Personalized virtual reality exposure for panic disorder and agoraphobia: A preliminary neurophysiological study.

BACKGROUND: Personalization is considered an important principle in virtual reality (VR) exposure therapy. We aimed to identify whether personalized VR exposure could provoke increased anxiety in patients with panic disorder and agoraphobia as it is considered the first step in successful treatment for anxiety. METHODS: We performed a double-arm, one-day preliminary study among 28 patients with panic disorder and agoraphobia. Three sessions of VR exposure, including a theater, train, and elevator scenario, were conducted in two groups. In the personalized group (n = 14), the brightness and crowd density were customized based on a pre-assessment. In the control group (n = 14), these conditions were fully randomized. Self-reported anxiety, heart rate, skin conductance, and electroencephalography were measured before, during, and after the VR sessions. RESULTS: In the later VR sessions, higher self-reported anxiety levels measured by the Visual Analogue Scale were observed in the personalized exposure group. Increased heart rates during and after the VR sessions were observed in the personalized group. The changes in skin conductance peaks were not significantly different between the groups, but the increase in skin conductance was associated with the participants' perception of presence. The electroencephalogram showed widespread increases in alpha waves in the frontal and temporal areas of the brain in the personalized group than in the control group. CONCLUSION: Personalized VR exposure elicits stronger anxiogenic effects in patients with panic disorder and agoraphobia as suggested by self-report and neurophysiological data. Personalization of VR exposure has the potential for effective behavioral therapy.

Altered Low Frequency Heart Rate Variability Associated with Agoraphobia in Panic Disorder: A Retrospective Study.

PURPOSE: This study aimed to compare the clinical features of panic disorder (PD) with comorbid agoraphobia to those of PD alone. We focused on autonomic nervous system (ANS) alterations reflected in heart rate variability (HRV) and executive function deficits reflected in the Stroop test. MATERIALS AND METHODS: We retrospectively compared psychometric features, Stroop test results, and resting-state HRV across three groups: a subclinical group with anxiety attack history, a PD group without agoraphobia, and a PD group with agoraphobia. The subclinical group included 10 male and 34 female, the PD without agoraphobia group included 17 male and 19 female, and the PD with agoraphobia group included 11 male and 18 female. RESULTS: The PD with agoraphobia group had higher Symptom Checklist-95 scores than the other groups. Both PD groups had longer reaction times in the Stroop test than the subclinical group. There were no significant differences in HRV parameters between the PD groups with and without agoraphobia. Compared with the subclinical group, the PD with agoraphobia group showed significantly lower values of the natural logarithm of low-frequency HRV. CONCLUSION: Our results do not support that executive function deficits and ANS alterations are more pronounced with comorbid agoraphobia among PD groups. However, PD with agoraphobia patients showed more complex and severe clinical symptoms in their self-reports. Compared with the subclinical group, PD patients with agoraphobia showed specific features in the natural logarithm of low-frequency HRV. Our findings suggest that agoraphobia comorbidity should be considered when evaluating or treating patients with PD.

The Bergen 4-day treatment for panic disorder: adapting to COVID-19 restrictions with a hybrid approach of face-to-face and videoconference modalities.

BACKGROUND: The Bergen 4-day treatment (B4DT) is a concentrated exposure-based therapy that has been shown to be effective in the treatment of anxiety disorders. The current study sought to examine the effectiveness of B4DT for panic disorder (PD), when delivered with a combination of face-to-face sessions and videoconferencing. METHODS: Treatment was delivered to 50 patients from April 2020 to May 2021. Because of regulations during the pandemic, a significant portion of the treatment was conducted via videoconference. The primary outcome measure was the clinician-rated Panic Disorder Severity Scale (PDSS), and secondary measures included patient-rated symptoms of panic disorder, agoraphobia, generalized anxiety, depression, and treatment satisfaction. Changes in symptom levels over time were estimated using multilevel models. RESULTS: Patients showed a significant reduction in clinician-rated symptoms of panic disorder (Measured by PDSS) from before treatment to post treatment (d = 2.18) and 3-month follow-up (d = 2.01). At three months follow-up 62% of patients were classified as in remission, while 70% reported a clinically significant response. We also found a reduction in symptoms of depression and generalized anxiety, and the patients reported high satisfaction with the treatment. CONCLUSION: The current study suggests that B4DT delivered in a combination of videoconference and face-to-face meetings may be a useful treatment approach. As the study is uncontrolled, future studies should also include more strictly designed investigations.

[Exposure therapy for panic disorder and agoraphobia in the context of existing antidepressive medication]. / Expositionstherapie bei Panikstörung und Agoraphobie im Kontext bestehender antidepressiver Medikation.

BACKGROUND: Cognitive behavioral therapy (CBT) and pharmacotherapy with antidepressants are both a highly effective treatment for agoraphobia and/or panic disorder; however, a combination of CBT and antidepressants is under debate due to potentially unfavorable interference effects. The associations of existing antidepressant medication with panic and agoraphobia symptom burden and their change in the context of a structured 5­week day hospital and exposure-focused treatment in a naturalistic setting were investigated. METHODS: Out of a total of n = 488 patients medication use during treatment was retrospectively determined for n = 380: n = 100 (26.3%) were taking antidepressants of different drug classes. Calculations were performed using multiple linear regression analysis, t­tests, response analyses, and χ2-tests. RESULTS: Patients with existing antidepressant medication more often met the criteria for comorbid depressive disorder (p < 0.001). The measure of symptom change and treatment response rates did not differ between patients with and without antidepressants with respect to anxiety symptoms. DISCUSSION: In the context studied, patients with and without existing antidepressant medication benefited equally from CBT with respect to anxiety symptoms.

Effective-and Tolerable: Acceptance and Side Effects of Intensified Exposure for Anxiety Disorders.

Despite striking empirical support, exposure-based treatments for anxiety disorders are underutilized. This is partially due to clinicians' concerns that patients may reject exposure or experience severe side effects, particularly in intensive forms of exposure. We examined acceptance and side effects of two randomly assigned variants of prediction error-based exposure treatment differing in temporal density (1 vs. 3 sessions/week) in 681 patients with panic disorder, agoraphobia, social anxiety disorder, and multiple specific phobias. Treatment acceptance included treatment satisfaction and credibility, engagement (i.e., homework completion), and tolerability (i.e., side effects, dropout, and perceived treatment burden). Side effects were measured with the Inventory for the Balanced Assessment of Negative Effects of Psychotherapy (INEP). We found treatment satisfaction, credibility, and engagement to be equally high in both variants of exposure-based treatment, despite higher treatment burden (ß = 0.25) and stronger side effects (ß = 0.15) in intensified treatment. 94.1% of patients reported positive effects in the INEP. 42.2% reported side effects, with treatment stigma (16.6%), low mood (14.8%) and the experience to depend on the therapist (10.9%) being the most frequently reported. The mean intensity of side effects was low. We conclude that prediction error-based exposure treatment is well accepted by patients with different anxiety disorders and that patients also tolerate temporally intensified treatment, despite higher perceived treatment burden and stronger side effects. Clinicians should be aware of the most frequent side effects to take appropriate countermeasures. In sum, temporal intensification appears to be an acceptable strategy to achieve faster symptom reduction, given patients' well-informed consent.

Virtual reality interventions for the treatment of anxiety disorders: A scoping review.

BACKGROUND: & Objectives: Virtual Reality (VR) refers to an artificial, immersive three-dimensional environment with interactive sensory stimuli. VR is typically incorporated into the psychotherapeutic process as a means of providing exposure therapy. The objectives of this scoping review were to synthesize the most up-to-date evidence on the outcomes, acceptability, and side effects of VR interventions for treating anxiety disorders in adults. METHODS: This scoping review is grounded in the methodological framework of Arksey and O'Malley (2005). The databases searched were PubMed, EMBASE, Web of Science, PsycINFO, and ProQuest Dissertations and Theses. RESULTS: The search process identified 112 unique citations. 52 (46%) of the eligible articles examined participants with specific phobias, 25 (22%) with PTSD, 21 (19%) with social anxiety disorder, 12 (10%) with panic disorder with or without agoraphobia, and 3 (3%) with generalized anxiety disorder. VR interventions often led to statistically significant and meaningful reductions in symptoms for people with anxiety disorders. Additionally, they were acceptable to clients and associated with minimal side effects for all types of anxiety disorders, except for Combat-Related PTSD in Vietnam veterans. LIMITATIONS: Limitations included the fact that the studies in this review were of varying quality, and that articles in languages other than English and French were excluded. CONCLUSION: VR interventions appeared to be a viable alternative to conventional exposure therapy. Future research should include more male participants and have a stronger emphasis on acceptability and side effects. Increased traction for VR interventions for generalized anxiety disorder and panic disorder is also important.

[Prescription-based digital interventions in psychiatry : Methodology, possible areas of application, and legal framework of digital tools for panic disorder and agoraphobia available in Germany]. / Digitale Gesundheitsanwendungen mit psychotherapeutischem Fokus : Therapieprinzipien, Einsatzmöglichkeiten, rechtlicher Rahmen und Verordnungspraxis am Beispiel der Anwendungen für die Panikstörung und Agoraphobie.

In 2020, prescription-based digital interventions were introduced in Germany. These digital courses have to meet safety and data privacy requirements and must prove positive effects on symptoms and/or other outcome parameters. Interventions are available for a range of mental disorders. For patients with panic disorder and agoraphobia, several applications based on cognitive behavioral therapy have been developed. Within these digital courses, patients can typically access psychoeducational content and practice psychotherapeutic strategies such as exposure therapy. Recent meta-analyses prove the effectiveness of such interventions when compared with waitlist control conditions. According to current German guidelines, digital courses can be used to prepare psychotherapy and as an accompanying tool during psychotherapy. In Germany, physicians and psychotherapist can prescribe digital interventions for outpatients and as a post-hospital treatment..

The moderating and mediating role of telepresence and cognitive change in cognitive behaviour therapy delivered via videoconference.

In this study, we combined the results of two controlled trials and examined the relationships between working alliance, telepresence, cognitive change and treatment outcome. Sixty-five participants with a primary diagnosis of generalized anxiety disorder (GAD) or panic disorder with agoraphobia (PDA) received cognitive behaviour therapy delivered via videoconference. Participants completed measures of working alliance and telepresence after three psychotherapy sessions. They also completed measures of treatment outcome and dysfunctional beliefs (cognitive change) specific to PDA and GAD at pretreatment and posttreatment. Results revealed that telepresence at the fifth session moderated the relationship between the working alliance at the first and fifth sessions. As telepresence increased, its impact on the working alliance diminished. Cognitive change mediated the relationship between the working alliance at the fifth session and treatment outcome.

Agoraphobic avoidance in patients with psychosis: Severity and response to automated VR therapy in a secondary analysis of a randomised controlled clinical trial.

BACKGROUND: The social withdrawal of many patients with psychosis can be conceptualised as agoraphobic avoidance due to a range of long-standing fears. We hypothesised that greater severity of agoraphobic avoidance is associated with higher levels of psychiatric symptoms and lower levels of quality of life. We also hypothesised that patients with severe agoraphobic avoidance would experience a range of benefits from an automated virtual reality (VR) therapy that allows them to practise everyday anxiety-provoking situations in simulated environments. METHODS: 345 patients with psychosis in a randomised controlled trial were categorised into average, moderate, high, and severe avoidance groups using the Oxford Agoraphobic Avoidance Scale. Associations of agoraphobia severity with symptom and functioning variables, and response over six months to brief automated VR therapy (gameChange), were tested. RESULTS: Greater severity of agoraphobic avoidance was associated with higher levels of persecutory ideation, auditory hallucinations, depression, hopelessness, and threat cognitions, and lower levels of meaningful activity, quality of life, and perceptions of recovery. Patients with severe agoraphobia showed the greatest benefits with gameChange VR therapy, with significant improvements at end of treatment in agoraphobic avoidance, agoraphobic distress, ideas of reference, persecutory ideation, paranoia worries, recovering quality of life, and perceived recovery, but no significant improvements in depression, suicidal ideation, or health-related quality of life. CONCLUSIONS: Patients with psychosis with severe agoraphobic avoidance, such as being unable to leave the home, have high clinical need. Automated VR therapy can deliver clinical improvement in agoraphobia for these patients, leading to a number of wider benefits.

The Bergen 4-day treatment for panic disorder: replication and implementation in a new clinic.

BACKGROUND: Bergen 4-day treatment (B4DT) is a concentrated exposure-based treatment (cET), where the patient receives concentrated, individually tailored cognitive behavioral therapy (CBT) during four consecutive days. Previous findings have indicated that B4DT could be a promising treatment for panic disorder (PD). AIM: The aim of the present study was to evaluate the implementation of B4DT for panic disorder with- and without agoraphobia, at a new clinic. This is the first replication study for B4DT on panic disorder. METHOD: Thirty consecutively recruited patients with PD were included in an open trial design. Assessment of symptoms of panic disorder were measured with Panic Disorder Severity Scale (PDSS), while symptoms of generalized anxiety were assessed by Generalized Anxiety Disorder-7 (GAD-7) and depressive symptoms by Patient Health Questionnaire (PHQ-9) pre-treatment, post-treatment and at 3-month follow-up. Treatment satisfaction was measured with Client Satisfaction Questionnaire (CSQ-8) post-treatment. RESULTS: The results showed a significant reduction in symptom severity from pre-treatment to post-treatment (d = 4.32), and at 3-month follow-up (d = 4.91). The proportion of patients classified as fulfilling the criteria for remission was 80.0% at post-treatment and 86.7% at follow up. There was a significant reduction in symptoms of depression and generalized anxiety. Treatment satisfaction was high and none of the patients dropped out. CONCLUSION: The current study replicated the results from the original study and indicate that the treatment can be successfully implemented at new clinics. B4DT may be a promising treatment for panic disorder and comorbid symptoms of generalized anxiety and depression. Larger and more controlled studies are needed to establish the efficacy of B4DT for panic disorder.

Patient characteristics and changes in anxiety symptoms in patients with panic disorder: Post-hoc analysis of the PARADIES cluster randomised trial.

Anxiety disorders are among the most common mental health problems in primary care. The PARADIES (Patient Activation foR Anxiety DIsordErS) intervention combined elements of cognitive behavioural therapy with case management and has demonstrated efficacy. Our aim was to explore patient characteristics, which may influence the course of anxiety symptoms over a 12 months period. Multiple linear regression was used to quantify associations of baseline characteristics (demographics, clinical parameters, medication use) with changes in anxiety symptoms as measured by the Beck anxiety inventory. Treatment modalities (e.g. adherence to appointment schedules) were considered as confounders. We examined univariate associations between dependent and independent variables before considering all independent variables in a multivariate final model. To find the best model to explain BAI score changes, we performed step-wise selection of independent variables based on Akaike information criteria. We tested for interaction terms between treatment allocation (intervention vs control) and independent variables using the multivariate model. We repeated these analyses in control vs intervention groups separately. From the original trial (N = 419), 236 patients (56.3%) were included. In the multivariate model, receiving the intervention (p<0.001), higher anxiety symptom severity (p<0.001) and longer illness duration at baseline (p = 0.033) were significantly associated with changes in anxiety symptom severity to the better while depression severity at baseline (p<0.001) was significantly associated with changes in anxiety symptoms to the worse. In stratified analyses, the control group showed significant associations between depression symptom severity and illness duration with anxiety symptom changes while baseline severity of anxiety symptoms remained significantly associated with anxiety symptom changes in both groups. A brief primary-care-based exposure training combined with case management is effective in a broad range of patients with panic disorder with/without agoraphobia, including those with longer illness duration and co-existing symptoms of depression at baseline.

Internet psychotherapeutic interventions for anxiety disorders - a critical evaluation.

BACKGROUND: During the COVID-19 pandemic, internet-delivered psychotherapeutic interventions (IPI) move increasingly into the focus of attention. METHOD: We reviewed 39 randomized controlled studies of IPIs with 97 study arms (n = 4122 patients) for anxiety disorders (panic disorder/agoraphobia, generalized anxiety disorder, and social anxiety disorder) and performed a meta-analysis. Most studies were conducted with cognitive behavioural approaches (iCBT). Results were compared with a previous meta-analysis examining medications and face-to-face (F2F) psychotherapy. RESULTS: In direct comparisons, IPIs were as effective as F2F-CBT and superior to waitlist controls. Programs with more intensive therapist contact yielded higher effect sizes (ES). We compared the obtained ES with a previous comprehensive meta-analysis of 234 studies. In this comparison, iCBT was less effective than individual F2F-CBT and medications, not different from pill placebos, and more effective than psychological placebo and waitlist (p > .0001 for all comparisons). ES of IPIs may be overestimated. Treatments were only compared to waitlist, which is not a sufficient control condition. 97% of the studies were not blinded with regard to the main outcome measure. 32% of the participants received antianxiety drugs during the trials. In 89%, participants were recruited by advertisements rather than from clinical settings, and 63% of the participants had an academic background (students or university employees) which might affect the generalizability of the findings. Remote diagnoses were often made by students without completed training in psychotherapy. In only 15% of the studies, diagnoses were made in personal contact with a psychiatrist or psychologist. In 44% of the studies, the 'therapists' maintaining remote contact with the participants were mostly students without completed psychotherapy education. CONCLUSIONS: IPIs may be a useful tool when face-to-face psychotherapy is not easily available, or as an add-on to standard psychotherapeutic or psychopharmacological treatments but should perhaps not be used as monotherapy. We have suggested standards for future research and the practical use of IPIs.

Self-guided digital treatment with virtual reality for panic disorder and agoraphobia: a study protocol for a randomized controlled trial.

BACKGROUND: Cognitive behavioral therapy is the first-line treatment for patients with panic disorder (PD) and agoraphobia (AG). Yet, many patients remain untreated due to limited treatment resources. Digital self-guided short-term treatment applications may help to overcome this issue. While some therapeutic applications are already supported by health insurance companies, data on their efficacy is limited. The current study investigates the effect of self-guided digital treatment comprising psychoeducation and virtual reality exposure therapy (VRET). METHODS: Thirty patients diagnosed with PD, AG, or panic disorder with agoraphobia (PDA) will be randomly assigned to either the experimental group (EG) or the control group (CG). Participants of both groups will undergo baseline diagnostics in the first two sessions. The subsequent treatment for the EG consists of a self-guided 6-week phase of application-based psychoeducation, one therapy session preparing for the VRET, and 4 weeks of application-based self-guided VRET. To control for the potential effects of the therapy session with the therapist, the CG will receive relaxation and stress-reduction training instead. All patients will then undergo a closing session which terminates with the post-assessment (~ 10 weeks after baseline assessment) and a follow-up assessment 6 weeks following the closing session. Symptom severity (primary outcome) will be assessed at baseline, interim, post-treatment, and follow-up. Additionally, remission status (secondary outcome) will be obtained at follow-up. Both measures will be compared between the groups. DISCUSSION: The current study aims at providing insights into the efficacy of short-term treatment applications including psychoeducation and self-guided VRET. If successful, this approach might be a feasible and promising way to ease the burden of PD, AG, and PDA on the public health system and contribute to a faster access to treatment. TRIAL REGISTRATION: ISRCTN ISRCTN10661970 . Prospectively registered on 17 January 2022.

Cognitive changes in health locus of control attributions after behavioral analysis in patients with panic disorder and/or agoraphobia.

Patients with Panic Disorder and / or Agoraphobia (PD +/- Ag) attribute their mental health more to external factors and less to internal, while after behavior treatment (BT) their external attributions decrease and internal attributions increase. We examined whether these cognitive changes observed at the end of BT, begin earlier. Forty patients with PD +/- Ag were assessed on the Multidimensional Health Locus of Control Scale, before and after the diagnostic and psychoeducational sessions that precede the clinical implementation of BT. Decreased health attributions to significant others (t = 4.22, p < 0.01), and an increase trend to self (t = -0.78, p = 0.43) were observed, which are compatible with the active role patients need to adopt in the clinical application of BT.

Maximizing the non-specific factors in brief cognitive behavioral therapy for panic disorder and agoraphobia: A multiple baseline case series documenting feasibility and initial efficacy.

There is evidence for non-specific factors impacting treatment outcomes, with pragmatic concerns regarding the need to popularize briefer formats of cognitive behavioral therapy (CBT). The need to have more culturally suitable and acceptable forms of CBT is also indicated. We evaluated the feasibility and efficacy of a brief 5 session CBT (bCBT) in participants (N = 4) with panic disorder (PD) and agoraphobia, using a non-concurrent multiple baseline design. In this case series, efforts were made to maximize non-specific factors of psychotherapy in bringing about treatment outcomes. Reliable and significant treatment effects were observed at post-intervention and follow-up assessments. The present study offers preliminary evidence of a bCBT protocol that comprises the efforts to maximize the non-specific factors in psychotherapy such as credibility, expectancy, and the therapeutic alliance in bringing treatment outcomes; however, further controlled evaluation is warranted. We also discuss the mechanisms contributing to these treatment outcomes in the present protocol.

A pragmatic randomized controlled trial of a group self-management support program versus treatment-as-usual for anxiety disorders: study protocol.

BACKGROUND: The integration of a personal recovery-oriented practice in mental health services is an emerging principle in policy planning. Self-management support (SMS) is an intervention promoting recovery that aims at educating patients on the nature of their mental disorder, improving their strategies to manage their day-to-day symptoms, fostering self-efficacy and empowerment, preventing relapse, and promoting well-being. While SMS is well established for chronic physical conditions, there is a lack of evidence to support the implementation of structured SMS programs for common mental disorders, and particularly for anxiety disorders. This study aims to examine the effectiveness of a group-based self-management support program for anxiety disorders as an add-on to treatment-as-usual in community-based care settings. METHODS/DESIGN: We will conduct a multicentre pragmatic randomized controlled trial with a pre-treatment, post-treatment (4-month post-randomization), and follow-ups at 8, 12 and 24-months. TREATMENT AND CONTROL GROUPS: a) group self-management support (10 weekly 2.5-h group web-based sessions with 10-15 patients with two trained facilitators); b) treatment-as-usual. Participants will include adults meeting DSM-5 criteria for Panic Disorder, Agoraphobia, Social Anxiety Disorder, and/or Generalized Anxiety Disorder. The primary outcome measure will be the Beck Anxiety Inventory; secondary outcome measures will comprise self-reported instruments for anxiety and depressive symptoms, recovery, self-management, quality of life, and service utilisation. STATISTICAL ANALYSIS: Data will be analysed based on intention-to-treat with a mixed effects regression model accounting for between and within-subject variations in the effects of the intervention. DISCUSSION: This study will contribute to the limited knowledge base regarding the effectiveness of structured group self-management support for anxiety disorders. It is expected that changes in patients' self-management behaviour will lead to better anxiety management and, consequently, to improved patient outcomes. TRIAL REGISTRATION: ClinicalTrials.gov: NCT05124639 . Prospectively registered 18 November 2021.

Group cognitive behavioural therapy with virtual reality exposure versus group cognitive behavioural therapy with in vivo exposure for social anxiety disorder and agoraphobia: a protocol for a randomised clinical trial.

INTRODUCTION: Anxiety disorders have a high lifetime prevalence, early-onset and long duration or chronicity. Exposure therapy is considered one of the most effective elements in cognitive behavioural therapy (CBT) for anxiety, but in vivo exposure can be challenging to access and control, and is sometimes rejected by patients because they consider it too aversive. Virtual reality allows flexible and controlled exposure to challenging situations in an immersive and protected environment. AIM: The SoREAL-trial aims to investigate the effect of group cognitive behavioural therapy (CBT-in vivo) versus group CBT with virtual reality exposure (CBT-in virtuo) for patients diagnosed with social anxiety disorder and/or agoraphobia, in mixed groups. METHODS AND ANALYSIS: The design is an investigator-initiated randomised, assessor-blinded, parallel-group and superiority-designed clinical trial. Three hundred two patients diagnosed with social anxiety disorder and/or agoraphobia will be included from the regional mental health centres of Copenhagen and North Sealand and the Northern Region of Denmark. All patients will be offered a manual-based 14-week cognitive behavioural group treatment programme, including eight sessions with exposure therapy. Therapy groups will be centrally randomised with concealed allocation sequence to either CBT-in virtuo or CBT-in vivo. Patients will be assessed at baseline, post-treatment and 1-year follow-up by treatment blinded researchers and research assistants. The primary outcome will be diagnosis-specific symptoms measured with the Liebowitz Social Anxiety Scale for patients with social anxiety disorder and the Mobility Inventory for Agoraphobia for patients with agoraphobia. Secondary outcome measures will include depression symptoms, social functioning and patient satisfaction. Exploratory outcomes will be substance and alcohol use, working alliance and quality of life. ETHICS AND DISSEMINATION: The trial has been approved by the research ethics committee in the Capital Region of Denmark. All results, positive, negative as well as inconclusive, will be published as quickly as possible and still in concordance with Danish law on the protection of confidentially and personal information. Results will be presented at national and international scientific conferences. The trial has obtained approval by the Regional Ethics Committee of Zealand (H-6-2013-015) and the Danish Data Protection Agency (RHP-2014-009-02670). The trial is registered at ClinicalTrial.gov as NCT03845101. The patients will receive information on the trial both verbally and in written form. Written informed consent will be obtained from each patient before inclusion in the trial. The consent form will be scanned and stored in the database system and the physical copy will be destroyed. It is emphasised that participation in the trial is voluntary and that the patient can withdraw his or her consent at any time without consequences for further and continued treatment. TRIAL REGISTRATION NUMBER: NCT03845101.

Comparative efficacy and acceptability of psychotherapies for panic disorder with or without agoraphobia: systematic review and network meta-analysis of randomised controlled trials.

BACKGROUND: Psychotherapies are the treatment of choice for panic disorder, but which should be considered as first-line treatment is yet to be substantiated by evidence. AIMS: To examine the most effective and accepted psychotherapy for the acute phase of panic disorder with or without agoraphobia via a network meta-analysis. METHOD: We conducted a systematic review and network meta-analysis of randomised controlled trials (RCTs) to examine the most effective and accepted psychotherapy for the acute phase of panic disorder. We searched MEDLINE, Embase, PsycInfo and CENTRAL, from inception to 1 Jan 2021 for RCTs. Cochrane and PRISMA guidelines were used. Pairwise and network meta-analyses were conducted using a random-effects model. Confidence in the evidence was assessed using Confidence in Network Meta-Analysis (CINeMA). The protocol was published in a peer-reviewed journal and in PROSPERO (CRD42020206258). RESULTS: We included 136 RCTs in the systematic review. Taking into consideration efficacy (7352 participants), acceptability (6862 participants) and the CINeMA confidence in evidence appraisal, the best interventions in comparison with treatment as usual (TAU) were cognitive-behavioural therapy (CBT) (for efficacy: standardised mean differences s.m.d. = -0.67, 95% CI -0.95 to -0.39; CINeMA: moderate; for acceptability: relative risk RR = 1.21, 95% CI -0.94 to 1.56; CINeMA: moderate) and short-term psychodynamic therapy (for efficacy: s.m.d. = -0.61, 95% CI -1.15 to -0.07; CINeMA: low; for acceptability: RR = 0.92, 95% CI 0.54-1.54; CINeMA: moderate). After removing RCTs at high risk of bias only CBT remained more efficacious than TAU. CONCLUSIONS: CBT and short-term psychodynamic therapy are reasonable first-line choices. Studies with high risk of bias tend to inflate the overall efficacy of treatments. Results from this systematic review and network meta-analysis should inform clinicians and guidelines.

Using 360-degree videos for virtual reality exposure in CBT for panic disorder with agoraphobia: a feasibility study.

BACKGROUND: Cognitive behavioural therapy (CBT) is an effective treatment for panic disorder with agoraphobia (PDA). However, implementation of some of the procedures involved, particularly in vivo exposure, can be time consuming and taxing for routine health care services. CBT with exposure taking place in virtual reality (VR-CBT) is a more time-efficient option and has shown promising results in the treatment of PDA. However, VR-CBT requires expensive equipment and appropriate virtual environments, which historically has been costly and cumbersome to produce. Thus, access to VR-CBT has been sparse in regular care environments. AIMS: The aim of this study was to investigate whether VR-CBT using filmed virtual environments produced with a low-cost 360-degree film camera can be a feasible and acceptable treatment for PDA when implemented in a primary care context. METHOD: This was an open feasibility trial with a within-group design, with assessments conducted at pre-test, post-test, and 6-month follow-up. Participants (n = 12) received a 10-12 week treatment programme of VR-CBT and PDA-related symptoms were assessed by the primary outcome measure The Mobility Inventory for Agoraphobia (MIA) and the Panic-Disorder Severity Scale-Self Rated (PDSS-SR). RESULTS: The results showed that treatment satisfaction was high and participants were significantly improved on PDA-related measures at post-treatment and at 6-month follow-up with large effect sizes (Cohen's d range = 1.46-2.82). All 12 participants completed the treatment. CONCLUSIONS: These findings suggest that VR-CBT with 360-degree video virtual environments delivered to primary care patients with PDA is feasible, acceptable, and potentially efficacious.