Spaced conditioned stimulus presentation facilitates the extinction of strong fear memory in mice.

Inducing fear memory extinction by re-presenting a conditioned stimulus (CS) is the foundation of exposure therapy for post-traumatic stress disorder (PTSD). Investigating differences in the ability of different CS presentation patterns to induce extinction learning is crucial for improving this type of therapy. Using a trace fear conditioning paradigm in mice, we demonstrate that spaced presentation of the CS facilitated the extinction of a strong fear memory to a greater extent than continuous CS presentation. These results lay the groundwork for developing more effective exposure therapy techniques for PTSD.

Correspondence to Antici et al. Salivary CRP predicts treatment response to virtual reality exposure therapy for social anxiety disorder.

The study by Antici et al. (2024) investigates the effects of virtual reality exposure therapy on social anxiety disorder (SAD), focusing on the relationship between C-reactive protein (CRP) levels in saliva and therapy outcomes. Findings indicate that this therapy not only reduces SAD symptoms and discomfort but also correlates with decreased systemic inflammation, as evidenced by lowered CRP levels. Remarkably, higher baseline CRP levels predicted a greater reduction in anxiety symptoms, suggesting a unique response pattern in SAD compared to other psychological disorders. This study highlights systemic inflammation's significance in SAD and the promise of non-invasive biomarkers like salivary CRP for managing psychological disorders. It calls for more research to understand the underlying mechanisms and validate these initial findings.

Salivary CRP predicts treatment response to virtual reality exposure therapy for social anxiety disorder.

BACKGROUND: Social anxiety disorder (SAD) places a profound burden on public health and individual wellbeing. Systemic inflammation may be important to the onset and maintenance of SAD, and anti-inflammatory treatments have shown promise in relieving symptoms of SAD. In the present study, we conducted secondary analyses on data from a randomized clinical trial to determine whether C-reactive protein (CRP) concentrations and social anxiety symptoms decreased over the course of virtual reality exposure therapy, and whether changes in social anxiety symptoms as a function of treatment varied as a function of CRP. METHOD: Adult participants (N = 78) with a diagnosis of SAD (59 % female) were randomized to receive exposure therapy alone, or exposure therapy supplemented with scopolamine. Social anxiety symptoms, salivary CRP, and subjective units of distress were measured across three exposure therapy sessions, at a post-treatment extinction retest, and at a 1-month follow-up. RESULTS: CRP decreased over the course of treatment, b = -0.03 (SE = 0.01), p =.02 95 %CI [-0.06, -0.004], as did all social anxiety symptom domains and subjective distress. Higher CRP was associated with greater decreases from pre-treatment to 1-month follow-up in fear, b = -0.45 (SE = 0.15), p =.004 95 %CI [-0.74, -0.15], and avoidance, b = -0.62 (SE = 0.19), p =.002 95 %CI [-1.01, -0.23], and in-session subjective distress from pre-treatment to post-treatment, b = -0.42 (SE = 0.21), p =.05 95 %CI [-0.83, -0.001]. However, declines in CRP were not correlated with declines in fear, r = -0.07, p =.61, or avoidance, r = -0.10, p =.49, within-persons. CONCLUSIONS: Virtual reality exposure therapy may be associated with an improvement in systemic inflammation in patients with severe SAD. Pre-treatment CRP may also be of value in predicting which patients stand to benefit the most from this treatment.

Advancing the treatment of anxiety disorders in transition-age youth: a review of the therapeutic effects of unconscious exposure.

BACKGROUND: The real-world effectiveness of exposure-based therapies for youth depends on the willingness and ability of young people to tolerate confronting their fears, which can be experienced as highly aversive and create problems with treatment engagement and acceptance. Recently, neuroscientific research on the nonconscious basis of fear has been translated into novel exposure interventions that bypass conscious processing of feared stimuli and that thus do not cause phobic youth to experience distress. We present a review of these unconscious exposure interventions. METHODS: A PRISMA-based search yielded 20 controlled experiments based on three paradigms that tested if fear-related responses could be reduced without conscious awareness in highly phobic, transition-age youth: 14 randomized controlled trials (RCTs), 5 fMRI studies (1 was also an RCT), 4 psychophysiological studies (3 were also RCTs), and 1 ERP study. We conducted meta-analyses of outcomes where feasible. RESULTS: Unconscious exposure interventions significantly (1) reduced avoidance behavior (range of Cohen's d = 0.51-0.95) and self-reported fear (d = 0.45-1.25) during in vivo exposure to the feared situation; (2) reduced neurobiological indicators of fear (d = 0.54-0.62) and concomitant physiological arousal (d = 0.55-0.64); (3) activated neural systems supporting fear regulation more strongly than visible exposure to the same stimuli (d = 1.2-1.5); (4) activated regions supporting fear regulation that mediated the reduction of avoidance behavior (d = 0.70); (5) evoked ERPs suggesting encoding of extinction memories (d = 2.13); and (6) had these effects without inducing autonomic arousal or subjective fear. CONCLUSIONS: Unconscious exposure interventions significantly reduce a variety of symptomatic behaviors with mostly moderate effect sizes in transition-age youth with specific phobias. fMRI and physiological findings establish a neurophysiological basis for this efficacy, and suggest it occurs through extinction learning. Unconscious exposure was well tolerated, entirely unassociated with drop out, and is highly scalable for clinical practice. However, a number of limitations must be addressed to assess potential clinical impacts, including combining unconscious exposure with exposure therapy to boost treatment acceptance and efficacy.

Assessing the post hoc effectiveness of tixagevimab-cilgavimab for prevention of SARS-CoV-2 infections in solid organ transplant recipients.

BACKGROUND: Tixagevimab-cilgavimab (Tix-Cil) was authorized for prophylaxis against COVID-19 in immunocompromised patients from December 2021 through January 2023. Real-world effectiveness for solid organ transplant (SOT) recipients has been unclear. METHODS: We enrolled 911 SOT recipients into a longitudinal COVID-19 serology study, of whom 381 (42%) received ≥1 dose of Tix-Cil. We collected and analyzed data on incident SARS-CoV-2 infections and antibody kinetics for all patients from January 2022 to March 2023, including periods dominated by Omicron BA and BQ subvariants. RESULTS: Over 253 ± 131 days of follow-up, there were 324 new-onset SARS-CoV-2 infections: 117 (31%) in Tix-Cil treated and 207 (39%) in Tix-Cil untreated patients (p = .012). In analyses adjusting for demographic, clinical, and COVID-19 exposure factors, any Tix-Cil treatment was associated with lower infection risk (OR 0.52, 95% CI 0.27-0.96, p = .039) throughout the surveillance period including when more resistant BQ.1 and BQ.1.1 subvariants had emerged (12/1/2022 onwards). Among treated patients, receiving a Tix-Cil dose was associated with substantial and sustained increase in anti-spike IgG antibody and angiotensin-converting enzyme 2 binding inhibition levels (Abbott Architect assay) that together also demonstrated association with lower infection risk (p = .042). During the full surveillance period, the frequency of infections requiring hospitalization was low overall (N = 26, 2.9% of the total cohort) and not significantly different between Tix-Cil recipients (N = 12, 3.2% of treated patients) and non-Tix-Cil recipients (N = 14, 2.6% of untreated patients) with unadjusted p = .31 for between-group difference. CONCLUSION: In a large cohort of SOT recipients, we found that Tix-Cil reduced infection risk even amidst emergent Omicron subvariants. Additionally, the extent of measurable humoral response to Tix-Cil may indicate relative effectiveness. Pre-exposure monoclonal antibody therapy may represent a strategy that will continue to offer clinical benefit for immunocompromised persons who are known to derive limited protection from vaccinations.

Harnessing Immersive Virtual Reality: A Comprehensive Scoping Review of its Applications in Assessing, Understanding, and Treating Eating Disorders.

BACKGROUND: Immersive Virtual Reality (IVR) has shown promise in the assessment, understanding, and treatment of eating disorders (EDs), providing a dynamic platform for clinical innovation. This scoping review aims to synthesize the recent advancements and applications of IVR in addressing these complex psychological disorders. METHODS: This review followed the Preferred Reporting Items for Systematic Reviews and Meta-analysis Protocols, focusing on studies published in the past five years. It included peer-reviewed papers that used IVR for ED assessment, examination, or treatment. A comprehensive database search provided a selection of relevant articles, which were then methodically screened and analyzed. RESULTS: Twenty studies met the inclusion criteria, with a primary focus on Anorexia Nervosa (AN), Bulimia Nervosa (BN), and Binge Eating Disorder (BED). The application of IVR was categorized into three areas: assessment, understanding, and treatment. IVR was found to be an effective tool in assessing body image distortions and emotional responses to food, providing insights that are less accessible through traditional methods. Furthermore, IVR offers innovative treatment approaches by facilitating exposure therapy, modifying body-related biases, and enabling emotional regulation through embodied experiences. The studies demonstrate IVR's potential to improve body image accuracy, reduce food-related anxieties, and support behavioral changes in ED patients. CONCLUSION: IVR stands out as a transformative technology in the field of EDs, offering comprehensive benefits across diagnostic, therapeutic, and experiential domains. The IVR's ability to simulate the brain's predictive coding mechanisms provides a powerful avenue for delivering embodied, experiential interventions that can help recalibrate distorted body representations and dysfunctional affective predictive models implicated in EDs. Future research should continue to refine these applications, ensuring consistent methodologies and wider clinical trials to fully harness IVR's potential in clinical settings.

Effects of a Stimulus Response Task Using Virtual Reality on Unilateral Spatial Neglect: A Randomized Controlled Trial.

OBJECTIVE: To investigate the effects of a stimulus response task using virtual reality (VR) for unilateral spatial neglect (USN). DESIGN: Double-blind randomized controlled trial. SETTING: Acute phase hospital where stroke patients are hospitalized. PARTICIPANTS: The participants were 42 patients (N=42) with right-hemisphere cerebral damage who had been experiencing USN in their daily lives. They were randomly assigned to 3 groups: a stimulus response task with a background shift (SR+BS group), a stimulus response task without a background shift (SR group), and an object gazing task (control group). INTERVENTIONS: The stimulus response task was to search for balloons that suddenly appeared on the VR screen. A background shift was added to highlight the search in the neglected space. The control task was to maintain a controlled gaze on a balloon that appeared on the VR screen. The intervention period was 5 days. MAIN OUTCOME MEASURES: The primary outcome was the participants' scores on a stimulus-driven attention test (SAT) using the reaction time. The stimuli of the SAT were divided into 6 blocks of 3 lines on each side (-3 to +3). The secondary outcomes were their scores on the Behavioral Intention Test conventional, Catherine Bergego Scale, and straight ahead pointing tests. RESULTS: In the SAT, there were significant interaction effects of reaction time between time and group factors in left-2, right+2, and right+3. The SR+BS and SR groups showed significant improvements in the reaction time of left-2 and right+3 compared with the control group. Moreover, the SR+BS group showed a significant improvement in the reaction time of left-2, which was the neglected space, compared with the SR group. However, there were no significant interaction effects of Behavioral Intention Test conventional, Catherine Bergego Scale, and straight ahead pointing. CONCLUSIONS: Our results suggest that the use of stimulus response tasks using VR combined with background shifts may improve left-sided USN.

An investigation of the role of estradiol in fear reduction during a single session of exposure therapy.

Research suggests that estradiol may moderate fear extinction. It is unclear whether these results generalize to exposure therapy. The aim of the current study was to determine whether estradiol moderates outcomes in exposure therapy among women with anxiety disorders. Participants were 35 women with a primary diagnosis of an anxiety disorder who participated in the study as part of routine care at an anxiety specialty clinic. Endogenous estradiol was assessed via saliva. They provided subjective distress ratings before (pre) and after (post) an exposure session, as well as after a brief delay (recall). Contrary to predictions, there were no significant differences in exposure outcomes between the high and low estradiol groups. However, among participants with primary obsessive-compulsive disorder (OCD), results were partially consistent with the hypotheses. Women with lower estradiol initially demonstrated more improvement in subjective distress from pre- to post-exposure, but after the delay, significantly greater distress (attenuated extinction recall). Results suggest that women with lower estradiol may respond less favorably to exposure therapy for OCD relative to women with higher estradiol. These findings await replication in larger samples with longer recall delays. Should replication occur, these results may inform the use of estradiol to augment exposure therapy.

Perfectionism as a predictor of change in digital self-guided interventions for public speaking anxiety in adolescents: A secondary analysis of a four-armed randomized controlled trial.

Public Speaking Anxiety (PSA) interventions targeting adolescents exist; however, not all gain improvement. This exploratory study investigated whether PSA interventions resulted in a decrease in perfectionism and whether pre-treatment level and changes in perfectionism moderated the effects on PSA and social anxiety. The sample consisted of 100 adolescents from junior high schools randomized to four groups: 1) VR only (n = 20), 2) VR + online exposure program (n = 20), 3) online psychoeducation and online exposure program (n = 40), 4) waitlist and online psychoeducation program (n = 20). Self-reported symptoms of PSA, social anxiety, and perfectionism were measured at pre, week 3, post, and 3-months follow-up. Level and change in outcome variables were analyzed using latent growth curve modeling. Results revealed that the interventions did not lead to a reduction in perfectionism. Reduction in perfectionism was associated with a larger reduction in all outcome measures from post to follow-up. No interaction was found between pre-treatment perfectionism and PSA symptoms. High pre-treatment levels of perfectionism were associated with poorer outcomes on social anxiety symptoms from post to follow-up for online exposure groups. The results indicate that one should assess and address high pre-treatment levels of perfectionism during PSA interventions.

Virtual reality exposure therapy for fear of spiders: an open trial and feasibility study of a new treatment for arachnophobia.

PURPOSE: This analogue pilot study examined the feasibility (i.e. preliminary results, safety, acceptability) of a new single-session treatment for adults with a fear of spiders. MATERIALS: It used state-of-the-art consumer available VR-hardware for therapist-assisted exposure (VRET-AP). The VRET-AP is largely adapted from Öst's one-session treatment for arachnophobia (Öst, 1987), with the aim of addressing shortcomings of previous VRET treatments, such as marked differences in procedures compared to available and evidence based in-vivo treatments. METHOD: Participants (N = 12) were screened for fear of spiders using the Spider Phobia Questionnaire (SPQ), Fear Questionnaire (FQ) and the Behavioral Approach Test (BAT), prior to and directly after treatment in a repeated measures quasi-experimental design. In addition, acceptance and completion rates were measured and participants were interviewed about their experience of the treatment. Mean ratings as well as Reliable Change Index (RCI) for individual trajectories were analyzed. RESULTS: The results from the preliminary data indicates potential for improvements with large effect sizes (d = 0.90-1,384) in all measurements of spider fear at post-treatment. Reliable Change Index (RCI) analysis showed that spider fear diminished in all twelve participants although the change was certain in only two. None deteriorated. All that responded accepted the treatment and all 11 participants completed all levels in the treatment. No concerns or adverse effects were reported in the interviews which largely confirm the quantitative results. CONCLUSION: VRET-AP is a feasible alternative for delivering effective treatment for fear of spiders and the results motivate larger, randomized trials of VRET-AP involving participants diagnosed with arachnophobia.

Moving beyond symptom reduction: A meta-analysis on the effect of exposure therapy for PTSD on quality of life.

OBJECTIVES: Quality of life (QOL) is a multidimensional construct including emotional well-being, life satisfaction, and physical health. Individuals with posttraumatic stress disorder (PTSD) consistently report low QOL, highlighting the importance of assessing the effectiveness of first-line PTSD treatments (e.g., exposure-based therapies) on QOL. This meta-analysis examined the efficacy of exposure therapy for PTSD on QOL compared to control conditions (e.g., waitlist, medication, treatment-as-usual) at posttreatment and follow-up (ranging from 1 month to 2 years). METHODS: Building on a previous meta-analysis of exposure-based therapy for PTSD, we searched PsycINFO and Medline in December 2021, July 2022, and March 2023 to include randomized controlled trials of exposure-based treatments for adult PTSD assessing QOL. We screened 295 abstracts for initial eligibility; 20 articles met inclusion criteria and were included (N = 2729 participants). Risk of bias was evaluated using the Cochrane Risk of Bias tool 2.0. RESULTS: At posttreatment, exposure-based therapies showed a medium effect on QOL relative to control conditions (k = 25, g = 0.67). This effect was not observed at follow-up for the small subset of studies with follow-up data (k = 8, g = 0.16). At posttreatment, effect size varied significantly as a function of the control condition (p < .0001). There were no differences in QOL effects across exposure therapies at posttreatment or follow-up (p = .09). CONCLUSION: Exposure therapy was associated with greater improvement in QOL compared to control conditions at posttreatment. Exposure was not superior to control conditions at follow-up, and the longer-term impact of exposure on QOL is unclear. The implications of these findings are discussed, along with the need for more PTSD treatment studies to examine QOL outcomes at posttreatment and follow-up.

[VR-supported therapy for anxiety and posttraumatic stress disorder: current possibilities and limitations]. / VR-gestützte Therapie bei Angst und posttraumatischer Belastungsstörung: aktuelle Möglichkeiten und Grenzen.

BACKGROUND: Virtual reality (VR) is increasingly used in psychotherapy, and the speed of development of therapeutic VR tools is continuously increasing. OBJECTIVE: This narrative review provides an overview of the state of the art regarding VR applications for psychotherapy. MATERIAL AND METHODS: The current state of VR therapy research for anxiety disorders and posttraumatic stress disorder (PTSD) is summarized. The focus lies on VR exposure therapy. Current developments in the field are outlined. RESULTS: For anxiety disorders, especially phobic disorders, there are already positive recommendations in the current German S3 guidelines. For PTSD, the development of VR therapy tools is still in a relatively early stage. CONCLUSION: The development of mobile cost-effective VR solutions in recent years has enabled entirely new applications for VR. The empirical challenges of these new developments are considerable. Nevertheless, the chances for an improvement of psychotherapeutic routine care are good.

Behavioural interventions to treat anxiety in adults with autism and moderate to severe intellectual disabilities: The BEAMS-ID feasibility study.

BACKGROUND: The aim of this feasibility study was to adapt and model a behavioural intervention for anxiety with autistic adults with moderate to severe intellectual disabilities. METHOD: Twenty-eight autistic adults with moderate or severe intellectual disabilities, 37 carers, and 40 therapists took part in this single-group non-randomised feasibility study designed to test intervention feasibility and acceptability, outcome measures, and research processes. RESULTS: The intervention was judged as feasible and acceptable by autistic adults with intellectual disabilities, carers, and therapists. Minor intervention revisions were suggested. Carers completed 100% of outcome measures and the missing data rate was low. Complying with legislation governing the inclusion of participants who lack capacity to decide whether they wanted to take part in this study led to an average 5-week enrolment delay. CONCLUSION: The intervention and associated study processes were judged to be feasible and acceptable and should now be tested within a larger randomised trial.

The impact of hormonal contraceptives on anxiety treatments: From preclinical models to clinical settings.

Exposure therapy is a central component of the first-line treatment for anxiety disorders, a common mental health condition that is twice as prevalent in women relative to men. A key underlying mechanism of exposure therapy is fear extinction, which is an active learning process supported by a neural circuitry that is highly regulated by ovarian hormones. This review synthesises research examining the impact of hormonal contraceptives on laboratory fear extinction tasks in female rats and women, and on exposure therapy in women with anxiety disorders. The evidence indicates that hormonal contraceptives have a detrimental impact on fear extinction and exposure therapy that is consistent across species, and from laboratory to clinical settings. Candidate pathways by which hormonal contraceptives impede fear extinction and exposure therapy include suppression of endogenous ovarian hormones and glucocorticoids, and downregulation of signalling pathways that support extinction learning. Key areas of focus for future research are discussed.

Inactivation of medial or lateral orbitofrontal cortex during fear extinction did not interfere with fear renewal.

Hyperactive orbitofrontal cortical activation is commonly seen in patients of obsessive-compulsive disorder (OCD). Previous studies from our laboratory showed that for rats with aberrant activation of the orbitofrontal cortex (OFC) during the extinction phase, they were unable to use contexts as the reference for proper retrieval of fear memory during renewal test. This result supported the phenomenon that many OCD patients show poor regulation of fear-related behavior. Since there are robust anatomical connections of the OFC with the fear-circuit, we aim to further examine whether the OFC is actively engaged in fear regulation under normal circumstances. In this study, the lateral or medial OFC was inactivated during the extinction phase using the ABA fear renewal procedure. We found that these animals showed intact fear renewal during retrieval test with their freezing levels equivalent to the control rats, revealing that the OFC did not have decisive roles in extinction acquisition. Together with our previous study, we suggest that the OFC only interferes with fear regulation when it becomes pathophysiologically hyperactive.

Effect of massed v. standard prolonged exposure therapy on PTSD in military personnel and veterans: a non-inferiority randomised controlled trial.

BACKGROUND: A short, effective therapy for posttraumatic stress disorder (PTSD) could decrease barriers to implementation and uptake, reduce dropout, and ameliorate distressing symptoms in military personnel and veterans. This non-inferiority RCT evaluated the efficacy of 2-week massed prolonged exposure (MPE) therapy compared to standard 10-week prolonged exposure (SPE), the current gold standard treatment, in reducing PTSD severity in both active serving and veterans in a real-world health service system. METHODS: This single-blinded multi-site non-inferiority RCT took place in 12 health clinics across Australia. The primary outcome was PTSD symptom severity measured by the Clinician-Administered PTSD Scale for DSM-5 (CAPS-5) at 12 weeks. 138 military personnel and veterans with PTSD were randomised. 71 participants were allocated to SPE, with 63 allocated to MPE. RESULTS: The intention-to-treat sample included 138 participants, data were analysed for 134 participants (88.1% male, M = 46 years). The difference between the mean MPE and SPE group PTSD scores from baseline to 12 weeks-post therapy was 0.94 [95% confidence interval (CI) -4.19 to +6.07]. The upper endpoint of the 95% CI was below +7, indicating MPE was non-inferior to SPE. Significant rates of loss of PTSD diagnosis were found for both groups (MPE 53.8%, SPE 54.1%). Dropout rates were 4.8% (MPE) and 16.9% (SPE). CONCLUSIONS: MPE was non-inferior to SPE in significantly reducing symptoms of PTSD. Significant reductions in symptom severity, low dropout rates, and loss of diagnosis indicate MPE is a feasible, accessible, and effective treatment. Findings demonstrate novel methods to deliver gold-standard treatments for PTSD should be routinely considered.

Virtual reality cue exposure therapy for tobacco relapse prevention: a comparative study with standard intervention.

BACKGROUND: Successful interventions have been developed for smoking cessation although the success of smoking relapse prevention protocols has been limited. Cognitive behavioural therapy (CBT) in particular has been hampered by a high relapse rate. Because relapse can be due to conditions associated with tobacco consumption (such as drinking in bars with friends), virtual reality cue exposure therapy (VRCE) can be a potential tool to generate 3D interactive environments that simulate risk situations for relapse prevention procedures. METHODS: To assess the effectiveness of VRCE with CBT, a comparative trial involving 100 smoking abstinent participants was designed with all required virtual environments (VE) created with an inexpensive graphic engine/game level editor. RESULTS: Outcome measures confirmed the immersive and craving eliciting effect of these VEs. Results demonstrated that more participants in the VRCE group did not experience smoking relapse and that VRCE is at least as efficacious as traditional CBT in terms of craving reduction and decrease in nicotine dependence. Dropout and relapse rate in the VRCE group was noticeably lower than the CBT group. Aside from mood scores, no significant differences were found regarding the other scales. CONCLUSION: The present clinical trial provides evidence that VRCE was effective in preventing smoking relapse. Improvement in technology and methodology for future research and applications is delineated.

Massed v. standard prolonged exposure therapy for PTSD in military personnel and veterans: 12-month follow-up of a non-inferiority randomised controlled trial.

BACKGROUND: The utilisation of massed therapy for treating posttraumatic stress disorder (PTSD) is gaining strength, especially prolonged exposure. However, it is unknown whether massed prolonged exposure (MPE) is non-inferior to standard prolonged exposure (SPE) protocols in the long term. The current study aimed to assess whether MPE was non-inferior to SPE at 12 months post-treatment, and to ascertain changes in secondary measure outcomes. METHODS: A multi-site non-inferiority randomised controlled trial (RCT) compared SPE with MPE in 12 clinics. The primary outcome was PTSD symptom severity (CAPS-5) at 12 months post-treatment commencement. Secondary outcome measures included symptoms of depression, anxiety, anger, disability, and quality of life at 12 weeks and 12 months post-treatment commencement. Outcome assessors were blinded to treatment allocation. The intention-to-treat sample included 138 Australian military members and veterans and data were analysed for 134 participants (SPE = 71, MPE = 63). RESULTS: Reductions in PTSD severity were maintained at 12 months and MPE remained non-inferior to SPE. Both treatment groups experienced a reduction in depression, anxiety, anger, and improvements in quality of life at 12 weeks and 12 months post-treatment commencement. Treatment effects for self-reported disability in the SPE group at 12 weeks were not maintained, with neither group registering significant effects at 12 months. CONCLUSIONS: The emergence of massed protocols for PTSD is an important advancement. The current study provides RCT evidence for the longevity of MPE treatment gains at 12 months post-treatment commencement and demonstrated non-inferiority to SPE. Promisingly, both treatments also significantly reduced the severity of comorbid symptoms commonly occurring alongside PTSD.

Effectiveness and comparative effectiveness of evidence-based psychotherapies for posttraumatic stress disorder in clinical practice.

BACKGROUND: While evidence-based psychotherapy (EBP) for posttraumatic stress disorder (PTSD) is a first-line treatment, its real-world effectiveness is unknown. We compared cognitive processing therapy (CPT) and prolonged exposure (PE) each to an individual psychotherapy comparator group, and CPT to PE in a large national healthcare system. METHODS: We utilized effectiveness and comparative effectiveness emulated trials using retrospective cohort data from electronic medical records. Participants were veterans with PTSD initiating mental healthcare (N = 265 566). The primary outcome was PTSD symptoms measured by the PTSD Checklist (PCL) at baseline and 24-week follow-up. Emulated trials were comprised of 'person-trials,' representing 112 discrete 24-week periods of care (10/07-6/17) for each patient. Treatment group comparisons were made with generalized linear models, utilizing propensity score matching and inverse probability weights to account for confounding, selection, and non-adherence bias. RESULTS: There were 636 CPT person-trials matched to 636 non-EBP person-trials. Completing ⩾8 CPT sessions was associated with a 6.4-point greater improvement on the PCL (95% CI 3.1-10.0). There were 272 PE person-trials matched to 272 non-EBP person-trials. Completing ⩾8 PE sessions was associated with a 9.7-point greater improvement on the PCL (95% CI 5.4-13.8). There were 232 PE person-trials matched to 232 CPT person-trials. Those completing ⩾8 PE sessions had slightly greater, but not statistically significant, improvement on the PCL (8.3-points; 95% CI 5.9-10.6) than those completing ⩾8 CPT sessions (7.0-points; 95% CI 5.5-8.5). CONCLUSIONS: PTSD symptom improvement was similar and modest for both EBPs. Although EBPs are helpful, research to further improve PTSD care is critical.

Singular and combined effects of transcranial infrared laser stimulation and exposure therapy on pathological fear: a randomized clinical trial.

BACKGROUND: Preclinical findings suggest that transcranial infrared laser stimulation (TILS) improves fear extinction learning and cognitive function by enhancing prefrontal cortex (PFC) oxygen metabolism. These findings prompted our investigation of treating pathological fear using this non-invasive stimulation approach either alone to the dorsolateral PFC (dlPFC), or to the ventromedial PFC (vmPFC) in combination with exposure therapy. METHODS: Volunteers with pathological fear of either enclosed spaces, contamination, public speaking, or anxiety-related bodily sensations were recruited for this randomized, single-blind, sham-controlled trial with four arms: (a) Exposure + TILS_vmPFC (n = 29), (b) Exposure + sham TILS_vmPFC (n = 29), (c) TILS_dlPFC alone (n = 26), or (d) Sham TILS _dlPFC alone (n = 28). Post-treatment assessments occurred immediately following treatment. Follow-up assessments occurred 2 weeks after treatment. RESULTS: A total of 112 participants were randomized [age range: 18-63 years; 96 females (85.71%)]. Significant interactions of Group × Time and Group × Context indicated differential treatment effects on retention (i.e. between time-points, averaged across contexts) and on generalization (i.e. between contexts, averaged across time-points), respectively. Among the monotherapies, TILS_dlPFC outperformed SHAM_dlPFC in the initial context, b = -13.44, 95% CI (-25.73 to -1.15), p = 0.03. Among the combined treatments, differences between EX + TILS_vmPFC and EX + SHAM_vmPFC were non-significant across all contrasts. CONCLUSIONS: TILS to the dlPFC, one of the PFC regions implicated in emotion regulation, resulted in a context-specific benefit as a monotherapy for reducing fear. Contrary to prediction, TILS to the vmPFC, a region implicated in fear extinction memory consolidation, did not enhance exposure therapy outcome.