Slow vs standard up-titration of paroxetine in the treatment of panic disorder: a prospective randomized trial

Aim: Patients with panic disorder (PD) might be sensitive to the stimulating effects of selective serotonin reuptake inhibitors (SSRI), thus requiring low dosages at treatment initiation. The aim of the present study was to assess eventual differences in terms of effectiveness and tolerability between a slow up‐titration with paroxetine and a standard one. Methods: In an open randomized, multicenter, primary‐care study, 60 patients (44 women and 16 men) with PD with or without agoraphobia were enrolled and randomized to receive a slow up‐titration with paroxetine (increments of 2.5 mg/day every 2 days) or a standard one (increments of 10 mg/day every week) up to a maximum daily dose of 20 mg. Repeated‐measures anova on sub‐items scores of the Panic Attack Anticipatory Anxiety Scale (PAAS) and Dosage Record and Treatment Emergent Symptom Scale (DOTES), respectively, used as outcome measures of effectiveness and tolerability, were performed. Significance level was set at 0.05 and it was not corrected. Results: anova showed no differences between the two treatments in terms of effectiveness and tolerability. Post hoc analysis found only one significant difference in the intensity of spontaneous panic attacks (Panic and Anticipatory Anxiety Scale) in the first 9 days of treatment between the two treatment groups, which was that this item was less intense in the slow‐titration group (treatment effect: F = 4.89, P = 0.03, effect size = 0.1). Conclusion: Present findings suggest only a small superiority for a slow up‐titration regimen of paroxetine compared to a standard one in the first 9 days of treatment but no differences at end‐point.     

Pharmacological management of panic disorder

Panic disorder (PD) is a disabling condition which appears in late adolescence or early adulthood and affects more frequently women than men. PD is frequently characterized by recurrences and sometimes by a chronic course and, therefore, most patients require long-term treatments to achieve remission, to prevent relapse and to reduce the risks associated with comorbidity. Pharmacotherapy is one of the most effective treatments of PD. In this paper, the pharmacological management of PD is reviewed. Many questions about this effective treatment need to be answered by the clinician and discussed with the patients to improve her/his collaboration to the treatment plan: which is the drug of choice; when does the drug become active; which is the effective dose; how to manage the side effects; how to manage nonresponse; and how long does the treatment last. Moreover, the clinical use of medication in women during pregnancy and breastfeeding or in children and adolescents was reviewed and its risk-benefit balance discussed.     

Psychoeducation in panic disorder patients: effect of a self-information booklet in a randomized,masked-rater study

The aim of our study was to evaluate the effectiveness of a self-information booklet (SIB) in decreasing anxiety and panic attacks in Panic Disorder (PD) patients. Eighty-four patients attending an outpatient clinic due to panic disorder were randomly chosen to receive paroxetine with/without a friendly-designed brochure. Follow-up was done by a masked rater after 1, 3,and 12 weeks in order to evaluate whether the co-administration of paroxetine and the brochure (Group A) had a beneficial effect over the administration of paroxetine alone (Group B). After 3 weeks of therapy, Group A patients had significantly greater improvement and lower scores on the Hamilton Anxiety Scale, the Panic Self Questionnaire, and the Visual Analog Scale. After 12 weeks, the differential improvement was not statistically significant and both groups had improved as compared to baseline. The administration of a psychoeducational brochure (SIB) to PD patients at the initiation of therapy had beneficial effects during the first weeks of treatment. Although this effect fades away, the role of the SIB is overstressed in its ability to increase well being and compliance, and reduce anxiety and panic attacks.     

Review of the long-term effectiveness of cognitive behavioral therapy compared to medications in panic disorder

Panic disorder is a recurrent and disabling illness. It is believed that Cognitive Behavioral Therapy (CBT) has a long-term protective effect for this disorder. This would offer CBT considerable advantage over medication management of panic disorder, as patients often relapse when they are tapered off their medications. This is a review of the literature about the long-term effectiveness of CBT. We searched for follow-up studies of panic disorder using CBT. Of the 78 citations produced in the initial search, most had major methodological flaws, including ignoring losses to follow-up, not accounting for interval treatment, and unclear reporting. Three papers met strict methodological criteria, and two of these demonstrated a modest protective effect of CBT in panic disorder patients. We make recommendations for well-designed studies involving comparisons of medications and cognitive behavior therapy.     

Sertraline treatment of panic disorder: results of a long-term study.

OBJECTIVE: To investigate the long-term efficacy, prevention of relapse and safety of sertraline in the treatment of panic disorder. METHOD: This study consisted of 52 weeks of open-label sertraline treatment (n=398) followed by a 28 weeks of a double-blind, placebo-controlled discontinuation trial (n=183). RESULTS: Ninety-three patients were randomized to sertraline and 90 were randomized to placebo. Discontinuation due to insufficient clinical response occurred in 23.6% of placebo-treated patients and 12.0% of sertraline-treated patients (log-rank test, P=0.040). Thirty-three per cent of placebo-treated patients had an exacerbation of panic symptomatology, versus 13% of sertraline-treated patients (log-rank test, P=0.005). Abrupt cessation of sertraline resulted in dizziness (4.3% sertraline vs. 16.9% placebo; P=0.007) and insomnia (4.3% sertraline vs. 15.7% placebo; P=0.013) occurring at significantly higher rates. CONCLUSION: Long-term sertraline treatment was effective in preventing relapse of panic disorder, well tolerated and associated with minimal discontinuation symptoms.     

Koro in a Caucasian male with panic disorder

A case of koro in a white English male is described. This is followed by a brief review of other similar cases and possible psychophysiological mechanisms     

Noradrenergic neuronal dysregulation in panic disorder: the effects of intravenous yohimbine and clonidine in panic disorder patients.

In order to evaluate possible abnormal noradrenergic neuronal functional regulation in patients with panic disorder, the behavioral, biochemical and cardiovascular effects of intravenous yohimbine (0.4 mg/kg) and clonidine (2 micrograms/kg) were determined in 15 healthy subjects and 38 patients with panic disorder. A subgroup of 24 panic disorder patients were observed to experience yohimbine-induced panic attacks and had larger yohimbine-induced increases in plasma 3-methoxy-4-hydroxyphenylglycol (MHPG) than healthy subjects and other panic disorder patients. A blunted growth hormone response to clonidine and a significant clonidine-induced decrease in plasma MHPG was also observed in this subgroup of panic disorder patients. These data replicate and extend previous investigations, which are consistent with a large body of preclinical and human data relating increased noradrenergic neuronal function to human anxiety and fear states.     

Coping behavior in patients with panic disorder

The purpose of the present paper was to investigate the role of coping behavior in patients with panic disorder (PD). This was done by evaluating three items of coping behavior (seeking of social support, wishful thinking and avoidance) in the Ways of Coping Checklist. The subjects consisted of 30 patients with PD (26 with agoraphobia). Coping behavior and the severity of PD was investigated at baseline and at 24 months (the final outcome). At baseline there were no gender differences in coping behavior. The severity of panic attacks significantly correlated with that of agoraphobia. The baseline severity of PD (panic attacks and agoraphobia) did not correlate with coping behavior. At the outcome assessment there was no significant correlation between the severity of panic attack and coping behavior. The severity of agoraphobia at final outcome and the coping behavior (seeking of social support) at baseline were significantly correlated. In the group that had remission in agoraphobia (the good outcome group), the severity of agoraphobia at baseline was significantly lower and the seeking of social support coping behavior was significantly higher than that of the poor outcome group. No significant difference in panic attack severity was noted between the good and poor outcome groups. Discriminant analysis revealed that seeking of social support coping behavior was a significant discriminant factor of agoraphobia. Although these are preliminary data, special coping behavior might be related to improvement of agoraphobia in patients with PD.     

A comparison of paroxetine,clomipramine and placebo in the treatment of panic disorder

The aim of this 12-week, double-blind, parallel group, placebo-controlled study was to compare paroxetine with clomipramine in 367 patients with DSM-III-R defined panic disorder. Efficacy assessments included the daily panic attack diary, the Clinical Global Impression Scale, the Hamilton Anxiety Rating Scale, the Marks Sheehan Phobia Scale and the Sheehan Disability Scale. Paroxetine produced significant improvements compared with placebo in various measurements of panic attack frequency, and was as effective as clomipramine. However, paroxetine appeared to have a more rapid onset of action than clomipramine in reducing the number of panic attacks to zero. There was an equivalent improvement with both paroxetine and clomipramine in the supportive efficacy variables which assessed associated aspects of therapeutic improvement. Significantly more adverse effects were reported in the clomipramine group compared with the paroxetine group, while there was no difference between the paroxetine and placebo groups.     

Platelet serotonin levels in panic disorder

Platelet serotonin levels were examined in 18 patients with panic disorder and compared to platelet serotonin levels of eight healthy controls. There was no statistically significant difference in the platelet serotonin levels between the two groups.     

Frequency of panic attacks and panic disorder in adolescents

By using data from the Bremer Adolescent Study, this report presents findings on the frequency, comorbidity, and psychosocial impairment of panic disorder and panic attacks among 1,035 adolescents. The adolescents were randomly selected from 36 schools in the province of Bremen, Germany. Panic disorder and other psychiatric disorders were coded based on DSM-IV criteria using the computerized-assisted personal interview of the Munich version of the Composite International Diagnostic Interview. Panic disorder occurred rather rare, with only 0.5% of all the adolescents met the DSM-IV criteria for this disorder sometimes in their live. Panic attack occurred more frequently, with 18% of the adolescents reported having had at least one panic attack. Slightly more girls than boys had panic attack and panic disorder. The occurrence of panic attack and panic disorder were the greatest among the 14–15 year olds. The experience of having a panic attack was associated with a number of problems, the most frequent being avoiding the situation for fear of having another attack. Four most common symptoms associated with a panic attack were that of palpitations, trembling/shaking, nausea or abdominal distress, and chills or hot flushes. Panic disorder comorbid highly with other psychiatric disorders covered in our study, especially with that of major depression. Among those with a panic disorder, about 40% of them were severely impaired during the worst episode of their illness. Only one out of five adolescents with panic disorder sought professional help for emotional and psychiatric problems. The implication of our findings for research and clinical practice are discussed. Depression and Anxiety 9:19–26, 1999. © 1999 Wiley-Liss, Inc.     

艾司西酞普兰治疗惊恐障碍对照研究

目的：研究艾司西酞酱兰和舍曲林治疗惊恐障碍的有效性和安全性。方法：65例惊恐障碍患者随机分入艾司西酞普兰组与舍曲林组治疗10周,在治疗前和治疗期间隔周测定惊恐症状评定量表（PASS）、临床总体印象一严重性（CGI—SI）、患者总体评价（PGE）,汉密尔顿焦虑量表（HAMA）及每周发作次数,以治疗中出现的症状量表（TESS）评定不良反应。结果：艾司西酞普兰组有效率为96．8％,舍曲林组为93．3％,二药相近。两组患者在治疗10周PASS、CGI—SI、PGE、HAMA的减分率差异无显著性。艾司西酞普兰组的起效时间快于舍曲林组．差异具有显著性（P〈0．01）,两组患者均有良好的耐受性。结论：艾司西酞普兰是一种起效快、疗效好、安全性高的治疗惊恐障碍的药物。     

The prediction of nonresponse to pharmacotherapy in panic disorder: a review.

Several effective pharmacotherapeutic treatments exist for panic disorder; however, not all patients respond to treatment: between 20% to 40% are non‐responders. Recent studies have reported several predictors of nonresponse to pharmacotherapy. In this review two questions are addressed: is there consensus with respect to predictors of nonresponse and are there any differences between short‐term and long‐term predictors? In this review both short‐term and long‐term outcome studies are discussed. Studies were included if at least DSM‐III criteria were used and baseline variables were investigated as possible predictor of response, or nonresponse, to pharmacotherapy. Of each clinical predictor, tallies were made of the particular predictors employed and of those predictors that predicted nonresponse. It appears that a long duration of illness and severe agoraphobic avoidance are robust predictors of nonresponse, particularly in long‐term studies. Personality disorders, or even personality traits, are possibly the most robust predictors of nonresponse. Several factors appear to be robust predictors of nonresponse: factors that are present before treatment and exert their influence on short‐term and long‐term treatment outcome. Prospective studies are needed to further investigate these factors and to test whether it is viable to intervene in an attempt to increase treatment response. Depression and Anxiety 14:112–122, 2001. © 2001 Wiley‐Liss, Inc.     

Patterns of response during placebo treatment of panic disorder

Data from the cross-national study of panic disorder are used for an analysis of response patterns. The main purpose of the study is a search for specific placebo patterns and a discussion of possible differences in patterns from patients treated with alprazolam, imipramine, and placebo. Four outcome measures were registered at baseline and weekly during the treatment period: the number of panic attacks, Physician's Global Evaluation of treatment effect, the Overall Phobia Score and the level on the Hamilton Rating Scale for Anxiety. Response patterns from the 3 treatment groups are described and compared, and subsequently categorized with regard to completeness and persistency. No specific placebo pattern is recognized. Some differences are found, however, as many placebo patients demonstrate an early and temporary remission. The variations in response patterns do not compromise the blindness of the study, and their predictive validity is low.     

Respiratory variability in panic disorder.

Disordered breathing may play an important role in the pathophysiology of panic disorder. Several studies have now indicated that panic disorder patients have greater respiratory variability than normal controls. In this study, we examine baseline respiratory measures in four diagnostic groups to determine whether greater respiratory variability is specific to panic disorder and whether effective anti-panic treatment alters respiratory variability. Patients with panic disorder, major depression, or premenstrual dysphoric disorder, and normal control subjects underwent two respiratory exposures (5% and 7% CO(2) inhalation), while in a canopy system. Panic disorder patients returned after 12 weeks of either anti-panic medication or cognitive behavioral therapy, and were retested. Normal control subjects were also retested after a period of 12 weeks. Panic disorder patients had significantly greater respiratory variability at baseline than normal control subjects and patients with major depression. The premenstrual dysphoric patients also had greater variability than the normal control group. Panic disorder patients who panicked to 7% CO(2) inhalation had significantly greater baseline variability than panic disorder patients who did not panic. Anti-panic treatment did not significantly alter baseline respiratory variability. Our data suggest that increased respiratory variability may be an important trait feature for some panic disorder patients and may make them more vulnerable to CO(2)-induced panic.     

Panic disorder versus panic disorder with major depression: Defining and understanding differences in psychiatric morbidity

The present study examined the impact of comorbid major depressive disorder (MDD) on psychiatric morbidity, panic symptomatology and frequency of other comorbid psychiatric conditions in subjects with panic disorder (PD). Four hundred thirty-seven patients with PD were evaluated at intake as part of a multicenter longitudinal study of anxiety disorders; 113 of these patients were also in an episode of MDD. Patients were diagnosed by DSM-III-R criteria utilizing structured clinical interviews. The 113 PD/MDD patients were compared with the 324 remaining PD subjects regarding panic symptoms at intake, sociodemographic, quality of life and psychiatric morbidity variables. Differences in frequency of other comorbid Axis I psychiatric disorders were assessed at intake; personality disorders were evaluated twelve months after intake. The results revealed that PD/MDD patients exhibit increased morbidity and decreased psychosocial functioning as compared to PD patients. Personality disorders were more prevalent in the PD/MDD group at six month follow-up assessment; the PD/MDD group also had an increased frequency of posttraumatic stress disorder (PTSD) and more comorbid Axis I anxiety disorders as compared to the PD group. The total number and frequency of panic symptoms was highly consistent between the two patient groups. Depression and Anxiety 5:12–20, 1997. © 1997 Wiley-Liss, Inc.     

Panic disorder: a review of DSM‐IV panic disorder and proposals for DSM‐V

This review covers the literature since the publication of DSM‐IV on the diagnostic criteria for panic attacks (PAs) and panic disorder (PD). Specific recommendations are made based on the evidence available. In particular, slight changes are proposed for the wording of the diagnostic criteria for PAs to ease the differentiation between panic and surrounding anxiety; simplification and clarification of the operationalization of types of PAs (expected vs. unexpected) is proposed; and consideration is given to the value of PAs as a specifier for all DSM diagnoses and to the cultural validity of certain symptom profiles. In addition, slight changes are proposed for the wording of the diagnostic criteria to increase clarity and parsimony of the criteria. Finally, based on the available evidence, no changes are proposed with regard to the developmental expression of PAs or PD. This review presents a number of options and preliminary recommendations to be considered for DSM‐V. Depression and Anxiety, 2010. © 2010 Wiley‐Liss, Inc.