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Cited by 143Treatment of Major DepressionAnxiety, Depression, Psychometrics, Treatment, Cognitive ProcessesElectroconvulsive Therapy Studies

Ketamine for Social Anxiety Disorder: A Randomized, Placebo-Controlled Crossover Trial

Open access
Taylor, Jerome H, Landeros-Weisenberger, Angeli, Coughlin, Catherine, Mulqueen, Jilian, Johnson, Jessica A, Gabriel, Daniel, Reed, Margot O, Jakubovski, Ewgeni +1 more·2018·Neuropsychopharmacology
DOI 10.1038/npp.2017.194PMC PMC5729569
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Abstract

Many patients with social anxiety disorder (SAD) experience inadequate symptom relief from available treatments. Ketamine is a potent N-methyl-D-aspartate receptor antagonist with a potentially novel mechanism of action for the treatment of anxiety disorders. Therefore, we conducted a double-blind, randomized, placebo-controlled crossover trial in 18 adults with DSM-5 SAD and compared the effects between intravenous ketamine (0.5 mg/kg over 40 min) and placebo (normal saline) on social phobia symptoms. Ketamine and placebo infusions were administered in a random order with a 28-day washout period between infusions. Ratings of anxiety were assessed 3-h post-infusion and followed for 14 days. We used linear mixed models to assess the impact of ketamine and placebo on anxiety symptoms. Outcomes were blinded ratings on the Liebowitz Social Anxiety Scale (LSAS) and self-reported anxiety on a visual analog scale (VAS-Anxiety). We also used the Wilcoxon signed-rank test to compare the proportion of treatment responders. Based on prior studies, we defined response as a greater than 35% LSAS reduction and 50% VAS-Anxiety reduction. We found ketamine resulted in a significantly greater reduction in anxiety relative to placebo on the LSAS (Time × Treatment: F 9,115 =2.6, p=0.01) but not the VAS-Anxiety (Time × Treatment: F 10,141 =0.4, p=0.95). Participants were significantly more likely to exhibit a treatment response after ketamine infusion relative to placebo in the first 2 weeks fol…

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Crossref · 10.1038/npp.2017.194

Cites

58 of 58 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

18 of 46 cited sources checked · 9 supported · 0 flagged · accuracy not yet measured

  • Premisecitation

    Roughly one-third to one-half of patients with SAD do not experience significant clinical benefit from current evidence-based treatment for SAD such as pharmacotherapy with SSRIs or venlafaxine and CBT.

    “Roughly one-third to one-half of patients with SAD do not experience significant clinical benefit from current evidence-based treatment for SAD such as pharmacotherapy with selective serotonin reuptake inhibitors (SSRI) or venlafaxine and cognitive behavioral therapy (CBT) (Kelly et al, 2014;Roy-Byrne et al, 2010;Taylor et al, 2015;Taylor et al, 2017b).”
    Quote in the paperSubstantial claim1 of 3 sources checked
    • cites Kelly et al, 2014 source
    • cites Roy-Byrne et al, 2010 source
    • cites Taylor et al, 2015 source

      The Methods report that CALM offered CBT and/or pharmacotherapy, including SSRIs, and that 36% of participants with anxiety disorders met the remission criterion at six months. The Discussion includes SAD among those disorders, but neither passage establishes that one-third to one-half of patients with SAD failed to obtain significant clinical benefit from SSRIs, venlafaxine, or CBT. Nonremission across the mixed-disorder sample is not the same measure or population as the claimed SAD-specific lack of benefit. (LLM, conf=0.83)

      Experimental — accuracy not yet measured
  • Premisecitation

    Converging lines of evidence from neuroimaging and pharmacological studies support the importance of glutamate abnormalities in the pathogenesis of SAD.

    “Converging lines of evidence from neuroimaging and pharmacological studies support the importance of glutamate abnormalities in the pathogenesis of SAD (Freitas-Ferrari et al, 2010).”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites Freitas-Ferrari et al, 2010 source
  • Study design and conductcitation

    A power analysis based on ketamine's antidepressant effects was used to determine the sample size of 18.

    “A power analysis based on ketamine's antidepressant effects was used to determine the sample size of 18 (Murrough et al, 2013a;Zarate et al, 2006).”
    Quote in the paperNot a substantial claim2 of 2 sources checked
    • cites Murrough et al, 2013a source

      The Statistical Analysis section says the authors used estimated ketamine effects to calculate statistical power, but their planned study group was 72 patients, not 18. The source supports the use of a power analysis, not the attributed sample size. (LLM, conf=0.91)

      Experimental — accuracy not yet measured
    • cites Zarate et al, 2006 source

      The Efficacy and Comment sections report ketamine’s antidepressant effects, including effect sizes, which could inform a later power analysis. But this paper does not report a power analysis determining a sample size of 18; Patient Selection says its own study initially planned to include 22 patients and describes an interim analysis. (LLM, conf=0.86)

      Experimental — accuracy not yet measured
  • Premisecitation

    Several clinical studies suggest that ketamine may also have significant anxiolytic effects.

    “Several clinical studies suggest that ketamine may also have significant anxiolytic effects.”
    Quote in the paperSubstantial claim1 of 2 sources checked
    • cites Salvadore et al, 2009 source
    • cites Zarate et al, 2006 source
  • Interpretationreasoning

    The lack of efficacy in this trial is likely due to the fact that most patients had mild to moderate depression as opposed to the more severe treatment-resistant major depression studied in ketamine clinical trials.

    “The lack of efficacy in our trial is likely due the fact that in our study most patients had mild to moderate depression as opposed to the more severe treatment-resistant major depression studied in ketamine clinical trials (Murrough et al, 2013a;Murrough et al, 2013b;Zarate et al, 2006).”
    Quote in the paperSubstantial claim3 of 3 sources checked
    • cites Murrough et al, 2013a source
    • cites Murrough et al, 2013b source
    • cites Zarate et al, 2006 source
  • Classified as probably not a substantial claim. 19
  • May combine two claims. 19

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    Ketamine's antidepressant effects peak 1 day following infusion and typically dissipate 1-2 weeks after a single infusion.

    “Ketamine's antidepressant effects peak 1 day following infusion and typically dissipate 1-2 weeks after a single infusion (Kishimoto et al, 2016).”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites Kishimoto et al, 2016 source

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Ketamine's antidepressant effect is observed long after ketamine has been metabolized and excreted from the body and after ketamine's sedative and dissociative effects have dissipated.

    “Ketamine's antidepressant effect is observed long after ketamine has been metabolized and excreted from the body and after ketamine's sedative and dissociative effects have dissipated (Krystal et al, 2013).”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites Krystal et al, 2013 source

      In “NMDA receptor antagonists as rapid-acting antidepressants” (page unavailable), the paper says antidepressant effects emerge after ketamine’s psychotigenic and euphoric effects disappear and may last days or longer. It does not establish that ketamine has been metabolized and excreted by then, or specifically discuss the dissipation of sedative effects. (LLM, conf=0.86)

      Experimental — accuracy not yet measured

  • May combine two claims.

    Premisecitation

    Ketamine's anxiolytic effects have been supported by placebo-controlled trials which demonstrated that the psychic anxiety item on the 21-item HAM-D significantly improved after ketamine infusion compared to saline; the psychic anxiety item was one of only four items to improve.

    “Ketamine's anxiolytic effects have also been supported by placebo-controlled trials which demonstrated that the psychic anxiety item on the 21item HAM-D significantly improved after ketamine infusion (compared to saline); the psychic anxiety item was one of only four items to improve (Zarate et al, 2006).”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites Zarate et al, 2006 source

      Split into 2 atoms — 0 confirmed, 2 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.

      Experimental — accuracy not yet measured

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    In controlled clinical studies ketamine has produced a rapid antidepressant effect in unipolar and bipolar depression.

    “In controlled clinical studies ketamine has produced a rapid antidepressant effect in unipolar and bipolar depression (Abdallah et al, 2016;Berman et al, 2000;Carreno et al, 2015;Dwyer et al, 2017;Krystal et al, 2013;Maeng and Zarate, 2007;Milak et al, 2015;Murrough et al, 2013a;Murrough et al, 2013b;Niciu et al, 2014;Sanacora et al, 2016;Valentine et al, 2011;Zarate et al, 2006).”
    Quote in the paperNot a substantial claim1 of 3 sources checked
    • cites Abdallah et al, 2016 source

      The Introduction reports rapid antidepressant effects in treatment-resistant major depressive disorder (unipolar depression), with peak response rates within 24 hours. The Results also report reduced depression severity after ketamine, but this paper does not report a controlled comparison in its own study or ketamine outcomes in bipolar depression. No page numbers are available in our copy. (LLM, conf=0.87)

      Experimental — accuracy not yet measured
    • cites Berman et al, 2000 source
    • cites Carreno et al, 2015 source

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Several ketamine-like glutamate modulators, including AXS-05 and esketamine, are under investigation by pharmaceutical companies and in Clinical Trial phases II and III for depression.

    “Several ketamine-like glutamate modulators, including AXS-05 and esketamine, are under investigation by pharmaceutical companies and in Clinical Trial phases II and III for depression (Liu et al, 2016;Murrough, 2016).”
    Quote in the paperNot a substantial claim1 of 2 sources checked
    • cites Liu et al, 2016 source

      The Introduction (page unavailable) describes GLYX-13 as a glutamatergic compound with preliminary evidence of antidepressant effects in patients, and the Funding section identifies support from Naurex. This supports the general point that a ketamine-related glutamate modulator was being investigated for depression. The paper does not identify AXS-05 or esketamine or establish phase II or III trial status for them. (LLM, conf=0.82)

      Experimental — accuracy not yet measured
    • cites Murrough, 2016 source

  • Classified as probably not a substantial claim.

    Premisecitation

    Increased exposure to social activities is a treatment for SAD (e.g., CBT).

    “Increased exposure to social activities is a treatment for SAD (eg CBT) (Peris et al, 2015;Roy-Byrne et al, 2010;Taylor et al, 2015;Taylor et al, 2017b)”
    Quote in the paperSubstantial claim2 of 3 sources checked
    • cites Peris et al, 2015 source

      The Discussion reports that exposure tasks are central to CBT and were followed by faster improvement in youth anxiety symptoms and impairment. The Methods (Participants) include youth with social phobia, but the paper does not specifically evaluate increased social activities as a treatment for social anxiety disorder; its exposure findings concern a mixed youth anxiety sample. (LLM, conf=0.85)

      Experimental — accuracy not yet measured
    • cites Roy-Byrne et al, 2010 source
    • cites Taylor et al, 2015 source

      The Methods (page not provided) say that patients with anxiety disorders, including SAD, could receive CBT as part of collaborative care. The paper does not describe increased exposure to social activities as a treatment component, so it supports the CBT example but not the specific exposure claim. (LLM, conf=0.84)

      Experimental — accuracy not yet measured

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Ketamine has anxiolytic effects in patients with major depression.

    “The results of the study are consistent with previous work suggesting that ketamine has anxiolytic effects in patients with major depression (Salvadore et al, 2009;Zarate et al, 2006).”
    Quote in the paperNot a substantial claim1 of 2 sources checked
    • cites Salvadore et al, 2009 source
    • cites Zarate et al, 2006 source

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Prior work has found that ketamine reduced OCD symptoms.

    “Prior work has also found that ketamine reduced OCD symptoms (Bloch et al, 2012;Rodriguez et al, 2013).”
    Quote in the paperNot a substantial claim1 of 2 sources checked
    • cites Bloch et al, 2012 source
    • cites Rodriguez et al, 2013 source

  • May combine two claims.

    Findingown data

    Ketamine was safe and generally well tolerated by all subjects, and all ketamine infusions were completed.

    “Ketamine was safe and generally well tolerated by all subjects, and all ketamine infusions were completed.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Sixteen of 18 (88.89%) subjects experienced a treatment response as indicated by a greater than 50% reduction on the VAS after ketamine infusion compared to 9 of 17 (52.94%) subjects receiving placebo.

    “Sixteen of 18 (88.89%)subjects experienced a treatment response as indicated by a greater than 50% reduction on the VAS after ketamine infusion compared to 9 of 17 (52.94%)subjects receiving placebo.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: Blinding of participants and raters was maintained despite ketamine's dissociative side effects.

  • May combine two claims.

    Findingown data

    LSAS measures demonstrated significant carryover effects 28 days following infusion with an effect size = 0.93 at 14 days.

    “The LSAS measures demonstrated significant carryover effects 28 days following infusion with an effect size = 0.93 at 14 days.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    There were no significant differences in reducing depressive symptoms when results were examined in both phases of the crossover trial (Time: F 8,56.9 = 2.0, p = 0.07, Treatment: F 1,12.4 = 1.5, p = 0.24 and Time × Treatment: F 8,56.9 = 1.0, p = 0.49) or restricted to phase 1 (Time: F 8,56.9 = 2.0, p = 0.07 and Time × Treatment: F 9,54.6 = 0.9, p = 0.52).

    “There were no significant differences in reducing depressive symptoms when results were examined in both phases of the crossover trial (Time: F 8,56.9 = 2.0, p = 0.07, Treatment: F 1,12.4 = 1.5, p = 0.24 and Time × Treatment: F 8,56.9 = 1.0, p = 0.49) or restricted to phase 1 (Time: F 8,56.9 = 2.0, p = 0.07 and Time × Treatment: F 9,54.6 = 0.9, p = 0.52).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Ketamine demonstrated a significantly greater number of treatment responders as assessed by both LSAS and VAS ratings.

    “Ketamine also demonstrated significantly greater number of treatment responders as assessed by both LSAS and VAS ratings.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    The most common side effects of ketamine were paresthesias and numbness (n = 9), feeling disconnected from reality (n = 7), vision changes (n = 6), feeling confused/difficulties thinking (n = 6), dizziness (n = 6), distorted sense of time (n = 4), tachycardia >100 beats per minute (n = 4, max heart rate 120), diastolic hypertension >90 mm Hg (n = 3, max diastolic blood pressure 106), bouts of laug

    “The most common side effects of ketamine were paresthesias and numbness (n = 9), feeling disconnected from reality (n = 7), vision changes (n = 6), feeling confused/difficulties thinking (n = 6), dizziness (n = 6), distorted sense of time (n = 4), tachycardia 4100 beats per minute (n = 4, max heart rate 120), diastolic hypertension 490 mm Hg (n = 3, max diastolic blood pressure 106), bouts of laug”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Ketamine demonstrated significantly greater dissociative side effects compared to placebo on the CADSS (Time: F 4,131 = 19.5, po0.001, Treatment: F 1,73 = 6.3, p = 0.01 and Time × Treatment: F 4,131 = 13.1, po0.01) that peaked during infusion (1 h: difference = 7.25 ± 0.70, ES = 2.53, F = 56.1, po0.001) and dissipated within 2 h following infusion (2 h: difference = 0.02 ± 0.70, ES = 0, F = 0, p =

    “Ketamine demonstrated significantly greater dissociative side effects compared to placebo on the CADSS (Time: F 4,131 = 19.5, po0.001,Treatment: F 1,73 = 6.3, p = 0.01 and Time × Treatment: F 4,131 = 13.1, po0.01) that peaked during infusion (1 h: difference = 7.25 ± 0.70, ES = 2.53, F = 56.1,po0.001) and dissipated within 2 h following infusion (2 h: difference = 0.02 ± 0.70, ES = 0, F = 0, p = 0”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim.

    Study design and conductown data

    The trial was randomized.

    “Ketamine and placebo infusions were administered in a random order with a 28-day washout period between infusions.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Study design and conductnone given

    Randomization was conducted by the Yale Investigational Drug Service and kept separate from any other investigators involved in the trial.

    “Randomization was conducted by the Yale Investigational Drug Service and kept separate from any other investigators involved in the trial.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Randomized, placebo-controlled trials also suggest the possible benefit of ketamine for treating symptoms of obsessive-compulsive disorder and post-traumatic stress disorder.

    “Randomized, placebo-controlled trials also suggest the possible benefit of ketamine for treating symptoms of obsessive-compulsive disorder (OCD) and post-traumatic stress disorder (Feder et al, 2014;Rodriguez et al, 2013).”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites Feder et al, 2014 source
    • cites Rodriguez et al, 2013 source

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Ketamine is a potent antagonist of the N-methyl-D-aspartate receptor, a major type of glutamate receptor in the brain.

    “Ketamine is a potent antagonist of the N-methyl-Daspartate receptor, a major type of glutamate receptor in the brain (Gould et al, 2017).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Gould et al, 2017 source

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Elevated thalamic glutamine levels have been documented in patients with SAD.

    “Others have documented elevated thalamic glutamine levels in patients with SAD (Pollack et al, 2008).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Pollack et al, 2008 source

  • Classified as probably not a substantial claim.

    Study design and conductreasoning

    Participants were instructed to not discuss any aspects of the infusion with blinded raters in order to avoid inadvertent unblinding.

    “Also, participants were instructed to not discuss any aspects of the infusion with blinded raters in order to avoid inadvertent unblinding by the patient discussing dissociative symptoms that frequently occurred during ketamine infusions.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Study design and conductnone given

    Blinded raters were not present for the 3 h following infusions and conducted assessments at a site different from the clinical unit where the infusion took place.

    “Blinded raters were not present for the 3 h following infusions and conducted assessments at a site different from the clinical unit where the infusion took place.”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim. May combine two claims.

    Study design and conductnone given

    Ketamine and placebo infusions were administered in a random order with a 28-day washout period between infusions.

    “Ketamine and placebo infusions were administered in a random order with a 28-day washout period between infusions.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    Multiple controlled clinical studies indicate that ketamine effectively reduces symptoms of depression and is particularly effective in anxious depression.

    “In addition to these dissociative properties, multiple controlled clinical studies indicate that ketamine effectively reduces symptoms of depression and is particularly effective in anxious depression (Ionescu et al, 2014).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Ionescu et al, 2014 source

  • May combine two claims.

    Study design and conductcitation

    The LSAS, VAS, and STAI-S have demonstrated reliability and validity.

    “The LSAS (Heimberg et al, 1999;Mennin et al, 2002), VAS (Cella and Perry, 1986;Davey et al, 2007;Williams et al, 2010), and STAI-S (Spielberger, 1983) have demonstrated reliability and validity.”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites Heimberg et al, 1999 source
    • cites Mennin et al, 2002 source
    • cites Cella and Perry, 1986 source

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    A 2017 study of 12 adults with generalized anxiety disorder and/or social anxiety found ketamine reduced anxiety symptoms.

    “Furthermore, a 2017 study of 12 adults with generalized anxiety disorder and/or social anxiety found ketamine reduced anxiety symptoms; however, the study was open label and there was no placebo control (Glue et al, 2017).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Glue et al, 2017 source

  • May combine two claims.

    Study design and conductown data

    This is a small, proof-of-concept study that did not show significant benefit on all outcome measures.

    “this is a small, proof-ofconcept study that did not show significant benefit on all outcome measures”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    The 2017 study of 12 adults with generalized anxiety disorder and/or social anxiety was open label and had no placebo control.

    “Furthermore, a 2017 study of 12 adults with generalized anxiety disorder and/or social anxiety found ketamine reduced anxiety symptoms; however, the study was open label and there was no placebo control (Glue et al, 2017).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Glue et al, 2017 source

  • Probably not a substantial claim: may not pass S2 (checkable). May combine two claims.

    Interpretationown data

    Ketamine-like compounds may also be effective in SAD and could be investigated for other anxiety disorders.

    “Our findings suggest ketamine-like compounds may also be effective in SAD and could be investigated for other anxiety disorders.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Rodriguez et al, 2013 found post-infusion ratings were lower 1 week post-infusion on the Yale-Brown Obsessive Compulsive Scale (YBOCS).

    “For example, Rodriguez et al, 2013 found post-infusion ratings were lower 1 week post-infusion on the Yale-Brown Obsessive Compulsive Scale (YBOCS) (Rodriguez et al, 2013).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Rodriguez et al, 2013 source

  • May combine two claims.

    Interpretationreasoning

    This functional unblinding may affect self-report measures (e.g., VAS) as well as lead to possible reporting bias even on ratings conducted by blinded raters (e.g., LSAS, HDRS-17).

    “This functional unblinding may affect self-report measures (eg VAS) as well as lead to possible reporting bias even on ratings conducted by blinded raters (eg LSAS, HDRS-17).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationreasoning

    A midazolam-controlled trial would not fully eliminate the issue of functional unblinding with ketamine but may reduce the issue somewhat.

    “A midazolam-controlled trial would not fully eliminate the issue of functional unblinding with ketamine but may reduce the issue somewhat.”
    Quote in the paperSubstantial claim
32 of 32

  • The paper relies on this without support.

    The modification of the LSAS to ask about symptoms since the previous assessment does not invalidate its use as a measure of social anxiety.

    “LSAS typically assesses symptoms during the prior week; however, the scale was modified so that participants were asked about their symptoms during the time since previous assessment.”

  • The paper relies on this without support.

    Blinding of participants and raters was maintained despite ketamine's dissociative side effects.

    “Also, participants were instructed to not discuss any aspects of the infusion with blinded raters in order to avoid inadvertent unblinding by the patient discussing dissociative symptoms that frequently occurred during ketamine infusions.”

  • The paper relies on this without support.

    Inadequate anxiety relief in patients with SAD is a source of substantial morbidity, distress, and decreases in quality of life.

    “Inadequate anxiety relief in patients with SAD is a source of substantial morbidity, distress, and decreases in quality of life.”

  • The paper relies on this without support.

    This is the first placebo-controlled study to investigate ketamine's efficacy in patients with a DSM-5 anxiety disorder.

    “To our knowledge, this is the first placebo-controlled study to investigate ketamine's efficacy in patients with a DSM-5 anxiety disorder.”
4 of 4

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?

  • In a randomized, placebo-controlled, crossover trial of 18 people with social anxiety disorder, ketamine effectively decreased anxiety ratings within three hours.

    “one randomized, placebo-controlled, crossover trial (n = 18) found that ketamine effectively decreased ratings of anxiety within three hours”

    From Ketamine in neuropsychiatric disorders: an update (2024) · cites this paper as [98]

    The Abstract describes a randomized, placebo-controlled crossover trial in 18 adults with social anxiety disorder and reports a greater overall reduction in clinician-rated anxiety with ketamine. But the Results report significant LSAS differences at 2, 5 and 10 days, not at the 3-hour assessment; the Self-Reported Ratings of Anxiety section says VAS anxiety ratings showed no significant benefit over placebo at any time point. The claim therefore overstates how soon the trial demonstrated an effect. (LLM, conf=0.88)

    Experimental — accuracy not yet measured

  • That effect was maintained for up to two days postinfusion.

    “an effect that was maintained for up to two days postinfusion [98]”

    From Ketamine in neuropsychiatric disorders: an update (2024) · cites this paper as [98]

  • Ketamine was shown to reduce anxiety symptoms in adults with treatment-refractory GAD and with SAD, with reported increased social engagement on subsequent days.

    “Ketamine was also shown to reduce anxiety symptoms in adults with treatment-refractory GAD (Glue et al., 2017) and with SAD, with reported increased social engagement on subsequent days (Taylor et al., 2018).”

    From Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders (2019) · cites this paper as Taylor et al., 2018

Statistics recomputed

Every reported test result, recomputed from its test statistic and degrees of freedom. A result shows as not adding up only once an independent check has confirmed it.

  • Consistentz = 2.24reported p = .025 · recomputed p = .025

    “z = 2.24, p = .025”

  • Consistentz = 2.12reported p = .034 · recomputed p = .034

    “z = 2.12, p = .034”

2 of 2

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

  • Overall baseline VAS mean does not match the two infusion-order groups

    Minor

    The two groups each contain nine participants, so their reported VAS-Anxiety means imply an overall mean of 52.50, not 50.00.

    Reported 50 · recomputed 52.5

1 of 1

Cites

Flagged first, then by citations

Research works printed but not linked: 2

  1. Aitken RC (1969). Measurement of feelings using visual analogue scales. Proc R Soc Med 62: 989.
  2. Taylor JH, Lebowitz ER, Silverman WK . Anxiety Disorders. In A. Martin, M.H. Bloch, F.R. Volkmar (eds.), Lewis’s child and adolescent psychiatry: A comprehensive textbook. 5th edition. Wolters Kluwer: Philadelphia, PA, 2017a, pp. 509–518..

Cited by

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Related

Authors
Taylor, J. H., Landeros-Weisenberger, A., Coughlin, C., Mulqueen, J., Johnson, J. A., Gabriel, D., Reed, M. O., Jakubovski, E., & Bloch, M. H.
Affiliations
Yale University (US)
Corresponding author
Taylor, Jerome H
ORCID
Venue
Neuropsychopharmacology
Publisher
Springer Science and Business Media LLC
Published
2017-08-29
Volume
43
Issue
2
Pages
325-333
ISSN
  • 0893-133X (ISSN-L)
  • 1740-634X
DOI
10.1038/npp.2017.194
PMC
PMC5729569
OpenAlex
W2752700145
Semantic Scholar
478a5261ae9b2bac8155c1e47216f6d3b3fa5e5e
Cited by
142
References
57
Citations by year
2026: 8 · 2025: 23 · 2024: 13 · 2023: 12 · 2022: 21 · 2021: 27 · 2020: 18 · 2019: 9 · 2018: 9 · 2017: 2
FWCI
7.26
Type
journal article
Language
en
Open access
Licence
www.springer.com/tdm (tdm)
Locations
  • Neuropsychopharmacology (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • Robert E. Leet and Clara Guthrie Patterson Trust
  • National Alliance for Research on Schizophrenia and Depression
  • National Institutes of Health (UL1TR001863)
  • National Institute of Mental Health (K23MH091240, T32MH019112, R25MH077823, T32MH019961, T32MH018268)
  • National Center for Advancing Translational Sciences
Topics
  • Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
  • Social Sciences › Psychology › Experimental and Cognitive Psychology › Anxiety, Depression, Psychometrics, Treatment, Cognitive Processes
  • Health Sciences › Medicine › Psychiatry and Mental health › Electroconvulsive Therapy Studies
Keywords
ketamine, social anxiety disorder, NMDA receptor antagonists, intravenous infusion, anxiety symptoms, treatment response, Liebowitz Social Anxiety Scale
MeSH terms
Phobia, Social, Adult, Double-Blind Method, Female, Humans, Ketamine, Male, Psychiatric Status Rating Scales, Anti-Anxiety Agents, Receptors, N-Methyl-D-Aspartate, Outcome Assessment, Health Care, Cross-Over Studies, Excitatory Amino Acid Antagonists, Young Adult

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Claims read by deepseek-v4.1-flash under definition version 3 (extract-v3) on 2026-10-11.

Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-10-11.

Cited sources are checked by gpt-6-sol.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

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