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Cited by 117Posttraumatic Stress Disorder ResearchNeuroendocrine regulation and behaviorPsychoanalysis and Psychopathology Research

Augmenting Prolonged Exposure therapy for PTSD with intranasal oxytocin: a randomized, placebo-controlled pilot trial

Open access
Flanagan, Julianne C., Sippel, Lauren M., Wahlquist, Amy, Moran-Santa Maria, Megan M., Back, Sudie E.·2018·Journal of Psychiatric Research
DOI 10.1016/j.jpsychires.2017.12.014PMC PMC5800951
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Abstract

Posttraumatic stress disorder (PTSD) is a chronic, debilitating condition for which Prolonged Exposure (PE) therapy is highly efficacious. However, for some individuals, premature dropout and residual PTSD symptoms remain obstacles. The neuropeptide oxytocin is a promising candidate to enhance PE due to its ability to enhance 1) prosocial cognition and behavior, which are theorized to promote positive working alliance, and 2) extinction learning, which is the central mechanism of action underlying successful PE treatment. Despite a robust theoretical rationale, no studies to date have combined evidence-based psychotherapy for PTSD with oxytocin. This randomized, placebo-controlled, double-blind pilot trial examined the feasibility, safety, and preliminary efficacy of augmenting PE with oxytocin. Participants were 17 individuals with diverse index traumas. Participants self-administered intranasal oxytocin (40 IU) or matching placebo 45 minutes prior to each weekly PE therapy session. One adverse event occurred in the placebo group and three individuals dropped out (17.6%; 2 oxytocin group and 1 placebo group). The oxytocin group demonstrated lower PTSD and depression symptoms during PE, and had higher working alliance scores, although these differences did not reach statistical significance. Although preliminary, the findings support the feasibility of oxytocin combined with PE. Adequately powered studies are necessary to determine whether oxytocin enhances PE treatment outcomes and to examine potential mechanisms, such as accelerating extinction learning, enhancing early response, and preventing premature dropout. NCT03238924.

AI snapshot

Written from the paper’s full text.

TL;DR

This randomized, placebo-controlled, double-blind pilot trial tested whether intranasal oxytocin (40 IU) administered before weekly Prolonged Exposure (PE) sessions improves PTSD treatment outcomes. It found the combination was feasible and safe, with no statistically significant between-group differences in PTSD, depression, or working alliance, though oxytocin was associated with lower symptoms at some timepoints.

Key findings

  • Seventeen participants were randomized to oxytocin (n=8) or placebo (n=9); three dropped out (17.6%; 2 oxytocin, 1 placebo), and one placebo-group participant reported an adverse event (chest pains).
  • No statistically significant treatment group*time interactions emerged for PTSD, depression, or working alliance outcomes; the oxytocin group had a marginally lower end-of-treatment PCL-5 score (31.0 vs. 40.9, p=0.09).
  • Session 3 PCL scores showed a statistically significant group difference favoring oxytocin (OT=30.3 vs. PL=45.4, p=0.03).
  • Both groups reported high treatment satisfaction and therapeutic alliance, with no significant between-group differences.

Methods

  • Pilot randomized, placebo-controlled, double-blind trial; participants self-administered intranasal oxytocin (40 IU) or matching placebo 45 minutes before weekly PE sessions (sessions 2–9) and received 10 individual, 90-minute PE sessions.
  • Participants were 17 adults with DSM-5 PTSD and diverse index traumas; 82.4% male, 58.8% military veterans, with no significant baseline demographic or clinical differences between groups.
  • Outcomes included CAPS-5, PCL-5, BDI-II, HAQ-II, CSQ, and adverse events; analyses used Wilcoxon ranked sum tests for feasibility outcomes and general linear mixed models for preliminary efficacy, with alpha set at .05.

Limitations

  • The paper states the primary limitation is the small sample size; the study was not designed or powered to adequately examine between-group differences in treatment outcomes.
  • The paper notes the limited ability to detect medication effects was coupled with a high level of effectiveness of the intervention.
  • The paper states it did not employ neuroimaging to examine potential treatment mechanisms; it also suggests future studies could consider daily rather than weekly dosing and examine moderators such as baseline severity, sex, and childhood maltreatment. Evident from the text: the sample was small, predominantly male, and largely veteran, which may limit generalizability.

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

Integrity signals

Registry

Crossref · 10.1016/j.jpsychires.2017.12.014

Cites

80 of 80 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

0 of 75 cited sources checked · 0 supported · 0 flagged

  • Findingown data

    The oxytocin group had a marginally lower estimated mean PCL-5 score at end of treatment as compared to the placebo group (31.0 v. 40.9, p=0.09).

    “the oxytocin group had a marginally lower estimated mean PCL-5 score at end of treatment as compared to the placebo group (31.0 v. 40.9, p=0.09).”
    Quote in the paperNot a substantial claim
  • Findingown data

    One adverse event (chest pains) was reported during the study by a participant randomized to the placebo condition.

    “One adverse event (i.e., chest pains) was reported during the study by a participant randomized to the placebo condition.”
    Quote in the paperNot a substantial claim
  • Findingown data

    No statistically significant differences between groups emerged on any of the three symptom variables.

    “While no statistically significant differences between groups emerged on any of the three symptom variables”
    Quote in the paperSubstantial claim
  • Findingown data

    Session 3 PCL scores showed a statistically significant group difference (OT=30.3 vs. PL=45.4, p=0.03).

    “session 3 PCL scores showed a statistically significant group difference (OT=30.3 vs. PL=45.4, p=0.03).”
    • Also stated in: § 4. Discussion · plain
      “In addition to consistently lower PTSD and depression symptom severity, oxytocin was associated with significantly lower PTSD symptom severity at session 3.”
    Quote in the paperSubstantial claim
  • Findingown data

    At end of treatment, participants in both treatment conditions reported high therapeutic alliance (oxytocin group M=101.17, SD=10.38; placebo group M=105.57, SD=9.62).

    “and therapeutic alliance (oxytocin group M=101.17, SD=10.38; placebo group M=105.57, SD=9.62)”
    Quote in the paperNot a substantial claim
  • Classified as probably not a substantial claim. 30
  • May combine two claims. 29

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

    Findingown data

    Three participants dropped out during treatment (at sessions 3, 4, and 6), and one participant was withdrawn after the first PE session and referred to more intensive clinical services.

    “Three participants dropped out during treatment (at sessions 3, 4, and 6), and one participant was withdrawn after the first PE session and referred to more intensive clinical services.”
    Quote in the paperNot a substantial claim

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

    Findingown data

    Reasons for declining participation included being unable to commit to weekly therapy sessions (n=3), already engaged in another therapy (n=4), not wanting to discuss trauma (n=1), and being uncomfortable taking a medication (n=2).

    “Reasons for declining participation included being unable to commit to weekly therapy sessions (n=3), already engaged in another therapy that they did not want to discontinue (n=4), not wanting to discuss their trauma (n=1), and being uncomfortable taking a medication (n=2).”
    Quote in the paperNot a substantial claim

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

    Findingown data

    The remaining 13 participants (OT=6) completed all 10 PE sessions.

    “The remaining 13 participants (OT=6) completed all 10 PE sessions.”
    Quote in the paperNot a substantial claim

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

    Findingown data

    Seventeen individuals enrolled and were randomized 1:1 to oxytocin (n=8) or placebo (n=9) and 10 individual manualized PE therapy sessions.

    “Seventeen individuals enrolled in the study and were randomized in a 1:1 manner to receive oxytocin (OT; n=8) or placebo (n=9) conditions as well as 10 individual, manualized PE therapy sessions.”
    Quote in the paperSubstantial claim

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

    Findingown data

    Of 36 respondents evaluated, 9 were ineligible and 10 declined participation.

    “Of 36 respondents evaluated, 9 were ineligible and 10 declined participation.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Mean scores between groups varied over time and were largely similar for all outcomes of interest.

    “mean scores between groups varied over time and were largely similar for all outcomes of interest.”
    Quote in the paperSubstantial claim

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

    Findingown data

    Treatment group*time interactions were not significant; therefore, the interactions were removed from the models.

    “the treatment group*time interactions were not significant; therefore, the interactions were removed from the models.”
    Quote in the paperSubstantial claim

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

    Findingown data

    An equal number of participants were White or African American (n=6; 35.3%, respectively), and Native American or Pacific Islander (5.9%; n=1, respectively), while 17.6% (n=3) identified as more than one race.

    “An equal number of participants were White or African American (n=6; 35.3%, respectively), and Native American or Pacific Islander (5.9%; n=1, respectively), while 17.6% (n=3) identified as more than one race.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    For all three models, both baseline and time were significantly related to the outcomes, indicating that scores on these instruments changed significantly over time among participants in both treatment conditions, and higher baseline values were related to higher scores at end of treatment.

    “For all three models, both baseline and time were significantly related to the outcomes, indicating that while there were no treatment group differences, scores on these instruments changed significantly over time among participants in both treatment conditions, and higher baseline values were related to higher scores at end of treatment.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    There were no significant between-group differences in satisfaction or therapeutic alliance.

    “and there were no significant between-group differences.”
    Quote in the paperNot a substantial claim

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

    Findingown data

    Participants were 82.4% male (n=14) and 58.8% (n=10) military veterans, among whom 38.5% (n=5) had served in Iraq or Afghanistan conflicts.

    “Participants were 82.4% male (n=14) and 58.8% (n=10) were military veterans, among whom 38.5% (n=5) had served in the Iraq or Afghanistan conflicts.”
    Quote in the paperNot a substantial claim

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

    Premisecitation

    Prolonged Exposure (PE) is a manualized, cognitive-behavioral therapy considered a gold standard treatment for PTSD.

    “Prolonged Exposure (PE; Foa et al., 2007) is a manualized, cognitive-behavioral therapy that is considered a “gold standard” treatment for PTSD (Institute of Medicine, 2008; The Management of Posttraumatic Stress Disorder Work Group, 2017).”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites Institute of Medicine, 2008

      Not checked in the free run.

    • cites The Management of Posttraumatic Stress Disorder Work Group, 2017

      Not checked in the free run.

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

    Premisecitation

    PE consistently outperforms control and waitlist conditions in randomized controlled trials.

    “PE consistently outperforms control and waitlist conditions in randomized controlled trials (Powers et al., 2010; Resick et al., 2002)”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites Powers et al., 2010 source

      Not checked in the free run.

    • cites Resick et al., 2002 source

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  • May combine two claims.

    Premisecitation

    Many patients struggle with distress and avoidance during treatment, and fail to receive an adequate dose of PE.

    “Many patients struggle with distress and avoidance during treatment, and fail to receive an adequate dose of PE (Foa et al., 2005; Tuerk, 2014).”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites Foa et al., 2005 source

      Not checked in the free run.

    • cites Tuerk, 2014 source

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

    Premisecitation

    Oxytocin may enhance retention in PE by reducing excessive distress and facilitating therapeutic alliance.

    “oxytocin may enhance retention by reducing excessive distress and facilitating therapeutic alliance.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Olff et al., 2010 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    The capacity to establish and navigate an effective working alliance is essential to maximize the benefits of behavioral intervention and is particularly integral to the success of PE.

    “The capacity to establish and navigate an effective working alliance is essential to maximize the benefits of behavioral intervention (Horvath and Luborsky, 1993), and particularly integral to the success of PE (Cloitre et al., 2004; McLaughlin et al., 2014).”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites Horvath and Luborsky, 1993 source

      Not checked in the free run.

    • cites Cloitre et al., 2004 source

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    • cites McLaughlin et al., 2014 source

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  • May combine two claims.

    Premisecitation

    A single dose of oxytocin had positive effects on anxiety, irritability, mood, intensity of intrusive thoughts, and desire for social interaction in one small laboratory study among participants with PTSD.

    “One small laboratory study among participants with PTSD found that a single dose of oxytocin had positive effects on anxiety, irritability, mood, intensity of intrusive thoughts, and desire for social interaction (Yatzkar and Klein, 2010).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Yatzkar and Klein, 2010

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Oxytocin has demonstrated the ability to enhance fear extinction in preclinical models and among healthy individuals.

    “Oxytocin has demonstrated the ability to enhance fear extinction in preclinical models (Eskandarian et al., 2013) and among healthy individuals (Acheson et al., 2013; Eckstein et al., 2014).”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites Eskandarian et al., 2013

      Not checked in the free run.

    • cites Acheson et al., 2013 source

      Not checked in the free run.

    • cites Eckstein et al., 2014 source

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  • May combine two claims.

    Premisecitation

    Two small preliminary studies augmented a single-session exposure therapy for social anxiety (N=25) and arachnophobia (N=44) with only one low dose (24 IU) of oxytocin with null findings.

    “two small preliminary studies augmented a single-session exposure therapy for social anxiety (N=25) and arachnophobia (N=44) with only one low dose (24 IU) of oxytocin with null findings (Acheson et al., 2015; Guastella et al., 2009).”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites Acheson et al., 2015 source

      Not checked in the free run.

    • cites Guastella et al., 2009 source

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  • Probably not a substantial claim: may not pass S1 (asserted). May combine two claims.

    Premisecitation

    Prevailing hypotheses suggest that oxytocin may uniquely help mitigate barriers to engaging in behavioral treatments that specifically target avoidance, which would thereby allow patients who might otherwise be unable to tolerate PE to engage effectively, complete the treatment, obtain an adequate therapeutic dose, and experience long-term remission of PTSD.

    “Prevailing hypotheses suggest that oxytocin may uniquely help mitigate barriers to engaging in behavioral treatments that specifically target avoidance (Preckel et al., 2014), which would thereby allow patients who might otherwise be unable to tolerate PE to engage effectively, complete the treatment, obtain an adequate therapeutic dose, and experience long-term remission of PTSD (Frijling et al.,”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites Preckel et al., 2014 source

      Not checked in the free run.

    • cites Frijling et al., 2014 source

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    • cites Koch et al., 2014 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    No previous studies pairing oxytocin with a behavioral intervention have taken place among PTSD populations, and studies in related clinical populations have not utilized more than a single intervention session.

    “First, no previous studies pairing oxytocin with a behavioral intervention have taken place among PTSD populations, and studies in related clinical populations have not utilized more than a single intervention session.”
    Quote in the paperSubstantial claim

  • Classified as probably not a substantial claim.

    Premisecitation

    A single dose of oxytocin was not effective in reducing physiological reactivity during one-session exposure therapy for PTSD.

    “One study found that a single dose of oxytocin was not effective in reducing physiological reactivity during one-session exposure therapy for PTSD (Pitman et al., 1993).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Pitman et al., 1993 source

      Not checked in the free run.

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

    Premisecitation

    Depression commonly co-occurs with PTSD and is typically identified as an important outcome in clinical trials treating these disorders.

    “Because depression commonly co-occurs with PTSD, and is typically identified as an important outcome in clinical trials treating these disorders (see Stander et al., 2014, for review)”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Stander et al., 2014 source

      Not checked in the free run.

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

    Study design and conductnone given

    Intranasal oxytocin spray (40 IU) and matching placebo were compounded and dispensed by the research pharmacy, which also oversaw randomization.

    “Intranasal oxytocin spray (40 IU) and matching placebo were compounded and dispensed by the research pharmacy, which also oversaw randomization.”
    Quote in the paperNot a substantial claim

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

    Study design and conductnone given

    All study procedures were IRB-approved, and all participants provided written informed consent.

    “All study procedures were IRB-approved, and all participants provided written informed consent.”
    Quote in the paperNot a substantial claim

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

    Study design and conductnone given

    Study therapists were three female Masters or Doctoral-level clinicians who received weekly supervision during the trial.

    “Study therapists were three female Masters or Doctoral-level clinicians who received weekly supervision during the trial.”
    Quote in the paperNot a substantial claim

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

    Study design and conductnone given

    Medication administration was observed by research staff to ensure proper procedures were followed.

    “Medication administration was observed by research staff to ensure proper procedures were followed.”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim.

    Study design and conductnone given

    General linear mixed models controlling for baseline values and repeated measurement effects were used to examine treatment group, time, and treatment group*time interactions.

    “general linear mixed models (GLMMs) controlling for baseline values and repeated measurement effects were used to examine treatment group, time, and treatment group*time interactions.”
    Quote in the paperSubstantial claim

  • Classified as probably not a substantial claim.

    Interpretationown data

    These preliminary findings support the rationale for a larger randomized controlled trial to assess the efficacy of oxytocin for enhancing PE outcomes.

    “These preliminary findings support the rationale for a larger randomized controlled trial to assess the efficacy of oxytocin for enhancing PE outcomes.”
    Quote in the paperSubstantial claim

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

    Premisecitation

    The dose and timing of medication administration is based on past research in our group and others.

    “The dose and timing of medication administration is based on past research in our group and others (Cardoso et al., 2013; Flanagan et al., 2015; MacDonald et al., 2011).”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites Cardoso et al., 2013 source

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    • cites Flanagan et al., 2015 source

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    • cites MacDonald et al., 2011 source

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  • May combine two claims.

    Interpretationown data

    While statistically significant group differences in treatment outcomes were limited, participants randomized to the oxytocin condition reported consistently lower symptom severity despite similar baseline PTSD symptom severity.

    “While statistically significant group differences in treatment outcomes were limited, results demonstrate that participants randomized to the oxytocin condition reported consistently lower symptom severity despite similar baseline PTSD symptom severity.”
    Quote in the paperSubstantial claim

  • Classified as probably not a substantial claim.

    Study design and conductnone given

    CAPS-5 was administered at baseline, session 5 and session 10 by trained evaluators blind to treatment condition.

    “The CAPS-5 was administered at baseline, session 5 and session 10 by trained evaluators blind to treatment condition.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationown data

    Results support the safety, feasibility, and preliminary efficacy of augmenting PE with weekly doses of oxytocin in a sample of individuals who were diverse with respect to trauma exposure, race and ethnicity, and veteran vs. non-veteran status.

    “Results support the safety, feasibility, and preliminary efficacy of augmenting PE with weekly doses of oxytocin in a sample of individuals who were diverse with respect to trauma exposure, race and ethnicity, and veteran vs. non-veteran status.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationown data

    Participants in both conditions improved symptom severity during treatment and reported high treatment satisfaction.

    “improved symptom severity during treatment, and reported high treatment satisfaction.”
    Quote in the paperNot a substantial claim

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

    Premisecitation

    Individuals with PTSD often perceive their environments as threatening and experience distrust of others.

    “Individuals with PTSD often perceive their environments as threatening and experience distrust of others (Ehlers and Clark, 2000).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Ehlers and Clark, 2000 source

      Not checked in the free run.

  • May combine two claims.

    Interpretationown data

    Participants in the current study self-administered oxytocin starting in session 2, a design selected so that oxytocin would coincide with exposure sessions of PE based on extinction being the hypothesized target of oxytocin; the differential symptom severity at session 3 supports this hypothesis.

    “Participants in the current study self-administered oxytocin starting in session 2, a design selected so that oxytocin would coincide with exposure sessions of PE based on extinction being the hypothesized target of oxytocin; the differential symptom severity at session 3 supports this hypothesis.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    Evidence suggests that oxytocin mitigates prefrontal cortex-amygdala dysregulation in healthy samples and in individuals with PTSD.

    “evidence suggests that oxytocin mitigates prefrontal cortex-amygdala dysregulation in healthy samples (Sripada et al., 2013) and in individuals with PTSD (Koch et al., 2016).”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites Sripada et al., 2013 source

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    • cites Koch et al., 2016 source

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

    Premisecitation

    Oxytocin effects can vary as a function of emotion regulation skills.

    “previous research has shown that oxytocin effects can vary as a function of emotion regulation skills (Quirin et al., 2011), social context history of childhood maltreatment (Ebert et al., 2013; Flanagan et al., 2015), and sex (Ditzen et al., 2012; Rilling et al., 2014).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Quirin et al., 2011 source

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  • Classified as probably not a substantial claim.

    Interpretationcitation

    There may be subpopulations of individuals with PTSD who derive more benefit from oxytocin-enhanced treatment.

    “It is therefore possible that there are subpopulations of individuals with PTSD who might derive more benefit from oxytocin-enhanced treatment, as has been the case for other therapy enhancers like d-cycloserine and methylene blue.”
    Quote in the paperSubstantial claim

  • Classified as probably not a substantial claim.

    Interpretationnone given

    Oxytocin could enhance retention in treatment via its anxiolytic and prosocial properties.

    “Oxytocin could enhance early treatment response via promoting extinction learning and/or enhance retention in treatment via its anxiolytic and prosocial properties.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: Oxytocin has anxiolytic and prosocial properties.

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

    Premisecitation

    Oxytocin effects can vary as a function of social context history of childhood maltreatment.

    “previous research has shown that oxytocin effects can vary as a function of emotion regulation skills (Quirin et al., 2011), social context history of childhood maltreatment (Ebert et al., 2013; Flanagan et al., 2015), and sex (Ditzen et al., 2012; Rilling et al., 2014).”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites Ebert et al., 2013 source

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    • cites Flanagan et al., 2015 source

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

    Premisecitation

    Some studies have found no relationship between patient-therapist gender match and psychotherapy retention or outcome.

    “Although some studies have found no relationship between patient-therapist gender match and psychotherapy retention or outcome (Shiner et al., 2017; Sterling et al., 1998)”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites Shiner et al., 2017 source

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    • cites Sterling et al., 1998 source

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

    Premisecitation

    Oxytocin effects can vary as a function of sex.

    “previous research has shown that oxytocin effects can vary as a function of emotion regulation skills (Quirin et al., 2011), social context history of childhood maltreatment (Ebert et al., 2013; Flanagan et al., 2015), and sex (Ditzen et al., 2012; Rilling et al., 2014).”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites Ditzen et al., 2012 source

      Not checked in the free run.

    • cites Rilling et al., 2014 source

      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Interpretationnone given

    Oxytocin could enhance early treatment response via promoting extinction learning.

    “Oxytocin could enhance early treatment response via promoting extinction learning and/or enhance retention in treatment via its anxiolytic and prosocial properties.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: Oxytocin enhances extinction learning.
44 of 44

  • The paper relies on this without support.

    Oxytocin enhances extinction learning.

    “guided again by the premise that oxytocin enhances extinction learning.”

  • The paper relies on this without support.

    Oxytocin has anxiolytic and prosocial properties.

    “via its anxiolytic and prosocial properties”
2 of 2

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?

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.

  • Abstract says medication preceded every session, but methods limit it to sessions 2-9

    Minor

    The abstract describes administration before each weekly PE session, whereas the methods specify administration only before sessions 2-9 of the 10-session course.

  • Count of previous PTSD oxytocin studies omits a study described earlier

    Minor

    The paper says only two previous studies examined oxytocin in the context of PTSD, but it also describes a study of a single oxytocin dose among participants with PTSD, in addition to the two studies named after that count.

  • Claim of no prior PTSD behavioral-intervention pairing conflicts with the next paragraph

    Minor

    The paper says no prior study paired oxytocin with a behavioral intervention in a PTSD population, then describes a prior oxytocin study conducted during one-session exposure therapy for PTSD.

  • Percentage of veterans who served in Iraq or Afghanistan is incorrect

    Minor

    Five of the 10 military veterans is 50%, not 38.5%.

    Reported 38.5 · recomputed 50

4 of 4

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Related

Authors
Flanagan, J. C., Sippel, L. M., Wahlquist, A., Moran-Santa Maria, M. M., & Back, S. E.
Affiliations
  • Medical University of South Carolina (US)
  • Dartmouth College (US)
Corresponding author
Flanagan, Julianne C.
ORCID
Venue
Journal of Psychiatric Research
Publisher
Elsevier BV
Published
2018-03
Volume
98
Pages
64-69
ISSN
0022-3956 (ISSN-L)
DOI
10.1016/j.jpsychires.2017.12.014
PMC
PMC5800951
OpenAlex
W2779008721
Semantic Scholar
ff83837e3a19194edd1cca26fb7f7f81cfe0a08c
Cited by
117
References
80
Citations by year
2026: 6 · 2025: 3 · 2024: 13 · 2023: 15 · 2022: 16 · 2021: 19 · 2020: 18 · 2019: 17 · 2018: 10
FWCI
15.22
Type
journal article
Language
en
Open access
Licence
Locations
  • Journal of Psychiatric Research (acceptedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • National Institutes of Health (UL1TR000062)
  • National Institute on Alcohol Abuse and Alcoholism (K23AA023845)
  • National Institute on Drug Abuse (K02DA039229)
  • National Center for Advancing Translational Sciences
Topics
  • Social Sciences › Psychology › Clinical Psychology › Posttraumatic Stress Disorder Research
  • Social Sciences › Psychology › Social Psychology › Neuroendocrine regulation and behavior
  • Social Sciences › Psychology › Clinical Psychology › Psychoanalysis and Psychopathology Research
Keywords
post-traumatic stress disorder, prolonged exposure therapy, intranasal oxytocin, augmentation therapy, extinction learning, therapeutic relationship, depressive symptoms, treatment discontinuation, neuropeptides, feasibility and safety
MeSH terms
Adult, Combined Modality Therapy, Double-Blind Method, Female, Humans, Implosive Therapy, Male, Middle Aged, Oxytocin, Pilot Projects, Stress Disorders, Post-Traumatic, Veterans, Outcome Assessment, Health Care

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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