Relapse prevention in panic disorder with pharmacotherapy: where are we now?

Introduction: A substantial number of patients with PD experience relapse after the discontinuation of effective pharmacotherapy, leading to detrimental effects on the individuals and considerable societal costs. This suggests the need to optimize pharmacotherapy to minimize relapse risk. Area covered: The present systematic review examines randomized, double-blind, placebo-controlled relapse prevention studies published over the last 20 years involving recommended medications. The authors aim to provide an overview of this topic and evaluate whether recent advances were achieved. Only seven studies were included, providing limited results. One-year maintenance pharmacotherapy with constant doses had protective effects against relapse in patients who had previously exhibited satisfactory responses to the same medication at the same doses. The duration of maintenance treatment did not influence relapse risk. No data were available concerning the use of lower doses or the predictors of relapse. Expert opinion: Relapse prevention in PD has received limited attention. Recent progress and conclusive indications are lacking. Rethinking pharmacological research in PD may be productive. Collecting a wide range of clinical and individual features/biomarkers in large-scale, multicenter long-term naturalistic studies, and implementing recent technological innovations (e.g., electronic medical records/'big data' platforms, wearable devices, and machine learning techniques) may help identify reliable predictive models.

Modifiable risk and protective factors for anxiety disorders among adults: A systematic review.

Anxiety disorders are highly prevalent in the general population and associated with high rates of impairment and disability. This burden highlights the need to identify risk factors that individuals can modify without professional intervention. A systematic review was conducted to identify studies that examined modifiable risk and protective factors for anxiety disorders among adults in the general population. Searches were conducted in PubMed, PsycINFO and MEDLINE using medical subject headings and text words related to risk factors, protective factors, and each anxiety disorder. Screening, data extraction, and quality assessment were performed by three study authors. Modifiable risk and protective factors from 19 studies across seven countries were identified. Risk factors identified included cigarette smoking, alcohol use, cannabis use, negative appraisals of life events, avoidance, and occupational factors. Protective factors included social support, coping, and physical activity. Cigarette smoking was the most studied risk factor. Support was found for cigarette smoking as a risk factor for agoraphobia and panic disorder. Mixed results were found for generalized anxiety disorder and specific phobia. Across disorders, smoking frequency was associated with greater risk. Results indicate an important gap in the literature in that few studies have examined modifiable risk factors for anxiety disorders.

Technical Issues and Patient Safety in Nonintubated Thoracic Anesthesia.

Nonintubated thoracic surgery (NITS) has a good safety record in experienced hands, but has pitfalls for beginners. The main aim of NITS is to keep the patient under spontaneous respiration, avoiding adverse effects, such as hypoxemia, hypercapnia, panic attacks, and finally conversion to general anesthesia. In this paper, the safety aspects of anesthesia for NITS is discussed based on data from the literature and personnel clinical experiences.

Panicolytic-like effect of µ1-opioid receptor blockade in the inferior colliculus of prey threatened by Crotalus durissus terrificus pit vipers.

BACKGROUND: The endogenous opioid peptide system has been implicated in the neural modulation of fear and anxiety organised by the dorsal midbrain. Furthermore, previous results indicate a fundamental role played by inferior colliculus (IC) opioid mechanisms during the expression of defensive behaviours, but the involvement of the IC µ1-opioid receptor in the modulation of anxiety- and panic attack-related behaviours remains unclear. Using a prey-versus-snake confrontation paradigm, we sought to investigate the effects of µ1-opioid receptor blockade in the IC on the defensive behaviour displayed by rats in a dangerous situation. METHODS: Specific pathogen-free Wistar rats were treated with microinjection of the selective µ1-opioid receptor antagonist naloxonazine into the IC at different concentrations (1.0, 3.0 and 5.0 µg/0.2 µL) and then confronted with rattlesnakes ( Crotalus durissus terrificus). The defensive behavioural repertoire, such as defensive attention, flat back approach (FBA), startle, defensive immobility, escape or active avoidance, displayed by rats either during the confrontations with wild snakes or during re-exposure to the experimental context without the predator was analysed. RESULTS: The blockade of µ1-opioid receptors in the IC decreased the expression of both anxiety-related behaviours (defensive attention, FBA) and panic attack-related responses (startle, defensive immobility and escape) during the confrontation with rattlesnakes. A significant decrease in defensive attention was also recorded during re-exposure of the prey to the experimental apparatus context without the predator. CONCLUSION: Taken together, these results suggest that a decrease in µ1-opioid receptor signalling activity within the IC modulates anxiety- and panic attack-related behaviours in dangerous environments.

Hypothalamic endocannabinoid signalling modulates aversive responses related to panic attacks.

Recurrent panic attacks, comprising emotional and cardiovascular aversive responses, are common features in panic disorder, a subtype of anxiety disorder. The underlying brain circuitry includes nuclei of the hypothalamus, such as the dorsomedial hypothalamus (DMH). The endocannabinoid system has been proposed to modulate several biological processes in the hypothalamus. Thus, we tested the hypothesis that hypothalamic endocannabinoid signalling controls aversive responses in an animal model of panic attacks. Local infusion of NMDA into the DMH of rats induced panic-like behaviour. This effect was prevented by local, but not intraperitoneal, injection of a 2-arachidonoylglycerol (2-AG) hydrolysis inhibitor (MAGL inhibitor, URB602). The anandamide hydrolysis inhibitor (FAAH inhibitor), URB597, was ineffective. The anti-aversive action of URB602 was reversed by CB1 and CB2 antagonists (AM251 and AM630, respectively), and mimicked by CB1 and CB2 agonists (ACEA and JWH133, respectively). URB602 also prevented the cardiovascular effects of DMH-stimulation in anaesthetised animals. None of the treatments modified blood corticosterone levels. In conclusion, facilitation of 2-AG-signalling in the DMH modulates panic-like responses. The possible mechanisms comprise activation of both CB1 and CB2 receptors in this brain region.

Chess therapy: A new approach to curing panic attack.

OBJECTIVES: To study the effect of playing cell phone chess game on treating panic attack. METHODS: The chess game on an android cell phone was played by the researcher who was affected by panic attack as a post-traumatic disorder immediately after or before feeling of the start of symptoms. The right level of difficulty, i.e., levels 2-4, was selected for optimal results. RESULTS: Playing chess game on the android cell phone prevented the manifestation of panic attack and led to the cure of this traumatic condition. CONCLUSION: Chess therapy with the right level of difficulty can be recommended as a very effective non-pharmaceutical method for the successful treatment of panic attacks.

Influence of vulnerability factors in panic disorder severity / Influencia de factores de vulnerabilidad en la gravedad del trastorno de pánico

BACKGROUND: we studied herein the predictive value for panic severity of three well-based vulnerability factors: personality traits (neuroticism and extraversion; NEO-PI-R), anxiety sensitivity (ASI), and perceived control (ACQ-R). METHOD: the sample was composed of 52 participants diagnosed with panic disorder, with or without agoraphobia, according to DSM-IV-TR criteria. RESULTS: our results revealed that the anxiety facet is a better predictor of panic severity than neuroticism. Anxiety sensitivity increases the predictive value for panic severity and, finally, perception of control of emotions is the only perception control subscale that increases the predictive value for panic severity more than the anxiety facet and anxiety sensitivity. CONCLUSIONS: this finding supports the assumption of the importance of taking into account the assessment of the lower order dimensions of the vulnerability factors in the field of psychopathology studies. Furthermore, the predictive value of perception of control of emotions indicates the importance of this specific vulnerability factor in the etiology of panic disorder (with or without agoraphobia) and, thus, shows the necessity to include emotion regulation strategies in the psychological treatments

ANTECEDENTES: en este trabajo se estudia el valor predictivo sobre la gravedad del pánico de tres factores de vulnerabilidad bien establecidos: rasgos de personalidad (neuroticismo y extraversión; NEO-PI-R), sensibilidad a la ansiedad (ASI) y percepción de control (ACQ-R). MÉTODO: la muestra fue de 52 participantes con diagnóstico de trastorno de pánico, con o sin agorafobia, según criterios DSM-IV-TR.RESULTADOS: nuestros resultados revelan que la faceta de ansiedad es mejor predictor de la gravedad del pánico que el neuroticismo. La sensibilidad a la ansiedad aumenta el valor predictivo sobre la gravedad del pánico y, finalmente, la percepción de control de las emociones es la única subescala de la percepción de control que aumenta la capacidad predictiva más allá de la faceta de ansiedad y la sensibilidad a la ansiedad. CONCLUSIONES: estos resultados apoyan el supuesto sobre la importancia de evaluar las dimensiones de orden inferior de los factores de vulnerabilidad en los estudios psicopatológicos. Además, el valor predictivo de la percepción de control de las emociones indica la importancia de este factor específico de vulnerabilidad en la etiología del trastorno de pánico (con o sin agorafobia) lo que muestra la necesidad de incluir estrategias de regulación emocional en los tratamientos psicológicos

Anxiety sensitivity risk reduction in smokers: A randomized control trial examining effects on panic.

Empirical evidence has identified several risk factors for panic psychopathology, including smoking and anxiety sensitivity (AS; the fear of anxiety-related sensations). Smokers with elevated AS are therefore a particularly vulnerable population for panic. Yet, there is little knowledge about how to reduce risk of panic among high AS smokers. The present study prospectively evaluated panic outcomes within the context of a controlled randomized risk reduction program for smokers. Participants (N = 526) included current smokers who all received a state-of-the-art smoking cessation intervention with approximately half randomized to the AS reduction intervention termed Panic-smoking Program (PSP). The primary hypotheses focus on examining the effects of a PSP on panic symptoms in the context of this vulnerable population. Consistent with prediction, there was a significant effect of treatment condition on AS, such that individuals in the PSP condition, compared to those in the control condition, demonstrated greater decreases in AS throughout treatment and the follow-up period. In addition, PSP treatment resulted in lower rates of panic-related symptomatology. Moreover, mediation analyses indicated that reductions in AS resulted in lower panic symptoms. The present study provides the first empirical evidence that brief, targeted psychoeducational interventions can mitigate panic risk among smokers.

Does help-seeking alter the risk for incident psychopathology in adolescents and young adults with and without fearful spells or panic attacks? Findings from a 10-year prospective-longitudinal community study.

BACKGROUND: Although fearful spells (FS) and panic attacks (PA) increase the risk for various mental disorders, few studies have examined whether help-seeking in those with FS/PA attenuates the risk for incident psychopathology. METHODS: A community sample of adolescents and young adults (N=2978, aged 14-24 at baseline) was followed up in up to 3 assessment waves over 10 years. FS, PA, psychopathology, and help-seeking were assessed using the DSM-IV/M-CIDI. Logistic regressions with interaction terms (adjusted for sex and age) were used to test interactions between FS/PA and help-seeking at baseline on predicting incident psychopathology at follow-up. Cases with panic disorder (PD) at baseline were excluded from all analyses. RESULTS: FS/PA at baseline predicted the onset of any disorder, any anxiety disorder, PD, agoraphobia, generalized anxiety disorder, social phobia, and depression at follow-up (Odds Ratios, OR 1.62-5.80). FS/PA and help-seeking at baseline interacted on predicting incident PD (OR=0.09) and depression (OR=0.22) at follow-up in a way that FS/PA only predicted the respective disorders in individuals not seeking help at baseline. In those with FS/PA, a higher number of panic symptoms interacted with help-seeking on predicting incident PD (OR=0.63) in a way that a higher number of panic symptoms only increased the risk for PD in those without help-seeking at baseline. LIMITATIONS: Help-seeking at baseline was not restricted to panic-specific interventions, but included treatment due to other psychological problems as well. CONCLUSIONS: Findings suggest that early help-seeking might modify psychopathology trajectories and prevent incident disorders in high-risk individuals with FS/PA.

Trastorno de pánico y fibrilación auricular / Panic disorder and atrial fibrillation

Este trabajo analiza la relación bidireccional entre la fibrilación auricular y el trastorno de pánico. El diagnóstico diferencial se plantea frecuentemente en los servicios de urgencias y en la consulta del médico de atención primaria. Diferentes estudios nos hablan de una alta tasa de prevalencia de trastornos de ansiedad en pacientes que han recibido el diagnóstico de fibrilación auricular. Por otra parte, se ha observado que los pacientes con trastornos de ansiedad presentan una mayor prevalencia de enfermedades cardiovascular. Los pacientes con trastorno de pánico presentarán con frecuencia quejas somáticas indicativas de enfermedad cardíaca que es obligatorio descartar mediante pruebas complementarias. El correcto diagnóstico conlleva, además, el tratamiento considerado óptimo para cada afección y, como consecuencia, la reducción del gasto sanitario (AU)

This paper studies the relationship between atrial fibrillation and panic disorder. There are often doubts on the differential diagnosis in emergency services and general medical settings. Panic disorder prevalence rates have been found to be high in patients suffering from atrial fibrillation. Various studies have observed that patients diagnosed with anxiety disorders frequently have higher cardiovascular disease rates compared to the general population. Usually, patients suffering from panic disorder exhibit somatic complaints suggesting coronary disease, such as chest pain or palpitations. The aim is to make the correct diagnosis and treatment for these different illnesses, and to decrease the costs due to misdiagnosis (AU)

Vitamin D and common mental disorders in mid-life: cross-sectional and prospective findings.

BACKGROUND & AIMS: The relationship between vitamin D and common mental disorders (CMDs) remains unclear. We aimed to determine if behaviours affecting vitamin D concentrations differ between individuals with or without CMDs and evaluate, cross-sectionally and prospectively, the extent to which the association between 25(OH)D and CMDs are explained by these behaviours. METHODS: Data are from the 1958 British birth cohort (n = 7401). Behaviours were ascertained by questionnaire at age 45 years. CMDs (depression, anxiety, panic, phobia) were assessed using the Clinical Interview Schedule-Revised at 45 years and depression using Mental Health Inventory-5 at 50 years. RESULTS: Participants with CMDs at 45 years differed from others on some but not all vitamin D related behaviours. There were inverse, cross-sectional associations at 45 years of 25(OH)D with depression and panic, which persisted after adjustment for vitamin D related behaviours (OR = 0.57, 95% CI: 0.40,0.81 and OR = 0.33, 95% CI: 0.40,0.81, respectively). Association between 25(OH)D and subsequent (50 years) risk of depression was non-linear (p = 0.01), with lower risk for participants with 25(OH)D between 50 and 85 nmol/l compared with those with lower or higher concentrations. CONCLUSION: This study provides support for an association of low 25(OH)D concentrations with current and subsequent risk of depression in mid-adulthood.

Involvement of serotonin-mediated neurotransmission in the dorsal periaqueductal gray matter on cannabidiol chronic effects in panic-like responses in rats.

RATIONALE: Cannabidiol (CBD) is a non-psychotomimetic constituent of Cannabis sativa plant that promotes antianxiety and anti-panic effects in animal models after acute systemic or intra-dorsal periaqueductal gray (DPAG) administration. However, the effects of CBD repeated administration, and the possible mechanisms involved, in animal models of anxiety- and panic-related responses remain poorly understood. OBJECTIVE: The present study evaluates the role of the serotonergic neurotransmission within the DPAG in the modulation of escape responses of rats chronically treated with CBD. METHODS: Male Wistar rats received acute or repeated (5 mg/Kg/daily/21 days) administration of CBD and were submitted to the elevated T-maze (ETM). We also investigated if CBD effects on the ETM depend on facilitation of 5-HT1A-mediated neurotransmission in the DPAG. To this latter aim, we verified if these effects would be prevented by intra-DPAG injection of the 5-HT1A receptor antagonist WAY100635 (0.37 nmol/0.2 µL). Also, we verified, by in vivo microdialysis, if CBD chronic treatment increases serotonin (5-HT) release and, by quantitative polymerase chain reaction, if there are changes in 5HT-1A or 5HT-2C mRNA expression in DPAG. RESULTS: The results showed that repeated but not acute peripheral administration of CBD decreases escape responses in the ETM, suggesting a panicolytic effect. This treatment did not change 5HT-1A or 5-HT-2C receptor mRNA expression nor modify serotonin extracellular concentrations in the DPAG. CBD effects were prevented by DPAG injection of the 5-HT1A receptor antagonist. CONCLUSIONS: Together, these findings suggest that repeated treatment with CBD induces anti-panic effects by acting on 5-HT1A receptors in DPAG.

Importance of personal dose equivalent evaluation in Fukushima in overcoming social panic.

The relationship between the reported ambient dose equivalent (H*(10)) and the individual dose rate recorded by medical staff in Fukushima City after the accident at the Fukushima Daiichi nuclear power plant was evaluated, following a 9.0-magnitude earthquake that struck the east coast of Japan. Personal dose equivalent (H(p)(10)) ranged from 0.08 to 1.63 µSv h(-1) and H*(10) ranged from 0.86 to 12.34 µSv h(-1). H(p)(10) from March to July 2011 were significantly lower than H*(10). The relationships between these dose equivalents were moderately correlated. The regression equation was calculated as follows: H(p)(10)=0.0696×H*(10)+0.0538. The preliminary data of this study show that, in Fukushima, the individual dose is much lower than that determined H*(10). It is important to evaluate H(p)(10) in order to lessen the anxiety of the general population in Fukushima.