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Cited by 212Posttraumatic Stress Disorder ResearchMemory and Neural MechanismsPsychotherapy Techniques and Applications

D-cycloserine augmentation of exposure therapy for post-traumatic stress disorder: a pilot randomized clinical trial

Open access
Difede, JoAnn, Cukor, Judith, Wyka, Katarzyna, Olden, Megan, Hoffman, Hunter, Lee, Francis S, Altemus, Margaret·2014·Neuropsychopharmacology
DOI 10.1038/npp.2013.317PMC PMC3957110
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Abstract

Viewing post-traumatic stress disorder (PTSD) as a disorder of emotional learning, this study used a cognitive enhancer synergistically with virtual reality exposure (VRE) therapy for the treatment of PTSD. The main objective was to determine if a novel pharmacotherapy, D-cycloserine (DCS), enhanced the efficacy of the psychotherapy. Pre-clinical studies suggest that when fear extinction occurs during DCS administration, neuroplasticity may be enhanced. VRE therapy is a particularly promising format to test the hypothesis that DCS enhances extinction learning, as sensory fear cues are standardized across patients. In a pilot randomized, double-blind, placebo-controlled trial, 100 mg of DCS or placebo was administered 90 min before each weekly VRE session, to ensure peak plasma concentrations during the sessions in 25 patients with chronic PTSD. The primary outcome measure was the Clinician Administered PTSD Scale (CAPS). Secondary outcome measures included the Beck Depression Inventory-II and the State-Trait Anger Expression Inventory-2. Assessments occurred at pre-treatment, following sessions 3, 6, 10, post-treatment, and at 6 months. The difference in CAPS between the VRE-DCS (n=13) and VRE-placebo (n=12) groups increased over time beginning at 6 weeks, with medium to large between-group effect sizes immediately post-treatment and 6 months later (d=0.68 and d=1.13, respectively). A similar pattern was observed for depression, anger expression, and sleep. PTSD remission rates were significantly greater for the VRE-DCS group (46% vs 8% at post-treatment; 69% vs 17% at 6 months). Patients in the VRE-DCS group showed earlier and greater improvement in PTSD symptoms compared with the VRE-placebo group. These results suggest a promising new treatment for PTSD.

AI snapshot

Written from the paper’s full text.

TL;DR

In a pilot randomized, double-blind, placebo-controlled trial, 100 mg D-cycloserine (DCS) given 90 min before weekly virtual reality exposure (VRE) therapy produced earlier and greater PTSD symptom improvement than placebo in 25 patients with chronic WTC-related PTSD. Between-group differences were significant at 6-month follow-up, with higher remission rates in the VRE-DCS group.

Key findings

  • CAPS difference scores favored VRE-DCS over VRE-placebo, with a medium effect at post-treatment (Hodges g=0.68, p=0.131) and a significant large effect at 6 months (Hodges g=1.13, p=0.010).
  • PTSD remission was significantly greater for VRE-DCS: 46% vs 8% at post-treatment and 69% vs 17% at 6 months.
  • Secondary outcomes also favored VRE-DCS, including significant 6-month differences for depression (BDI-II, p<0.001), anger expression (STAXI-2, p=0.009), PTSD Checklist (PCL, p=0.008), and CAPS sleep disturbance (p=0.014, g=0.82).
  • The VRE-DCS group showed earlier improvement, with a substantial between-group difference in mean percent CAPS decrease after session 6 (45.86% vs 29.59%, p=0.060).

Methods

  • Pilot randomized, double-blind, placebo-controlled trial; 25 adults with chronic PTSD following the World Trade Center attacks were randomized to VRE-DCS (n=13) or VRE-placebo (n=12); 22 completed the intervention and 6-month follow-up.
  • Participants received 100 mg DCS or placebo 90 min before each weekly VRE session (sessions 2–11); VRE therapy consisted of 12 weekly 90-min sessions.
  • Primary outcome was Clinician Administered PTSD Scale (CAPS); assessments occurred pre-treatment, after sessions 3, 6, and 10, post-treatment, and at 6 months. Analyses used ANCOVA, Fisher’s exact test, intent-to-treat with last observation carried forward, and completer analysis.

Limitations

  • The paper states the sample size was small, limiting conclusions about differential response to DCS associated with concurrent psychotropic medication use.
  • The paper states ancillary analyses were not adjusted for multiple comparisons.
  • The paper notes all three dropouts were in the VRE-placebo group and that this may be an artifact of the small sample size; the pilot design and small groups also make the findings preliminary and in need of further study.

Model-written summary. Check it against the paper before relying on it.

Integrity signals

Registry

Crossref · 10.1038/npp.2013.317

Cites

34 of 34 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

0 of 40 cited sources checked · 0 supported · 0 flagged

  • Findingown data
    § Abstract

    PTSD remission rate was significantly greater for VRE-DCS than VRE-placebo at post-treatment (46% vs 8%).

    “PTSD remission rates were significantly greater for the VRE-DCS group (46% vs 8% at post-treatment; 69% vs 17% at 6 months).”
    • Also stated in: § RESULTS · plain
      “Remission rates were significantly higher in the VRE-DCS group at both post-treatment (6/13, 46% vs 1/12, 8%) and 6-month follow-up (9/13, 69% vs 2/12, 17%).”
    Quote in the paperSubstantial claim
  • Findingown data
    § RESULTS

    At 6-month follow-up, there was a significant group difference in CAPS with large effect size (d=1.13).

    “and significant group differences at 6-month follow-up (F=7.85, df=1, 22, p=0.010), with large effect size Hodges g=1.13 (Figure 2).”
    Quote in the paperSubstantial claim
  • Findingown data
    § RESULTS

    VRE-DCS group reported less sleep disturbance than VRE-placebo group at 6-month follow-up.

    “Further post-hoc analysis showed that the VRE-DCS group reported less sleep disturbance (as measured by CAPS sleep item) than the VRE-placebo group at the 6-month follow-up (p=0.014, g=0.82; Supplementary Figure S2).”
    Quote in the paperNot a substantial claim
  • Findingown data
    § MATERIALS AND METHODS

    No side effects were reported.

    “A side-effect questionnaire was completed at each session; no side effects were reported.”
    Quote in the paperNot a substantial claim
  • Findingown data
    § RESULTS

    These gains were maintained through the 6-month follow-up.

    “These gains were maintained through the 6-month follow-up (Table 2).”
    Quote in the paperSubstantial claim
  • May combine two claims. 21
  • Classified as probably not a substantial claim. 18

  • May combine two claims.

    Findingown data
    § RESULTS

    At post-treatment, the between-group effect size for CAPS difference was medium (d=0.68) but statistically nonsignificant.

    “Analyses of covariance on CAPS difference scores showed a pattern favoring the VRE-DCS group with a statistically nonsignificant medium effect at the conclusion of treatment (F=2.42, df=1, 22, p=0.131, Hodges g=0.68)”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data
    § Abstract

    The difference in CAPS between the VRE-DCS and VRE-placebo groups increased over time beginning at 6 weeks, with medium to large between-group effect sizes immediately post-treatment and 6 months later.

    “The difference in CAPS between the VRE-DCS (n=13) and VRE-placebo (n=12) groups increased over time beginning at 6 weeks, with medium to large between-group effect sizes immediately post-treatment and 6 months later (d=0.68 and d=1.13, respectively).”
    • Also stated in: § RESULTS · plain
      “The difference between the VRE-DCS and VRE-placebo groups increased over time (Figure 1).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data
    § RESULTS

    In the analysis of covariance on BDI-II difference scores, there was a trend toward a between-group effect at post-treatment (F=3.74, df=1,22, p=0.066) and a significant between-group effect at 6-month follow-up (F=19.78, df=1,22, p<0.001).

    “The analysis of covariance on the BDI-II difference scores showed a trend at post-treatment and significant between-group effects at the 6-month follow-up (F=3.74, df=1, 22, p=0.066 and F=19.78, df=1, 22, p<0.001, respectively).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data
    § RESULTS

    Overall, use of psychotropic medications did not have a significant effect on CAPS scores at post-treatment (F=1.67, df=1,22, p=0.210) or 6-month follow-up (F=1.67, df=1,22, p=0.210).

    “However, overall, the use of psychotropic medications did not have an effect on CAPS scores at either post-treatment (F=1.67, df=1, 22, p=0.210) or the 6-month follow-up (F=1.67, df=1, 22, p=0.210).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data
    § RESULTS

    The smallest treatment gains were observed in the VRE-placebo group regardless of concurrent medication use (no medications n=7 vs medication n=5; CAPS change post-treatment M=32.71, SD=17.52 vs M=33.20, SD=30.26; 6-month M=31.29, SD=27.56 vs M=26.20, SD=33.62).

    “The smallest gains were observed in the VRE-placebo group, regardless of concurrent medication use (no medications n=7 vs medication n=5, CAPS change score at post-treatment M=32.71, SD=17.52 vs M=33.20, SD=30.26; at the 6-month follow-up M=31.29, SD=27.56 vs M=26.20, SD=33.62).”
    Quote in the paperNot a substantial claim

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

    Findingown data
    § RESULTS

    All three dropouts were in the VRE-placebo group.

    “All three dropouts were in the VRE-placebo group”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data
    § RESULTS

    Among VRE-placebo completers with MDD at baseline (n=5), three remitted at post-treatment but relapsed at 6-month follow-up, one remitted at 6-month follow-up, and one maintained MDD diagnosis at all three time-points.

    “Among study completers with MDD in the VRE-placebo group (n=5), three participants remitted at post-treatment but relapsed at the 6-month follow-up, one remitted at the 6-month follow-up, and one maintained MDD diagnosis at all three time-points.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data
    § DISCUSSION

    The DCS-enhanced VRE group showed statistically and clinically significantly greater improvement in PTSD symptoms and in secondary outcomes of sleep, depression, and anger expression compared with the VRE-placebo group.

    “Patients in the DCS-enhanced VRE group showed statistically and clinically significantly greater improvement in PTSD symptoms, as well as on secondary outcome measures of sleep, depression, and anger expression compared with the VRE-placebo group.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data
    § RESULTS

    Treatment gains (CAPS change scores) were larger in the VRE-DCS subgroup not using concurrent medication (n=4) than in the VRE-DCS subgroup on stable medications (n=9) at post-treatment (M=61.50, SD=27.67 vs M=43.78, SD=21.45) and 6-month follow-up (M=67.25, SD=21.91 vs M=54.00, SD=18.65).

    “Treatment gains were the largest in the VRE-DCS subgroup that did not use concurrent medication (n=4), as compared with VRE-DCS subgroup on stable medications (n=9) (CAPS change score at post-treatment M=61.50, SD=27.67 vs M=43.78, SD=21.45; at the 6-month follow-up M=67.25, SD=21.91 vs M=54.00, SD=18.65).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data
    § RESULTS

    Among VRE-DCS participants diagnosed with MDD at baseline (n=9), seven showed remission at post-treatment and one additional showed remission at 6-month follow-up.

    “Seven of nine participants in VRE-DCS who were diagnosed with MDD at baseline showed remission at post-treatment and an additional participant showed remission at the 6-month follow-up.”
    Quote in the paperNot a substantial claim

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

    Findingown data
    § RESULTS

    About half of participants (n=14, 56%) were on a stable dose of psychotropic medications (9 VRE-DCS, 5 VRE-placebo).

    “About half of participants (n=14, 56%) were on a stable dose of psychotropic medications (n=9 in the VRE-DCS group, n=5 in the VRE-placebo group, Table 1).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data
    § DISCUSSION

    No significant medication side effects were reported, and dropouts were not related to medication side effects or inability to tolerate VRE.

    “No significant medication side effects were reported, nor were dropouts related to medication side effects or inability to tolerate the VRE.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation
    § INTRODUCTION

    Repeatedly re-experiencing the traumatic memory in a safe environment until fear is extinguished is hypothesized to be the mechanism of action in exposure therapy, the treatment with the strongest empirical evidence for PTSD.

    “This process is hypothesized to be the mechanism of action in exposure therapy, the treatment with the strongest empirical evidence for PTSD (Foa et al, 2000; Institute of Medicine (IOM), 2008).”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites Foa et al, 2000

      Not checked in the free run.

    • cites Institute of Medicine (IOM), 2008

      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Premisecitation
    § INTRODUCTION

    VRE therapy was chosen because of the potential to standardize sensory stimuli across participants.

    “Although other effective variations of exposure therapy exist (Institute of Medicine (IOM), 2008), VRE therapy was chosen because of the potential to standardize sensory stimuli across participants.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Institute of Medicine (IOM), 2008

      Not checked in the free run.

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

    Premisecitation
    § INTRODUCTION

    Effective treatments for post-traumatic stress disorder (PTSD) remain elusive.

    “Effective treatments for post-traumatic stress disorder (PTSD) remain elusive (Institute of Medicine (IOM), 2008).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Institute of Medicine (IOM), 2008

      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Premisecitation
    § INTRODUCTION

    PTSD is a disorder of emotional learning.

    “One novel treatment approach follows from the hypothesis that PTSD is a disorder of emotional learning (Foa and Kozak, 1986).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Foa and Kozak, 1986 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation
    § INTRODUCTION

    PTSD may manifest from a persisting conditioned fear response independent of the original trauma and difficulty learning that stimuli previously associated with a trauma are no longer so.

    “Thus, PTSD may manifest from a persisting conditioned fear response independent of the original trauma and difficulty learning that stimuli previously associated with a trauma are no longer so.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Foa and Kozak, 1986 source

      Not checked in the free run.

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

    Study design and conductnone given
    § MATERIALS AND METHODS

    Completer analysis was performed to evaluate robustness of study results.

    “Completer analysis was performed to evaluate robustness of study results.”
    Quote in the paperNot a substantial claim

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

    Study design and conductnone given
    § MATERIALS AND METHODS

    Ancillary analyses were not adjusted for the effect of multiple comparisons.

    “Ancillary analyses were not adjusted for the effect of multiple comparisons.”
    Quote in the paperNot a substantial claim

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

    Study design and conductnone given
    § MATERIALS AND METHODS

    All analyses adhered to intent-to-treat principle, with the last available observation used as the outcome data (ITT/LOCF).

    “All analyses adhered to intent-to-treat principle, with the last available observation used as the outcome data (ITT/LOCF).”
    Quote in the paperSubstantial claim

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

    Study design and conductnone given
    § MATERIALS AND METHODS

    The study was registered with ClinicalTrials.gov (NCT00632632).

    “The study was registered with ClinicalTrials.gov (NCT00632632).”
    Quote in the paperNot a substantial claim

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

    Study design and conductnone given
    § MATERIALS AND METHODS

    Medication was administered double-blind; the research pharmacy oversaw randomization.

    “Medication was administered double-blind; the research pharmacy oversaw randomization.”
    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
    § MATERIALS AND METHODS

    All therapy sessions were videotaped, with a subset reviewed for protocol adherence.

    “All therapy sessions were videotaped, with a subset reviewed for protocol adherence.”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim.

    Study design and conductown data
    § MATERIALS AND METHODS

    Twenty-two participants completed the study intervention and 6-month follow-up.

    “Twenty-two participants completed the study intervention and 6-month follow-up.”
    Quote in the paperSubstantial claim

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

    Study design and conductown data
    § MATERIALS AND METHODS

    Compliance was assessed by verbal inquiry; less than 1% of the time participants reported forgetting to take the study medication.

    “Compliance was assessed by verbal inquiry about the exact timing of medication ingestion. Less than 1% of the time (2 of 255 sessions) participants reported forgetting to take the study medication; in these instances the session was rescheduled.”
    Quote in the paperNot a substantial claim

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

    Study design and conductown data
    § MATERIALS AND METHODS

    A psychologist who was blind to the medication condition conducted assessments at six time points.

    “A psychologist who was blind to the medication condition conducted assessments at six time points: pre-treatment, following sessions 3, 6, 10, immediately post-treatment, and 6 months later.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Study design and conductown data
    § Abstract

    The trial was randomized, double-blind, and placebo-controlled.

    “In a pilot randomized, double-blind, placebo-controlled trial, 100 mg of DCS or placebo was administered 90 min before each weekly VRE session, to ensure peak plasma concentrations during the sessions in 25 patients with chronic PTSD.”
    • Also stated in: § MATERIALS AND METHODS · plain
      “Medication was administered double-blind; the research pharmacy oversaw randomization.”
    Quote in the paperSubstantial claim

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

    Study design and conductown data
    § MATERIALS AND METHODS

    Three participants dropped out, all in the VRE-placebo group.

    “Three participants dropped out (after sessions 3, 6, and 7); all were in the VRE-placebo group.”
    Quote in the paperNot a substantial claim

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

    Premisecitation
    § DISCUSSION

    Sleep disturbance is widely regarded as one of the most tenacious PTSD symptoms.

    “Sleep disturbance, a salient cluster D symptom, is widely regarded as one of the most tenacious PTSD symptoms (Spoormaker and Montgomery, 2008).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Spoormaker and Montgomery, 2008 source

      Not checked in the free run.

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

    Study design and conductown data
    § DISCUSSION

    Our sample size is too small to draw conclusions about medication effects; future studies with sufficient sample sizes are needed.

    “Although our data are consistent with this pre-clinical data, our sample size is too small to draw any conclusions, which must await future studies with sample sizes sufficient for such analyses.”
    Quote in the paperSubstantial claim

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

    Interpretationreasoning
    § DISCUSSION

    The fact that all dropouts were in the VRE-placebo group may be an artifact of the small sample size.

    “Given the small number of dropouts, the fact that all dropouts were in the VRE-placebo group may be an artifact of the small sample size.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationcitation
    § DISCUSSION

    The treatment dropout rate was 12%, which is low compared with other PTSD treatment trials.

    “Our treatment dropout rate of 12% is strikingly low in comparison with other PTSD treatment trials (Schottenbauer et al, 2008).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Schottenbauer et al, 2008 source

      Not checked in the free run.

  • May combine two claims.

    Interpretationreasoning
    § DISCUSSION

    Both the amount and timing of DCS may account for the differences in results.

    “Thus, both the amount and timing of DCS may account for the differences in results.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation
    § DISCUSSION

    de Kleine et al (2012) used 50 mg DCS given 1 h before the exposure session in a mixed trauma sample, half of whom reported PTSD secondary to childhood sexual assault.

    “de Kleine et al (2012) also used a 50 mg dose given 1 h before the exposure session with a mixed trauma sample; half of whom reported PTSD secondary to childhood sexual assault.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites de Kleine et al, 2012 source

      Not checked in the free run.

34 of 34

  • The paper relies on this without support.

    DCS is a partial agonist at the NMDA receptor.

    “D-cycloserine (DCS) (Seromycin) is a partial agonist at the N-methyl-D-aspartate (NMDA) receptor, a member of the glutamate receptor family, which has an essential role in mediating learning and memory.”

  • The paper relies on this without support.

    DCS is an FDA-approved antibiotic that has been previously used in clinical trials as a cognitive enhancer.

    “DCS is an FDA-approved antibiotic that has been previously used in clinical trials as a cognitive enhancer.”

  • The paper relies on this without support.

    VRE therapy is a particularly promising format to test the hypothesis that DCS enhances extinction learning because sensory fear cues are standardized across patients.

    “VRE therapy is a particularly promising format to test the hypothesis that DCS enhances extinction learning, as sensory fear cues are standardized across patients.”

  • The paper relies on this without support.

    DCS acts by facilitating extinction learning, the mechanism hypothesized to underlie exposure therapy.

    “As a partial agonist at the NMDA receptor, DCS purportedly acts by facilitating extinction learning—the mechanism of action hypothesized to underlie exposure therapy.”
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?

  • D-cycloserine administered with VRET for PTSD patients has been proven effective in reducing PTSD symptoms.

    “VRET has also been augmented pharmacologically by administering D-cycloserine with VRET for PTSD patients. This combination has been proven effective in reducing PTSD symptoms (Rothbaum et al., 2014; Difede et al., 2014)”

    From Virtual Reality exposure therapy in the treatment of public speaking anxiety and social anxiety disorder (2024) · cites this paper as Difede et al., 2014

    The Discussion reports significantly greater PTSD-symptom improvement with D-cycloserine plus virtual reality exposure therapy than with therapy plus placebo. But this was a small pilot trial, and the Abstract calls the combination a promising treatment rather than an established, proven one. (LLM, conf=0.86)

    Experimental — accuracy not yet measured

  • Supplementation of D-cycloserine increased treatment efficacy over standard VRET in one trial.

    “with the supplementation of D-cycloserine increasing treatment efficacy over standard VRET in one trial (Difede et al., 2014).”

    From Virtual Reality exposure therapy in the treatment of public speaking anxiety and social anxiety disorder (2024) · cites this paper as Difede et al., 2014

  • Previous trials of therapy-enhancing medications for PTSD have similarly shown medication-related differential trajectories of improvement.

    “Previous trials of therapy-enhancing medications for PTSD have similarly shown medication-related differential trajectories of improvement (Difede et al., 2014; Zoellner et al., in press).”

    From Augmenting Prolonged Exposure therapy for PTSD with intranasal oxytocin: a randomized, placebo-controlled pilot trial (2018) · cites this paper as Difede et al., 2014

  • When DCS was administered prior to virtual reality exposure therapy, subjects showed earlier, enhanced symptom reduction and greater PTSD remission rates.

    “Specifically, when DCS was administered prior to virtual reality exposure therapy subjects showed earlier, enhanced symptom reduction and greater PTSD remission rates (78).”

    From Conditioned fear associated phenotypes as robust, translational indices of trauma-, stressor-, and anxiety-related behaviors (2014) · cites this paper as [78]

  • Trials of D-cycloserine to augment exposure therapy for PTSD have yielded mixed results: one found faster symptom reduction, one found a detrimental effect, and three found no effect.

    “One study found evidence of a faster rate of symptom reduction 141 , while another reported a detrimental effect 142 , and three further trials found no effect 143-145 .”

    From Post‐traumatic stress disorder: a state‐of‐the‐art review of evidence and challenges (2019) · cites this paper as [145]

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.

  • Consistentt(23) = -1.98reported p = .06 · recomputed p = .060

    “t(23)=−1.98, p = .060”

1 of 1

Self-check

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

Each contradiction between two passages listed here was confirmed by an independent check.

  • Two different six-month placebo CAPS standard deviations

    Minor

    Table 2 gives 25.66 as the six-month placebo CAPS standard deviation, while the sensitivity analysis gives 22.66 for the same intent-to-treat mean of 45.92.

1 of 1

Cites

Flagged first, then by citations

Research works printed but not linked: 4

  1. Beck AT, Steer RA, Brown GK (1996) Manual for the Beck Depression Inventory-II. Psychological Corporation: San Antonio, TX, USA.
  2. Blake DD, Weathers FW, Nagy LM, Kalopek DG, Charney DS, Keane TM (1998) Clinician-Administered PTSD Scale for DSM-IV. Boston VA Medical Center, National Center for Posttraumatic Stress Disorder, Behavioral Science Division: Boston, MA, USA.
  3. Institute of Medicine (IOM) (2008) Treatment of Posttraumatic Stress Disorder: An Assessment of the Evidence. The National Academies Press: Washington, DC, USA.
  4. Weathers FW, Litz FW, Herman DS, Huska JA, Keane TM (1993) The PTSD Checklist (PCL): reliability, validity, and diagnostic utility Annual Meeting of the International Society for Traumatic Stress Studies San Antonio, TX, USA.

Cited by

Sorted by citations

Related

Authors
Difede, J., Cukor, J., Wyka, K., Olden, M., Hoffman, H., Lee, F. S., & Altemus, M.
Affiliations
  • NewYork–Presbyterian Hospital (US)
  • Weill Cornell Medicine (US)
  • University of Washington (US)
Corresponding author
Difede, JoAnn
ORCID
Venue
Neuropsychopharmacology
Publisher
Springer Science and Business Media LLC
Published
2013-11-12
Volume
39
Issue
5
Pages
1052-1058
ISSN
  • 0893-133X (ISSN-L)
  • 1740-634X
DOI
10.1038/npp.2013.317
PMC
PMC3957110
OpenAlex
W1994673996
Semantic Scholar
54220cd84b9159bc57a92ac2681d7381ee91c28e
Cited by
212
References
34
Citations by year
2026: 1 · 2025: 7 · 2024: 11 · 2023: 10 · 2022: 17 · 2021: 14 · 2020: 12 · 2019: 26 · 2018: 21 · 2017: 25 · 2016: 14 · 2015: 27 · 2014: 26 · 2013: 1
FWCI
25.22
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)
Topics
  • Social Sciences › Psychology › Clinical Psychology › Posttraumatic Stress Disorder Research
  • Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
  • Social Sciences › Psychology › Clinical Psychology › Psychotherapy Techniques and Applications
Keywords
D-cycloserine, post-traumatic stress disorder, virtual reality exposure therapy, fear extinction, nootropic drugs, neuroplasticity, depression, anger expression, sleep, PTSD remission
MeSH terms
Adult, Aged, Anger, Chronic Disease, Cycloserine, Depression, Double-Blind Method, Extinction, Psychological, Fear, Female, Humans, Implosive Therapy, Male, Middle Aged, Pilot Projects, Psychiatric Status Rating Scales, Psychotropic Drugs, Sleep, Stress Disorders, Post-Traumatic, Time Factors, Treatment Outcome, Chemotherapy, Adjuvant

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 2026-10-09.

Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-10-09.

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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