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

Mindfulness-based cognitive therapy (MBCT) has been studied to treat patients with depressive or anxiety disorders. The aim of this study was to examine whether MBCT is effective as an adjunct to pharmacotherapy in the treatment of patients with panic disorder. Twenty-three patients with panic disorder were included in a MBCT program for a period of 8 weeks. The Hamilton Anxiety Rating Scale (HAM-A), Beck Anxiety Inventory (BAI), Beck Depression Inventory (BDI), Anxiety Sensitivity Index-Revised (ASI-R), Albany Panic and Phobia Questionnaire (APPQ), and Panic Disorder Severity Scale (PDSS) were used to assess the patients during the MBCT program. Both HAM-A and PDSS scores were significantly decreased at the 2nd, 4th and 8th weeks compared to baseline in the patients with panic disorder (HAM-A, p < 0.01; PDSS, p < 0.01). Also, BAI, APPQ and ASI-R were improved significantly after MBCT program (BAI, p < 0.01; APPQ, p < 0.01; ASI-R, p < 0.01). In addition, all subscale scores of ASI-R decreased significantly. MBCT could be effective as an adjunct to pharmacotherapy in patients with panic disorder. However, randomized controlled trials are needed.     

Clinical Characteristics of the Respiratory Subtype in Panic Disorder Patients

Objective

Panic disorder has been suggested to be divided into the respiratory and non-respiratory subtypes in terms of its clinical presentations. The present study aimed to investigate whether there are any differences in treatment response and clinical characteristics between the respiratory and non-respiratory subtypes of panic disorder patients.

Methods

Among the 48 patients those who completed the study, 25 panic disorder patients were classified as the respiratory subtype, whereas 23 panic disorder patients were classified as the non-respiratory subtype. All patients were treated with escitalopram or paroxetine for 12 weeks. We measured clinical and psychological characteristics before and after pharmacotherapy using the Panic Disorder Severity Scale (PDSS), Albany Panic and Phobic Questionnaire (APPQ), Anxiety Sensitivity Index-Revised (ASI-R), State-Trait Anxiety Inventory (STAI-T, STAI-S), Hamilton Anxiety Rating Scale (HAM-A), and Hamilton Depression Rating Scale (HAM-D).

Results

The prevalence of the agoraphobia was significantly higher in the respiratory group than the non-respiratory group although there were no differences in gender and medication between the two groups. The respiratory group showed higher scores on the fear of respiratory symptoms of the ASI-R. In addition, after pharmacotherapy, the respiratory group showed more improvement in panic symptoms than the non-respiratory group.

Conclusion

Panic disorder patients with the respiratory subtype showed more severe clinical presentations, but a greater treatment response to SSRIs than those with non-respiratory subtype. Thus, classification of panic disorder patients as respiratory and non-respiratory subtypes may be useful to predict clinical course and treatment response to SSRIs.     

Tryptophan hydroxylase and serotonin transporter gene polymorphism does not affect the diagnosis, clinical features and treatment outcome of panic disorder in the Korean population

Panic disorder may be associated with defective serotonin (5-HT) neurotransmission. This study was to investigate the association between the tryptophan hydroxylase (TPH) gene and a serotonin transporter gene promoter polymorphism (5-HTTLPR), with panic disorder in a Korean population.

244 Korean patients with panic disorder and the 227 controls were genotyped by a polymerase chain reaction-based method. The severity of panic disorders was assessed by number of panic attacks during the previous 1 month, as well as scores for anticipatory anxiety, panic distress, and agoraphobic distress, as determined by a visual analogue scale (VAS). All the subjects completed the assessment measures including Spielberger State-Trait Anxiety Inventory-State (STAI-S), Spielberger State-Trait Anxiety Inventory-Trait (STAI-T), Beck Depression Inventory (BDI), Symptom Checklist-90-Revised (SCL-90-R), Revised Anxiety Sensitivity Index (ASI-R), Clinical Global Impression Scale – Severity of Illness (CGI-S), Panic Disorder Severity Scale (PDSS), and the Hamilton Depression Rating Scale (HAMD). Responder analyses were conducted based on changes in CGI-I scores after 10 weeks of treatment.

We found no significant differences in the genotype and allele frequencies in TPH A218C and 5-HTTLPR polymorphisms between the panic patients and the control group. Subgroup analyses in terms of comorbidities, response, and other primary clinical variables, indicated no differences in these polymorphisms. Our findings suggest that the TPH A218C polymorphism and 5-HTTLPR play no significant roles in the pathogenesis and clinical symptomatologies, at least in a Korean population.     

Functional Impairment in Patients with Panic Disorder

Objective Anxiety and depression and sociodemographic factors such as age, gender, education level, income, and marital status among people with panic disorder (PD) are associated with functional impairment in the areas of work, social, and family. Although both PD-specific scales such as the Panic Disorder Severity Scale (PDSS) and Anxiety Sensitivity Inventory-Revised (ASI-R) and early trauma have been investigated, their relationship with functional impairment in PD patients has not been clarified. Methods This study included 267 PD patients. The PDSS, Beck Depression Inventory (BDI), ASI-R, and Early Trauma Inventory were used. Pearson’s correlation and multiple linear regression analyses were performed. The Sheehan Disability Scale (SDS) was administered to assess the functional impairment level in PD patients. Results Our findings showed that high levels of PDSS, BDI, and ASI-R were significantly correlated with the functional impairment among PD patients. Multiple regression analyses showed that PDSS, BDI, and ASI-R can predict the functional impairment levels, and PDSS and ASI-R were significantly associated with lost and underproductive days in PD patients. Conclusion Panic-specific symptoms, depression, and AS are associated with functional impairment level in PD patients. Elevated symptom severity can play a role by affecting productivity and daily responsibilities in PD patients.     

Daily life situations and anxiety in panic disorder and agoraphobia

Naturally occuring daily life situations and anxiety experiences were studied in panic-disordered patients with different levels of agoraphobic fear. Time-sampled self-reports of mental state, social context, and setting, obtained with the Experience Sampling Method (ESM), have been compared for panic patients with high scores on the agoraphobia scale of the Fear Questionnaire (n = 19), panic patients with low to medium agoraphobia scores (n = 23), and a normal reference group (n = 20). Panic patients with high agoraphobia scores reported more anxiety than panic patients with limited agoraphobic fear. In general, agoraphobic subjects, as defined by the Fear Questionnaire, demonstrated higher frequencies of being at home and with the family. Panic patients with limited agoraphobic fear reported being alone more often when anxious, while patients with extensive agoraphobia were more often in the company of family members during moments of high anxiety. Individual variations in time-sampled anxiety ratings and time allocation data found in this study challenge the validity of retrospective reports about anxiety and avoidance. These results suggest that further research into anxiety disorders should link experimental and natural environment methods.     

Evidence‐based guidelines for interpretation of the Panic Disorder Severity Scale

Background: The Panic Disorder Severity Scale (PDSS) is promising to be a standard global rating scale for panic disorder. In order for a clinical scale to be useful, we need a guideline for interpreting its scores and their changes, and for defining clinical change points such as response and remission. Methods: We used individual patient data from two large randomized controlled trials of panic disorder (total n=568). Study participants were administered the PDSS and the Clinical Global Impression (CGI)—Severity and —Improvement. We applied equipercentile linking technique to draw correspondences between PDSS and CGI‐Severity, numeric changes in PDSS and CGI‐Improvement, and percent changes in PDSS and CGI‐Improvement. Results: The interpretation of the PDSS total score differed according to the presence or absence of agoraphobia. When the patients were not agoraphobic, score ranges 0–1 corresponded with “Normal,” 2–5 with “Borderline,” 6–9 with “Slightly ill,” 10–13 with “Moderately ill,” and 14 and above with “Markedly ill.” When the patients were agoraphobic, score ranges 3–7 meant “Borderline ill,” 8–10 “Slightly ill,” 11–15 “Moderately ill,” and 16 and above “Markedly ill.” The relationship between PDSS change and CGI‐Improvement was more linear when measured as percentile change than as numeric changes, and was indistinguishable for those with or without agoraphobia. The decrease by 75–100% was considered “Very much improved,” that by 40–74% “Much improved,” and that by 10–39% “Minimally improved.” Conclusion: We propose that “remission” of panic disorder be defined by PDSS scores of five or less and its “response” by 40% or greater reduction. Depression and Anxiety, 2009. © 2008 Wiley‐Liss, Inc.     

The Effects of 5-HTR1A Polymorphism on Cingulum Connectivity in Patients with Panic Disorder

Objective

Serotonin-1A receptors (5-HTR1A) is suggested to be involved in the etiology of several psychiatric disorders including panic disorder (PD). A few imaging studies have suggested the alterations of the cingulum bundle in PD. The objective of this study is to examine the structural changes of cingulum related to the 5-HTR1A polymorphism rs6295 in the patients with PD.

Methods

Thirty-two right-handed patients with PD [11 men, 21 women; 40.34±13.17 (mean±SD) age] who met the diagnostic criteria in Structured Clinical Interview for DSM-IV were examined by means of MRI at 3 Tesla. We divided the patients with PD into CC genotype group and non CC genotype group (GG/CG genotype group) of the 5-HTR1A rs6295 polymorphism to compare the cingulum white matter connectivity.

Results

Tract-based spatial statistics showed significantly increased fractional anisotropy (FA) values in cingulate gyrus process of left cingulum in 5-HTR1A CC genotype compared to GG/CG genotype in PD. Significant positive correlations were shown between the Albany Panic and Phobia Questionnaire (APPQ) interoceptive fear subscale scores, the Anxiety Sensitivity Inventory-Revised fear of publicly observable anxiety reaction subscale scores and FA values of cingulate gyrus process of left cingulum in 5-HTR1A rs6295 GG/CG genotype group. In CC genotype group, APPQ total, APPQ agoraphobia subscale and APPQ social phobia subscale scores also showed significant positive correlations with FA values of hippocampal process of right cingulum.

Conclusion

This preliminary study suggests that 5-HTR1A polymorphism may be associated with the cingulum white matter connectivity in PD.     

Panic Disorder Severity Scale: reliability and validity of the Turkish version

We assessed the reliability and validity of the Turkish version of the seven-item Panic Disorder Severity Scale (PDSS). We recruited 174 subjects, including 104 with current DSM-IV panic disorder with (n=76) or without(n=28)agoraphobia, 14 with a major depressive episode, 24 with a non-panic anxiety disorder, and 32 healthy controls. Assessment instruments were Panic Disorder Severity Scale, Panic and Agoraphobia Scale, both the observer-rated (P&Ao) and self-rating (P& Asr); Clinical Global Impression Scale (CGI); Hamilton Anxiety Scale, and Beck Depression Inventory. We repeated the measures for a group of panic disorder patients (n = 51) after 4 weeks to assess test-retest reliability. The internal consistency (Cronbach's alpha) of the PDSS was .92-94. The inter-rater correlation coefficient was .79. The test-retest correlation coefficient after 4 weeks was .63. In discriminant validity analyses, the highest correlation for PDSS was with P&Ao, P&Asr (r=.87 and.87, respectively) and CGI (r=.76) and the lowest with Beck Depression Inventory (r=.29). The cut-off point was six/seven, associated with high sensitivity (99%) and specificity (98%). This study confirmed the objectivity, reliability and validity of the Turkish version of the PDSS.     

A double-blind study of the efficacy of venlafaxine extended-release, paroxetine, and placebo in the treatment of panic disorder

To date, no large-scale, controlled trial comparing a serotonin-norepinephrine reuptake inhibitor and selective serotonin reuptake inhibitor with placebo for the treatment of panic disorder has been reported. This double-blind study compares the efficacy of venlafaxine extended-release (ER) and paroxetine with placebo. A total of 664 nondepressed adult outpatients who met DSM-IV criteria for panic disorder (with or without agoraphobia) were randomly assigned to 12 weeks of treatment with placebo or fixed-dose venlafaxine ER (75 mg/day or 150 mg/day), or paroxetine 40 mg/day. The primary measure was the percentage of patients free from full-symptom panic attacks, assessed with the Panic and Anticipatory Anxiety Scale (PAAS). Secondary measures included the Panic Disorder Severity Scale, Clinical Global Impressions--Severity (CGI-S) and--Improvement (CGI-I) scales; response (CGI-I rating of very much improved or much improved), remission (CGI-S rating of not at all ill or borderline ill and no PAAS full-symptom panic attacks); and measures of depression, anxiety, phobic fear and avoidance, anticipatory anxiety, functioning, and quality of life. Intent-to-treat, last observation carried forward analysis showed that mean improvement on most measures was greater with venlafaxine ER or paroxetine than with placebo. No significant differences were observed between active treatment groups. Panic-free rates at end point with active treatment ranged from 54% to 61%, compared with 35% for placebo. Approximately 75% of patients given active treatment were responders, and nearly 45% achieved remission. The placebo response rate was slightly above 55%, with remission near 25%. Adverse events were mild or moderate and similar between active treatment groups. Venlafaxine ER and paroxetine were effective and well tolerated in the treatment of panic disorder.     

Pathological Worry is Related to Poor Long-Term Pharmacological Treatment Response in Patients With Panic Disorder

ObjectiveSeveral predictors of unfavorable pharmacological treatment response (PTR) in panic disorder (PD) patients have been suggested, such as the duration of the illness, presence of agoraphobia, depression, being a woman, and early trauma. This study aimed to examine whether pathological worry is associated with PTR in PD patients. MethodsThis study included 335 PD patients and 418 healthy controls (HCs). The Penn State Worry Questionnaire (PSWQ), the Early Trauma Inventory Self Report-Short Form (ETISR-SF), Beck Depression Inventory (BDI), Panic Disorder Severity Scale (PDSS), and Anxiety Sensitivity Inventory-Revised (ASI-R) were administered. We measured the PTR at 8 weeks and 6 months. Student t-test, chi-square tests, Pearson’s correlation analyses, and binary logistic regression model were used. ResultsOur results showed that the total scores of the PSWQ correlated with the ETISR-SF, BDI, and ASI-R were significantly higher in patients with PD compared with HCs. The PSWQ and BDI could predict unfavorable PTR at 6 months in PD patients. ConclusionThis is the first study to demonstrate that pathological worry may contribute to poor long-term PTR in PD patients. Therefore, our research suggests that clinicians must be aware of worry to optimize PTR for PD patients.     

Anxiety sensitivity as a predictor of panic attacks

Anxiety sensitivity (AS) is the fear of physical symptoms of anxiety and related sensations believed to have harmful consequences. AS may play a central role in the nature and etiology of panic disorder (PD) and the genesis of panic attacks. We collected Anxiety Sensitivity Index (ASI) scores from PD patients and controls to determine if AS accurately predicts panic. ASIs were completed prior to panic induction using the modified Read rebreathing test in both hypoxic and hyperoxic conditions. Total scores first-order factors, and individual item ASI scores were correlated with panic presence (Spearman correlation) for each of the hypoxic and hyperoxic rebreathing tests for both study populations. Control subjects' data correlated significantly for items 4, 8, and 11 of the ASI for the hyperoxic (n=9; r_S=0.63, 0.70, and 0.63, respectively) and items 4 and 8 for the hypoxic rebreathing tests (n=9; r_S=0.63 and 0.70, respectively). Panic patients' data correlated significantly for item 1 of the ASI for hyperoxic tests (n=8; r_S=0.76) and item 5 for the hypoxic tests (n=8; r_S=0.95). Total ASI scores or first-order factors (physical, social concerns, and mental incapacitation) scores of either study group did not correlate significantly with panic presence. AS may not be a reliable predictor of panicogenic responses to CO₂-induced panic in either PD or normal control populations. AS may not be an ultimate causal element in eliciting panic attacks.     

Higher postdexamethasone serum cortisol levels in agoraphobic than in nonagoraphobic panic disorder patients

The dexamethasone suppression test (DST) was performed in panic disorder (PD) patients with (n = 32) or without (n = 31) agoraphobia and in normal controls (n = 49). Postdexamethasone serum cortisol levels were significantly higher in agoraphobic PD patients (105.3 +/- 19.3 nmol/L) both when compared to PD patients without agoraphobia (47.3 +/- 7.7 nmol/L; p less than 0.01) and when compared to healthy controls (51.7 +/- 8.3 nmol/L; p less than 0.01). The rate of nonsuppressors (i.e., subjects displaying postdexamethasone cortisol levels greater than 138 nmol/L) was 28% and 3% in agoraphobic and nonagoraphobic PD patients, respectively, and 12% in controls. In patients, the postdexamethasone cortisol levels did not correlate with the number of panic attacks per week, baseline anxiety as measured using the Hamilton Anxiety Scale, depressive symptoms as measured using the Montgomery-Asberg Depression scale, or duration of illness. Data from eight patients in whom a second DST was performed after treatment with imipramine or clomipramine for three months indicate that a marked reduction of the number of anxiety attacks is not necessarily accompanied by a normalization of a pathological DST. In conclusion, it is suggested that the elevated postdexamethasone cortisol levels sometimes observed in agoraphobic PD patients are more closely related to the agoraphobic behavior than to the panic attacks per se.     

Psychiatry to dermatology; panic disorder

ObjectiveAnxiety is commonly observed together with skin diseases and can aggravate them, while skin diseases can increase anxiety. The relationship of skin diseases observed in panic disorder with quantitative electroencephalography (QEEG) findings has not been investigated yet. The aim of this study is to compare the absolute alpha and delta power of panic disorder patients with and without skin disease.Methods246 panic disorder patients, 19 of whom had skin disease and 227 of whom did not have skin disease, were included in the study. Panic disorder severity scale (PDSS) scores of patients were recorded, and QEEG recording was performed. Absolute alpha and delta power and PDSS scores were compared between the two groups.ResultsIt was found that the absolute delta power in the left hemisphere was lower and PDSS scores were higher in the patients with skin diseases compared to the control group. In the patients with skin disease, decreased delta power in the left hemisphere may cause impairment in the processing of positive emotions and may cause trait anxiety.ConclusionTrait anxiety may increase susceptibility to skin diseases by disrupting cutaneous homeostasis resulting from the prolonged sympathetic nervous system activation.     

The association between serotonin-related gene polymorphisms and panic disorder

Dysfunction of the serotonergic system has been hypothesized to play an important role in panic disorder. We investigated the 5-HT2A receptor (5HTR2A) and tryptophan hydroxylase (TPH) genes for an association with panic disorder (PD). Patients with PD (n=107) and control subjects (n=161) were genotyped for 5HTR2A 1438A/G, 5HTR2A 102T/C, and TPH218 A/C. The severity of their symptoms was measured using the Spielberger State-Trait Anxiety Inventory (STAI), Panic Disorder Severity Scale (PDSS), Anxiety Sensitivity Index (ASI), Acute Panic Inventory (API), and Hamilton's Rating Scale for Depression (HAMD). There were no significant differences in the genotype distributions or allelic frequencies in the three serotonergic polymorphisms between PD patients and normal controls. However, we found a significant difference in symptom severity among the genotypes of both the 5HTR2A 1438A/G and 102T/C polymorphisms. Although there were no significant differences in the genotype and allele distributions, we found a significant association between panic symptom severity and the serotonin 2A receptor gene. This result suggests that 5HTR2A 1438A/G and 102T/C polymorphic regions can be associated with the phenotype or the pathogenesis of panic disorder.     

Panic disorder patients at the time of air strikes

We assessed the impact of real danger on several aspects of the panic disorder (PD) patients' psychopathology and level of disability. At the time of the NATO air strikes on Belgrade, 84 PD patients who were in partial or complete remission were administered the Panic and Agoraphobia Scale (PAS). All had been treated previously, and the majority (58.3%) were taking antipanic medications. The PAS, which was used as part of the regular follow-up assessment battery for PD patients, measures the overall severity of PD and the severity of key aspects and components of PD. Compared to the PAS assessments made before the onset of air strikes, the PAS assessments made at the time of air strikes showed significant differences in terms of decreased overall severity of PD, fewer health concerns, decrease in the level of disability, and greater intensity and frequency of anticipatory anxiety. Differences on the measures of panic attacks and agoraphobic avoidance were negligible. These results suggest that there is no relationship between panic attacks and real danger and lend support to the notion that panic attacks and fear induced by real danger are different phenomena. Contrary to the expectations of many PD patients, the presence of real danger does not seem to be associated with deterioration in their functioning, and PD patients can be reassured that they are not likely to cope worse under conditions of danger.     

Derealization and panic attacks: a clinical evaluation on 150 patients with panic disorder/agoraphobia

One hundred fifty patients with Panic Disorder (PD) with or without Phobic Avoidance were subdivided into two groups on the basis of presence/absence of derealization and/or depersonalization (D-D) during panic attacks. D-D was found in 34.7% of the sample. By comparing the two groups, the patients with D-D were found to be younger and had an earlier onset of the disorder; they had a higher prevalence of avoidance behavior and a higher severity of the agoraphobic spectrum phobias. They were also more frequently subject to concomitant disorders such as Generalized Anxiety, Obsessive-Compulsive, and depressive symptomatology. The authors have hypothesized a correlation between the presence of D-D during panic attacks and a more frequent clinical evolution toward agoraphobia. This view is supported by finding that D-D in panic attacks corresponds to severer forms of PD, both in terms of the earlier onset of PD, and because PD shows higher levels of anxiety, depression, and disability.     

Convergent and divergent validity of the Beck Anxiety Inventory for patients with panic disorder and agoraphobia

Psychometric properties of the Beck Anxiety Inventory (BAI) (Beck and Steer, 1990) were investigated in a sample of 82 patients suffering from panic disorder with agoraphobia. Before and after brief treatment, patients completed a battery of questionnaires and, for 2-week periods, kept a daily panic diary in which they recorded panic attacks, fear of panic, and average anxiety. The BAI demonstrated excellent internal consistency and good test–retest reliability over a 5-week interval. A partial multitrait, multimethod correlation matrix provided evidence of convergent validity with other measures of anxiety and of divergent validity vis á vis measures of depression. Factor analyses of pretest scores and residual gain scores used to address criticism that the BAI is excessively panic-centric yielded mixed results. In one analysis, the BAI was loaded with multimethod measures of panic and anxiety and, in the other, with questionnaire methods of assessing anxiety and depression. However, the BAI was clearly distinguished from measures of fear of fear, a central construct in panic disorder, and agoraphobic avoidance. Finally, the BAI proved sensitive to change with treatment, yielding effect sizes for improvement comparable to those of other anxiety measures. Depression and Anxiety 6:140–146, 1997. © 1997 Wiley-Liss, Inc.     

Anxiety sensitivity and modulation of the serotonergic system in patients with PD

Anxiety sensitivity, i.e., the fear of anxiety-related bodily sensations, is one of the most studied cognitive variables in panic disorder (PD). However, the effects of selective serotonergic antipanic agents on this variable have not yet been investigated. The present study examines the effects of 6 weeks of treatment with citalopram on anxiety sensitivity in patients with PD. Twenty patients entered the study. On day 0, before starting drug treatment, after 1 week and after 6 weeks of treatment, each patient was evaluated with the Anxiety Sensitivity Index (ASI); the severity of clinical symptomatology was assessed with standardized psychometric scales. Results showed a significant reduction of anxiety sensitivity after 6 weeks of treatment. There was a significant correlation between decrease of anxiety sensitivity and anticipatory anxiety, while no correlations were found between panic attacks and agoraphobic avoidance. These results suggest that antipanic drug treatment decreases anxiety sensitivity.     

Relations between anxiety sensitivity and panic symptoms in nonreferred children and adolescents

Anxiety sensitivity (AS), the fear of anxiety-related sensations, has been posited to be a cognitive risk factor for the development of anxiety disorders but has been understudied in youth. The purpose of the present investigations was to evaluate relations between AS and panic symptoms in nonreferred children and adolescents. In Study 1, (N = 113, mean age, 13.98). scores on the Childhood Anxiety Sensitivity Index (CASI) predicted the experience of uncued panic attacks after controlling for general anxiety and depression, although the total variance accounted for was small. In Study 2 (N = 52; mean age, 9.48), the Panic/ Agoraphobia subscale of the Spence Children's Anxiety Scale was used as the criterion variable. CASI score again predicted panic symptoms after controlling for trait anxiety and depression. Identification of a risk factor for panic attacks and panic disorder in youth will have important implications for etiologic theory, intervention, and prevention.