Electrocardiographic frontal QRS-T angle is independently associated with panic disorder.

OBJECTIVE: Panic disorder (PD) may cause serious cardiac arrhythmias by causing electrical abnormalities. Abnormal P-wave axis (aPwa), presence of fragmented QRS (fQRS), wide frontal QRS-T angle (fQRSTa), QRS duration corrected (QRSdc) and log/ logQRS duration/RR interval (log/logQRS/RR) have been correlated with increased risk of serious supraventricular and ventricular cardiac arrhythmias in a general population. The purpose of this study was to compare these newly explored atrial and ventricular arrhythmia indicators in patients with PD and in healthy subjects. METHOD: A total of 169 newly diagnosed PD patients and 128 healthy subjects were included in the study. The Panic and Agoraphobia Scale (PAS) was administered, and 12-lead electrocardiography (ECG) measurements were obtained. Electrocardiographic parameters including aPwa, fQRSTa, presence of fQRS, QRS duration corrected (QRSdc), and log/logQRS duration/RR distance (log/logQRS/RR) were compared between the two groups. RESULTS: aPwa and fQRS, in addition to fQRSTa, QRSdc, and log/ logQRS/RR ratio values, were significantly increased in the PD group compared to healthy controls. Correlation analyses revealed that wider fQRSTa, number of fQRS derivation, number of total fQRS, wider QRSdc, and log/logQRS/RR ratio significantly correlated with PAS score. Logistic regression analysis demonstrated that fQRSTa and the number of total fQRS were independently associated with PD. CONCLUSION: PD is associated with wider fQRSTa, QRSdc, and log/logQRS/RR in addition to the increased abnormal aPwa and presence of fQRS. These findings suggest that untreated PD patients may be susceptible to supraventricular and ventricular arrhythmia, indicating that ECG should be routinely obtained in the management of PD patients.

Childhood Trauma and Panic Disorder: The Impact of History of Child Abuse on Illness Severity and Treatment Response.

OBJECTIVE: Patients who have experienced child abuse often have complex clinical presentations; whether a history of child abuse (HCA) affects psychotherapy outcomes is unclear. The authors examined relationships between HCA, clinical baseline variables, and change in these variables after three different psychotherapies for panic disorder (PD). METHODS: Two hundred adults with PD (with or without agoraphobia) were randomly assigned to one of three treatments across two sites: panic-focused psychodynamic psychotherapy (PFPP), cognitive-behavioral therapy (CBT), or applied relaxation training (ART). Differences in demographic and clinical variables between those with and without HCA were compared. The primary analysis addressed odds of meeting clinical response criteria on the Panic Disorder Severity Scale (PDSS) between treatments, as moderated by HCA. This effect was examined via continuous outcomes on the PDSS and psychosocial functioning (Sheehan Disability Scale). RESULTS: Compared with patients without HCA (N=154), patients with HCA (N=46) experienced significantly more severe symptoms of PD (d=0.60), agoraphobia (d=0.47), and comorbid depression (d=0.46); significantly worse psychosocial impairment (d=0.63) and anxiety sensitivity (d=0.75); greater personality disorder burden (d=0.45)-particularly with cluster C disorders (d=0.47)-and more severe interpersonal problems (d=0.54). HCA significantly moderated the likelihood of clinical response, predicting nonresponse to ART (B=-2.05, 95% CI=-4.17 to -0.30, OR=0.13, z=-2.14, p=0.032) but not CBT or PFPP. HCA did not interact with treatment condition to predict slopes of PDSS change. CONCLUSIONS: The results of this study highlight the importance of HCA in formulating treatment recommendations. Increased awareness of HCA's effects on severity of PD and treatment responsiveness among patients with PD may improve outcomes.

When to panic about a panic attack: A challenging case of hypersensitivity pneumonitis.

The COVID-19 pandemic has created diagnostic difficulties with the increase in mental health illnesses that often present with nonspecific symptoms, like hypersensitivity pneumonitis. Hypersensitivity pneumonitis is a complex syndrome of varying triggers, onset, severity, and clinical manifestations that can be challenging to diagnose in many cases. Typical symptoms are nonspecific and can be attributed to other entities. There are no pediatric guidelines, which contributes to diagnostic difficulties and delays in treatment. It is particularly important to avoid diagnostic biases, have an index of suspicion for hypersensitivity pneumonitis, and to develop pediatric guidelines as outcomes are excellent when diagnosed and treated promptly. This article discusses hypersensitivity pneumonitis with a focus on the causes, pathogenesis, diagnostic approach, outcomes, and prognosis while using a case to illustrate the diagnostic difficulties worsened by the COVID-19 pandemic.

Agoraphobia and panic attacks complicated by primary aldosteronism improved by treatment with eplerenone: a case report.

BACKGROUND: Primary aldosteronism (PA) is an adrenal gland disease, that induces increased secretion of the mineralocorticoid, aldosterone, resulting in symptoms such as hypertension. This study reports a patient with agoraphobia and panic attacks, associated with PA. This patient's psychiatric symptoms improved after treatment with eplerenone, a mineralocorticoid receptor antagonist. CASE PRESENTATION: The patient was a 40-year-old female with agoraphobia, which refers to the irrational fear of situations that may cause anxiety, and panic attacks characterized by profuse sweating, palpitations, and generalized weakness. She was diagnosed with hypertension from PA. Subsequently, she received treatment with eplerenone, which improved her agoraphobia and panic attacks. CONCLUSIONS: There have been no previous reports on PA associated with agoraphobia and panic attacks that improved with pharmacotherapy. Patients with agoraphobia and panic attacks should be evaluated for PA. In patients with PA, pharmacotherapy with eplerenone should be considered.

Pharmacological treatments in panic disorder in adults: a network meta-analysis.

BACKGROUND: A panic attack is a discrete period of fear or anxiety that has a rapid onset and reaches a peak within 10 minutes. The main symptoms involve bodily systems, such as racing heart, chest pain, sweating, shaking, dizziness, flushing, churning stomach, faintness and breathlessness. Other recognised panic attack symptoms involve fearful cognitions, such as the fear of collapse, going mad or dying, and derealisation (the sensation that the world is unreal). Panic disorder is common in the general population with a prevalence of 1% to 4%. The treatment of panic disorder includes psychological and pharmacological interventions, including antidepressants and benzodiazepines. OBJECTIVES: To compare, via network meta-analysis, individual drugs (antidepressants and benzodiazepines) or placebo in terms of efficacy and acceptability in the acute treatment of panic disorder, with or without agoraphobia. To rank individual active drugs for panic disorder (antidepressants, benzodiazepines and placebo) according to their effectiveness and acceptability. To rank drug classes for panic disorder (selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants (TCAs), mono-amine oxidase inhibitors (MAOIs) and benzodiazepines (BDZs) and placebo) according to their effectiveness and acceptability. To explore heterogeneity and inconsistency between direct and indirect evidence in a network meta-analysis. SEARCH METHODS: We searched the Cochrane Common Mental Disorders Specialised Register, CENTRAL, CDSR, MEDLINE, Ovid Embase and PsycINFO to 26 May 2022. SELECTION CRITERIA: We included randomised controlled trials (RCTs) of people aged 18 years or older of either sex and any ethnicity with clinically diagnosed panic disorder, with or without agoraphobia. We included trials that compared the effectiveness of antidepressants and benzodiazepines with each other or with a placebo. DATA COLLECTION AND ANALYSIS: Two authors independently screened titles/abstracts and full texts, extracted data and assessed risk of bias. We analysed dichotomous data and continuous data as risk ratios (RRs), mean differences (MD) or standardised mean differences (SMD): response to treatment (i.e. substantial improvement from baseline as defined by the original investigators: dichotomous outcome), total number of dropouts due to any reason (as a proxy measure of treatment acceptability: dichotomous outcome), remission (i.e. satisfactory end state as defined by global judgement of the original investigators: dichotomous outcome), panic symptom scales and global judgement (continuous outcome), frequency of panic attacks (as recorded, for example, by a panic diary; continuous outcome), agoraphobia (dichotomous outcome). We assessed the certainty of evidence using threshold analyses. MAIN RESULTS: Overall, we included 70 trials in this review. Sample sizes ranged between 5 and 445 participants in each arm, and the total sample size per study ranged from 10 to 1168. Thirty-five studies included sample sizes of over 100 participants. There is evidence from 48 RCTs (N = 10,118) that most medications are more effective in the response outcome than placebo. In particular, diazepam, alprazolam, clonazepam, paroxetine, venlafaxine, clomipramine, fluoxetine and adinazolam showed the strongest effect, with diazepam, alprazolam and clonazepam ranking as the most effective. We found heterogeneity in most of the comparisons, but our threshold analyses suggest that this is unlikely to impact the findings of the network meta-analysis. Results from 64 RCTs (N = 12,310) suggest that most medications are associated with either a reduced or similar risk of dropouts to placebo. Alprazolam and diazepam were associated with a lower dropout rate compared to placebo and were ranked as the most tolerated of all the medications examined. Thirty-two RCTs (N = 8569) were included in the remission outcome. Most medications were more effective than placebo, namely desipramine, fluoxetine, clonazepam, diazepam, fluvoxamine, imipramine, venlafaxine and paroxetine, and their effects were clinically meaningful. Amongst these medications, desipramine and alprazolam were ranked highest. Thirty-five RCTs (N = 8826) are included in the continuous outcome reduction in panic scale scores. Brofaromine, clonazepam and reboxetine had the strongest reductions in panic symptoms compared to placebo, but results were based on either one trial or very small trials. Forty-one RCTs (N = 7853) are included in the frequency of panic attack outcome. Only clonazepam and alprazolam showed a strong reduction in the frequency of panic attacks compared to placebo, and were ranked highest. Twenty-six RCTs (N = 7044) provided data for agoraphobia. The strongest reductions in agoraphobia symptoms were found for citalopram, reboxetine, escitalopram, clomipramine and diazepam, compared to placebo. For the pooled intervention classes, we examined the two primary outcomes (response and dropout). The classes of medication were: SSRIs, SNRIs, TCAs, MAOIs and BDZs. For the response outcome, all classes of medications examined were more effective than placebo. TCAs as a class ranked as the most effective, followed by BDZs and MAOIs. SSRIs as a class ranked fifth on average, while SNRIs were ranked lowest. When we compared classes of medication with each other for the response outcome, we found no difference between classes. Comparisons between MAOIs and TCAs and between BDZs and TCAs also suggested no differences between these medications, but the results were imprecise. For the dropout outcome, BDZs were the only class associated with a lower dropout compared to placebo and were ranked first in terms of tolerability. The other classes did not show any difference in dropouts compared to placebo. In terms of ranking, TCAs are on average second to BDZs, followed by SNRIs, then by SSRIs and lastly by MAOIs. BDZs were associated with lower dropout rates compared to SSRIs, SNRIs and TCAs. The quality of the studies comparing antidepressants with placebo was moderate, while the quality of the studies comparing BDZs with placebo and antidepressants was low. AUTHORS' CONCLUSIONS: In terms of efficacy, SSRIs, SNRIs (venlafaxine), TCAs, MAOIs and BDZs may be effective, with little difference between classes. However, it is important to note that the reliability of these findings may be limited due to the overall low quality of the studies, with all having unclear or high risk of bias across multiple domains. Within classes, some differences emerged. For example, amongst the SSRIs paroxetine and fluoxetine seem to have stronger evidence of efficacy than sertraline. Benzodiazepines appear to have a small but significant advantage in terms of tolerability (incidence of dropouts) over other classes.

Cognitive-Behavioral Therapy for Panic Disorder in Patients with Stable Coronary Artery Disease: A Feasibility Study.

Implementing cognitive-behavioral therapy (CBT), the first-line psychological treatment for panic disorder (PD), may be challenging in patients with comorbid coronary artery disease (CAD).This study aimed at assessing the feasibility and acceptability of a CBT for PD protocol that was adapted to patients suffering from comorbid CAD. It also aimed at evaluating the efficacy of the intervention to reduce PD symptomatology and psychological distress and improve quality of life. This was a single-case experimental design with pre-treatment, post-treatment and 6-month follow-up measures. Patients with PD and stable CAD received 14 to 17 individual, 1-h sessions of an adapted CBT for PD protocol. They completed interviews and questionnaires at pre-treatment, post-treatment and at a 6-month follow-up assessing intervention acceptability, PD symptomatology, psychological distress and quality of life. A total of 6 patients out of 7 completed the intervention and 6-month follow-up, indicating satisfactory feasibility. Acceptability was high (medians of ≥ 8.5 out of 9 and ≥ 80%) both at pre and post treatment. Remission rate was of 83% at post-treatment and 6-month follow-up. The intervention appeared to have positive effects on comorbid anxiety and depression symptoms and quality of life. The intervention appeared feasible and acceptable in patients with comorbid CAD. The effects of the adapted CBT protocol on PD symptoms, psychological distress and quality of life are promising and were maintained at the 6-month follow-up. Further studies should aim at replicating the present results in randomized-controlled trials.

Cognitive behavioral therapy (CBT) plus attention bias modification (ABM) reduces anxiety sensitivity and depressive symptoms in panic disorder: A pilot randomized trial.

BACKGROUND: Cognitive bias theories propose that reducing threat hypervigilance in mental disorders can augment cognitive behavioral therapy (CBT) outcomes. However, no studies have tested whether adding attention bias modification (ABM) can effectively enhance CBT's effects on anxiety sensitivity (AS), electromyography (EMG), and skin conductance (SC) for panic disorder (PD). This pilot randomized controlled trial (RCT) thus aimed to evaluate the efficacy of CBT + ABM (vs. CBT plus attention training placebo; PBO) on those outcomes. METHOD: This study is a secondary analysis (Baker et al., 2020). Adults with PD were randomized to receive CBT + ABM (n = 11) or CBT + PBO (n = 12). Before each of the first five CBT sessions, CBT + ABM and CBT + PBO participants completed a 15-min ABM task or attention training PBO, respectively. AS and depression severity as well as SC and EMG during habituation to a loud-tone startle paradigm were assessed. Hierarchical Bayesian analyses were conducted. RESULTS: During pre-post-treatment and pre-follow-up, CBM + ABM (vs. CBT + PBO) led to a notably greater reduction in ASI-Physical (between-group d = -1.26 to -1.25), ASI-Cognitive (d = -1.16 to -1.10), and depression severity (d = -1.23 to -0.99). However, no between-group difference was observed for ASI-Social, EMG, or SC indices. DISCUSSION: Adding a brief computerized ABM intervention to CBT for PD protocols may enhance therapeutic change.

Neural basis of implicit cognitive reappraisal in panic disorder: an event-related fMRI study.

BACKGROUND: Panic disorder (PD) is thought to be related with deficits in emotion regulation, especially in cognitive reappraisal. According to the cognitive model, PD patients' intrinsic and unconscious misappraisal strategies are the cause of panic attacks. However, no studies have yet been performed to explore the underlying neuromechanism of cognitive reappraisal that occur on an unconscious level in PD patients. METHODS: Twenty-six patients with PD and 25 healthy controls (HC) performed a fully-verified event-block design emotional regulation task aimed at investigating responses of implicit cognitive reappraisal during an fMRI scan. Participants passively viewed negatively valanced pictures that were beforehand neutrally, positively, or adversely portrayed in the task. RESULTS: Whole-brain analysis of fMRI data showed that PD patients exhibited less activation in the right dorsolateral prefrontal cortex (dlPFC) and right dorsomedial prefrontal cortex (dmPFC) compared to HC, but presented greater activation in parietal cortex when negative pictures were preceded by positive/neutral vs negative descriptions. Simultaneously, interactive effects of Group × Condition were observed in the right amygdala across both groups. Furthermore, activation in dlPFC and dmPFC was is negatively correlated to severity of anxiety and panic in PD when negative images were preceded by non-negative vs negative descriptions. CONCLUSIONS: Emotional dysregulation in PD is likely the result of deficient activation in dlPFC and dmPFC during implicit cognitive reappraisal, in line with impaired automatic top-down regulation. Correlations between severity of anxiety and panic attack and activation of right dlPFC and dmPFC suggest that the failure to engage prefrontal region during implicit cognitive reappraisal might be associated wtih the severity of anxiety and panic; such functional patterns might be the target of possible treatments.

The Mediating Effect of Insomnia on the Relationship between Panic Symptoms and Depression in Patients with Panic Disorder.

BACKGROUND: This study aimed to determine if sleep disturbances may mediate the relationship between panic symptoms and depression in patients with panic disorder (PD). METHODS: Electronic medical records were retrospectively reviewed for 110 consecutive patients with diagnosed PD in an outpatient clinic between October 2018 and December 2019. Measurements include the PD Severity Scale, Beck Depression Inventory-II (BDI-II) and Insomnia Severity Index (ISI). Statistical analyses were performed to assess any potential relationship between PD, insomnia and depression. RESULTS: Of the PD patients, 88 (80%) and 89 (80.9%) had comorbid depression (BDI-II ≥ 14) and insomnia (Korean version of the ISI ≥ 8), respectively. In a mediation model using insomnia as the mediating variable, the total effect of panic symptom severity on depression was significant (t = 7.23, P < 0.001). There were significant effects of panic symptoms on insomnia (t = 4.62, P < 0.001) and of insomnia on depression (t = 6.69, P < 0.001). The main effect of panic symptom severity on depression was also significant, after controlling for the effect of insomnia (t = 5.10, P < 0.001), suggesting partial mediation. CONCLUSION: Both depressive symptoms and insomnia are common in patients with PD and depression was partially mediated by insomnia in these patients. These results suggest that an intervention for insomnia in patients with PD might help prevent the development of depression.

A Narrative Literature Review of the Epidemiology, Etiology, and Treatment of Co-Occurring Panic Disorder and Opioid Use Disorder.

OBJECTIVE: Panic disorder is a debilitating psychiatric disorder that often co-occurs with substance use disorders. Given the current opioid epidemic, the high reported rates of comorbid panic disorder and opioid use disorder are particularly concerning. In this narrative review, we describe the literature on panic disorder and opioid use disorder co-occurrence. METHODS: 86 studies, 26 reviews, 2 commentaries, and 5 guidelines pertaining to opioid use disorder, panic disorder, and their comorbidity were identified using all EBSCO databases, PubMed, and Google Scholar. RESULTS: First, we review epidemiological literature on the prevalence of the comorbid condition above and beyond each disorder on its own. Additionally, we discuss the challenges that complicate the differential diagnosis of panic disorder and opioid use disorder and contribute to difficulties establishing rates of comorbidity. Second, we review three theoretical models that have been proposed to explain high rates of co-occurring panic disorder and opioid use disorder: the precipitation hypothesis, the self-medication hypothesis, and the shared vulnerability hypothesis. Third, we outline how co-occurring panic and opioid use disorder may impact treatment for each condition. CONCLUSION: Based on findings in the field, we provide recommendations for future research as well as treatment considerations for co-occurring panic and opioid use disorders.

DNA hypomethylation of the Krüppel-like factor 11 (KLF11) gene promoter: a putative biomarker of depression comorbidity in panic disorder and of non-anxious depression?

Panic disorder (PD) is one of the most common anxiety disorders and often occurs comorbidly with major depressive disorder (MDD). Altered methylation of the monoamine oxidase A (MAOA) gene has been implicated in the etiology of both PD and MDD. The Krüppel-like factor 11 (KLF11; alias TIEG2), an activating transcription factor of the MAOA gene, has been found to be increased in MDD, but has not yet been investigated in PD. In an effort to further delineate the effects of the KLF11-MAOA pathway in anxiety and affective disorders, KLF11 promoter methylation was analyzed via pyrosequencing of sodium bisulfite-treated DNA isolated from human peripheral blood in two independent samples of PD patients with or without comorbid MDD in a case-control design (sample 1: N = 120) as well as MDD patients with and without anxious depression (sample 2: N = 170). Additionally, in sample 1, KLF11 methylation was correlated with Beck Depression Inventory (BDI-II) scores. No overall association of KLF11 promoter methylation with PD was detected. However, PD patients with comorbid MDD showed significant hypomethylation relative to both healthy controls (p = 0.010) and PD patients without comorbid MDD (p = 0.008). Furthermore, KLF11 methylation was negatively correlated with BDI-II scores in PD patients (p = 0.013). MDD patients without anxious features showed nominally decreased KLF11 methylation in comparison to MDD patients with anxious depression (p = 0.052). The present results suggest KLF11 promoter hypomethylation as a potential epigenetic marker of MDD comorbidity in PD or of non-anxious depression, respectively, possibly constituting a differential pathomechanism in anxiety and mood disorders.

Anxiety Disorders and Medical Comorbidity: Treatment Implications.

Anxiety disorders are debilitating psychological disorders characterized by a wide range of cognitive and somatic symptoms. Anxiety sufferers have a higher lifetime prevalence of various medical problems. Chronic medical conditions furthermore increase the likelihood of psychiatric disorders and overall dysfunction. Lifetime rates of cardiovascular, respiratory, gastrointestinal, and other medical problems are disproportionately high in anxiety and panic/fear sufferers. The heightened comorbidity is not surprising as many symptoms of anxiety and panic/fear mimic symptoms of medical conditions. Panic disorder specifically is strongly linked to medical conditions due to its salient somatic symptoms, such as dyspnea, dizziness, numbness, chest pain, and heart palpitations, all of which can signal danger and deterioration for chronic disease sufferers. This chapter identifies shared correlates of medical illness and anxiety disorders and evidence for misinterpretation of symptoms as medically relevant and offers an analysis of implications for treatment of both types of conditions. We will concentrate on medical conditions with high associations for anxiety and panic by aspects of symptomatology, specifically neurological disorders (fibromyalgia, epilepsy, cerebral palsy), diabetes, gastrointestinal illness (irritable bowel syndrome, gastroesophageal reflux disease), and cardiovascular and respiratory illnesses (asthma).

Role of Benzodiazepines in Anxiety Disorders.

This chapter reviews the role of benzodiazepines (BZs) in the treatment of anxiety disorders, specifically panic disorder with or without agoraphobia, generalized anxiety disorder, and social anxiety disorder (social phobia). BZs pharmacology, classification, efficacy, adverse effects, withdrawal symptoms, possible dependence, and abuse; their positioning among pharmacological treatment; and guidance on how to use them are discussed.

Internet-delivered cognitive behavioral therapy for panic disorder with or without agoraphobia: a systematic review and meta-analysis.

The current systematic review and meta-analysis examined the efficacy and effectiveness of internet-delivered cognitive behavioral therapy (iCBT) on panic disorder and agoraphobia symptom severity. Twenty-seven studies were identified. Results from nine randomised controlled trials (RCTs) showed that iCBT outperformed waiting list and information controls for panic (g = 1.22) and agoraphobia (g = .91) symptoms, but the quality of RCTs varied and heterogeneity was high. Results from three RCTs suggested iCBT may have similar outcomes to face-to-face CBT in reducing panic and agoraphobia symptoms. Within-group effect sizes between baseline and post-treatment were large for panic (n = 29, g = 1.16) and medium for agoraphobia symptom severity (n = 18, g = .73). Subgroup analyses of within-group pre/post treatment effect sizes showed larger within-group effect sizes for efficacy studies (n = 15) compared to effectiveness studies (n = 14) for panic severity (g = 1.38 vs. g = .98) but not agoraphobia severity. There was no impact of program length, inclusion or arousal reduction techniques, or degree of clinician support. Within-group effects of iCBT suggest the reduction in panic and agoraphobia symptom severity is maintained at 3-6 month follow-up (n = 12).

Evaluation of TP-E Interval and TP-E/QT Ratio in Panic Disorder.

Background and Objectives: The autonomic nervous system (ANS) is involved in panic disorders. ANS dysfunction has been shown to be associated with ventricular arrhythmia and increased heterogeneity of ventricular repolarization. However, there remains limited evidence of the relationship between panic disorders and ventricular depolarization markers, including the Tp-e interval and Tp-e/QT ratio. This study aimed to evaluate ventricular repolarization parameters in patients with panic disorder. Materials and Methods: In total, 40 patients with panic disorder, diagnosed using the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) criteria, were included in the study group. The control group comprised of 50 age- and sex-matched healthy individuals. A standard 12 lead electrocardiogram was recorded on all participants, and heart rate, QT interval, QRS duration, Tp-e interval, and Tp-e/QT ratio were measured. Results: QRS durations and QT intervals were similar in the study and control groups. Compared to the control group, QTd, Tp-e, and cTp-e intervals as well as Tp-e/QT and Tp-e/QTc ratios were significantly increased in patients with panic disorder (p < 0.05 for all). In the study group, the Severity Measure for Panic Disorder-Adult score had a significant positive correlation with the Tp-e interval (r = 0.369, p < 0001), cTp-e interval (r = 0.531, p < 0.001), Tp-e/QT ratio (r = 0.358, p = 0.001), and Tp-e/QTc ratio (r = 0.351, p = 0.001). Conclusion: These findings indicate that panic disorders are associated with increased ventricular repolarization heterogeneity, which may be attributed to ANS dysregulation.

Explaining the association between anxiety disorders and alcohol use disorder: A twin study.

BACKGROUND: It is unknown whether social anxiety disorder (SAD) has a unique association with alcohol use disorder (AUD) over and beyond that of other anxiety disorders, how the associations develop over time, and whether the associations are likely to be causal. METHODS: Diagnoses of AUD, SAD, generalized anxiety disorder, panic disorder, agoraphobia, and specific phobias were assessed twice using the Composite International Diagnostic Interview among 2,801 adult Norwegian twins. The data were analyzed using logistic regression analyses and multivariate biometric structural equation modeling. RESULTS: SAD had the strongest association with AUD, and SAD predicted AUD over and above the effect of other anxiety disorders. In addition, SAD was prospectively associated with AUD, whereas other anxiety disorders were not. AUD was associated with a slightly elevated risk of later anxiety disorders other than SAD. Biometric modeling favored a model where SAD influenced AUD compared to models where the relationship was reversed or due to correlated risk factors. Positive associations between AUD and other anxiety disorders were fully explained by shared genetic risk factors. CONCLUSIONS: Unlike other anxiety disorders, SAD plausibly has a direct effect on AUD. Interventions aimed at prevention or treatment of SAD may have an additional beneficial effect of preventing AUD, whereas interventions aimed at other anxiety disorders are unlikely to have a similar sequential effect on AUD.

Validity of the DSM-5 anxious distress specifier for major depressive disorder.

BACKGROUND: DSM-5 introduced the anxious distress specifier in recognition of the clinical significance of anxiety in depressed patients. Recent studies that supported the validity of the specifier did not use measures that were designed to assess the criteria of the specifier but instead approximated the DSM-5 criteria from scales that were part of an existing data base. In the present report from the Rhode Island Methods to Improve Diagnostic Assessment and Services (MIDAS) project, we examined the validity of the specifier diagnosed with a semistructured interview. METHODS: Two hundred sixty patients with a principal diagnosis of major depressive disorder were evaluated with semistructured diagnostic interviews. The patients were rated on clinician rating scales of depression, anxiety and irritability, and completed self-report measures. RESULTS: Approximately three-quarters of the depressed patients met the criteria for the anxious distress specifier. Patients with anxious distress had a higher frequency of anxiety disorders, particularly panic disorder and generalized anxiety disorder, as well as higher scores on measures of anxiety, depression, and anger. The patients meeting the anxious distress subtype reported higher rates of drug use disorders, poorer functioning during the week before the evaluation, and poorer coping ability compared to the patients who did not meet the anxious distress specifier. Moreover, anxious distress was associated with poorer functioning and coping after controlling for the presence of an anxiety disorder. CONCLUSIONS: The results of the present study indicate that anxious distress is common in depressed patients and support the validity of the DSM-5 anxious distress specifier.

Pre-treatment peripheral biomarkers associated with treatment response in panic symptoms in patients with major depressive disorder and panic disorder: A 12-week follow-up study.

OBJECTIVE: Peripheral biomarkers have been studied to predict treatment response of panic symptoms. We hypothesized that depressive disorder (MDD) vs. panic disorder (PD) would exhibit different peripheral biomarkers, and their correlation with severity of panic attacks (PA) would also differ. METHODS: Forty-one MDD patients, 52 PD patients, and 59 healthy controls were followed for 12 weeks. We measured peripheral biomarkers along with the Panic Disorder Severity Scale (PDSS) at each visit-pre-treatment, 2, 4, 8, and 12 weeks on a regular schedule. Peripheral biomarkers including serum cytokines, plasma and serum brain-derived neurotrophic factor (BDNF), leptin, adiponectin, and C-reactive protein (CRP) were quantified using enzyme-linked immunosorbent assay (ELISA). RESULTS: Patients with MDD and PD demonstrated significantly higher levels of pre-treatment IL-6 compared to controls, but no differences were seen in plasma and serum BDNF, leptin, adiponectin, and CRP. Pre-treatment leptin showed a significant clinical correlation with reduction of panic symptoms in MDD patients at visit 5 (p=0.011), whereas pre-treatment IL-6 showed a negative correlation with panic symptom reduction in PD patients (p=0.022). An improvement in three panic-related items was observed to be positively correlated with pre-treatment leptin in MDD patients: distress during PA, anticipatory anxiety, and occupational interference. CONCLUSION: Higher pre-treatment leptin was associated with better response to treatment regarding panic symptoms in patients with MDD, while higher IL-6 was associated with worse response regarding panic symptoms in PD patients. Different predictive peripheral biomarkers observed in MDD and PD suggest the need for establishing individualized predictive biomarkers, even in cases of similar symptoms observed in different disorders.

Benzodiazepines versus placebo for panic disorder in adults.

BACKGROUND: Panic disorder is characterised by recurrent unexpected panic attacks consisting of a wave of intense fear that reaches a peak within a few minutes. Panic disorder is a common disorder, with an estimated lifetime prevalence of 1% to 5% in the general population and a 7% to 10% prevalence in primary care settings. Its aetiology is not fully understood and is probably heterogeneous.Panic disorder is treated with psychological and pharmacological interventions, often used in combination. Although benzodiazepines are frequently used in the treatment of panic disorder, guidelines recommend antidepressants, mainly selective serotonin reuptake inhibitors (SSRIs), as first-line treatment for panic disorder, particularly due to their lower incidence of dependence and withdrawal reaction when compared to benzodiazepines. Despite these recommendations, benzodiazepines are widely used in the treatment of panic disorder, probably because of their rapid onset of action. OBJECTIVES: To assess the efficacy and acceptability of benzodiazepines versus placebo in the treatment of panic disorder with or without agoraphobia in adults. SEARCH METHODS: We searched the Cochrane Common Mental Disorders Controlled Trials Register (CCMDCTR Studies and References), the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (1950-), Embase (1974-), and PsycINFO (1967-) up to 29 May 2018. We handsearched reference lists of relevant papers and previous systematic reviews. We contacted experts in the field for supplemental data. SELECTION CRITERIA: All double-blind (blinding of patients and personnel) controlled trials randomising adults with panic disorder with or without agoraphobia to benzodiazepine or placebo. DATA COLLECTION AND ANALYSIS: Two review authors independently checked the eligibility of studies and extracted data using a standardised form. Data were then entered data into Review Manager 5 using a double-check procedure. Information extracted included study characteristics, participant characteristics, intervention details, settings, and outcome measures in terms of efficacy, acceptability, and tolerability. MAIN RESULTS: We included 24 studies in the review with a total of 4233 participants, of which 2124 were randomised to benzodiazepines and 1475 to placebo. The remaining 634 participants were randomised to other active treatments in three-arm trials. We assessed the overall methodological quality of the included studies as poor. We rated all studies as at unclear risk of bias in at least three domains. In addition, we judged 20 of the 24 included studies as having a high risk of bias in at least one domain.Two primary outcomes of efficacy and acceptability showed a possible advantage of benzodiazepines over placebo. The estimated risk ratio (RR) for a response to treatment was 1.65 (95% confidence interval (CI) 1.39 to 1.96) in favour of benzodiazepines, which corresponds to an estimated number needed to treat for an additional beneficial outcome (NNTB) of 4 (95% CI 3 to 7). The dropout rate was lower among participants treated with benzodiazepines (RR 0.50, 95% CI 0.39 to 0.64); the estimated NNTB was 6 (95% CI 5 to 9). We rated the quality of the evidence as low for both primary outcomes. The possible advantage of benzodiazepine was also seen for remission (RR 1.61, 95% CI 1.38 to 1.88) and the endpoint data for social functioning (standardised mean difference (SMD) -0.53, 95% CI -0.65 to -0.42), both with low-quality evidence. We assessed the evidence for the other secondary outcomes as of very low quality. With the exception of the analyses of the change score data for depression (SMD -0.22, 95% CI -0.48 to 0.04) and social functioning (SMD -0.32, 95% CI -0.88 to 0.24), all secondary outcome analyses showed an effect in favour of benzodiazepines compared to placebo. However, the number of dropouts due to adverse effects was higher with benzodiazepines than with placebo (RR 1.58, 95% CI 1.16 to 2.15; low-quality evidence). Furthermore, our analyses of adverse events showed that a higher proportion of participants experienced at least one adverse effect when treated with benzodiazepines (RR 1.18, 95% CI 1.02 to 1.37; low-quality evidence). AUTHORS' CONCLUSIONS: Low-quality evidence shows a possible superiority of benzodiazepine over placebo in the short-term treatment of panic disorders. The validity of the included studies is questionable due to possible unmasking of allocated treatments, high dropout rates, and probable publication bias. Moreover, the included studies were only short-term studies and did not examine the long-term efficacy nor the risks of dependency and withdrawal symptoms. Due to these limitations, our results regarding the efficacy of benzodiazepines versus placebo provide only limited guidance for clinical practice. Furthermore, the clinician's choice is not between benzodiazepines and placebo, but between benzodiazepines and other agents, notably SSRIs, both in terms of efficacy and adverse effects. The choice of treatment should therefore be guided by the patient's preference and should balance benefits and harms from treatment in a long-term perspective.