after eskeatmine administration, peaked at around 40 min with 1.1 to 1.5 times of baseline and resolved at approximately 2 h 24,25 .”
InfluentialVinarcsik, L., Smoller, C., & Grossberg, G. T. (2025) · Drugs & Aging · doi:10.1007/s40266-025-01221-5 · Cited by 1
“To treat older adults, the APA Clinical Practice Guidelines recommend three kinds of psycho-therapy (Group Cognitive-Behavioral Therapy and Group Life-Review/Reminiscence Therapy) in addition to medications (specifically second-generation antidepressants such as SSRIs, SNRIs, or NDRIs) [20, 21].”
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
Fairness and Protection for the Vulnerable: Lessons from Esketamine
Malhi, G. S., & Savulescu, J. (2020) · The American Journal of Bioethics · doi:10.1080/15265161.2020.1795537 · Cited by 1
Ketamina eta esketaminaren erabilera depresioerresistentea tratatzeko: etorkizunerako erronkak
Elexpe, A., Bruzos-Cidón, C., Cabrera, M., Barreda‐Gómez, G., & Torrecilla, M. (2020) · EKAIA Euskal Herriko Unibertsitateko Zientzi eta Teknologi Aldizkaria · doi:10.1387/ekaia.21862
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
Novel Antidepressant Approaches for Refractory Depression
Postorivo, D., & Tye, S. J. (2021) · Current Treatment Options in Psychiatry · doi:10.1007/s40501-021-00246-y · Cited by 1
Ketamine and Other Glutamate Receptor Antagonists As Fast-Actin
Chen, M., Su, T., & Tsai, S. (2022) · Neuromethods · doi:10.1007/978-1-0716-2083-0_19 · Cited by 1
Fava, V. A. R., Sarin, L. M., Lucchese, A. C., et al. (2021) · Revista de Psiquiatría y Salud Mental (English Edition) · doi:10.1016/j.rpsmen.2021.11.003 · Cited by 1
Marcatili, M., Borgonovo, R., Cimminiello, N., Cornaggia, R. D., Casati, G., Pellicioli, C., Maggioni, L., Motta, F. L., Chiara, R., Ledda, L., et al. (2022) · Journal of Personalized Medicine · doi:10.3390/jpm12091524 · Cited by 1
Ketamine in Psychiatric Disorders
Danyeli, L. V., Götting, F. N., Şen, Z. D., Li, M., & Walter, M. (2022) · Springer eBooks · doi:10.1007/978-3-030-62059-2_420 · Cited by 1
Ketamines for Treatment Resistant Depression in Patients with Chronic Pain and Opioid Use
Hart, M., & Cernovsky, Z. Z. (2019) · Archives of Psychiatry and Behavioral Sciences · doi:10.22259/2638-5201.0202008 · Cited by 1
Stahl, S. M. (2020) · Cambridge University Press eBooks · doi:10.1017/9781108921275.083 · Cited by 1
Depression and Anxiety Disorders
(2021) · Wiley eBooks · doi:10.1002/9781119870203.mpg003 · Cited by 1
Stahl, S. M. (2020) · Cambridge University Press eBooks · doi:10.1017/9781108921275.018 · Cited by 1
Stahl, S. M. (2020) · Cambridge University Press eBooks · doi:10.1017/9781108921275.032 · Cited by 1
Stahl, S. M. (2020) · Cambridge University Press eBooks · doi:10.1017/9781108921275.017 · Cited by 2
Stahl, S. M. (2020) · Cambridge University Press eBooks · doi:10.1017/9781108921275.086 · Cited by 1
Stahl, S. M. (2020) · Cambridge University Press eBooks · doi:10.1017/9781108921275.046 · Cited by 1
Stahl, S. M. (2020) · Cambridge University Press eBooks · doi:10.1017/9781108921275.055 · Cited by 1
Stahl, S. M. (2020) · Cambridge University Press eBooks · doi:10.1017/9781108921275.071 · 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
Plöderl, M., Cooper, R. E., Walker, T., Shah, V., Horowitz, M. A., Volkmann, C., & Moncrieff, J. (2025) · medRxiv · doi:10.1101/2025.08.19.25333796 · Cited by 1
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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