Anxiety sensitivity and panic disorder.

Anxiety sensitivity refers to fears of anxiety-related sensations. Most often measured by the Anxiety Sensitivity Index (ASI), anxiety sensitivity is a dispositional variable especially elevated in people with panic disorder. Regardless of diagnosis, ASI scores often predict panic symptoms in response to biological challenges (e.g., carbon dioxide inhalation) that provoke feared bodily sensations. Prospective longitudinal studies indicate that scores on the ASI predict subsequent spontaneous attacks, indicating that elevated anxiety sensitivity is a risk factor for panic and perhaps panic disorder. Cognitive behavioral treatment reduces anxiety sensitivity in panic patients, perhaps protecting against relapse. Imipramine likewise decreases anxiety sensitivity.     

Anxiety sensitivity as a predictor of the development of panic symptoms,panic attacks,and panic disorder: a prospective study

The purpose of the study was to examine how anxiety sensitivity (AS) acts as a dispositional factor in the development of panic symptoms, panic attacks, and panic disorder. Between 1986 and 1988, data were collected from 505 undergraduates at an urban university. At Time 1, measures used were the ASI to assess AS, the trait scale of the State-Trait Anxiety Inventory (STAI-T) to measure trait anxiety, and self-report questionnaires to measure personal and family history of panic and anxiety symptoms. During the Spring of 1999, 178 of these subjects were re-contacted, and information was gathered on subjects' subsequent development of panic symptoms, panic attacks, panic disorder, and trait anxiety (STAI-T). The ASI was the strongest predictor of the development of panic symptoms and panic attacks. After controlling for trait anxiety, the ASI was not predictive of the development of panic disorder.     

心理行为干预联合帕罗西汀治疗惊恐障碍患者的临床疗效

目的:观察心理行为干预联合帕罗西汀对惊恐障碍的治疗效果。方法:60例住院惊恐障碍患者随机分为,研究组和对照组各30例。研究组给予心理行为干预联合帕罗西汀治疗,对照组单用帕罗西汀治疗。观察12周。采用汉密尔顿焦虑量表(HAMA)、临床疗效总评量表-病情严重程度(CGI-SI)在治疗前及治疗2、4、8和12周评定疗效;以治疗中出现的症状量表(TESS)评定不良反应。结果:两组治疗后HAMA及CGI-SI评分较治疗前均显著降低(P<0.05),两组比较,研究组下降更为明显(P<0.05)。结论:心理行为干预联合帕罗西汀治疗惊恐障碍效果优于单用帕罗西汀治疗。     

Anxiety sensitivity does not predict fearful responding to 35% carbon dioxide in patients with panic disorder

The aim of the present study was to examine the relationship between anxiety sensitivity, as measured by the Anxiety Sensitivity Index (ASI), and four dimensions of behavioural reactivity to a single inhalation of 35% carbon dioxide (CO(2)) in 31 patients with panic disorder. ASI scores correlated positively with baseline State-Trait Anxiety Inventory scores but did not correlate with post-CO(2) scores. Correlational analyses revealed a significant, albeit modest, correlation between anxiety sensitivity and cognitive symptoms induced with CO(2). However, no significant association was found between anxiety sensitivity and other dimensions of CO(2)-induced anxiety, including severity of somatic symptoms, subjective levels of anxiety, fear or apprehension, and fear of the somatic symptoms induced by CO(2). Overall, these data do not support the view that anxiety sensitivity plays a key role in mediating behavioural sensitivity to CO(2) inhalation in panic disorder.     

Double-blind acute clonazepam vs. placebo in carbon dioxide-induced panic attacks

The inhalation of 35% carbon dioxide has consistently been shown to provoke panic attacks in panic disorder patients. We aim to determine if an acute dose of clonazepam (2 mg) attenuates the panic attacks induced by an inhalation of 35% carbon dioxide in panic disorder. Twenty-two panic disorder patients who had been drug-free for 1 week participated in a carbon dioxide challenge test 1 h after a dose of either 2 mg of clonazepam or placebo with a randomized double-blind method. Also in a double-blind design during the tests the patients inhaled either atmospheric compressed air ('placebo control') or the carbon dioxide mixture. All patients participated in both tests which were done with a 20-min interval. Immediately before and after the inhalation, the anxiety levels and the symptoms of panic were always assessed. In the clonazepam group (n=11) two patients (18.2%) had a mild panic attack and in the placebo group (n=11) nine patients (81.8%) had a moderate to severe panic attack in the CO(2) challenge test. No patient had panic attacks during inhalation of atmospheric compressed air although anticipatory anxiety levels tended to be higher than in the CO(2) tests. After the CO(2) test anxiety levels were significantly greater in the CO(2) group (three-way ANOVA with Geisser-Greenhouse adjustments, F(31.92,1.86)=17.15, d.f.=7, P=0.013). Although a small sample was studied, the findings suggest the efficacy of an acute dose of clonazepam in attenuating panic attacks induced by carbon dioxide inhalation.     

Double-blind clonazepam vs placebo in panic disorder treatment

OBJECTIVE: To assess the effectiveness of clonazepam, in a fixed dose (2 mg/day), compared with placebo in the treatment of panic disorder patients. METHOD: 24 panic disorder patients with agoraphobia were randomly selected. The diagnosis was obtained using the structured clinical interview for DSM-IV. All twenty-four subjects were randomly assigned to either treatment with clonazepam (2 mg/day) or placebo, during 6 weeks. Efficacy assessments included: change from baseline in the number of panic attacks; CGI scores for panic disorder; Hamilton rating scale for anxiety; and panic associated symptoms scale. RESULTS: At the therapeutic endpoint, only one of 9 placebo patients (11.1%) were free of panic attacks, compared with 8 of 13 (61.5%) clonazepam patients (Fisher exact test; p=0,031). CONCLUSION: the results provide evidence for the efficacy of clonazepam in panic disorder patients.     

Anxiety sensitivity in social phobia: comparison between social phobics with and without panic attacks

The current study examines levels of anxiety sensitivity among social phobic patients with and without panic attacks. Two-hundred fourteen individuals with a primary diagnosis of social phobia completed the Anxiety Sensitivity Index (ASI) prior to treatment. Social phobics who experienced panic attacks reported higher levels of anxiety sensitivity than those without panic attacks. Patterning of response to ASI items differed between panicking and non-panicking patients, with the panicking patients reporting greater fear of catastrophic consequences of bodily sensations. Individuals with an additional diagnosis of panic disorder did not differ from those with exclusively situational panic attacks. The findings suggest the importance of examining differences between anxiety-disordered individuals who experience panic attacks and their non-panicking counterparts.     

Double-blind, placebo-controlled assessment of combined clonazepam with paroxetine compared with paroxetine monotherapy for generalized social anxiety disorder

BACKGROUND: Generalized social anxiety disorder (GSAD) is a pervasive form of social anxiety that affects approximately 5% of persons in the community. Among evidence-based pharmacologic treatments for the disorder, selective serotonin reuptake inhibitors (SSRIs) have become widely used and are known to be efficacious. Monotherapy with the benzodiazepine clonazepam is also efficacious for GSAD, but the adjunctive use of clonazepam with an SSRI to potentially improve outcomes has not been studied to date. METHOD: Twenty-eight patients (22 men and 6 women) with DSM-IV-defined GSAD were randomly assigned to receive double-blind clonazepam (or placebo), 1.0 to 2.0 mg/day (divided b.i.d.) along with open-label paroxetine, 20 to 40 mg/day, for 10 weeks. A 2-week taper of double-blind medication was followed by an additional 8 weeks of open-label paroxetine treatment (during which the dose of paroxetine could be increased to a maximum of 50 mg/day). Twenty-three patients (82%) met DSM-IV criteria for avoidant personality disorder. The patients' mean +/- SD age was 31.2 +/- 7.7 years, and their mean duration of illness was 12.1 +/- 5.8 years. Data were gathered from August 2001 to April 2002. RESULTS: Nineteen (68%) of 28 patients completed treatment. At the end of the 10-week double-blind treatment, there was a trend (p <.06) favoring the paroxetine/clonazepam group, who had a 79% response rate (Clinical Global Impressions-Global Improvement scale [CGI-I] score of 1 or 2) compared with a 43% response rate for the paroxetine/placebo group. However, no significant differences on other outcome measures were noted between the 2 groups in an intent-to-treat analysis, in terms of either very early (2-4 weeks) or not as early (5-10 weeks) responses during treatment. Dropout rates due to adverse events were rare (1 patient in each group), indicating that the paroxetine/clonazepam combination was well tolerated. CONCLUSION: Coadministration of clonazepam with an SSRI, in contrast to findings in panic disorder, did not lead to more rapid resolution of symptoms in GSAD. On the other hand, there is some evidence that the clonazepam-added group had superior global outcomes (e.g., as measured on the CGI-I), although power to detect such differences in this study was small. These observations suggest that a role for adjunctive benzodiazepines in patients with GSAD (e.g., for augmenting SSRI partial response or nonresponse) is deserving of further controlled investigation.     

A randomized,double-blind,placebo-controlled study of the effects of adjunctive paroxetine in panic disorder patients unsuccessfully treated with cognitive-behavioral therapy alone

BACKGROUND: Both cognitive-behavioral therapy and treatment with selective serotonin reuptake inhibitors (SSRIs) have proved to be effective in the treatment of panic disorder. The present study examined the effects of paroxetine added to continued cognitive-behavioral therapy in patients who were unsuccessfully treated with initial cognitive-behavioral therapy alone. METHOD: 161 patients with panic disorder with or without agoraphobia (DSM-IV criteria) underwent a manual-guided cognitive-behavioral therapy of 15 sessions. Forty-three unsuccessfully treated patients from this group were included in a double-blind, placebo-controlled, next-step treatment study consisting of continued cognitive-behavioral therapy plus adjunctive paroxetine at a dose of 40 mg/day or continued cognitive-behavioral therapy plus placebo. RESULTS: Overall, patients in the cognitive-behavioral therapy plus paroxetine condition improved significantly on agoraphobic behavior (p < .05) and anxiety discomfort (p < .01), whereas patients in the cognitive-behavioral therapy plus placebo condition did not. Effect sizes in the cognitive-behavioral therapy plus paroxetine condition ranged from 1.0 to 1.8 and in the cognitive-behavioral therapy plus placebo condition, from 0.4 to 1.0. CONCLUSION: Patients with panic disorder who are unsuccessfully treated with initial cognitive-behavioral therapy may benefit from the addition of an SSRI as a second treatment modality. The importance of timely evaluation of treatment results is emphasized.     

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.     

Efficacy, safety, and gradual discontinuation of clonazepam in panic disorder: a placebo-controlled, multicenter study using optimized dosages.

BACKGROUND: The purpose of this multicenter, double-blind, placebo-controlled study was to evaluate the efficacy and safety of optimized dosages of clonazepam for the treatment of panic disorder and assess the tolerability of a schedule for gradual discontinuation. METHOD: Adult patients with panic disorder with or without agoraphobia (DSM-III-R criteria) were randomly assigned to receive either placebo or clonazepam in individually adjusted doses over 3 weeks to approximate an optimal dosage, which was then maintained for an additional 3 weeks, amounting to a 6-week therapeutic phase. The daily dose range was 0.25 to 4.0 mg administered in 2 divided doses. In the following 7-week discontinuance phase, the doses were tapered gradually to cessation. RESULTS: At the therapeutic endpoint, clonazepam (N = 222) proved clinically and statistically superior to placebo (N = 216) in change in the number of panic attacks and in Clinical Global Impressions-Severity of Illness (CGI-S) and CGI-Change scores, Patient's Global Impression of Change scores, amount of fear and avoidance associated with phobic symptoms, and duration of anticipatory anxiety. The gradual tapering of clonazepam was not associated with symptoms suggestive of withdrawal syndrome. Although patients taking clonazepam experienced some clinical worsening compared with the status achieved at endpoint, particularly in terms of number of panic attacks, no deterioration was observed using their condition at baseline as point of reference. No overall evidence of rebound was found. All regimens were generally well tolerated. Somnolence was the main adverse event associated with clonazepam therapy. The percentage of patients who reported adverse events was higher in the clonazepam group than in the placebo group, as was the mean number of adverse events per patient. CONCLUSION: In this placebo-controlled trial, clonazepam was an efficacious and safe shortterm treatment of the symptoms of panic disorder. Discontinuance during and after slow tapering was well tolerated.     

Emergence of depressive symptoms during treatment for panic disorder with specific 5-hydroxytryptophan reuptake inhibitors

Selective serotonin reuptake inhibitors (SSRI) have been established as effective drugs in the treatment of depressive and anxiety disorders. However, there are also reports that they can induce depressive symptoms and suicidal thoughts in patients. Eighty of 230 patients who met the DSM-III-R criteria for panic disorder received, during the course of treatment, fluvoxamine (a selective serotonin reuptake inhibitor) at a dose level between 50–200 mg/day. The patients were clinically evaluated for a history of affective disorder and for the presence of affective symptoms before the treatment and for emergence of depressive symptoms during the treatment. Seven of the 80 patients (9%) developed symptoms of depression despite a good antianxiety response. Five of the 7 patients received fluvoxamine as second choice after tricyclic antidepressants (TCA). These patients had no history of affective disorder, and no symptoms of depression were present before the treatment with fluvoxamine. The depressive symptoms abated after the fluvoxamine was discontinued and TCA or clonazepam was prescribed. The depressive symptoms reappeared when fluoxetine was administered. None of these 7 patients developed depressive symptoms while treated with TCA or clonazepam. Among the 150 patients treated with TCA and benzodiazepines, not a single case of depression was seen in patients without a previous history of depression. These results suggest a vulnerability among some of panic disorder patients to noradrenergic-serotonergic imbalance caused by SSRI, which has to be taken into clinical consideration.     

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.     

New concepts in benzodiazepine therapy: Rebound anxiety and new indications for the more potent benzodiazepines

1. 1. Abrupt withdrawal of benzodiazepine treatment in generalized anxiety patients was found to induce a rebound anxiety state in addition to minor physical symptoms.

2. 2. Controlled clinical trials suggest that the newer high potency benzodiazepines (alprazolam, clonazepam and bromazepam) have novel psychiatric indications and greater anxiolytic effect than the classical benzodiazepines.

3. 3. Alprazolam, a triazolobenzodiazepine, was superior to placebo in the treatment of panic disorder, for which medium or low potency benzodiazepines are generally inefficacious.

4. 4. Clonazepam, an anticonvulsant which increases 5HT synthesis, was more efficacious than lithium in reducing manic symptoms.

5. 5. Bromazepam, a new potent benzodiazepine, was superior to diazepam in the treatment of generalized anxiety disorder.

Psychopathological correlates of anxiety sensitivity: evidence from clinical interviews and self-report measures

Most research on anxiety sensitivity (AS) and its relation to psychopathology has examined the Anxiety Sensitivity Index (ASI) in various clinical samples. The present study was the first to investigate psychopathological correlates of AS using self-report measures, the anxiety, somatoform, and substance use disorders sections of the Structured Clinical Interview for the DSM-IV (SCID), and open-ended interview questions about the subjective meaning and origins of AS. A college student sample (N=317) was used for the correlational analysis, and subsamples of high-AS (n=44) and low-AS (n=41) participants completed the interviews. Despite having an ASI score (Mean=35.0) that was equivalent to that observed in panic disorder samples, the screening questions in the clinical interview indicated that only 55% of high-AS participants had panic attacks and the diagnostic assessment indicated that only 30% met criteria for an anxiety disorder. Several findings suggested that AS, at least as measured by the ASI, was strongly related to anxiety disorder symptoms and diagnoses, although there was substantial variation within the anxiety disorder classifications. There was also evidence that AS might extend to a broader catastrophic style concerning bodily symptoms and health that go beyond anxiety symptoms per se. The subjective meaning of AS derived from the interview data stressed the need for a formal, structured interview of AS.     

Early coadministration of clonazepam with sertraline for panic disorder.

BACKGROUND: There is debate about combining benzodiazepines with selective serotonin reuptake inhibitors in the acute treatment of panic disorder. Although this medication combination is widely used in clinical practice, there is no well-tested, optimal method of coadministering these medications for the treatment of panic disorder. The purpose of this study was to test the efficacy of early coadministration of clonazepam with sertraline in the treatment of panic disorder. METHODS: Fifty patients with panic disorder were randomized into a double-blind clinical trial. Patients received open-label sertraline for 12 weeks (target dose, 100 mg/d), and in addition were randomized to groups receiving either 0.5 mg of active clonazepam 3 times daily or placebo clonazepam for the first 4 weeks of the trial. The clonazepam dose was then tapered during 3 weeks and discontinued. RESULTS: Thirty-four (68%) of 50 patients completed the trial. Drop-out rates were similar in the sertraline/placebo vs the sertraline/clonazepam group (38% vs 25%) (P =.5). An intent-to-treat analysis (on last observation carried forward data) revealed a much greater proportion of responders in the sertraline/clonazepam compared with the sertraline/placebo group at the end of week 1 of the trial (41% vs 4%) (P =.003). There was also a significant between-group difference at the end of week 3 with 14 (63%) of 22 of the sertraline/clonazepam group responding to treatment vs 8 (32%) of 25 of the sertraline/placebo group (P =.05). This difference was not observed at other times during the trial. CONCLUSION: These data indicate that rapid stabilization of panic symptoms can be safely achieved with a sertraline/clonazepam combination, supporting the clinical utility of this type of regimen for facilitating early improvement of panic symptoms relative to sertraline alone.     

Effects of paroxetine on heart period variability in patients with panic disorder: a study of holter ECG records.

We investigated cardiac autonomic function in 16 patients with panic disorder before and after treatment with paroxetine using Holter ECG records. Our previous data suggest a relative increase in sympathetic activity in patients with panic disorder, especially during sleep. Data for 20 h and awake and sleep periods were analyzed using spectral analysis to quantify absolute and relative heart period variability in ultra low (ULF: <0.0033 Hz), very low (VLF: 0.0033-0.04 Hz), low (LF: 0.04-0.15 Hz) and high (HF: 0.15-0.5 Hz) frequency bands. We also obtained fractal dimensions (FD) for the 20-hour, awake and sleep time series of RR intervals. Paroxetine treatment (19.7 +/- 4.7 mg/day for 105 +/- 37 days) resulted in a significant improvement in the frequency and intensity of panic attacks and also on the state anxiety inventory. Paroxetine treatment produced a significant decrease of 20-hour absolute HF power, awake absolute LF power and sleep absolute HF power. There was also a significant decrease of FDs after treatment with paroxetine for the sleep period. The decrease in LF and HF powers, and sleep FD is likely due to the antimuscarinic effect of paroxetine. The decrease in day-time LF power may also be due to a decrease in relative cardiac sympathetic activity after paroxetine treatment.     

惊恐障碍病人药物治疗前后状态-特质焦虑问卷结果分析

目的　探讨氟西汀联用氯硝西泮治疗惊恐障碍前后状态—特质焦虑问卷 (STAI)测查结果变化特点。方法　对 2 8例惊恐障碍病人治疗 6个月 ,分别于疗前、疗后 1、3、6月末以SAI评定焦虑症状 ,以TAI评定焦虑特质 ,以CGI中GI评定临床疗效。结果　药物治疗对焦虑症状有明显疗效 ,疗后各时段与疗前、疗后各时段之间差异均有显著性 (P <0 .0 1) ,而焦虑特质的变化与焦虑症状的变化不同 ,疗后各时段与疗前差异有显著性 (P <0 .0 1) ,但疗后各时段之间基本无变化 (P >0 .0 5 )。GI评定疗后 6月末显效率 85 .7% ,有效率10 0 %。结论　药物治疗对焦虑症状近、远期均有效 ,对焦虑特质近期有效 ,远期基本无效 ,近期效果可能与惊恐情绪所致认知偏差有关 ,故需配合心理治疗     

Remission rates in patients with anxiety disorders treated with paroxetine

BACKGROUND: Approximately 50% to 60% of patients with depression and/or anxiety respond to treatment, but only a minority achieve remission. The continued presence of subsyndromal symptoms in treated depressed (and probably anxious) patients leads to higher relapse rates and increased utilization of health care resources. It is proposed that remission is the appropriate target in the treatment of both depression and the anxiety disorders. AIMS: Rigorous criteria for remission have been proposed for the anxiety disorders and are currently being applied in clinical studies. Using these criteria, data from the paroxetine clinical study database were retrospectively analyzed to determine remission rates following paroxetine treatment across a range of anxiety disorders in the largest analysis of remission data in the anxiety disorders to date. METHOD: These analyses included data from 16 short-term and 6 long-term, randomized, placebo-controlled studies in panic disorder, social anxiety disorder, obsessive-compulsive disorder, posttraumatic stress disorder (short term only), and generalized anxiety disorder (DSM-III-R or DSM-IV). Separate analyses were performed for each disorder, with short- and long-term data analyzed separately. RESULTS: In general, across the range of anxiety disorders studied, in both short- and long-term studies, remission rates were higher for paroxetine compared with placebo, using disorder-specific, global, and functional remission criteria both individually and combined. Remission occurred in a moderate proportion of paroxetine-treated patients after only 8 to 12 weeks of treatment, and longer-term therapy led to even higher remission rates. CONCLUSION: Paroxetine has demonstrated efficacy in treating patients to remission across the range of anxiety disorders studied. Our findings strongly suggest that continuing treatment with paroxetine (and probably other SSRI antidepressants) for 2 to 12 months increases the proportion of patients achieving clinical remission.     

Response to lactate infusion in generalized anxiety disorder

Intravenous sodium lactate infusion provokes symptoms of panic in patients with panic disorder at a significantly higher rate than in normal controls. Lactate sensitivity has been postulated to be specific for patients with panic attacks regardless of frequency of attacks or coexisting diagnoses. The authors present results of a pilot study of lactate infusions in patients with generalized anxiety disorder (GAD) without any history of panic attacks. Patients with GAD reacted more like panic disorder patients than like normal controls in anxiety and symptom scores during lactate infusion and in the rate of positive responses to lactate. Although preliminary, these findings raise questions regarding the specificity of lactate sensitivity and the relationship of GAD to panic disorder.