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OBJECTIVE: Despite considerable research examining the efficacy of psychedelic-assisted therapies (PATs) for treating psychiatric disorders, assessment of adverse events (AEs) in PAT research has lagged. Current AE reporting standards in PAT trials are poorly calibrated to features of PAT that distinguish it from other treatments, leaving many potential AEs unassessed. METHODS: A multidisciplinary working group of experts involved in PAT pooled formally and informally documented AEs observed through research experience and published literature. This information was integrated with (a) current standards and practices for AE reporting in pharmacotherapy and psychotherapy trials and (b) published findings documenting post-acute dosing impacts of psychedelics on subjective states, meaning, and psychosocial health variables, to produce a set of AE constructs important to evaluate in PAT as well as recommended methods and time frames for their assessment and monitoring. Correspondence between identified potential AEs and current standards for AE assessment was examined, including the extent of coverage of identified AE constructs by 25 existing measures used in relevant research. RESULTS: Fifty-four potential AE terms warranting systematized assessment in PAT were identified, defined, and categorized. Existing measures demonstrated substantial gaps in their coverage of identified AE constructs. Recommendations were developed for how to assess PAT AEs (including patient, clinician, and informant reports), and when to assess over preparation, dosing session, integration, and follow-up. Application of this framework is demonstrated in a preliminary assessment protocol (available in the supplement). CONCLUSIONS: This assessment framework addresses the need to capture post-acute dosing AEs in PAT, accounting for its pharmacotherapy and psychotherapy components, as well as documented impacts of psychedelics on worldviews and spirituality.
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Alucinógenos , Transtornos Mentais , Humanos , Alucinógenos/efeitos adversos , Alucinógenos/administração & dosagem , Transtornos Mentais/tratamento farmacológico , Psicoterapia/métodos , Sistemas de Notificação de Reações Adversas a Medicamentos/normas , Efeitos Colaterais e Reações Adversas Relacionados a MedicamentosRESUMO
This brief review article will describe treatment approaches for posttraumatic stress disorder (PTSD) based on findings from basic research. The focus of this review will be fear conditioning and extinction models, which provide a translational model of PTSD that can help translate basic research in nonhuman animals through well-controlled trials confirming the efficacy of treatment approaches in humans with PTSD such as prolonged exposure therapy. Specific cognitive aspects of fear extinction processes, including consolidation and reconsolidation, are reviewed along with behavioral and pharmacological treatment strategies based on basic research in these areas including attempts to prevent the development of PTSD as well as the treatment of chronic PTSD. Pharmacological, behavioral, and device-based augmentation strategies of PTSD treatment based in basic science findings are reviewed, including those that disrupt noradrenergic receptor processes, medications that act on NMDA receptors, physical exercise, cannabinoids, estradiol, dexamethasone, yohimbine, losartan, dopamine, and MDMA, along with the evidence for their efficacy in human clinical samples. While fear extinction provides an exciting translational opportunity to improve PTSD based on basic science findings, we review limitations and challenges of the extant literature as well as future directions.
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BACKGROUND: Preoperative state anxiety (PSA) is distress and anxiety directly associated with perioperative events. PSA is associated with negative postoperative outcomes such as longer hospital length of stay, increased pain and opioid use, and higher rates of rehospitalization. Psychological prehabilitation, such as education, exposure to hospital environments, and relaxation strategies, has been shown to mitigate PSA; however, there are limited skilled personnel to deliver such interventions in clinical practice. Immersive virtual reality (VR) has the potential for greater accessibility and enhanced integration into an immersive and interactive experience. VR is rarely used in the preoperative setting, but similar forms of stress inoculation training involving exposure to stressful events have improved psychological preparation in contexts such as military deployment. OBJECTIVE: This study seeks to develop and investigate a targeted PSA intervention in patients undergoing oncological surgery using a single preoperative VR exposure. The primary objectives are to (1) develop a novel VR program for patients undergoing oncological surgery with general anesthesia; (2) assess the feasibility, including acceptability, of a single exposure to this intervention; (3) assess the feasibility, including acceptability, of outcome measures of PSA; and (4) use these results to refine the VR content and outcome measures for a larger trial. A secondary objective is to preliminarily assess the clinical utility of the intervention for PSA. METHODS: This study comprises 3 phases. Phase 1 (completed) involved the development of a VR prototype targeting PSA, using multidisciplinary iterative input. Phase 2 (data collection completed) involves examining the feasibility aspects of the VR intervention. This randomized feasibility trial involves assessing the novel VR preoperative intervention compared to a VR control (ie, nature trek) condition and a treatment-as-usual group among patients undergoing breast cancer surgery. Phase 3 will involve refining the prototype based on feasibility findings and input from people with lived experience for a future clinical trial, using focus groups with participants from phase 2. RESULTS: This study was funded in March 2019. Phase 1 was completed in April 2020. Phase 2 data collection was completed in January 2024 and data analysis is ongoing. Focus groups were completed in February 2024. Both the feasibility study and focus groups will contribute to further refinement of the initial VR prototype (phase 3), with the final simulation to be completed by mid-2024. CONCLUSIONS: The findings from this work will contribute to the limited body of research examining feasible and broadly accessible interventions for PSA. Knowledge gained from this research will contribute to the final development of a novel VR intervention to be tested in a large population of patients with cancer before surgery in a randomized clinical trial. TRIAL REGISTRATION: ClinicalTrials.gov NCT04544618; https://www.clinicaltrials.gov/study/NCT04544618. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/55692.
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Ansiedade , Estudos de Viabilidade , Neoplasias , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Ansiedade/prevenção & controle , Ansiedade/terapia , Neoplasias/cirurgia , Cuidados Pré-Operatórios/métodos , Angústia Psicológica , Estresse Psicológico , Realidade Virtual , Terapia de Exposição à Realidade Virtual/métodos , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
BACKGROUND: Psychedelic-assisted therapies hold early promise for treating multiple psychiatric conditions. However, absent standards for the care, teams providing psychedelic-assisted therapy pose a major roadblock to safe administration. Psychedelics often produce spiritually and existentially meaningful experiences, and spiritual health practitioners have been involved in administering psychedelic-assisted therapies in multiple settings, suggesting important qualifications for delivering these therapies. However, the roles and competencies of spiritual health practitioners in psychedelic-assisted therapies have not been described in research. METHOD: This study examined interviews with 15 spiritual health practitioners who have facilitated psychedelic-assisted therapy. Thematic analyses focused on their contributions, application of expertise and professional background, and roles in administering these therapies. RESULTS: Seven themes emerged, comprising two domains: unique and general contributions. Unique contributions included: competency to work with spiritual material, awareness of power dynamics, familiarity with non-ordinary states of consciousness, holding space, and offer a counterbalance to biomedical perspectives. General contributions included use of generalizable therapeutic repertoire when conducting PAT, and contributing to interdisciplinary collaboration. IMPLICATIONS: Spiritual health practitioners bring unique and specific expertise to psychedelic-assisted therapy based on their training and professional experience. They are skilled at interprofessional collaboration in a way that complements other clinical team members. Psychedelic-assisted therapy teams may benefit from including spiritual health practitioners. In order to ensure rigorous standards and quality care, further efforts to delineate the roles and necessary qualifications and training of spiritual health clinicians for psychedelic-assisted therapy are needed.
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Alucinógenos , Alucinógenos/uso terapêutico , Qualidade da Assistência à SaúdeRESUMO
BACKGROUND: The Emory Healthcare Veterans Program (EHVP) is a multidisciplinary intensive outpatient treatment program for post-9/11 veterans and service members with invisible wounds, including posttraumatic stress disorder (PTSD), traumatic brain injury (TBI), substance use disorders (SUD), and other anxiety- and depression-related disorders. OBJECTIVE: This article reviews the EHVP. METHODS: The different treatment tracks that provide integrated and comprehensive treatment are highlighted along with a review of the standard, adjunctive, and auxiliary services that complement individualized treatment plans. RESULTS: This review particularly emphasizes the adjunctive neurorehabilitation service offered to veterans and service members with a TBI history and the EVHP data that indicate large reductions in PTSD and depression symptoms across treatment tracks that are maintained across 12 months follow up. Finally, there is a discussion of possible suboptimal treatment response and the pilot programs related to different treatment augmentation strategies being deploying to ensure optimal treatment response for all. CONCLUSION: Published data indicate that the two-week intensive outpatient program is an effective treatment program for a variety of complex presentations of PTSD, TBI, SUD, and other anxiety- and depression-related disorders in veterans and active duty service members.
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BACKGROUND: Clinically elevated preoperative distress and anxiety are common among patients undergoing cancer surgery. Preoperative interventions have been developed to mitigate this distress and anxiety but are inconsistent in efficacy and feasibility for broad implementation. OBJECTIVE: This preliminary pilot study aims to assess the feasibility and utility of a newly developed virtual reality (VR) intervention to expose patients awaiting breast cancer surgery to the operating room environment and a simulation of anesthetic induction. METHODS: Patients undergoing breast cancer surgery (N=7) were assigned to the VR intervention or control (treatment as usual) group and completed self-report measures of distress and anxiety before surgery, on the day of surgery, and after surgery (5 and 30 d postoperatively). Those in the intervention group trialed the VR simulation 1 to 2 weeks preoperatively and provided qualitative and quantitative feedback. We assessed the feasibility of recruitment capability and study design and evaluated participants' impressions of the intervention using self-report rating scales and open-ended questions. We also descriptively examined distress and anxiety levels throughout the duration of the study. RESULTS: Recruitment occurred between December 2021 and December 2022 and progressed slowly (rate: 1 participant/7 wk on average; some hesitancy because of stress and being overwhelmed). All participants who consented to participate completed the entire study. All participants were female and aged 56 (SD 10.56) years on average. In total, 57% (4/7) of the participants were assigned to the intervention group. On average, intervention participants spent 12 minutes engaged in the VR simulation. In general, the intervention was rated favorably (eg, clear information, enjoyable, and attractive presentation; mean% agreement 95.00-96.25, SD 4.79-10.00) and as helpful (mean% agreement 87.50, SD 25.00). Participants described the intervention as realistic (eg, "It was realistic to my past surgical experiences"), impacting their degree of preparedness and expectations for surgery (eg, "The sounds and sights and procedures give you a test run; they prepare you for the actual day"), and having a calming or relaxing effect (eg, "You feel more relaxed for the surgery"). CONCLUSIONS: This preoperative VR intervention demonstrated preliminary feasibility among a sample of patients undergoing breast cancer surgery. Results and participant feedback will inform modifications to the VR intervention and the study design of a large-scale randomized controlled trial to examine the efficacy of this intervention. TRIAL REGISTRATION: ClinicalTrials.gov NCT04544618; https://clinicaltrials.gov/study/NCT04544618.
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The focus of this chapter is an overview of integrating virtual reality (VR) technology within the context of exposure therapy for anxiety disorders, a gold standard treatment, with a focus on how VR can help facilitate extinction learning processes integral to these interventions. The chapter will include an overview of advantages of incorporating VR within exposure therapy, and benefits specifically within an inhibitory learning approach for extinction training. A review of the empirical literature on the effectiveness of VR exposure therapy for specific phobia and PTSD will be provided, as well as practical overview of how to effectively incorporate VR within exposure therapy.
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Terapia Implosiva , Transtornos Fóbicos , Terapia de Exposição à Realidade Virtual , Realidade Virtual , Humanos , Transtornos Fóbicos/terapia , Transtornos de AnsiedadeRESUMO
OBJECTIVE: This study aimed to determine the relationship between stages of the menopause transition (premenopausal, perimenopausal, and postmenopausal) on symptoms of posttraumatic stress disorder (PTSD) and depression in trauma-exposed women. METHODS: A cross-sectional study conducted between 2005 and 2017 recruited and enrolled an urban community sample (n = 6,093) from nonpsychiatric medical clinic waiting rooms of Grady Memorial Hospital, a public safety net hospital in Atlanta, Georgia. Participants were female, 18 to 65 years old, and predominantly Black/African American. RESULTS: Of the 6,093 participants, 93.8% were Black/African American, 2.5% were White, and 3.8% were of all other races (Hispanic/Latino, Asian, multiracial). Participants younger than 40 years were categorized as premenopausal (n = 3,166), between 40 and 55 years of age were categorized as perimenopausal (n = 2,127), and older than 55 years were categorized as postmenopausal (n = 790). Menopause status was associated with total PTSD symptom severity ( F2,5416 = 9.61, P < 0.001), symptom severity within all three PTSD symptom clusters (avoidance/numbing symptoms: F2,5416 = 7.10, P < 0.001; intrusive symptoms: F2,5416 = 7.04, P < 0.001; hyperarousal symptoms: F2,5409 = 8.31, P < 0.001), and depression symptom severity ( F2,5148 = 11.4, P < 0.001). Compared with both premenopausal and postmenopausal women, perimenopausal women reported significantly worse total PTSD symptoms, symptoms in the hyperarousal cluster, and depressive symptoms. CONCLUSIONS: The current cross-sectional data show that symptoms of PTSD and depression in women are associated with reproductive age, such that perimenopausal women show higher symptom severity than premenopausal and postmenopausal women. Future longitudinal studies can reveal how changes in hormones over the course of the menopause transition impact the symptoms, neurobiology, and psychophysiology of PTSD.
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Transtornos de Estresse Pós-Traumáticos , Feminino , Humanos , Adolescente , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Idoso , Masculino , Transtornos de Estresse Pós-Traumáticos/psicologia , Depressão/diagnóstico , Estudos Transversais , Perimenopausa , MenopausaRESUMO
Importance: Mounting evidence supports the role of spiritual, existential, religious, and theological components in mediating psychedelic-assisted therapy, yet integration of these elements into the clinical setting is lagging. Observations: Although psychedelic-assisted therapy commonly produces spiritually, existentially, religiously, or theologically relevant experiences for patients, these have not been systematically integrated into the psychotherapies that accompany therapeutic uses of psychedelics. As a key feature and potential mediator of therapeutic effects, evidence-based psychedelic-assisted therapies should include these topics in the treatment model. Research across multiple diagnostic targets and treatment contexts suggests that spiritually integrated psychotherapies are effective, feasible, and produce add-on benefits in spiritually, existentially, religiously, and theologically relevant outcomes, which are particularly germane to psychedelics. Established standards in spiritually integrated psychotherapy may be fruitfully applied to psychedelic-assisted therapy. Objectives for spiritually, existentially, religiously, and theologically integrated psychedelic-assisted therapy based on these standards and informed by considerations specific to psychedelics are recommended. Conclusions and Relevance: Spiritual, existential, religious, and theological topics' integration in psychedelic-assisted therapy is needed to ensure culturally competent, evidence-based treatment aligned with the highest standards of clinical care. Neglecting to address these topics can detract from cultural competence, contribute to risks for patients, and potentially undermine treatment success.
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Alucinógenos , Humanos , Alucinógenos/farmacologia , Alucinógenos/uso terapêutico , Psicoterapia , Resultado do TratamentoRESUMO
INTRODUCTION: Posttraumatic stress disorder (PTSD) and depression are common in service members and veterans, and the response to currently available treatments is often modest at best. Recent studies suggest potential benefit with psychedelic-assisted therapies (PATs), particularly 3,4-methylenedioxymethamphetamine-assisted therapy for PTSD and psilocybin-assisted therapy for depression. This study examined beliefs and perceived barriers regarding PAT among service members and veterans to inform the delivery of these treatments if they are approved by the FDA. MATERIALS AND METHODS: Twenty-one service members and veterans (67% male, 81% White, and 43% active duty) with a history of traumatic brain injury and co-occurring cognitive and psychological symptoms completed a measure assessing baseline knowledge and views of PAT, read a brief psychoeducation regarding PAT, and then responded to questions related to their beliefs and perceived barriers to PAT. RESULTS: Before psychoeducation, participants reported a neutral view of psychedelic drugs (M = 2.76; range: 1-5), PAT (M = 3.33), and interest in PAT (M = 3.10). After psychoeducation, participants reported a significantly more positive view of psychedelic drugs (M = 3.24, P = .014) and interest in PAT (M = 3.67, P = .016). Overall, participants indicated that they would support PAT availability in medical settings if proven beneficial (M = 4.52; 5 = "agree strongly") and they would support a loved one engaging in PAT (M = 4.29). The most frequently reported health concerns were concern of long-term effects (43%), fear of losing their mind (33%), fear of personality changes (33%), and fear of traumatic brain injury complications (24%). The most frequently endorsed barriers were time commitment, transportation, financial concerns, work, and childcare (33%-19%), with 48% reporting no barriers. CONCLUSIONS: This is the first study to explore beliefs and perceived barriers regarding PAT among service members and veterans. These results indicate that military populations may be interested in PAT, particularly if psychoeducation and outreach regarding these treatments occurred. If FDA approved, it will be important to facilitate command support and address logistical barriers to ensure appropriate access within military contexts.
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Lesões Encefálicas Traumáticas , Alucinógenos , Militares , Transtornos de Estresse Pós-Traumáticos , Veteranos , Masculino , Humanos , Feminino , Veteranos/psicologia , Alucinógenos/farmacologia , Alucinógenos/uso terapêutico , Projetos Piloto , Militares/psicologia , Lesões Encefálicas Traumáticas/complicações , Lesões Encefálicas Traumáticas/tratamento farmacológico , Transtornos de Estresse Pós-Traumáticos/tratamento farmacológico , Transtornos de Estresse Pós-Traumáticos/diagnósticoRESUMO
BACKGROUND: Psilocybin is being studied for use in treatment-resistant depression. METHODS: In this phase 2 double-blind trial, we randomly assigned adults with treatment-resistant depression to receive a single dose of a proprietary, synthetic formulation of psilocybin at a dose of 25 mg, 10 mg, or 1 mg (control), along with psychological support. The primary end point was the change from baseline to week 3 in the total score on the Montgomery-Åsberg Depression Rating Scale (MADRS; range, 0 to 60, with higher scores indicating more severe depression). Secondary end points included response at week 3 (≥50% decrease from baseline in the MADRS total score), remission at week 3 (MADRS total score ≤10), and sustained response at 12 weeks (meeting response criteria at week 3 and all subsequent visits). RESULTS: A total of 79 participants were in the 25-mg group, 75 in the 10-mg group, and 79 in the 1-mg group. The mean MADRS total score at baseline was 32 or 33 in each group. Least-squares mean changes from baseline to week 3 in the score were -12.0 for 25 mg, -7.9 for 10 mg, and -5.4 for 1 mg; the difference between the 25-mg group and 1-mg group was -6.6 (95% confidence interval [CI], -10.2 to -2.9; P<0.001) and between the 10-mg group and 1-mg group was -2.5 (95% CI, -6.2 to 1.2; P = 0.18). In the 25-mg group, the incidences of response and remission at 3 weeks, but not sustained response at 12 weeks, were generally supportive of the primary results. Adverse events occurred in 179 of 233 participants (77%) and included headache, nausea, and dizziness. Suicidal ideation or behavior or self-injury occurred in all dose groups. CONCLUSIONS: In this phase 2 trial involving participants with treatment-resistant depression, psilocybin at a single dose of 25 mg, but not 10 mg, reduced depression scores significantly more than a 1-mg dose over a period of 3 weeks but was associated with adverse effects. Larger and longer trials, including comparison with existing treatments, are required to determine the efficacy and safety of psilocybin for this disorder. (Funded by COMPASS Pathfinder; EudraCT number, 2017-003288-36; ClinicalTrials.gov number, NCT03775200.).
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Antidepressivos , Transtorno Depressivo Maior , Transtorno Depressivo Resistente a Tratamento , Psilocibina , Adulto , Humanos , Antidepressivos/efeitos adversos , Antidepressivos/uso terapêutico , Depressão/tratamento farmacológico , Transtorno Depressivo Maior/tratamento farmacológico , Transtorno Depressivo Maior/psicologia , Método Duplo-Cego , Psilocibina/efeitos adversos , Psilocibina/uso terapêutico , Resultado do Tratamento , Transtorno Depressivo Resistente a Tratamento/tratamento farmacológico , Transtorno Depressivo Resistente a Tratamento/psicologiaRESUMO
OBJECTIVE: Post-9/11 U.S. veterans and servicemembers are at increased risk for suicide, indicating an important need to identify and mitigate suicidal ideation and behaviors in this population. METHOD: Using data modeling techniques, we examined correlates of suicidal ideation and behavior at intake in 261 Post-9/11 veterans and servicemembers seeking mental health treatment. RESULTS: Our sample endorsed high rates of suicidal ideation and behavior. Approximately 40% of our sample scored in a range on the Suicide Behaviors Questionnaire-Revised (SBQ-R), indicating high clinical risk for suicide. Results from multivariate analyses indicate that greater state and/or trait depression severity, greater anger and anger expression, less impulse control, and lower rank were consistently associated with suicidal ideation and behavior across our models. Negative posttraumatic thoughts about the self, gender, and military branch of service were also significantly associated with suicidal ideation and behavior. CONCLUSIONS: Suicidal ideation and behaviors are common in veterans seeking mental health treatment. State and/or trait depression, anger and impulse control were predictors of increased risk for suicidal ideation and behavior across models. Consistencies and differences across models as well as limitations and practical implications for the findings are discussed.
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Militares , Transtornos de Estresse Pós-Traumáticos , Veteranos , Humanos , Militares/psicologia , Fatores de Risco , Transtornos de Estresse Pós-Traumáticos/epidemiologia , Transtornos de Estresse Pós-Traumáticos/psicologia , Ideação Suicida , Veteranos/psicologiaRESUMO
Empirically-supported psychotherapies for posttraumatic stress disorder (PTSD) are highly effective and recommended as first-line treatments, yet dropout rates from standard outpatient therapy are high. Intensive outpatient programs (IOPs) that provide these therapies in condensed format with complementary interventions show promise, as they have demonstrated similar efficacy and higher retention rates. The current study examined initial and long-term outcomes up to 12-months following a 2-week PTSD IOP involving daily prolonged exposure therapy (PE) and adjunctive interventions for veterans and military service members. Participants (N = 376) demonstrated high retention (91%) and large effect size reductions in self-reported PTSD and depression symptoms after two weeks. Small increases in symptoms occurred after 3 months but these stabilized and large reductions compared to baseline were maintained up to 12 months. Piecewise multilevel modeling indicated that demographic variables did not predict PTSD or depression symptom trajectories. Higher PTSD and depression severity at intake predicted higher symptomatology across timepoints and larger relative gains during treatment. Greater alcohol use prior to treatment was associated with higher PTSD symptomatology but did not affect the magnitude of gains. A history of childhood sexual abuse was associated with greater reduction in depression symptoms over treatment, although this effect faded over follow-up. Together these findings underscore the long-term effectiveness of a PE-based IOP across a diverse range of veterans and service members.
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Terapia Implosiva , Delitos Sexuais , Transtornos de Estresse Pós-Traumáticos , Veteranos , Humanos , Pacientes Ambulatoriais , Transtornos de Estresse Pós-Traumáticos/complicações , Transtornos de Estresse Pós-Traumáticos/terapia , Resultado do TratamentoRESUMO
Posttraumatic stress disorder (PTSD) is prevalent and associated with significant morbidity. Mild traumatic brain injury (mTBI) concurrent with psychiatric trauma may be associated with PTSD. Prior studies of PTSD-related structural brain alterations have focused on military populations. The current study examined correlations between PTSD, acute mTBI, and structural brain alterations longitudinally in civilian patients (N = 504) who experienced a recent Criterion A traumatic event. Participants who reported loss of consciousness (LOC) were characterized as having mTBI; all others were included in the control group. PTSD symptoms were assessed at enrollment and over the following year; a subset of participants (n = 89) underwent volumetric brain MRI (M = 53 days posttrauma). Classes of PTSD symptom trajectories were modeled using latent growth mixture modeling. Associations between PTSD symptom trajectories and cortical thicknesses or subcortical volumes were assessed using a moderator-based regression. mTBI with LOC during trauma was positively correlated with the likelihood of developing a chronic PTSD symptom trajectory. mTBI showed significant interactions with cortical thickness in the rostral anterior cingulate cortex (rACC) in predicting PTSD symptoms, r = .461-.463. Bilateral rACC thickness positively predicted PTSD symptoms but only among participants who endorsed LOC, p < .001. The results demonstrate positive correlations between mTBI with LOC and PTSD symptom trajectories, and findings related to mTBI with LOC and rACC thickness interactions in predicting subsequent chronic PTSD symptoms suggest the importance of further understanding the role of mTBI in the context of PTSD to inform intervention and risk stratification.
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Concussão Encefálica , Militares , Transtornos de Estresse Pós-Traumáticos , Encéfalo/diagnóstico por imagem , Concussão Encefálica/complicações , Concussão Encefálica/diagnóstico por imagem , Concussão Encefálica/psicologia , Humanos , Militares/psicologia , Transtornos de Estresse Pós-Traumáticos/complicações , Transtornos de Estresse Pós-Traumáticos/diagnóstico por imagem , Transtornos de Estresse Pós-Traumáticos/psicologia , Inconsciência/diagnóstico por imagem , Inconsciência/etiologia , Inconsciência/psicologiaRESUMO
Prolonged exposure (PE) therapy is a first-line treatment for posttraumatic stress disorder (PTSD) and involves repeated presentation of trauma-related cues without aversive outcomes. A primary learning mechanism of PE is fear extinction (new learning that a dangerous cue is now safe) and its retention (maintaining this new learning over time). Extant research suggests extinction is impaired in PTSD patients. In this study, we employed an established fear-potentiated startle-based paradigm to examine fear acquisition, extinction learning and retention before and after completion of intensive outpatient treatment. First, PTSD patients undergoing PE (n = 55) were compared to trauma-exposed patients without PTSD (n = 57). We identified excessive fear in PTSD patients during acquisition and extinction before treatment compared to non-PTSD patients. At post-treatment, we examined the return of fear after extinction in PTSD patients showing high or low treatment response to PE (≥50% change in PTSD symptom severity vs. < 50%). High PE responders maintained fear extinction learning whereas low PE responders showed significant return of fear at post-treatment. These results replicate and extend previous findings of impaired extinction in PTSD and provide support for the proposed theoretical link between fear extinction and PE response.
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Terapia Implosiva , Transtornos de Estresse Pós-Traumáticos , Veteranos , Extinção Psicológica/fisiologia , Medo/fisiologia , Humanos , Pacientes Ambulatoriais , Reflexo de Sobressalto/fisiologia , Transtornos de Estresse Pós-Traumáticos/terapiaRESUMO
BACKGROUND: Fear conditioning and extinction are well-characterized cross-species models of fear-related posttraumatic stress disorder (PTSD) symptoms, and recent animal data suggest that 3,4-methylenedioxymethamphetamine (MDMA) enhances fear extinction retention. AIMS: This study investigated the effect of MDMA on fear learning, extinction training, and retention in healthy humans. METHODS: The study involved a randomized placebo-controlled, two-group, parallel design trial in a sample of healthy adults, age 21-55 recruited from a major metropolitan area. The experimental paradigm included a fear acquisition session followed by an extinction training session 24 hours later, and 2 hours after study drug administration. Fear extinction retention was measured 48 hours after extinction training. Participants (N = 34; 70.6% male and 29.4% female) were randomly assigned in 1:1 ratio to 100 mg MDMA or placebo. All randomized participants completed the trial and were included in primary analyses. Safety was monitored via adverse events and vital signs. MDMA was well-tolerated with no serious adverse events. RESULTS: Results indicated a significant main effect of session between extinction training and retention with no significant group differences. Significantly more participants in the MDMA group retained extinction learning compared to the placebo group (χ2 = 7.29, p = 0.007). CONCLUSION: Although we did not observe the hypothesized facilitation of extinction retention, the findings from this initial human trial provide compelling rationale to continue to explore the potential for MDMA to impact extinction retention.Clinical Trials Registry Name and Identifier: Evaluation of MDMA on Startle Response (NCT0318176) https://clinicaltrials.gov/ct2/show/NCT03181763?term = MDMA&draw = 2&rank = 9.
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N-Metil-3,4-Metilenodioxianfetamina , Transtornos de Estresse Pós-Traumáticos , Animais , Extinção Psicológica , Medo , Feminino , Humanos , Masculino , N-Metil-3,4-Metilenodioxianfetamina/efeitos adversos , Reflexo de Sobressalto , Transtornos de Estresse Pós-Traumáticos/tratamento farmacológicoRESUMO
While inflammatory markers have been implicated in the link between PTSD and poor health outcomes, there is a paucity of research investigating C-reactive protein (CRP) and psychotherapy treatment response for posttraumatic stress disorder (PTSD). The present study utilized a large, well-characterized sample of veterans and service members (N = 493) engaged in intensive psychotherapy to investigate the associations between CRP, trauma exposure, related variables, and PTSD and depression, as well as investigating if CRP was associated with PTSD psychotherapy treatment response. Bivariate correlation results indicate that CRP was significantly associated with BMI (r = 0.48) and severity of experiences of childhood physical and sexual abuse (r = 0.14 and 0.15, respectively) and was not significantly associated with baseline PTSD total symptom severity, PTSD symptom clusters, or depression symptom severity (rs ranging from -0.03 to 0.04). In multivariate regression models investigating if CRP and related variables were associated with PTSD baseline symptom severity, CRP was not a significant predictor (ß = -0.03). Hierarchical linear modeling did not identify CRP as a significant predictor of PTSD psychotherapy outcome. Given that findings indicate that CRP was broadly elevated in this treatment seeking sample but not associated with PTSD and depression symptom severity, results suggest CRP may not be a specific biomarker for PTSD or depression but may be elevated in psychiatric disease more generally.
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Transtornos de Estresse Pós-Traumáticos , Veteranos , Biomarcadores , Proteína C-Reativa/metabolismo , Depressão/psicologia , Depressão/terapia , Humanos , Psicoterapia , Transtornos de Estresse Pós-Traumáticos/psicologia , Veteranos/psicologiaRESUMO
OBJECTIVE: Advocates of massed prolonged exposure (PE) argue an intensive approach may address between-session distraction, avoidance, and demotivation that can result in dropout or interference with treatment engagement. Despite growing empirical support for the efficacy and effectiveness of massed PE, little evidence suggests massed PE matches patient preferences. Further, program evaluation efforts have not assessed unforeseen or underestimated benefits and drawbacks of massed PE. The current study is the first known study to assess patient reactions to massed PE. METHOD: Participants were 25 military veterans diagnosed with posttraumatic stress disorder who were accepted into a 2-week massed PE program. After the final session, participants completed a written survey using open-ended questions regarding their perceived benefits and drawbacks of massing the full PE protocol into 2 weeks. After demonstrating interrater reliability, coders used a thematic analysis approach to identify themes and subthemes in the qualitative data. RESULTS: Overall, participant reactions were much more positive (51.27%) than negative (17.77%). Participants identified benefits that are largely consistent with the justification for massed PE: (a) The structure limits distractions and avoidance, and (b) quick gains enhance motivation and engagement. With respect to drawbacks, participants identified that massed PE causes short-term discomfort and is demanding in terms of effort and time, which is also consistent with clinical theory of PE and justification for massed delivery. CONCLUSIONS: Participant reactions correspond to the rationale for massed PE; that is, participants identified that despite short-term discomfort and demands, they tend to like and benefit from the intensity of massed PE. (PsycInfo Database Record (c) 2022 APA, all rights reserved).