A pragmatic randomized controlled trial of group transdiagnostic cognitive-behaviour therapy for anxiety disorders in primary care: study protocol.

BACKGROUND: Anxiety disorders are the most common mental disorders in community settings, and they are associated with significant psychological distress, functional and social impairment. While cognitive behaviour therapy (CBT) is the most consistently efficacious psychological treatment for anxiety disorders, barriers preclude widespread implementation of CBT in primary care. Transdiagnostic group CBT (tCBT) focuses on cognitive and behavioural processes and intervention strategies common to different anxiety disorders, and could be a promising alternative to conventional CBT. This study aims to examine the effectiveness of a transdiagnostic group CBT for anxiety disorders program as a complement to treatment-as-usual (TAU) in primary mental health care. METHODS/DESIGN: The trial is a multicentre pragmatic randomized controlled trial with a pre-treatment, post-treatment, and follow-up at 4, 8 and 12-months design. Treatment and control groups. a) tCBT (12 weekly 2-h group sessions following a manualized treatment protocol); b) TAU for anxiety disorders. Inclusion criteria comprise meeting DSM-5 criteria for primary Panic Disorder, Agoraphobia, Social Anxiety Disorder and/or Generalized Anxiety Disorder. Patients are recruited in three regions in the province of Quebec, Canada. The primary outcome measures are the self-reported Beck Anxiety Inventory and the clinician-administered Anxiety and Related Disorders Interview Schedule for DSM-5 (ADIS-5); secondary outcome measures include treatment responder status based on the ADIS-5, and self-reported instruments for specific anxiety and depression symptoms, quality of life, functioning, and service utilisation. STATISTICAL ANALYSIS: Intention-to-treat analysis. A mixed effects regression model will be used to account for between- and within-subject variations in the analysis of the longitudinal effects of the intervention. DISCUSSION: This rigorous evaluation of tCBT in the real world will provide invaluable information to decision makers, health care managers, clinicians and patients regarding the effectiveness of the intervention. Widespread implementation of tCBT protocols in primary care could lead to better effectiveness, efficiency, access and equity for the large number of patients suffering from anxiety disorders that are currently not obtaining evidence-based psychotherapy. TRIAL REGISTRATION: ClinicalTrials.gov: NCT02811458 .

Aerobic exercise training facilitates the effectiveness of cognitive behavioral therapy in panic disorder.

BACKGROUND: Physical activity has been discussed as a therapeutic alternative or add-on for the treatment of anxiety disorders. We studied whether aerobic exercise compared to physical activity with low impact can improve the effect of cognitive behavioral therapy (CBT) in patients with panic disorder (PD) with/without agoraphobia. METHODS: Forty-seven patients received group CBT treatment over 1 month, which was augmented with an 8-week protocol of either aerobic exercise (three times/week, 30 min, 70% VO(2) max; n = 24) or a training program including exercises with very low intensity (n = 23) in a randomized controlled double-blind design. The primary outcome measure was the total score on the Hamilton Anxiety Scale (Ham-A). A 2 × 3 analysis of covariance (ANCOVA) with baseline value as a covariate was conducted for data analysis. RESULTS: Time × group interaction for the Ham-A revealed a significant effect (P = .047, η(2) p = .072), which represented the significant group difference at a 7-month follow-up. For the other clinical outcome measures no statistical significance emerged, although improvement was more sustained in the exercise group. CONCLUSIONS: For patients with PD, regular aerobic exercise adds an additional benefit to CBT. This supports previous results and provides evidence about the intensity of exercise that needs to be performed.

Disorder-specific emotional imagery for differential and quantitative assessment of agoraphobia.

Visual emotional stimulation is supposed to elicit psycho-vegetative reactions, which are similar to as the ones elicited by exposure to actual experience. Visual stimulation paradigms have been widely used in studies on agoraphobia with and without panic disorder. However, the applied imagery has hardly ever been disorder- and subject- specific. 51 patients with an ICD-10 and DSM-IV diagnosis of agoraphobia with or without panic disorder (PDA) and matching healthy controls have been examined. Subjects were confronted with 146 picture showing characteristic agoraphobic situations (high places, narrow places, crowds, public transport facilities, or wide places) or pictures associated with acute physical emergency (panic) situations, which had been pre-selected by anxiety experts. Participants were asked to rate emotional arousal induced by the respective images on the Self- Assessment Manikin scale (SAM). Data on PDA severity (PAS) depressive symptoms (MADRS) and sociodemographic data were recorded. Saliva cortisol levels were measured before and after exposure in a second test applying the individually mostly feared stimuli combined with emotionally neutral pictures for every single patient. 117 of the PDA-specific images were rated significantly more fear-eliciting by patients than by healthy individuals. Sub-categorization into agoraphobia clusters showed differential effects of clusters with regard to gender distribution, severity of PDA and cortisol secretion during exposure. In this study disorder specific and individual characteristics of agoraphobia were assessed for use in future trials applying emotional imagery. It could be used for the differential assessment of PDA and associated neurobiological and psychological phenomena and in neuroimaging paradigms.

Respiratory and cognitive mediators of treatment change in panic disorder: evidence for intervention specificity.

OBJECTIVE: There are numerous theories of panic disorder, each proposing a unique pathway of change leading to treatment success. However, little is known about whether improvements in proposed mediators are indeed associated with treatment outcomes and whether these mediators are specific to particular treatment modalities. Our purpose in this study was to analyze pathways of change in theoretically distinct interventions using longitudinal, moderated mediation analyses. METHOD: Forty-one patients with panic disorder and agoraphobia were randomly assigned to receive 4 weeks of training aimed at altering either respiration (capnometry-assisted respiratory training) or panic-related cognitions (cognitive training). Changes in respiration (PCO2, respiration rate), symptom appraisal, and a modality-nonspecific mediator (perceived control) were considered as possible mediators. RESULTS: The reductions in panic symptom severity and panic-related cognitions and the improvements in perceived control were significant and comparable in both treatment groups. Capnometry-assisted respiratory training, but not cognitive training, led to corrections from initially hypocapnic to normocapnic levels. Moderated mediation and temporal analyses suggested that in capnometry-assisted respiratory training, PCO2 unidirectionally mediated and preceded changes in symptom appraisal and perceived control and was unidirectionally associated with changes in panic symptom severity. In cognitive training, reductions in symptom appraisal were bidirectionally associated with perceived control and panic symptom severity. In addition, perceived control was bidirectionally related to panic symptom severity in both treatment conditions. CONCLUSION: The findings suggest that reductions in panic symptom severity can be achieved through different pathways, consistent with the underlying models.

A randomized, controlled trial of aerobic exercise in combination with paroxetine in the treatment of panic disorder.

OBJECTIVES: Regular aerobic exercise (running) has been shown to be superior to a pill placebo in the treatment of panic disorder. Combined drug and exercise treatment has not been investigated in randomized controlled studies to date. METHODS: This is a randomized, 10-week, controlled, parallel group, pilot study. A total of 75 outpatients with panic disorder with or without agoraphobia (DSM-IV and ICD-10) received either (1) exercise plus paroxetine 40 mg/day (n=21), (2) relaxation plus paroxetine (n=17), (3) exercise plus pill placebo (n=20), or (4) relaxation plus pill placebo (n=17). Changes in the Panic and Agoraphobia Scale (P&A), and the Clinical Global Impression Scale (CGI) underwent repeated measure analysis. RESULTS: Effects sizes were large for all groups (d=1.53-3.87), however not significantly different. Paroxetine-treated patients were significantly more improved than placebo-treated patients. On the CGI, patients in the exercise groups (plus paroxetine or placebo) had a trend toward better improvement compared to relaxation (P=0.06). Response and remission rates were higher in the paroxetine compared to pill placebo groups. CONCLUSIONS: While paroxetine was superior to placebo, aerobic exercise did not differ from relaxation training in most efficacy measures.

Terapia cognitivo-comportamental no transtorno de pânico / Cognitive-behavioral therapy in panic disorder

OBJETIVO: O transtorno de pânico é uma condição crônica e recorrente que prejudica a qualidade de vida e o funcionamento psicossocial dos portadores. Embora os medicamentos sejam efetivos na redução dos ataques de pânico, muitos pacientes não respondem adequadamente a essas intervenções. A terapia cognitivo-comportamental fornece um método alternativo eficaz para tratar transtorno de pânico e evitação agorafóbica. O objetivo do estudo é o de descrever o uso de técnicas cognitivo-comportamentais no tratamento do transtorno de pânico. MÉTODO: Revisão narrativa a partir dos bancos de dados do Medline, SciELO e PsycInfo e de livros-texto especializados. RESULTADOS: Foram descritos os fundamentos da terapia cognitivo-comportamental no tratamento do transtorno pânico e revisadas as evidências de eficácia em curto e longo prazos. O uso de medicação concomitante a terapia cognitivo-comportamental foi também discutido. CONCLUSÕES: A terapia cognitivo-comportamental individual ou em grupo é eficaz para pacientes com transtorno de pânico, seja como tratamento de primeira linha ou como um próximo passo para pacientes com resposta parcial a outros tratamentos.

OBJECTIVE: Panic disorder is a chronic and recurrent condition that impairs an individual's psychosocial functioning and quality of life. Despite the efficacy of psychopharmacological treatment in reducing panic attacks, many patients fail to respond adequately to these interventions. Cognitive behavioral therapy provides an alternative and efficacious method for treating panic disorder and agoraphobic avoidance. The objective of the study is to describe the use of cognitive behavioral therapy for panic disorder. METHOD: Narrative review of data collected from Medline, SciELO and PsycInfo and specialized textbooks. RESULTS: We describe the cognitive-behavioral model for the treatment of panic disorder, and review both short and long-term efficacy findings. We also discuss the role of combined treatment (cognitive behavioral therapy and psychopharmacology). CONCLUSIONS: Cognitive behavioral therapy, either individual or in group, can be used as first-line therapy for panic disorder. This treatment modality can also be indicated as a next step for patients failing to respond to other treatments.

Usefulness of mindfulness-based cognitive therapy for treating insomnia in patients with anxiety disorders: a pilot study.

The objective of this study was to examine the usefulness of a mindfulness-based cognitive therapy (MBCT) for treating insomnia symptoms in patients with anxiety disorder. Nineteen patients with anxiety disorder were assigned to an 8-week MBCT clinical trial. Participants showed significant improvement in Pittsburgh Sleep Quality Index (Z = -3.46, p = 0.00), Penn State Worry Questionnaire (Z = -3.83, p = 0.00), Ruminative Response Scale (Z = -3.83, p = 0.00), Hamilton Anxiety Rating Scale (Z = -3.73, p = 0.00), and Hamilton Depression Rating Scale scores (Z = -3.06, p = 0.00) at the end of the 8-week program as compared with baseline. Multiple regression analysis showed that baseline Penn State Worry Questionnaire scores were associated with baseline Pittsburgh Sleep Quality Index scores. These findings suggest that MBCT can be effective at relieving insomnia symptoms by reducing worry associated sleep disturbances in patients with anxiety disorder. However, well-designed, randomized, controlled trials are needed to confirm our findings.

A randomized controlled clinical trial of psychoanalytic psychotherapy for panic disorder.

OBJECTIVE: The purpose of this study was to determine the efficacy of panic-focused psychodynamic psychotherapy relative to applied relaxation training, a credible psychotherapy comparison condition. Despite the widespread clinical use of psychodynamic psychotherapies, randomized controlled clinical trials evaluating such psychotherapies for axis I disorders have lagged. To the authors' knowledge, this is the first efficacy randomized controlled clinical trial of panic-focused psychodynamic psychotherapy, a manualized psychoanalytical psychotherapy for patients with DSM-IV panic disorder. METHOD: This was a randomized controlled clinical trial of subjects with primary DSM-IV panic disorder. Participants were recruited over 5 years in the New York City metropolitan area. Subjects were 49 adults ages 18-55 with primary DSM-IV panic disorder. All subjects received assigned treatment, panic-focused psychodynamic psychotherapy or applied relaxation training in twice-weekly sessions for 12 weeks. The Panic Disorder Severity Scale, rated by blinded independent evaluators, was the primary outcome measure. RESULTS: Subjects in panic-focused psychodynamic psychotherapy had significantly greater reduction in severity of panic symptoms. Furthermore, those receiving panic-focused psychodynamic psychotherapy were significantly more likely to respond at treatment termination (73% versus 39%), using the Multicenter Panic Disorder Study response criteria. The secondary outcome, change in psychosocial functioning, mirrored these results. CONCLUSIONS: Despite the small cohort size of this trial, it has demonstrated preliminary efficacy of panic-focused psychodynamic psychotherapy for panic disorder.

[Clinical and psychophysiological study of patients with panic attacks with or without agoraphobic disorders].

Seventy-seven patients with panic attacks (PA) with or without agoraphobic disorders and 28 healthy controls have been studied using clinico-neurological and psychological methods as well as EEG and auditory event-related evoked potentials (EP) recording. PA patients with agoraphobic disorders featured a significant decrease of density of a-rhythm power and an increase of b-rhythm power in the right hemisphere that reflected a substantial activation of the ascending mesencephalic reticular formation. At the same time, a significant increase of q-rhythm power in temporal areas of the right hemisphere was characteristic of patients without agoraphobia that suggested reinforcement of activity of temporal-limbic structures. Patients with agoraphobia demonstrated lower P300 wave amplitude, marked disturbances of its habituation, more impaired attention and higher level of anxiety and depression as compared to those without agoraphobia.

Occurrence of imagery and its link with early memories in agoraphobia.

Recent cognitive models suggest that mental imagery can help us understand the maintenance of anxiety disorders (e.g., de Silva, 1986; Hackmann, Surawy, & Clark, 1998). However, imagery is relatively unexplored within agoraphobia. Such images are also thought to be useful in uncovering memories that occurred around the onset of a disorder (Hackmann, Clark, & McManus, 2000). A total of 20 patients with agoraphobia and 20 matched controls took part in this investigation. Participants described any recurrent images they experienced in agoraphobic situations, and also any associated memories. All patients with agoraphobia (but no control participants) reported having distinct recurrent images in "agoraphobic situations". Most images involved several sensory modalities and in the majority of cases appeared to be linked with unpleasant memories of events experienced many years previously. While these exploratory findings require replication, potential treatment implications are discussed.

Reactivity to imagery and nocturnal panic attacks.

We assessed psychophysiological responses to imagery of traumatic events, panic attacks, and loss of vigilance (i.e., being hypnotized) in participants diagnosed with panic disorder. Participants were either currently experiencing nocturnal panic or daytime panics only. It was hypothesized that nocturnal panickers would exhibit heightened responsivity to imagery of their worst panic and worst trauma, as well as being hypnotized, compared to day panickers. Using established imagery procedures, heart rate, skin conductance, and frontalis electromyogram were recorded as participants imagined each scene. Nocturnal and day panickers differed in their responses to the hypnosis scene only. As predicted, nocturnal panickers endorsed more panic symptoms in response to imagery of being hypnotized. Contrary to expectation, nocturnal and daytime panickers showed no differences in physiologic reactivity or self-reported distress to worst trauma or worst panic imagery. The findings are discussed with respect to the role of fear of loss of vigilance for nocturnal panic.

Panic control treatment for agoraphobia.

The goal of the present study was to compare the efficacy of cognitive-behavioral treatment for panic control alone versus this treatment containing an additional in vivo exposure component. The sample was comprised of 68 individuals who met diagnosis for panic disorder with agoraphobia. Participants were randomly assigned to one of two 16-week treatment conditions, panic control only and panic control with in vivo exposure. Assessments were repeated at baseline, mid-treatment, posttreatment, and 6-month follow-up using diagnostic and behavioral measures. Results indicated that the two treatment conditions were equally efficacious for both panic disorder and agoraphobia. The intervention explicitly targeting agoraphobia appeared superfluous given the efficacy of panic control alone. On the other hand, reduction in panic frequency predicted reduction in agoraphobic avoidance overall. The practical and theoretical implications are discussed, as are limitations and directions for future research.

Evidence for disturbed cortical signal processing and altered serotonergic neurotransmission in generalized anxiety disorder.

BACKGROUND: Current pathophysiological concepts of generalized anxiety disorder (GAD) assume a disturbed exteroceptive sensory system. Furthermore, central serotonergic neurotransmission has been shown to play an important role in anxiety disorder. Cortical signal processing as measured by auditory evoked potentials (AEPs) may reflect the integrity of the exteroceptive sensory system. Because a special aspect of AEP, the loudness dependence of the N1/P2-component (LD), has been related to central serotonergic activity, the LD may be useful for investigating serotonergic dysfunctions in GAD. METHODS: The LD was recorded in 31 medication-free patients with GAD without any psychiatric co-morbidity and in 31 matched control subjects. Dipole source analysis was performed to separate the LD of regions including the primary (LD-tangential dipole) and regions including the secondary auditory cortex (LD-radial dipole). RESULTS: A shallower LD-tangential was observed in patients with GAD as compared to healthy control subjects [F(1,60) = 6.727, p =.012; one-way analysis of variance]. The LD-radial showed no differences between groups. Severity of the anxiety symptoms was not related to the LDs. CONCLUSIONS: The results indicate an altered exteroceptive sensory system in GAD occurring at the level of the primary but not secondary auditory cortex. Because a shallow LD of the primary auditory cortex was related to a high firing rate of neurons in the dorsal raphe nucleus, the results may support evidence for an enhanced serotonergic activity in GAD.

Effect of kava extract on vagal cardiac control in generalized anxiety disorder: preliminary findings.

Anxiety disorders are associated with low vagal control of heart rate and increased risk of cardiac mortality and sudden cardiac death. This study examined whether the herbal anxiolytic, kava, produces improvement in vagal control in generalized anxiety disorder. Before and after treatment with placebo (n = 7) or kava (n = 6), two indices of vagal control were measured under supine conditions using power spectral analysis: baroreflex control of heart rate (BRC) and respiratory sinus arrhythmia (RSA). Significantly more patients treated with kava showed improved BRC compared to the placebo group (p < 0.05). Furthermore, the magnitude of improvement in BRC was significantly correlated with the degree of clinical improvement (p < 0.05). RSA did not respond to treatment. These preliminary findings suggest that kava might exert a favourable effect on reflex vagal control of heart rate in generalized anxiety disorder patients. The parallel clinical and BRC responses may reflect an underlying common effect of this herbal anxiolytic.

[Acupuncture in patients with minor depressive episodes and generalized anxiety. Results of an experimental study]. / Akupunktur bei leichten bis mittelschweren depressiven Episoden und Angststörungen. Ergebnisse einer experimentellen Untersuchung.

In a placebo-controlled, randomized, modified double-blind study we investigated the effects of body needle acupuncture (n = 10) in 43 patients with minor depression (ICD 10 F32.0, F32.1) and 13 patients with generalized anxiety disorders (ICD10 F41.1). The severity of the disease was assessed by the Clinical Global Impression Scale (CGI). Treatment response was defined as a significant improvement in CGI. An intent-to-treat analysis was performed to compare treatment responses between verum- and placebo acupuncture. After completing an total of 10 acupuncture sessions the verum acupuncture group (n = 28) showed a significantly larger clinical improvement compared to the placebo group (Mann-Whitney test, p < 0.05). There were significantly more responders in the verum-compared to the placebo group (60.7% vs. 21.4%; chi-square test, p < 0.01). In contrast, no differences in the response rates were evident just after 5 acupuncture sessions. A multivariate analysis with the independent factor acupuncture (verum vs. placebo) and the results of the results of the additional rating scales (total score of HAMA, HAMD, Bf-S, BL) as dependent variables (ANOVA, 1:54 D.F.) revealed a clear trend towards lower HAMA scores in the verum group after completing 10 acupunctures (F3.29, p = 0.075). This corresponds well to the high response rate of 85.7% in patients with generalized anxiety disorders, in whom verum acupuncture was applied. Our results indicate that needle acupuncture (Du.20, Ex.6, He.7, Pe.6, Bl.62) leads to a significant clinical improvement as well as to a remarkable reduction in anxiety symptoms in patients with minor depression or with generalized anxiety disorders. The total sum of acupuncture sessions and the specific location of acupuncture needle insertions might be important factors for bringing about therapeutic success.

EMDR for panic disorder with agoraphobia: comparison with waiting list and credible attention-placebo control conditions.

In a randomized controlled trial, eye movement desensitization and reprocessing (EMDR) for panic disorder with agoraphobia (PDA) was compared with both waiting list and credible attention-placebo control groups. EMDR was significantly better than waiting list for some outcome measures (questionnaire, diary, and interview measures of severity of anxiety, panic disorder, and agoraphobia) but not for others (panic attack frequency and anxious cognitions). However, low power and, for panic frequency, floor effects may account for these negative results. Differences between EMDR and the attention-placebo control condition were not statistically significant on any measure, and, in this case, the effect sizes were generally small (eta2 = .00-.06), suggesting the poor results for EMDR were not due to lack of power. Because there are established effective treatments such as cognitive-behavior therapy for PDA, these data, unless contradicted by future research, indicate EMDR should not be the first-line treatment for this disorder.

The observer perspective: biased imagery in social phobia, agoraphobia, and blood/injury phobia.

Clark and Wells' (1995): 'A cognitive model of social phobia'. In Social phobia: Diagnosis, assessment, and treatment (pp. 69-93), R. G. Heimberg, M. R. Liebowitz, D. A. & F. R. Hope (eds.); cognitive model of social phobia proposes that social phobics generate a negative impression of how they appear to others. This impression often occurs in the form of an image from an "observer" perspective in which social phobics can see themselves as if from another person's vantage point. This study investigated the specificity of the observer perspective among patients with social phobia, agoraphobia, and blood/injury phobia. All participants were asked to recall and imagine a recent anxiety-provoking social situation and a non-social/non-anxiety-provoking situation, and rate their perspective for each. Consistent with predictions only patients with social-evaluative concerns (social phobics and agoraphobics) reported observer perspectives for anxiety-provoking social situations. Only social phobics showed a significant shift from an observer to a field perspective across the two conditions. The clinical implications of these findings are briefly discussed.

Rate of improvement during cognitive-behavioral group treatment for panic disorder.

This study examined the rate of symptom improvement in patients receiving cognitive-behavioral group treatment for panic disorder in an outpatient clinic setting. Treatment was a standard program of 12 sessions that emphasized information, interoceptive and situational exposure, and cognitive restructuring, but also included diaphragmatic breathing and relaxation training as elements of treatment. Subjects were 37 patients selected from sequential admissions into an outpatient treatment program; all data were derived from ongoing quality assurance measures that are a standard part of clinical monitoring. Consequently, this study provides data not on the relative efficacy of cognitive-behavioral therapy (CBT), but on rate of improvement and effectiveness of CBT for panic disorder in actual clinical practice. Patients achieved significant treatment gains on all panic disorder dimensions assessed, and the largest reduction in symptoms was during the first third of the treatment program, thereby challenging the notion that CBT delivers its gains slowly over time. Information on rats of symptom improvement is valuable for providing patients with accurate expectations about potential treatment benefits and for helping to maintain motivation during initial treatment sessions.

Gauging the effectiveness of extended imipramine treatment for panic disorder with agoraphobia.

BACKGROUND: Imipramine has proven efficacy for panic disorder. This study assesses the net effectiveness of systematic, open imipramine treatment in a homogenous sample of panic disorder patients with agoraphobia. METHODS: One hundred and ten consecutive patients with DSM-III-R moderate to severe panic disorder with agoraphobia were treated with a fixed regimen of imipramine 2.25 mg/kg/day for 24 weeks. No instructions or encouragement for self-directed exposure to phobic situations or other coping strategies with panic or fear were given. Assessments were conducted at the end of the 2-week placebo run-in and at weeks 8, 16, and 24 of treatment. RESULTS: Overall, 53% had a marked and stable response. Most measures revealed that substantial improvement continued beyond week 8 of treatment. Treatment success was accompanied with significant improvements in anxiety sensitivity, dysphoric mood, and functional well-being. CONCLUSIONS: These results provide a clinically relevant reference with which to compare the effectiveness of alternative treatments in providing nearly complete symptom remission in patients with primary panic disorder with agoraphobia.