Protocol for a multi-site randomized controlled trial of a stepped-care intervention for emergency department patients with panic-related anxiety.

BACKGROUND: Approximately 40% of Emergency Department (ED) patients with chest pain meet diagnostic criteria for panic-related anxiety, but only 1-2% are correctly diagnosed and appropriately managed in the ED. A stepped-care model, which focuses on providing evidence-based interventions in a resource-efficient manner, is the state-of-the art for treating panic disorder patients in medical settings such as primary care. Stepped-care has yet to be tested in the ED setting, which is the first point of contact with the healthcare system for most patients with panic symptoms. METHODS: This multi-site randomized controlled trial (RCT) aims to evaluate the clinical, patient-centred, and economic effectiveness of a stepped-care intervention in a sample of 212 patients with panic-related anxiety presenting to the ED of Singapore's largest public healthcare group. Participants will be randomly assigned to either: 1) an enhanced care arm consisting of a stepped-care intervention for panic-related anxiety; or 2) a control arm consisting of screening for panic attacks and panic disorder. Screening will be followed by baseline assessments and blocked randomization in a 1:1 ratio. Masked follow-up assessments will be conducted at 1, 3, 6, and 12 months. Clinical outcomes will be panic symptom severity and rates of panic disorder. Patient-centred outcomes will be health-related quality of life, daily functioning, psychiatric comorbidity, and health services utilization. Economic effectiveness outcomes will be the incremental cost-effectiveness ratio of the stepped-care intervention relative to screening alone. DISCUSSION: This trial will examine the impact of early intervention for patients with panic-related anxiety in the ED setting. The results will be used to propose a clinically-meaningful and cost-effective model of care for ED patients with panic-related anxiety. TRIAL REGISTRATION: ClinicalTrials.gov NCT03632356. Retrospectively registered 15 August 2018.

Psychophysiological assessment of stress reactivity and recovery in anxiety disorders.

The present study aimed to examine changes in psychophysiological arousal from baseline to a stressor phase (reactivity) and from the stressor phase to a second resting phase (recovery) in patients with anxiety disorders. Fifty adult patients with DSM-5 anxiety disorders (panic disorder, generalized anxiety disorder, or social anxiety disorder) and 28 healthy control (HC) participants underwent psychophysiological monitoring including electrocardiogram, respiration rate, electrodermal activity, gastrocnemius electromyograph, and end-tidal CO2 for a 3-min resting phase, a 6-min mild stressor phase, and a 3-min recovery phase. Anxious patients then went on to receive naturalistic cognitive-behavioral therapy (CBT) in a specialty outpatient clinic. Results for the reactivity phase indicated that compared to HCs, patients with social anxiety disorder exhibited heightened psychophysiological reactivity while patients with panic disorder and generalized anxiety disorder exhibited attenuated reactivity. Results for physiological recovery (return to baseline after the stressor was withdrawn) were mixed, but provided some support for slower autonomic recovery in patients with generalized anxiety disorder and panic disorder compared to HCs. Participants with all anxiety disorders exhibited diminished change in high frequency heart rate variability compared to HCs. Generally, psychophysiological reactivity and recovery were not associated with CBT outcome, though exploratory analyses indicated that greater respiration rate reactivity and stronger respiration rate recovery were associated with better CBT outcomes in patients with panic disorder.

Evaluating the Impact of Freespira on Panic Disorder Patients' Health Outcomes and Healthcare Costs within the Allegheny Health Network.

Panic disorder (PD) is a debilitating condition that drives medical spending at least twice as high as medically matched controls. Excessive utilization of healthcare resources comes from emergency department (ED), medications, diagnostic testing, and physician visits. Freespira is an FDA-cleared digital therapeutic that treats PD and panic attacks (PA) by correcting underlying abnormal respiratory physiology. Efficacy of Freespira has been established in prior studies. This paper reports on a quality improvement program that investigated whether treating PD patients with Freespira would reduce medical costs and improve outcomes over 12-months. Panic symptoms were assessed using the Panic Disorder Severity Scale (PDSS). Pre-and post-treatment insurance claims determined costs. At baseline, mean Clinician Global Impression (CGI-S) was 4.4 (moderately/markedly ill), mean PDSS was 14.4 and mean PA frequency/week was 2 (range 0-5). Immediately post-treatment (week 5) mean CGI-S, PDSS and weekly PA frequency declined to 2.8 (borderline/mildly ill, 4.9 (remission) and 0.2 (range 0-2) respectively, p < 0.001. 82% reported PDSS decrease of ≥ 40% (clinically significant), 86% were PA-free. One-year post treatment mean CGI-S, PDSS and PA remained low at 2.1, 4.4, and 0.3 (range 0-1) respectively. 91% had PDSS decrease of ≥ 40%, 73% were PA-free. The majority of patients were panic attack free and/or reduced their symptoms and avoidance behaviors 1-year post Freespira treatment. Mean overall medical costs were reduced by 35% from $548 to $358 PMPM (per member per month) or an annual reduction of $2280. at 12 months post-treatment. There was a 65% reduction in ED costs from $87 to $30 PMPM. Median pharmacy costs were reduced by 68% from $73 to $23 PMPM.

Cost-effectiveness of Practice Team-Supported Exposure Training for Panic Disorder and Agoraphobia in Primary Care: a Cluster-Randomized Trial.

BACKGROUND: Primary care is the main treatment setting for panic disorder and should be supplemented by collaborative care programs. However, shortage of mental health professionals prevents collaborative care programs from being effectively implemented. The PARADISE study showed the efficacy of a self-managed, cognitive-behavioural therapy (CBT)-oriented exposure training for patients with panic disorder with or without agoraphobia in primary care delivered by the family practice team. OBJECTIVE: To assess the cost-effectiveness of the PARADISE intervention. DESIGN: Cost-effectiveness analysis from the societal perspective based on data from a cluster-randomized controlled trial over a time horizon of 12 months. PARTICIPANTS: Four hundred nineteen adult panic disorder patients with or without agoraphobia. INTERVENTIONS: A self-managed, CBT-oriented exposure training for patients with panic disorder with or without agoraphobia in primary care delivered by the primary care practice team in comparison to routine care. MAIN MEASURES: Total costs from the societal perspective. Direct costs and disease-specific costs. Quality-adjusted life years based on the EQ-5D-3L. Incremental cost-effectiveness ratios and cost-effectiveness acceptability curves. KEY RESULTS: Patients in the intervention group caused lower costs (mean, €1017; 95% confidence interval [-€3306; €1272]; p = 0.38) and gained on average more QALY (mean, 0.034 QALY (95% confidence interval [0.005; 0.062]; p = 0.02). Therefore, the intervention dominated the control treatment. The probability of cost-effectiveness of the intervention at a willingness-to-pay margin of €50,000 per QALY was 96%. Results from supplementary analyses considering direct or disease-specific costs instead of total costs showed comparable results. CONCLUSION: The PARADISE intervention is cost effective. This conclusion is valid for total costs, generic health care (direct) costs, disease-specific health care costs. TRIAL REGISTRATION: German Clinical Trials Register: DRKS00004386 Current Controlled Trials: ISRCTN64669297.

Longitudinal association between panic disorder and health care costs in older adults.

BACKGROUND: To analyze whether probable panic disorder (PD) is associated with health care costs in older age over time. METHODS: Data regarding individuals aged 65 and over were derived from two waves of the ESTHER cohort study (nt1 = 2,348, nt2 = 2,090). Probable PD was assessed using the panic screening module from the Patient Health Questionnaire. Health care costs were obtained through monetary valuation of self-reported health care use data. Fixed effects regressions analyzed the association between transitions in probable PD status and change in health care costs, while adjusting for potential confounders. RESULTS: On a descriptive level, study participants with a positive PD screening displayed higher three-month health care costs compared to those without (incremental costs: € 259 for t1 , € 1,544 for t2 ). Transitions in probable PD were associated with an approximate increase of 65% in outpatient health care costs (ß = 0.50, p < .05). There was no significant association between probable PD transition and change in any other cost category. CONCLUSIONS: Using longitudinal data, our results highlight the economic consequences of probable PD in older adults. Future research should address whether reducing PD in older adults may reduce the associated economic burden and analyze underlying mechanisms.

Differences between the Canadian military's Regular and Reserve Forces in perceived need for care, mental health services use and perceived sufficiency of care: a cross-sectional survey.

OBJECTIVE: The primary objective was to explore differences in perceived need for care (PNC), mental health services use (MHSU) and perceived sufficiency of care (PSC) between Canadian Armed Forces Regular Force (RegF) and Reserve Force (ResF) personnel with an objective need for mental health services. DESIGN: Data came from the 2013 Canadian Armed Forces Mental Health Survey, a cross-sectional survey of serving personnel (n=72 629). Analyses were among those with an Afghanistan deployment and an identified mental disorder (population n=6160; sampled n=868). Logistic regression compared PNC, MHSU and PSC between RegF and ResF. Covariate-adjusted marginal prevalence difference estimates were computed. PRIMARY OUTCOME MEASURE: The primary outcomes were PNC, MHSU and PSC. Each had three service categories, including an aggregate 'any' of the three: (1) information about problems, treatments or services; (2) medication and (3) counselling. RESULTS: ResF had an 10.5% (95% CI -16.7% to -4.4%) lower perceived need for medication services but PNC differences were not significant for other service categories. MHSU tended to be lower for ResF; 9.1% (95%CI -15.5% to -2.6%) lower for medication, 5.4% (95% CI -11.5% to 0.7%) lower, with marginal significance, for counselling and 11.3% (95% CI -17.3% to -5.2%) lower for the 'any' service category. Additionally, ResF tended to have a lower fully met need for care; 13.4% (95% CI -22.1% to -4.6%) lower for information, 15.3% (95% CI -22.9% to -7.6%) lower for counselling and 14.6% (95% CI -22.4% to -6.8%) lower for the 'any' service category. CONCLUSIONS: Our findings suggest MHSU and PSC differences between Canadian RegF and ResF personnel that are not fully accounted for by PNC differences. Deficits in ResF members' perceptions of the sufficiency of information services and counselling services suggest perceived, or experienced, barriers to care beyond any PNC barriers. Additional research assessing barriers to mental healthcare is warranted.

[Development of virtual reality as an exposure technique]. / Die Entwicklung virtueller Realität als Expositionsverfahren.

BACKGROUND: Virtual reality (VR) has been investigated as a medium for exposure therapy of anxiety disorders for 20 years. Various meta-analyses have provided convincing evidence of the therapeutic efficacy of exposure therapy in VR. OBJECTIVE: In recent years VR technology and its applications have considerably improved. Therefore, the current state of the art of VR exposure therapy is presented. MATERIAL AND METHODS: This article provides a narrative review of current research on VR exposure therapy for anxiety disorders and major directions of development in this area. RESULTS: After an almost exclusive focus on specific phobias in the early days, research on more complex anxiety disorders (particularly on social anxiety disorder) is increasing. In addition, VR has become established as an experimental method to probe psychopathological processes and to elucidate the mechanism of action of (VR) exposure therapy. CONCLUSION: There is still a need for more research into VR exposure therapy, especially in complex anxiety disorders (e. g. panic disorder, agoraphobia and social anxiety disorder) and trauma-related disorders. Furthermore, VR has become established as a research tool. The rapid technological development gives reason to expect a continuing increase in VR research, in clinical as well as basic research.

Value of information analysis of an early intervention for subthreshold panic disorder: Healthcare versus societal perspective.

BACKGROUND: Panic disorder is associated with high productivity costs. These costs, which should be included in cost-effectiveness analyses (CEA) from a societal perspective, have a considerable impact on cost-effectiveness estimates. However, they are often omitted in published CEAs. It is therefore uncertain whether choosing a societal perspective changes priority setting in future research as compared to a healthcare perspective. OBJECTIVES: To identify research priorities regarding the cost-effectiveness of an early intervention for subthreshold panic disorder using value of information (VOI) analysis and to investigate to what extent priority setting depends on the perspective. METHODS: We calculated the cost-effectiveness of an early intervention for panic disorder from a healthcare perspective and a societal perspective. We performed a VOI analysis, which estimates the expected value of eliminating the uncertainty surrounding cost-effectiveness estimates, for both perspectives. RESULTS: From a healthcare perspective the early intervention was more effective at higher costs compared to usual care (€17,144 per QALY), whereas it was cost-saving from a societal perspective. Additional research to eliminate parameter uncertainty was valued at €129.7 million from a healthcare perspective and €29.5 million from a societal perspective. Additional research on the early intervention utility gain was most valuable from a healthcare perspective, whereas from a societal perspective additional research would generate little added value. CONCLUSIONS: Priority setting for future research differed substantially according to the perspective. Our study underlines that the health-economic perspective of CEAs on interventions for panic disorder must be chosen carefully in order to avoid inappropriate choices in research priorities.

Reduction in Costs after Treating Comorbid Panic Disorder with Agoraphobia and Generalized Anxiety Disorder.

BACKGROUND: Panic disorder with agoraphobia (PDA) and generalized anxiety disorder (GAD) are impairing and costly disorders that are often misdiagnosed and left untreated despite multiple consultations. These disorders frequently co-occur, but little is known about the costs associated with their comorbidity and the impact of cognitive-behavioral therapy (CBT) on cost reduction. AIMS OF THE STUDY: The first objective of this study was to assess the mental health-related costs associated with the specific concomitance of PDA and GAD. The second aim was to determine whether there is a reduction in direct and indirect mental health-related costs following conventional CBT for the primary disorder only (PDA or GAD) or combined CBT adapted to the comorbidity (PDA and GAD). METHODS: A total of 123 participants with a double diagnosis of PDA and GAD participated in this study. Direct and indirect mental health-related costs were assessed and calculated from a societal perspective at the pre-test, the post-test, and the three-month, six-month and one-year follow-ups. RESULTS: At the pre-test, PDA-GAD comorbidity was found to generate a mean total cost of CADUSD 2,000.48 (SD = USD 2,069.62) per participant over a three-month period. The indirect costs were much higher than the direct costs. Both treatment modalities led to significant and similar decreases in all cost categories from the pre-test to the post-test. This reduction was maintained until the one-year follow-up. DISCUSSION: Methodological choices may have underestimated cost evaluations. Nonetheless, this study supports the cost offset effects of both conventional CBT for primary PDA or GAD and combined CBT for PDA-GAD comorbidity. IMPLICATIONS FOR HEALTHCARE PROVISION AND USE: Treatment of comorbid and costly disorders with evidence-based treatments such as CBT may lead to considerable economic benefits for society. IMPLICATIONS FOR HEALTH POLICIES: Considering the limited resources of healthcare systems, it is important to make choices that will lead to better accessibility of quality services. The application of CBT for PDA, GAD or both disorders and training mental health professionals in this therapeutic approach should be encouraged. Additionally, it would be favorable for insurance plans to reimburse employees for expenses associated with psychological treatment for anxiety disorders. IMPLICATIONS FOR FURTHER RESEARCH: In addition to symptom reduction, it would be of great pertinence to explore which factors can contribute to reducing direct and indirect mental health-related costs.

Disentangling the change-alliance relationship: Observational assessment of the therapeutic alliance during change and stuck episodes.

The therapeutic alliance is considered the most robust process variable associated with positive therapeutic outcome in a variety of psychotherapeutic models [Alexander, L. B., & Luborsky, L. (1986). The Penn Helping Alliance Scales. In L. S. Greenberg & W. M. Pinsoff (Eds.), The psychotherapeutic process: A research handbook (pp. 325-356). New York: Guilford Press; Horvath, A. O., Gaston, L., & Luborsky, L. (1993). The alliance as predictor of benefits of counseling and therapy. In N. Miller, L. Luborsky, J. Barber, & J. P. Docherty (Eds.), Psychodynamic treatment research: A handbook for clinical practice (pp. 247-274). New York, NY: Basic Books; Horvath, A. O., Del Re, A. C., Flückiger, C., & Symonds, D. (2011). Alliance in individual psychotherapy. Psychotherapy, 48, 9-16; Orlinky, D., Grawe, K., & Parks, B. (1994). Process and outcome in psychotherapy: Noch einmal. In A. Bergin & J. S. Garfield (Eds.), Handbook of psychotherapy and behaviour change (4th ed., pp. 270-378). New York, NY: Wiley and Sons]. The relationship between alliance and outcome has traditionally been studied based on measures that assess these therapy factors at a global level. However, the specific variations of the alliance process and their association with therapy segments that are relevant for change have not yet been fully examined. The present study examines the variations in the therapeutic alliance in 73 significant in-session events: 35 change and 38 stuck episodes identified through the observation of 14 short-term therapies of different theoretical orientations. Variations in the alliance were assessed using the VTAS-SF [Shelef, K., & Diamond, G. (2008). Short form of the revised Vanderbilt Therapeutic Alliance Scale: Development, reliability, and validity. Psychotherapy Research, 18, 433-443]. Nested analyses (HLM) indicate a statistically significant better quality of the alliance during change episodes.

A feasibility study of the clinical effectiveness and cost-effectiveness of individual cognitive behavioral therapy for panic disorder in a Japanese clinical setting: an uncontrolled pilot study.

BACKGROUND: In Japan, cognitive behavioral therapy (CBT) for panic disorder (PD) is not well established. Therefore, a feasibility study of the clinical effectiveness and cost-effectiveness of CBT for PD in a Japanese clinical setting is urgently required. This was a pilot uncontrolled trial and the intervention consisted of a 16-week CBT program. The primary outcome was Panic Disorder Severity Scale (PDSS) scores. Quality of life was assessed using the EuroQol's EQ-5D questionnaire. Assessments were conducted at baseline, 8 weeks, and at the end of the study. Fifteen subjects completed outcome measures at all assessment points. RESULTS: At post-CBT, the mean reduction in PDSS scores from baseline was -6.6 (95 % CI 3.80 to -9.40, p < 0.001) with a Cohen's d = 1.77 (95 % CI 0.88-2.55). Ten (66.7 %) participants achieved a 40 % or greater reduction in PDSS. By calculating areas under the curve for EQ-5D index changes, we estimated that patients gained a minimum of 0.102 QALYs per 1 year due to the CBT. CONCLUSIONS: This study demonstrated that individual CBT for PD may be useful in Japanese clinical settings but further randomized control trials are needed. TRIAL REGISTRATION: UMIN-CTR UMIN000022693 (retrospectively registered).

Análisis de costo-efectividad del escitalopram comparado con paroxetina, sertralina, fluoxetina, imipramina y fluvoxamina como terapia de mantenimiento para pacientes con trastorno de pánico en Colombia / Cost-effectiveness analysis of escitalopram compared to paroxetine, sertraline, fluoxetine, imipramine and fluvoxamine as maintenance therapy for patients with panic disorder in Colombia

Problema de investigación: Describir los costos y la efectividad de escitalopram comparado con paroxetina, sertralina, fluoxetina, imipramina y fluvoxamina como terapia de mantenimiento en adultos con diagnóstico de trastorno de pánico en Colombia. Tipo de evaluación económica: Análisis de costo-efectividad. Población objetivo: Adultos colombianos con diagnóstico de trastorno de pánico. Intervención y comparadores: Intervención: escitalopram, Comparadores: paroxetina, sertralina, fluoxetina, imipramina y fluvoxamina. Horizonte temporal: 32 semanas. Perspectiva: SGSSS de Colombia. Tasa de descuento: No aplica. Estructura del modelo: Se estructuró un árbol de decisión, teniendo en cuenta modelos publicados en la literatura. Fuentes de datos de efectividad y seguridad: Reporte de efectividad y seguridad elaborado en diciembre de 2014 en el IETS, Ensayo s clínicos a leatorizados. Desenlaces y valoración: Ausencia de crisis de pánico, Semanas libres de crisis de pánico. Costos incluidos: Costo de los medicamentos, Costo de procedimientos, Costo de los eventos adversos. Fuentes de datos de costos: SISMED, Manual tarifario ISS 2001. Resultados del caso base: Para el caso base, escitalopram, fluvoxamina y fluoxetina e imipramina fueron tecnologías dominadas por sertralina y paroxetina. El costo adicional por crisis de pánico evitada en tratamiento con paroxetina comparado con trasertralina se estimó en $4.814.953. Análisis de sensibilidad: Los análisis de sensibilidad y el diagrama de tornado muestran a la probabilidad de lograr ausencia de crisis de pánico y la probabilidad de recaída, como a las variables con mayor impacto sobre las estimaciones de la razón de costo-efectividad. Conclusiones y discusión: De acuerdo con los hallazgos aquí presentados, paroxetina, ofrece mayor razón de costo-efectividad, respecto a sus comparadores. No obstante, es \r\nnecesario tener en cuenta que cualquiera de las alternativas aquí estudiadas, puede ser costo-efectiva, debido a que las pequeñas variaciones en la probabilidad de ausencia de crisis de pánico pueden cambiar el resultado. La principal limitación de este estudio es la ausencia de información roveniente de estudios de investigación clínica, que muestre el desempeño comparativo entre las tecnologías, así como el seguimiento de los participantes en los estudios, en escenarios de más largo plazo que los existentes al momento de elaborar este documento.(AU)

Análisis de impacto presupuestal de escitalopram, paroxetina y fluvoxamina como terapia de mantenimiento para pacientes adultos con trastorno de pánico en Colombia / Budget impact analysis of escitalopram, paroxetine and fluvoxamine as maintenance therapy for adult patients with panic disorder in Colombia

Tecnologías evaluadas: Nuevas: escitalopram, paroxetina y fluvoxamina. Actuales: sertralina, fluoxetina e imipramina. Población: Pacientes mayores de 18 años con trastorno de pánico en Colombia. Perspectiva\tLa perspectiva del presente AIP corresponde al tercero pagador, que en este caso es el SGSSS en Colombia. Horizonte temporal: El horizonte temporal de este AIP en el caso base corresponde a un año. Adicionalmente se reportan las estimaciones del impacto presupuestal para los años 2 y 3, bajo el supuesto de la inclusión en el POS en el año 1.Costos incluidos: Precios por mg de los medicamentos analizados. Fuente de costos: Los precios de cada tecnología fueron calculados con la base de datos SISMED. Escenarios: En el escenario 1 se considera una igualación progresiva de las participaciones de mercado de todos los medicamentos analizados, igualándose en el año 3. En el escenario 2, además de dicha igualación de participaciones de mercado, se asume un precio común para las nuevas alternativas, siguiendo las metodologías de inclusión de grupos terapéuticos definidas por el Ministerio de Salud y Protección Social. Resultados: Para la inclusión en el POS de escitalopram, paroxetina y fluvoxamina como terapia de mantenimiento para pacientes con trastorno de pánico en Colombia, se requeriría una inversión estimada de $12.563.676.367 en el año 1 y de $22.925.604.761 en el año 3. En el caso en el que los medicamentos del escenario nuevo sean incluidos con un precio común basado en las metodologías de grupos terapéuticos del Ministerio de Salud y Protección Social, el impacto presupuestal se reduciría a $1.318.634.602 en el año 1 y $2.861.023.939, en el año 3.(AU)

Cost-effectiveness of blended vs. face-to-face cognitive behavioural therapy for severe anxiety disorders: study protocol of a randomized controlled trial.

BACKGROUND: Anxiety disorders are among the most prevalent psychiatric conditions, and are associated with poor quality of life and substantial economic burden. Cognitive behavioural therapy is an effective treatment to reduce anxiety symptoms, but is also costly and labour intensive. Cost-effectiveness could possibly be improved by delivering cognitive behavioural therapy in a blended format, where face-to-face sessions are partially replaced by online sessions. The aim of this trial is to determine the cost-effectiveness of blended cognitive behavioural therapy for adults with anxiety disorders, i.e. panic disorder, social phobia or generalized anxiety disorder, in specialized mental health care settings compared to face-to-face cognitive behavioural therapy. In this paper, we present the study protocol. It is hypothesized that blended cognitive behavioural therapy for anxiety disorders is clinically as effective as face-to-face cognitive behavioural therapy, but that intervention costs may be reduced. We thus hypothesize that blended cognitive behavioural therapy is more cost-effective than face-to-face cognitive behavioural therapy. METHODS/DESIGN: In a randomised controlled equivalence trial 156 patients will be included (n = 78 in blended cognitive behavioural therapy, n = 78 in face-to-face cognitive behavioural therapy) based on a power of 0.80, calculated by using a formula to estimate the power of a cost-effectiveness analysis: [Formula: see text]. Measurements will take place at baseline, midway treatment (7 weeks), immediately after treatment (15 weeks) and 12-month follow-up. At baseline a diagnostic interview will be administered. Primary clinical outcomes are changes in anxiety symptom severity as measured with the Beck Anxiety Inventory. An incremental cost-effectiveness ratio will be calculated to obtain the costs per quality-adjusted life years (QALYs) measured by the EQ-5D (5-level version). Health-economic outcomes will be explored from a societal and health care perspective. DISCUSSION: This trial will be one of the first to provide information on the cost-effectiveness of blended cognitive behavioural therapy for anxiety disorders in routine specialized mental health care settings, both from a societal and a health care perspective. TRIAL REGISTRATION: Netherlands Trial Register NTR4912. Registered 13 November 2014.

Prognostic subgroups for remission and response in the Coordinated Anxiety Learning and Management (CALM) trial.

OBJECTIVE: Most patients with anxiety disorders receive treatment in primary care settings. Limited moderator data are available to inform clinicians of likely prognostic outcomes for individual patients. We identify baseline characteristics associated with outcome in adults seeking treatment for anxiety disorders. METHOD: We conducted an exploratory moderator analysis from the Coordinated Anxiety Learning and Management (CALM) trial. In the CALM trial, 1,004 adults who met DSM-IV criteria for generalized anxiety disorder (GAD), panic disorder, social anxiety disorder, and/or posttraumatic stress disorder (PTSD) were randomized to usual care (UC) or a collaborative care intervention (ITV) of cognitive-behavioral therapy and/or pharmacotherapy between June 2006 and April 2008. Logistic regression was used to examine baseline characteristics associated with remission and response overall and by treatment condition. Receiver operating curve (ROC) analyses identified subgroups associated with similar likelihood of response and remission of global anxiety symptoms. Remission was defined as score < 6 on the 12-item Brief Symptom Inventory (BSI-12) anxiety and somatization subscales. Response was defined as at least 50% reduction on BSI-12, or meeting remission criteria. RESULTS: Randomization to ITV over UC was often the strongest predictor of outcome. Several baseline patient characteristics were associated with poor treatment outcome including comorbid depression, increased severity of underlying anxiety disorder(s) (P < .001), low socioeconomic status (perceived [P < .001] and actual [P < .05]), and limited social support (P < .001). Patient characteristics associated with particular benefit from ITV were being female (P < .05), increased depression (P < .01)/GAD severity (P < .05), and low socioeconomic status (P < .05). ROC analysis demonstrated prognostic subgroups with large differences in response likelihood. CONCLUSIONS: Further research should focus on the effectiveness of implementing the ITV intervention of CALM in community treatment centers where patients typically are of low socioeconomic status and may particularly benefit from ITV. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT00347269.

Efficacy of a hybrid online training for panic symptoms and agoraphobia: study protocol for a randomized controlled trial.

BACKGROUND: Recently, internet-based interventions have been proposed as effective treatments for people with panic disorder (PD). However, little is known about the clinical effects of integrating mobile technology into these interventions. Because users carry their smartphones with them throughout the day, we hypothesize that this technology can be used to significantly support individuals with monitoring and overcoming their PD symptoms. The aim of the present study is to evaluate the efficacy and cost-effectiveness of a newly developed hybrid intervention that combines internet/PC with smartphone delivery to treat the symptoms of PD. The intervention is based on cognitive behavioral therapy and consists of six modules over a total of six weeks. METHODS/DESIGN: A two-arm randomized controlled trial (RCT) will be conducted to evaluate the effects of a hybrid online training module for PD. Based on a power calculation (d =0.60; 1-ß of 80%; α =0.05), 90 participants with mild to moderate panic symptoms with or without agoraphobia (as assessed by the Panic and Agoraphobia Scale) will be recruited from the general population and randomly assigned to either the intervention group or a six-month waitlist control group. The primary outcome measure will be the severity of panic symptoms. Secondary outcomes will include depression, quality of life, and an observer-based rating of panic severity. Furthermore, data regarding acceptance and the usability of the smartphone app will be assessed. Assessments will take place at baseline as well as eight weeks, three months, and six months after randomization. Moreover, a cost-effectiveness analysis will be performed from a societal perspective. Data will be analyzed on an intention-to-treat basis and per protocol. DISCUSSION: To our knowledge, this RCT is one of the first to examine the efficacy of a hybrid online training for adult PD. This study seeks to contribute to the emerging field of hybrid online training. If the intervention is efficacious, then research on this hybrid online training should be extended. The cost-effectiveness analysis will also indicate whether online training is an economical tool for treating PD among adults. TRIAL REGISTRATION: German Clinical Trial Register: DRKS00005223 (registered on 15 August 2013).

Cost utility analysis of a collaborative stepped care intervention for panic and generalized anxiety disorders in primary care.

OBJECTIVE: Generalized anxiety and panic disorders are a burden on the society because they are costly and have a significant adverse effect on quality of life. The aim of this study was to evaluate the cost-utility of a collaborative stepped care intervention for panic disorder and generalized anxiety disorder in primary care compared to care as usual from a societal perspective. METHODS: The design of the study was a two armed cluster randomized controlled trial. In total 43 primary care practices in the Netherlands participated in the study. Eventually, 180 patients were included (114 collaborative stepped care, 66 care as usual). Baseline measures and follow-up measures (3, 6, 9 and 12 months) were assessed using questionnaires. We applied the TiC-P, the SF-HQL and the EQ-5D respectively measuring health care utilization, production losses and health related quality of life. RESULTS: The average annual direct medical costs in the collaborative stepped care group were 1854 Euro (95% C.I., 1726 to 1986) compared to €1503 (95% C.I., 1374 to 1664) in the care as usual group. The average quality of life years (QALYs) gained was 0.05 higher in the collaborative stepped care group, leading to an incremental cost effectiveness ratio (ICER) of 6965 Euro per QALY. Inclusion of the productivity costs, consequently reflecting the full societal costs, decreased the ratio even more. CONCLUSION: The study showed that collaborative stepped care was a cost effective intervention for panic disorder and generalized anxiety disorder and was even dominant when a societal perspective was taken. TRIAL REGISTRATION: trialregister.nl, Netherlands Trial Register NTR107.

Evaluation of a practice team-supported exposure training for patients with panic disorder with or without agoraphobia in primary care - study protocol of a cluster randomised controlled superiority trial.

BACKGROUND: Panic disorder and agoraphobia are debilitating and frequently comorbid anxiety disorders. A large number of patients with these conditions are treated by general practitioners in primary care. Cognitive behavioural exposure exercises have been shown to be effective in reducing anxiety symptoms. Practice team-based case management can improve clinical outcomes for patients with chronic diseases in primary care. The present study compares a practice team-supported, self-managed exposure programme for patients with panic disorder with or without agoraphobia in small general practices to usual care in terms of clinical efficacy and cost-effectiveness. METHODS/DESIGN: This is a cluster randomised controlled superiority trial with a two-arm parallel group design. General practices represent the units of randomisation. General practitioners recruit adult patients with panic disorder with or without agoraphobia according to the International Classification of Diseases, version 10 (ICD-10). In the intervention group, patients receive cognitive behaviour therapy-oriented psychoeducation and instructions to self-managed exposure exercises in four manual-based appointments with the general practitioner. A trained health care assistant from the practice team delivers case management and is continuously monitoring symptoms and treatment progress in ten protocol-based telephone contacts with patients. In the control group, patients receive usual care from general practitioners. Outcomes are measured at baseline (T0), at follow-up after six months (T1), and at follow-up after twelve months (T2). The primary outcome is clinical severity of anxiety of patients as measured by the Beck Anxiety Inventory (BAI). To detect a standardised effect size of 0.35 at T1, 222 patients from 37 general practices are included in each group. Secondary outcomes include anxiety-related clinical parameters and health-economic costs. TRIAL REGISTRATION: Current Controlled Trials [http://ISCRTN64669297].

Perceived social support mediates anxiety and depressive symptom changes following primary care intervention.

BACKGROUND: The current study tested whether perceived social support serves as a mediator of anxiety and depressive symptom change following evidence-based anxiety treatment in the primary care setting. Gender, age, and race were tested as moderators. METHODS: Data were obtained from 1004 adult patients (age M = 43, SD = 13; 71% female; 56% White, 20% Hispanic, 12% Black) who participated in a randomized effectiveness trial (coordinated anxiety learning and management [CALM] study) comparing evidence-based intervention (cognitive-behavioral therapy and/or psychopharmacology) to usual care in the primary care setting. Patients were assessed with a battery of questionnaires at baseline, as well as at 6, 12, and 18 months following baseline. Measures utilized in the mediation analyses included the Abbreviated Medical Outcomes (MOS) Social Support Survey, the Brief Symptom Index (BSI)-Somatic and Anxiety subscales, and the Patient Health Questionnaire (PHQ-9). RESULTS: There was a mediating effect over time of perceived social support on symptom change following treatment, with stronger effects for 18-month depression than anxiety. None of the mediating pathways were moderated by gender, age, or race. CONCLUSIONS: Perceived social support may be central to anxiety and depressive symptom changes over time with evidence-based intervention in the primary care setting. These findings possibly have important implications for development of anxiety interventions.