Agoraphobic Avoidance Research Articles

Explaining paranoia: cognitive and social processes in the occurrence of extreme mistrust

BackgroundParanoia—incorrectly thinking that others are deliberating trying to harm you—causes distress, undermines social interactions and leads to withdrawal. It presents across multiple psychiatric diagnoses.ObjectiveThe primary aim was to determine the...

Application of Immersive Virtual Reality for Assessment and Intervention in Psychosis: A Systematic Review.

Virtual reality (VR) has emerged as a safe and non-invasive technology for the assessment of psychotic symptoms, social and cognitive impairments, and psychosocial intervention in improving outcomes in psychosis. This study systematically reviewed the current state of evidence in applying semi- and fully immersive VR for assessing and treating patients with psychosis. A systematic review was conducted adhering to the PRISMA statement and was conducted in Embase, PsycINFO, and PubMed databases for articles published between January 2013 and April 2022, which identified 28 eligible studies, including 12 for assessment and 16 for intervention. In the assessment studies, not all VR tasks could distinguish the differences between patients and healthy controls regarding their physiological responses, paranoid ideation, and certain aspects of cognitive functioning such as memory bias on the object tasks. Comparatively, VR-based interventions are more promising, especially for improving cognitive impairments, social skills, agoraphobic avoidance, negative and positive affective states, auditory verbal hallucination, paranoid ideation and persecutory delusions, and other psychiatric symptoms in patients. We conclude that more rigorous studies are needed to confirm treatment effectiveness and to understand the underlying mechanism of VR-based intervention for psychotic disorders. Future studies should also improve the reliability and validity of VR-based assessments for psychotic disorders.

A Safe Place to Learn: Peer Research Qualitative Investigation of gameChange Virtual Reality Therapy.

Automated virtual reality (VR) therapy has the potential to substantially increase access to evidence-based psychological treatments. The results of a multicenter randomized controlled trial showed that gameChange VR cognitive therapy reduces the agoraphobic avoidance of people diagnosed with psychosis, especially for those with severe avoidance. We set out to use a peer research approach to explore participants' experiences with gameChange VR therapy. This in-depth experiential exploration of user experience may inform the implementation in clinical services and future VR therapy development. Peer-led semistructured remote interviews were conducted with 20 people with a diagnosis of psychosis who had received gameChange as part of the clinical trial (ISRCTN17308399). Data were analyzed using interpretative phenomenological analysis and template analyses. A multiperspectival approach was taken to explore subgroups. Credibility checks were conducted with the study Lived Experience Advisory Panel. Participants reported the substantial impact of anxious avoidance on their lives before the VR intervention, leaving some of them housebound and isolated. Those who were struggling the most with agoraphobic avoidance expressed the most appreciation for, and gains from, the gameChange therapy. The VR scenarios provided "a place to practise." Immersion within the VR scenarios triggered anxiety, yet participants were able to observe this and respond in different ways than usual. The "security of knowing the VR scenarios are not real" created a safe place to learn about fears. The "balance of safety and anxiety" could be calibrated to the individual. The new learning made in VR was "taken into the real world" through practice and distilling key messages with support from the delivery staff member. Automated VR can provide a therapeutic simulation that allows people diagnosed with psychosis to learn and embed new ways of responding to the situations that challenge them. An important process in anxiety reduction is enabling the presentation of stimuli that induce the original anxious fears yet allow for learning of safety. In gameChange, the interaction of anxiety and safety could be calibrated to provide a safe place to learn about fears and build confidence. This navigation of therapeutic learning can be successfully managed by patients themselves in an automated therapy, with staff support, that provides users with personalized control. The clinical improvements for people with severe anxious avoidance, the positive experience of VR, and the maintenance of a sense of control are likely to facilitate implementation.

Reactivity to conditioned threat cues is distinct from exploratory drive in the elevated plus maze.

Fear and anxiety are adaptive states that allow humans and animals alike to respond appropriately to threatening cues in their environment. Commonly used tasks for studying behaviour akin to fear and anxiety in rodent models are Pavlovian threat conditioning and the elevated plus maze (EPM), respectively. In threat conditioning the rodents learn to associate an aversive event with a specific stimulus or context. The learnt association between the two stimuli (the 'memory') can then be recalled by re-exposing the subject to the conditioned stimulus. The elevated plus maze is argued to measure the agoraphobic avoidance of the brightly lit open maze arms in crepuscular rodents. These two tasks have been used extensively, yet research into whether they interact is scarce. We investigated whether recall of an aversive memory, across contextual, odour or auditory modalities, would potentiate anxiety-like behaviour in the elevated plus maze. The data did not support that memory recall, even over a series of time points, could influence EPM behaviour. Furthermore, there was no correlation between EPM behaviour and conditioned freezing in independent cohorts tested in the EPM before or after auditory threat conditioning. Further analysis found the production of 22 kHz ultrasonic vocalisations revealed the strongest responders to a conditioned threat cue. These results are of particular importance for consideration when using the EPM and threat conditioning to identify individual differences and the possibility to use the tasks in batteries of tests without cross-task interference.

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

BackgroundThe 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. Methods345 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. ResultsGreater 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. ConclusionsPatients 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.

Predictors of symptom reduction following intensive weekend treatment for panic disorder: An exploratory study of veterans

BackgroundRecent evidence implicates intensive panic control treatment (IPCT) – a full panic control treatment protocol compressed into a single weekend – as a viable alternative for Veterans with panic disorder who are unable or unwilling to commit to standard weekly cognitive behavioral therapy (CBT). However, no studies to date have examined pretreatment predictors of response to IPCT. Knowledge of such predictors may be important for understanding which Veterans are best suited for IPCT relative to standard CBT. MethodsParticipants were military Veterans with a primary diagnosis of panic disorder (N = 26) who participated in three open trials of IPCT. Pretreatment predictors were tested within linear regression models used to predict panic disorder severity at 2-week and 6-month follow-up assessments. Pretreatment predictors included: Panic disorder severity, agoraphobic avoidance, PTSD symptoms, anxiety sensitivity, and age. ResultsPretreatment symptoms of PTSD predicted reduced treatment response at 2-week but not 6-month follow-up, whereas pretreatment anxiety sensitivity predicted reduced response at 6-month but not 2-week follow-up. LimitationsCurrent findings are tempered by the exploratory nature of the analyses and a small sample. ConclusionsOur study offers tentative evidence that success in IPCT may be linked to a distinct pretreatment profile relative to that of standard weekly therapy. These preliminary findings should be confirmed in larger studies that directly compare pretreatment predictors of intensive versus standard weekly CBT for panic disorder.

Automated virtual reality therapy to treat agoraphobic avoidance and distress in patients with psychosis (gameChange): a multicentre, parallel-group, single-blind, randomised, controlled trial in England with mediation and moderation analyses

SummaryBackgroundAutomated delivery of psychological therapy using immersive technologies such as virtual reality (VR) might greatly increase the availability of effective help for patients. We aimed to evaluate the efficacy of an automated VR cognitive therapy (gameChange) to treat avoidance and distress in patients with psychosis, and to analyse how and in whom it might work.MethodsWe did a parallel-group, single-blind, randomised, controlled trial across nine National Health Service trusts in England. Eligible patients were aged 16 years or older, with a clinical diagnosis of a schizophrenia spectrum disorder or an affective diagnosis with psychotic symptoms, and had self-reported difficulties going outside due to anxiety. Patients were randomly assigned (1:1) to either gameChange VR therapy plus usual care or usual care alone, using a permuted blocks algorithm with randomly varying block size, stratified by study site and service type. gameChange VR therapy was provided in approximately six sessions over 6 weeks. Trial assessors were masked to group allocation. Outcomes were assessed at 0, 6 (primary endpoint), and 26 weeks after randomisation. The primary outcome was avoidance of, and distress in, everyday situations, assessed using the self-reported Oxford Agoraphobic Avoidance Scale (O-AS). Outcome analyses were done in the intention-to-treat population (ie, all participants who were assigned to a study group for whom data were available). We performed planned mediation and moderation analyses to test the effects of gameChange VR therapy when added to usual care. This trial is registered with the ISRCTN registry, 17308399.FindingsBetween July 25, 2019, and May 7, 2021 (with a pause in recruitment from March 16, 2020, to Sept 14, 2020, due to COVID-19 pandemic restrictions), 551 patients were assessed for eligibility and 346 were enrolled. 231 (67%) patients were men and 111 (32%) were women, 294 (85%) were White, and the mean age was 37·2 years (SD 12·5). 174 patients were randomly assigned to the gameChange VR therapy group and 172 to the usual care alone group. Compared with the usual care alone group, the gameChange VR therapy group had significant reductions in agoraphobic avoidance (O-AS adjusted mean difference –0·47, 95% CI –0·88 to –0·06; n=320; Cohen's d –0·18; p=0·026) and distress (–4·33, –7·78 to –0·87; n=322; –0·26; p=0·014) at 6 weeks. Reductions in threat cognitions and within-situation defence behaviours mediated treatment outcomes. The greater the severity of anxious fears and avoidance, the greater the treatment benefits. There was no significant difference in the occurrence of serious adverse events between the gameChange VR therapy group (12 events in nine patients) and the usual care alone group (eight events in seven patients; p=0·37).InterpretationAutomated VR therapy led to significant reductions in anxious avoidance of, and distress in, everyday situations compared with usual care alone. The mediation analysis indicated that the VR therapy worked in accordance with the cognitive model by reducing anxious thoughts and associated protective behaviours. The moderation analysis indicated that the VR therapy particularly benefited patients with severe agoraphobic avoidance, such as not being able to leave the home unaccompanied. gameChange VR therapy has the potential to increase the provision of effective psychological therapy for psychosis, particularly for patients who find it difficult to leave their home, visit local amenities, or use public transport.FundingNational Institute of Health Research Invention for Innovation programme, National Institute of Health Research Oxford Health Biomedical Research Centre.

Understanding agoraphobic avoidance: the development of the Oxford Cognitions and Defences Questionnaire (O-CDQ).

Many patients with mental health disorders become increasingly isolated at home due to anxiety about going outside. A cognitive perspective on this difficulty is that threat cognitions lead to the safety-seeking behavioural response of agoraphobic avoidance. We sought to develop a brief questionnaire, suitable for research and clinical practice, to assess a wide range of cognitions likely to lead to agoraphobic avoidance. We also included two additional subscales assessing two types of safety-seeking defensive responses: anxious avoidance and within-situation safety behaviours. 198 patients with psychosis and agoraphobic avoidance and 1947 non-clinical individuals completed the item pool and measures of agoraphobic avoidance, generalised anxiety, social anxiety, depression and paranoia. Factor analyses were used to derive the Oxford Cognitions and Defences Questionnaire (O-CDQ). The O-CDQ consists of three subscales: threat cognitions (14 items), anxious avoidance (11 items), and within-situation safety behaviours (8 items). Separate confirmatory factor analyses demonstrated a good model fit for all subscales. The cognitions subscale was significantly associated with agoraphobic avoidance (r = .672, p < .001), social anxiety (r = .617, p < .001), generalized anxiety (r = .746, p < .001), depression (r = .619, p < .001) and paranoia (r = .655, p < .001). Additionally, both the O-CDQ avoidance (r = .867, p < .001) and within-situation safety behaviours (r = .757, p < .001) subscales were highly correlated with agoraphobic avoidance. The O-CDQ demonstrated excellent internal consistency (cognitions Cronbach's alpha = .93, avoidance Cronbach's alpha = .94, within-situation Cronbach's alpha = .93) and test-re-test reliability (cognitions ICC = 0.88, avoidance ICC = 0.92, within-situation ICC = 0.89). The O-CDQ, consisting of three separate scales, has excellent psychometric properties and may prove a helpful tool for understanding agoraphobic avoidance across mental health disorders.

The Oxford Agoraphobic Avoidance Scale.

Agoraphobic avoidance of everyday situations is a common feature in many mental health disorders. Avoidance can be due to a variety of fears, including concerns about negative social evaluation, panicking, and harm from others. The result is inactivity and isolation. Behavioural avoidance tasks (BATs) provide an objective assessment of avoidance and in situ anxiety but are challenging to administer and lack standardisation. Our aim was to draw on the principles of BATs to develop a self-report measure of agoraphobia symptoms. The scale was developed with 194 patients with agoraphobia in the context of psychosis, 427 individuals in the general population with high levels of agoraphobia, and 1094 individuals with low levels of agoraphobia. Factor analysis, item response theory, and receiver operating characteristic analyses were used. Validity was assessed against a BAT, actigraphy data, and an existing agoraphobia measure. Test-retest reliability was assessed with 264 participants. An eight-item questionnaire with avoidance and distress response scales was developed. The avoidance and distress scales each had an excellent model fit and reliably assessed agoraphobic symptoms across the severity spectrum. All items were highly discriminative (avoidance: a = 1.24-5.43; distress: a = 1.60-5.48), indicating that small increases in agoraphobic symptoms led to a high probability of item endorsement. The scale demonstrated good internal reliability, test-retest reliability, and validity. The Oxford Agoraphobic Avoidance Scale has excellent psychometric properties. Clinical cut-offs and score ranges are provided. This precise assessment tool may help focus attention on the clinically important problem of agoraphobic avoidance.

Social anxiety and agoraphobia symptoms effectively treated by Prompt Mental Health Care versus TAU at 6- and 12-month follow-up: Secondary analysis from a randomized controlled trial.

BackgroundPrompt Mental Health Care (PMHC, Norwegian adaption of Improving Access to Psychological Therapies) has shown effects on symptoms of anxiety and depression compared to treatment as usual (TAU). In this secondary analysis, we examine the effectiveness of PMHC among clients presenting with symptoms of social anxiety disorder (SAD) and/or agoraphobia on core symptoms at 6‐ and 12‐month follow‐up.MethodsRandomized controlled trial in two PMHC sites (70:30 ratio PMHC:TAU). Of participants, 61.3% (n = 472) scored at caseness for SAD and 47.7% (n = 367) for agoraphobia (40% both). Effects on SAD avoidance and physiological discomfort (SPIN‐9), SAD cognitions (ATQ‐SA), agoraphobic avoidance (MIA‐8), and agoraphobic cognitions (ATQ‐AP) were examined in piecewise growth models.ResultsThe PMHC group showed substantially greater symptom reduction than the TAU group for all outcomes: At 6‐month follow‐up, the between‐group effect sizes were d −0.60 (95% CI: −0.94 to −0.26) for SPIN‐9, −0.45 (95% CI: −0.70 to −0.20) for ATQ‐SA, −0.50 (95% CI: −0.87 to −0.13) for MIA‐8, and −0.61 (95% CI: −0.92 to −0.31) for ATQ‐AP. All effects were sustained at similar level at a 12‐month follow‐up.ConclusionPMHC effectively alleviated SAD and agoraphobia symptoms, and individuals struggling with such symptoms constituted a large proportion of clients. Although results should be interpreted with caution due to risk of attrition bias, they lend further support for a scale‐up of PMHC and similar initiatives. Individuals struggling with SAD and/or agoraphobia stood out as relatively high burdened, whereas only one of five had sought help the last 12 months, underscoring the need for the PMHC service.

Role of panic appraisal in predicting the severity of panic and agoraphobic symptoms

The present study examined the contribution of panic appraisal (PA) dimensions to the prediction of panic and agoraphobic symptoms, above and beyond anxiety sensitivity (AS), among patients with panic disorder. PA dimensions consist of anticipated panic, perceived panic consequences, and panic coping efficacy. Panic disorder patients (N = 84, 60.7% female, M = 38 years) completed self-report measures of panic and agoraphobic symptoms, three dimensions of PA, AS, anxiety, and depression symptoms. PA dimensions significantly contributed to the prediction of overall and all facets of panic and agoraphobic symptoms, as well as anxiety symptoms, but not depressive symptoms, above and beyond AS. Of the three PA dimensions, both anticipated panic and panic coping efficacy uniquely contributed to agoraphobic avoidance after controlling for AS and the other dimensions of PA. PA dimensions may emerge as an important predictor of panic and agoraphobic or anxiety symptoms.

Avoidance Moderates Cognitive Behavioral Therapy for Panic Disorder and Agoraphobia.

Cognitive behavioral therapy (CBT), a well-validated treatment for panic disorder, includes interoceptive exposures and possibly in vivo exposures to agoraphobic situations. Testing predictors and moderators of CBT outcomes can improve treatment efficacy. Sixty-six individuals with panic disorder with or without agoraphobia were randomized to panic control therapy (PCT) (n = 32) or PCT and in vivo exposures to agoraphobic situations (PCT + IV) (n = 34). Secondary analyses using multilevel models with repeated measures design revealed that individuals who displayed more interoceptive avoidance and agoraphobic avoidance fared better after PCT than PCT + IV compared with individuals who displayed less avoidance. Results suggest that these individuals benefit from concentrated doses of exposures to their primary interoceptive concerns instead of additional exposures to agoraphobic situations. Exploratory analyses were also conducted on fear, demographic factors, and clinical characteristics. Findings inform clinical decision-making and personalized medicine. Limitations include low power for detecting small effect sizes.

Intensive one-week internet-delivered cognitive behavioral therapy for panic disorder and agoraphobia: A pilot study

This is the first pilot study to explore the feasibility, acceptability and preliminary efficacy of intensive cognitive behavioral therapy (CBT) for panic disorder and/or agoraphobia delivered via the internet. Ten participants who met DSM-5 criteria for panic disorder and/or agoraphobia (6 males; mean age = 43.40, SD = 15.25) completed The Intensive Panic Program: a six-lesson exposure-based CBT program, delivered online over seven days. Clinician support was provided via phone and email. All 10 participants completed the program (100% adherence) and high levels of satisfaction were reported. We found large and significant reductions in panic symptom severity at post-treatment (d = 1.40), which were maintained at two-month follow-up. We also found large reductions in agoraphobic avoidance (d = 0.92) and functional impairment (d = 1.04) at follow-up, and days out of role were halved. On average, 132 min (SD = 42, range: 47–183) of clinician time was spent per participant during the treatment week. The results provide promising preliminary evidence for the feasibility and acceptability of internet-delivered intensive CBT for panic disorder and/or agoraphobia. A larger, randomized control trial is now needed to evaluate the efficacy of this program compared to a control group and to explore long-term outcomes.Clinical trial registration numberACTRN12618001501235

A clinical staging approach to improving diagnostics in anxiety disorders: Is it the way to go?

Clinical staging is a paradigm in which stages of disease progression are identified; these, in turn, have prognostic value. A staging model that enables the prediction of long-term course in anxiety disorders is currently unavailable but much needed as course trajectories are highly heterogenic. This study therefore tailored a heuristic staging model to anxiety disorders and assessed its validity. A clinical staging model was tailored to anxiety disorders, distinguishing nine stages of disease progression varying from subclinical stages (0, 1A, 1B) to clinical stages (2A-4B). At-risk subjects and subjects with anxiety disorders (n = 2352) from the longitudinal Netherlands Study of Depression and Anxiety were assigned to these nine stages. The model's validity was assessed by comparing baseline (construct validity) and 2-year, 4-year and 6-year follow-up (predictive validity) differences in anxiety severity measures across stages. Differences in depression severity and disability were assessed as secondary outcome measures. Results showed that the anxiety disorder staging model has construct and predictive validity. At baseline, differences in anxiety severity, social avoidance behaviors, agoraphobic avoidance behaviors, worrying, depressive symptoms and levels of disability existed across all stages (all p-values < 0.001). Over time, these differences between stages remained present until the 6-year follow-up. Differences across stages followed a linear trend in all analyses: higher stages were characterized by the worst outcomes. Regarding the stages, subjects with psychiatric comorbidity (stages 2B, 3B, 4B) showed a deteriorated course compared with those without comorbidity (stages 2A, 3A, 4A). A clinical staging tool would be useful in clinical practice to predict disease course in anxiety disorders.

Treatable clinical intervention targets for patients with schizophrenia

BackgroundTreatment approaches for patients with psychosis need major improvement. Our approach to improvement is twofold: target putative causal mechanisms for psychotic experiences that are treatable and also that patients wish treated. This leads to greater treatment engagement and clinical benefit. To inform mental health service provision we assessed the presence of treatable causal mechanisms and patient treatment preferences. MethodsPatients with non-affective psychosis attending NHS mental health services completed assessments of paranoia, hallucinations, anxious avoidance, worry, self-esteem, insomnia, analytic reasoning, psychological well-being, and treatment preferences. Results1809 patients participated. Severe paranoia was present in 53.4% and frequent voices in 48.2%. Of the causal mechanisms, severe worry was present in 67.7%, avoidance at agoraphobic levels in 64.5%, analytic reasoning difficulties in 55.9%, insomnia in 50.1%, poor psychological well-being in 44.3%, strongly negative self-beliefs in 36.6%, and weak positive self-beliefs in 19.2%. Treatment target preferences were: feeling happier (63.2%), worrying less (63.1%), increasing self-confidence (62.1%), increasing activities (59.6%), improving decision-making (56.5%), feeling safer (53.0%), sleeping better (52.3%), and coping with voices (45.3%). Patients with current paranoia and/or hallucinations had higher levels of the causal factors and of wanting these difficulties treated. ConclusionsPatients with non-affective psychosis have high levels of treatable problems such as agoraphobic avoidance, worry, low self-esteem, and insomnia and they would like these difficulties treated. Successful treatment of these difficulties is also likely to decrease psychotic experiences such as paranoia.

Development of a very brief scale for detecting and measuring panic disorder using two items from the Panic Disorder Severity Scale-Self Report

ObjectiveTo minimize the burden in detecting and monitoring Panic Disorder and Agoraphobia by developing a very brief scale with selected items from the Panic Disorder Severity Scale-Self Report (PDSS-SR), and to investigate the proposed scale's psychometric properties in a comorbid sample. MethodsA sample of 5103 patients from the Internet Psychiatry Clinic in Sweden, diagnosed and treated with Internet-based cognitive behavioral therapy for panic disorder (n = 1390), social anxiety disorder (n = 1313) or depression (n = 2400), responded to the PDSS-SR. Six criteria related to factor structure, sensitivity to change and clinical representativeness were used to select items. Psychometric analyses for the selected very brief scale were performed. ResultsItems 2 (distress during panic attacks) and 4 (agoraphobic avoidance), were selected to create the very brief PDSS-SR version. Correlations with the full scale were high at screening, pre and post, and for change (0.87–0.93). Categorical Omega was ⍵C = 0.74. With a cut-off of 3 points, the scale could detect panic disorder in a psychiatric sample with a sensitivity of 85% and a specificity of 66%. LimitationsLimitations include lack of healthy controls and lack of blinding on secondary outcome measures. ConclusionThe proposed 2-item PDSS-SR version is a good candidate for a very brief panic disorder questionnaire, both for detecting cases and for measuring change. This is especially useful in clinical settings when measuring more than one condition at a time.

EFFECTIVENESS OF A CLOZAPINE–ARIPIPRAZOLE COMBINATION IN TOURETTE SYNDROME AND BIPOLAR SPECTRUM DISORDER

Introduction Antipsychotic combination is a common strategy used in both bipolar disorder and schizophrenia, although just a few trials are available exploring its effectiveness. We report herein the case of a patient suffering from severe Tourette syndrome (TS) and bipolar spectrum disorder who benefited from a combination of clozapine and aripiprazole. Case report “Mr. FS,”a 39-year-old art-craft worker, had been suffering from TS since his early childhood. During the adolescence, TS was character-ized by mouth opening and shoulder rotation, complex motor tics, such as trunk-bending or gyrating, screaming, and complex phonic tics. He was treated with pimozide 8 mg/day, which led to a complete remission of tics for about 20 years, although the clinical picture was complicated by the onset of mood shifts associated with impulsive behaviors and obsessions (numerical obsessions, rituals of order and symmetry, disproportionate aggressiveness). In 2007, when he was 35, he visited us for a major depressive episode with suicidal thoughts, panic attacks, and agoraphobic avoidance. Paroxetine (20 mg/day) led to a fast improvement of mood and anxiety symptoms, albeit being ineffective on tics. Only transient responses were obtained with the association of various drugs (haloperidol, risperidone, olanzapine, amisulpiride) to paroxetine and mood stabilizers (valproic acid, 600 mg/day). After about 2 years of different combinations, a significant improvement was obtained with tetrabenazine 75 mg/day1 clozapine 25mg/day1valproic acid 600 mg/day and fluvoxamine 150 mg/day. This strategy had a good impact only on the affective and obsessive symptoms, while tics remained stable. Therefore, tetra-benazine, fluvoxamine, and valproic acid were tapered down. At the same time, aripiprazole (15 mg/day) was introduced, and, after about 1month, we observed a dramatic improve-ment of TS symptoms. The improvement is still maintained at 2-year follow-up, so that currently the patient, who is regularly taking clozapine 25 mg/day and aripiprazole 15 mg/day with no significant side effects, shows a good affective balance, with no impulsive behavior, obsessions, or tics. Discussion Clozapine is considered a standard treatment for schizophrenia and bipolar disorder, whereas it has been reported to exacerbate obsessions and tics, although this topic is controversial. The effectiveness of aripiprazole in bipolar disorder is well documented, and preliminary data do exist for its possible use in obsessive-compulsive (OCD) and related disorders. Conclusions Our case report highlights the possible usefulness of combining clozapine and aripiprazole in TS comorbid with bipolar spectrum disorders, perhaps due to the different and not overlapping pharmacological profile of these two antipsychotics. Aripiprazole has much higher affinity for D2 receptors than clozapine and, since it behaves as a 5-HT2A antagonist and 5-HT2C partial agonist, may have a robust anti-obsessional (and perhaps anti-tic) activity. Further controlled studies are necessary to investigate the benefits of antipsychotic polypharmacy in patients suffering from both bipolar and OCD spectrum disorders.

Stress hormone response to the DEX\u2013CRH test and its relation to psychotherapy outcome in panic disorder patients with and without agoraphobia

This study tested whether the hormonal stress response to the DEX–CRH test may be predictive of the psychotherapy success for panic disorder (PD). Thirty-four patients diagnosed either with agoraphobia with PD or PD without agoraphobia were subjected to cognitive behavioural therapy (CBT). Patients (pre-therapy) and healthy volunteers were exposed to the DEX–CRH test. Blood samples were taken for cortisol and adrenocorticotropic hormone (ACTH) assessment. Established panic-specific questionnaires were handed out for the pre-therapy and post-therapy evaluation of disease severity (with reference to panic beliefs and agoraphobic cognitions, fear of bodily sensations, agoraphobic avoidance behaviour). Repeated measures ANCOVA were conducted for the analysis of the pre-therapy hormonal response, and Pearson’s correlation analysis to test for associations with the psychotherapy outcome. Data analyses revealed large effect sizes for CBT in the clinical measures (η2 ≥ 0.321), main effects of time for cortisol and ACTH with no differences between both groups, and significant associations between cortisol release and agoraphobic cognitions for the patients. PD diagnosis had no impact on the hormonal response. However, those patients with higher cortisol release showed less improvement after CBT (significantly for agoraphobic cognitions). Clinical implications of these findings are the prediction of the therapy success from a potential endocrine correlate whose persistency (if assessed repeatedly) during the treatment may predict (non-)response to the current treatment, possibly representing a decision support for a change in treatment to avoid the continuation of an inefficient treatment.

Agoraphobic avoidance predicts emotional distress and increased physical concerns in chronic obstructive pulmonary disease

BackgroundAnxiety and panic attacks are more common in chronic obstructive pulmonary disease (COPD) than in the overall population. Individuals with panic attacks often attempt to avoid situations perceived as at risk of eliciting bodily sensations such as dyspnea, which paradoxically may lead to anxiety-related responsivity. Although there is some evidence that COPD individuals restrict their participation in various life activities because they fear that these may trigger breathlessness, little is known about agoraphobic avoidance and its impact on cognitions and emotional distress in this population. It was thus our aim to investigate the degree of agoraphobic avoidance in COPD individuals, its clinical concomitants and consequences. MethodsA total of 48 patients with COPD and 48 matched controlled subjects completed measures of anxiety sensitivity, agoraphobic avoidance, anxiety and depression. Objective COPD severity was measured using forced expiratory volume in the first second. ResultsPatients showed significant impairment in respiratory functioning and psychological distress. Relative to the control, the COPD group exhibited greater depression, anxiety, physical symptom concerns and avoidance (alone and accompanied), irrespective of whether they were panickers or not. Patients with high avoidance showed more intense physical concerns when compared to those with low avoidance. Importantly, the level of avoidance predicted emotional distress and increased physical concerns in COPD. ConclusionsPhysical concerns scores in COPD patients are partially explained by avoidance in this group. The results of the study provide evidence for the importance of evaluating avoidance in COPD patients and implicate targeting this behavior in therapeutic interventions.

Evaluation of the Effectiveness and Transportability of Panic Control Treatment in a Private Practice Setting: Acute and Long Term Effects

Effectiveness studies have demonstrated the transportability of panic control treatment (PCT) to a variety of settings. The present study examined the acute and long-term effects of PCT in a private practice setting and explored correlates of treatment outcome. Participants (69% female, mean age = 34.8, SD = 8.8 years) were 100 consecutive private practice referrals who entered treatment for panic disorder. Using intent-to-treat analyses, 72% of patients were panic-free and 44% of patients achieved high end state functioning (HESF) at posttreatment. At 1-year follow-up, 75% of patients were panic-free and 55% of patients achieved HESF. Lower levels of agoraphobic avoidance when accompanied (MI-ACM), less misinterpretation of bodily sensations, and less frequent panic attacks at pretreatment were the strongest predictors of treatment outcome at follow-up. Pre-posttreatment changes in trait anxiety were most strongly associated with treatment response. Results support PCT as an effective, durable treatment and add to the body of evidence supporting the generalizability of PCT from research to real-world service settings.