The Effects of Breathing Training on Panic Disorder: A Systematic Review and Meta-analysis

Bupropion and Panic Disorder: Case Report and Review of the Literature

Background Panic disorders are prevalent psychiatric conditions affecting 1.6% to 2.2% of the global population. While selective serotonin reuptake inhibitors (SSRIs) are the first line of treatment, their initial exacerbation of symptoms presents challenges. Beta-blockers have shown promise in managing panic symptoms, but research comparing the efficacy of combined SSRI and beta-blocker therapy to SSRI monotherapy is limited, particularly in Saudi Arabia. Objective To assess the effectiveness of SSRIs combined with beta-blockers vs. SSRI monotherapy in improving panic disorder symptoms severity in patients at King Abdul-Aziz Hospital, Makkah, Saudi Arabia. Methods This prospective cohort study included 62 patients with panic disorder, divided into two groups: SSRI monotherapy (n=29) and SSRIs with beta-blockers (n=33). Panic disorder severity was assessed using the Panic Disorder Severity Scale (PDSS) after three months of treatment. Secondary outcomes included depression and anxiety symptoms, measured by the Patient Health Questionnaire (PHQ-9) and General Anxiety Disorder Scale (GAD-7), respectively.Statistical analysis involved Mann-Whitney U tests for comparing PDSS scores between the groups due to non-parametric distributionand Chi-square tests for categorical variables. Relative risks (RR) were calculated to assess the likelihood of abnormal PDSS, PHQ-9, and GAD-7 scores between the groups. Multivariable linear regression was used to adjust for potential confounding factors. Results No statistically significant difference in PDSS scores was found between SSRI monotherapy (median=6,interquartile range (IQR)=3-9) and combination therapy (median=8, IQR=3-13) groups (p=0.188). The relative risk of abnormal PDSS scores was 1.8 times higher in the combination therapy group (p=0.077). No significant differences in depression (p=0.386) or anxiety (p=0.182) symptoms were observed. Additionally, 66.7% of combination therapy patients had abnormal PDSS scores compared to 33.3% in the SSRI group. The mean PHQ-9 score was 11.08±6.93, and the mean GAD-7 score was 10.69±6.41 for the total sample. Conclusion This study found no significant difference in the effectiveness of SSRIs combined with beta-blockers vs. SSRI monotherapy for treating panic disorders. However, the trend towards higher PDSS scores in the combination therapy group suggests further investigation is needed. Study limitations included small sample size, single-center design, short follow-up period, and lack of randomization. Despite these, the study provided valuable insights into treatment approaches for panic disorders in the Saudi population. Larger, randomized controlled trials with longer follow-up periods and multi-center designs are recommended for future research.

Many patients with panic disorder (PD) experience nocturnal panic attacks. We investigated the differences in demographic variables and symptom characteristics as well as response to treatment among patients with primary day panic (DP), primary nocturnal panic (NP), and the coexistence of DP and NP (DP/NP), and discuss whether NP is a distinct disease category. One hundred one consecutive untreated patients with PD were enrolled and subsequently divided into the NP, DP, and DP/NP groups. The presence of 13 panic attack symptom items as well as scores on the Panic Disorder Severity Scale (PDSS) and the Pittsburgh Sleep Quality Index (PSQI) were compared among the groups. After 3 months of regular treatment, PDSS scores were assessed again to evaluate treatment response. Nocturnal panic attacks of the participants were mostly reported to occur in the first tertile of nocturnal sleep. The number of males, onset age, and presence of choking sensation were significantly higher, and the PDSS score was significantly lower in the NP group compared with the other groups. The DP/NP group showed the highest PDSS score, and participants in this group were prescribed the highest doses of medication among all groups. Only diagnostic sub-category was significantly associated with treatment response. The total score for PDSS and PSQI correlated significantly only in the NP group. DP/NP could be a severe form of PD, while primary NP could be a relatively mild subcategory that may partially share common pathophysiology with adult type night terror.

AimsTo ascertain if virtual reality exposure therapy (VRET) is an effective add-on tool in the treatment of Panic Disorder (PD).BackgroundThe exposure to virtual stimuli has been studied as a useful treatment for PD. However, the studies with PD are still scarce and use dissimilar protocols, with effectiveness varying according to the protocol applied.MethodEight PD patients received VRET as an add-on treatment to pharmacotherapy. The treatment protocol consisted of eight sessions. The first session is for the patient to understand the treatment and to answer the questionnaires. The second and third sessions were to prepare the patients for exposures with breathing training using diaphragmatic breathing and others breathing techniques to manage anxiety. From the fourth to eighth sessions, the patients followed a hierarchy of tasks during virtual reality exposure. Clinicians rated the Clinical Global Impression Scale (CGI) and the Panic Disorder Severity Scale (PDSS). The patients rated the Diagnostic Symptom Questionnaire (DSQ); the Mobility Inventory (MI), the Anxiety Sensibility Index (ASI-R), the Beck Depression Inventory (BDI), the Beck Anxiety Inventory (BAI) and the WHOQOL-BREF before and after the protocol. After all exposures, the Igroup Presence Questionnaire (IPQ) was applied to measure the sense of presence experienced in the virtual environment. The virtual environment simulated the subway of Rio de Janeiro.ResultThere were no statistically significant improvements in the CGI-S, PDSS, BAI, MI or WHOQOL. There was a significant improvement in the BDI scores (P = 0.033). There was a trend towards improvement of anxiety measured by the ASI-R (P = 0.084) and of panic symptoms measured by the DSQ (P = 0.081) scores. There was also a significant improvement of sense of presence (IPQ – general presence) through the exposure sessions.ConclusionOur study demonstrated that VRET as an add-on to pharmacological therapy could benefit PD patients. Despite the lack of significant differences in the means, the dispersion of PDSS and BAI scores were smaller after treatment compared to before treatment, suggesting that patients with more severe anxiety, panic and agoraphobia symptoms benefited more of the VRET protocol so, at the end of the treatment, differences were found in important measures of panic. Randomized controlled clinical trials are warranted to confirm the efficacy of VRET.This study was funded by the Brazilian National Council for Scientific Development (Cnpq). The authors report no conflicts of interest.

Psychiatry to dermatology; panic disorder

This study aimed to investigate whether separation anxiety (SA) constitutes a dimension related to age at onset of panic disorder (PD), in homogeneous subgroups of outpatients with PD, based on their age of onset and symptom severity. A sample of 232 outpatients with PD was assessed with the Panic Disorder Severity Scale (PDSS) and the Sheehan Disability Scale (SDS) for functional impairments. Separation anxiety was evaluated using structured interviews and questionnaires. We applied a K-Means Cluster Analysis based on the standardized "PD age of onset" and "the PDSS total score" to identify distinct but homogeneous groups. We identified three groups of patients: group 1 ("PD early onset/severe", N = 97, 42%, onset 23.2 ± 6.7 years), group 2 ("PD early onset/not severe", N = 76, 33%, onset 23.4 ± 6.0 years) and group 3 ("PD adult onset/not severe", N = 59, 25%, onset 42.8 ± 7.0 years). Patients with early onset/severe PD had significantly higher scores on all SA measures than PD late-onset/not severe. Regression analyses showed that SA scores, but not PDSS scores, were predictive of impairment in SDS work/school, social life, and family functioning domains. Our data indicate a significant relationship between SA and PD with an earlier age of onset and an impact on individual functioning. This may have important implications for implementing preventive interventions targeting early risk factors for the subsequent onset of PD.

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

ImportanceThis report details a case of effectively managing severe panic attacks in a panic disorder (PD) patient with agoraphobia by acupuncture treatment.Case presentationA 38-year-old Japanese woman suffering from PD with agoraphobia presented at our acupuncture clinic with complaints of repeated panic attacks and anxiety. Initially starting to experience symptoms in her late teens, she avoided psychiatric consultation due to reluctance toward psychotropic medications. An unbiased psychiatrist used the Panic Disorder Severity Scale (PDSS) to assess her PD severity. The PDSS score decreased from 21 on the first to 12 points on the sixth visit. The patient experienced reduced frequency and severity of panic attacks, with restored confidence to go into public despite agoraphobia.Conclusions and RelevanceThis is the first report to demonstrate the effectiveness of acupuncture on PD with agoraphobia using PDSS, suggesting its potential as a nonpharmacological treatment for patients with PD and agoraphobia.

Escitalopram Increased Gray Matter and White Matter in a First-Episode Drug-Naïve Panic Disorder Patient Within 6 Weeks

Open-longitudinal study of the effect of dissociative symptoms on the response of patients with panic disorder to venlafaxine

Background: This is a pilot study assessing the impact of polymorphisms of serotonin transporter (5-HTT; 5-HTTLPR (S/L)) and norepinephrine transporter (NET; rs2242446 (T/C)) genes on selective serotonin reuptake inhibitors (SSRIs) and serotonin/norepinephrine reuptake inhibitors (SNRIs) response in Korean panic disorder (PD) patients. Methods: PD patients were treated with SSRI (n = 18) or SNRI (n = 6) for 4 weeks. Panic Disorder Severity Scale (PDSS) was rated to evaluate the treatment response. Wilcoxon signed-rank test was used to compare PDSS scores before and after medication (SSRI or SNRI) as well as to compare those according to genotypes. Mann–Whitney U test was used to compare those between the two groups (SSRI or SNRI). Results: Both SSRI and SNRI treatments for 4 weeks significantly reduced PDSS scores. We assessed the impact of rs2242446 on this effect of SSRI and SNRI. The scores were significantly decreased after 4 weeks in the SSRI-treated group regardless of genotypes of rs2242446, whereas they were significantly decreased in the SNRI-treated group with only non-C carrier (TT) of rs2242446. On 5-HTTLPR we could not analyse because 22 patients had SS genotype. Conclusions: These results suggest that NET polymorphism may affect the SNRI response in Korean PD patients.

More data are needed to guide next-step interventions for panic disorder refractory to initial intervention. This 24-week randomized clinical trial (RCT) enrolled 46 patients with DSM-IV-defined panic disorder from November 2000 to April 2005 and consisted of 3 phases. Patients who failed to meet remission criteria were eligible for randomization in the next treatment phase. Phase 1 was a 6-week lead-in with open-label sertraline flexibly dosed to 100 mg (or escitalopram equivalent) to prospectively define treatment refractoriness (lack of remission). Phase 2 was a 6-week double-blind RCT of (1) increased-dose selective serotonin reuptake inhibitor (SSRI) versus (2) continued SSRI plus placebo. Phase 3 was a 12-week RCT of added cognitive-behavioral therapy (CBT) compared to "medication optimization" with SSRI plus clonazepam. Primary endpoints were remission and change in Panic Disorder Severity Scale (PDSS) score in the intent-to-treat sample in each phase. In phase 1, 20.5% (8/39) of the patients achieved remission, and only baseline severity predicted endpoint PDSS score (beta [SE] = 1.04 [0.15], t = 6.76, P < .001). In phase 2, increasing the SSRI dose did not result in greater improvement or remission rates (placebo 15% [n = 2] vs increased dose 9% [n = 1]: Fisher exact test P = NS). In phase 3, remission was minimal (medication optimization = 11% [n = 1]; CBT = 10% [n = 1]), with a lack of group difference in PDSS score reduction (t(17) = 0.51, P > .60) consistent with a small effect size (d = 0.24). Although power was limited and larger studies are needed, we failed to find evidence for greater benefit of increased SSRI dose versus continuation of current dose for panic disorder symptomatic after 6 weeks at moderate dose. Further, augmentation with CBT or medication optimization with clonazepam augmentation in nonremitted panic after 12 weeks of an SSRI did not differ, suggesting that both are reasonable next-step options. However, low overall remission rates in this comorbid refractory population suggest that better predictors of response to specific treatments over time and additional interventions are needed. clinicaltrials.gov Identifier: NCT00118417.

Effectiveness of a mindfulness-based cognitive therapy program as an adjunct to pharmacotherapy in patients with panic disorder

Panic disorder is a common and important disease in clinical practice that decreases individual productivity and increases health care use. Treatments comprise medication and cognitive behavioral therapy. However, adverse medication effects and poor treatment compliance mean new therapeutic models are needed. We hypothesized that digital therapy for panic disorder may improve panic disorder symptoms and that treatment response would be associated with brain activity changes assessed with functional near-infrared spectroscopy (fNIRS). Individuals (n=50) with a history of panic attacks were recruited. Symptoms were assessed before and after the use of an app for panic disorder, which in this study was a smartphone-based app for treating the clinical symptoms of panic disorder, panic symptoms, depressive symptoms, and anxiety. The hemodynamics in the frontal cortex during the resting state were measured via fNIRS. The app had 4 parts: diary, education, quest, and serious games. The study trial was approved by the institutional review board of Chung-Ang University Hospital (1041078-202112-HR-349-01) and written informed consent was obtained from all participants. The number of participants with improved panic symptoms in the app use group (20/25, 80%) was greater than that in the control group (6/21, 29%; χ21=12.3; P=.005). During treatment, the improvement in the Panic Disorder Severity Scale (PDSS) score in the app use group was greater than that in the control group (F1,44=7.03; P=.01). In the app use group, the total PDSS score declined by 42.5% (mean score 14.3, SD 6.5 at baseline and mean score 7.2, SD 3.6 after the intervention), whereas the PDSS score declined by 14.6% in the control group (mean score 12.4, SD 5.2 at baseline and mean score 9.8, SD 7.9 after the intervention). There were no significant differences in accumulated oxygenated hemoglobin (accHbO2) at baseline between the app use and control groups. During treatment, the reduction in accHbO2 in the right ventrolateral prefrontal cortex (VLPFC; F1,44=8.22; P=.006) and the right orbitofrontal cortex (OFC; F1,44=8.88; P=.005) was greater in the app use than the control group. Apps for panic disorder should effectively reduce symptoms and VLPFC and OFC brain activity in patients with panic disorder. The improvement of panic disorder symptoms was positively correlated with decreased VLPFC and OFC brain activity in the resting state. Clinical Research Information Service KCT0007280; https://cris.nih.go.kr/cris/search/detailSearch.do?seq=21448.

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