Panic disorder and bipolar disorder: anxiety sensitivity as a potential mediator of panic during manic states

BACKGROUND: Panic disorder (PD) occurs at high rates in bipolar disorder and more commonly than in unipolar depression. Reports of PD onset during hypomania and depressive mania (i.e., mixed states) raise questions about whether the affective disturbances of bipolar disorder play a specific role in the exacerbation or onset of PD. Anxiety sensitivity (AS), a risk factor for PD appears greater in bipolar disorder compared to unipolar depression, although the association of specific mood states with AS remains unknown. METHODS: We examined the association of current mood state (i.e., mixed state, mania or hypomania, bipolar depression, unipolar depression, and euthymia) with Anxiety Sensitivity Index (ASI) scores in 202 individuals with bipolar disorder (n=110) or major depressive disorder (n=92). RESULTS: Current mood state was significantly associated with ASI score (Chi-square=21.2, df=4, p=0.0003). In multiple regression analyses, including covariates for comorbid anxiety disorders, current mania or hypomania was a significant predictor of ASI scores (p<0.04). Current mixed state tended toward a similar association (p<0.10). LIMITATIONS: Conclusions are limited by the study's cross-sectional nature and relatively small sample size. CONCLUSIONS: These findings of elevated AS during manic states, independent of comorbid anxiety disorders, provide preliminary support for the hypothesis that manic states contribute to risk for the development or exacerbation of PD, and that AS may contribute to the high prevalence and severity of PD comorbid with bipolar disorder.     

Clinical subtypes in panic disorder: their descriptive and prospective validity

In a sample of 97 patients with panic attacks, presence of agoraphobia was associated with a more severe syndrome of panic anxiety both at index assessment and during one-year follow-up but was not associated with increased incidence of major depression. Groups with a history of depression--primary or secondary to the onset of panic--did not differ from the group without depression when severity of anxiety was concerned but were more severely impaired and had a higher incidence of further depressive episodes during follow-up. For future classification of panic disorder, subtypes defined according to associated syndromes of agoraphobia or depression are proposed, since these conditions appear constant through follow-up.     

Personality and symptom sensitivity predictors of alprazolam withdrawal in panic disorder

BACKGROUND: Discontinuation of benzodiazepine (BZ) treatment results in a well-characterized withdrawal syndrome in 40-50% of anxious patients. While numerous studies have established the role of BZ dose, treatment duration, half-life, potency, rate of withdrawal and severity of underling anxiety disorder in predicting severity of withdrawal symptoms, fewer studies have examined the role of psychological and personality factors. METHOD: In 123 panic disorder patients undergoing gradual tapered discontinuation of alprazolam in conjunction with pre-treatment with carbamazepine or placebo, the relationship between measures of 'symptom sensitivity' and 'harm avoidance', and severity of withdrawal symptoms measured as peak severity of symptoms, time before taper needed to be slowed due to symptoms, and ability to complete taper, was examined. RESULTS: After controlling for the less substantial effects of dose, treatment duration, pre-taper anxiety and panic attack frequency, measures of symptom sensitivity and harm avoidance accounted for an additional 3-6% of withdrawal variance. CONCLUSIONS: These results show an effect of symptom sensitivity and harm avoidance on BZ withdrawal symptoms, comparable to prior findings linking dependent personality characteristics to withdrawal severity. Failure to show the expected effect on ability to complete taper may be due to either the more symptomatic nature of the patients in this study.     

Suicide and panic disorder: a review

This article reviews the risk of suicide in panic disorder beginning with early studies showing increased mortality, including suicide, among patients belonging to the broad category of neuroses. More recent follow-up studies of patients with anxiety disorders have found about 20% of deaths due to suicide, a proportion similar to that found in depressive disorders. Also, suicide attempts have been reported by similar proportions of subjects with panic disorder and major depression from the general population. Preliminary data indicate that more severely ill patients with coexisting depression and substance abuse are more likely to attempt or complete suicide. Thus, although limited, the data indicate that the risk of suicide in panic disorder is substantial. As a consequence, clinicians should alert themselves to this preventable outcome and approach treatment with added caution.     

Panic disorder: Description, conceptualization, and implications for treatment

This paper reviews the Panic Disorder from diagnostic, clinical, and psychophysiological vantage points and concludes in suggestions for therapeutic intervention. The Panic Disorder is characterized by the repetitive onset of acute panic attacks. Evidence suggests that phasic panic anxiety is distinct from tonic, generalized anxiety, with each type having different treatment requirements. An integrated psychophysiological model incorporating cognitive appraisal theory and interoceptive conditioning theory was developed to conceptualize the panic attack. Stated briefly, stressful conditions or the perception of threat in panic patients elicit autonomic hyperactivity. Through a recurrent feedback loop, these aversive sensations become interoceptive conditional stimuli which elicit further anxiety responses and perceptions of threat. The development and implementation of adaptive coping skills is impeded by high physiological arousal, cognitive disorientation, and behavioral avoidance. The self-appraisal of inadequate coping skills intensifies anticipatory anxiety, further feeding into the cycle of panic escalation. This model suggests three fronts for intervention: (1) alleviating the antecedent stresses and conflicts which result in panic, (2) directly suppressing the physiological responses associated with panic, and (3) reducing the panic-maintaining anticipatory fear of panic through the training of cognitive and behavioral coping skills.     

The Galway Study of Panic Disorder. I: Clomipramine and lofepramine in DSM III-R panic disorder: a placebo controlled trial.

Among 79 volunteer, unpaid, family doctor-referred psychiatric out patients with DSM III-R panic disorder, with and without agoraphobia, 66 completed a six week placebo-controlled trial of lofepramine versus clomipramine and 57 survivors were followed up for 6 months. All subjects received one hour per week concurrent behavioural counselling in the acute phase. Of 13 dropouts in the first 3 weeks, 9 (of 27) were on clomipramine, 2 (of 26) were on lofepramine and 2 (of 26) were on placebo. The high (30%) early dropout from the clomipramine group was largely due to medication intolerance. Both drugs were superior to placebo by the end of week 6 on several standard rating scales but not on panic attack frequency. No significant differences in efficacy were found between the two drugs tested to the end of 6 months. No tendency for relapse was noted in the three months following taper-off of medication from week 12 to week 24. The study provides evidence that both drugs, in the dosages used, are superior to placebo in the acute phase of panic disorder in treatment-naive subjects concurrently receiving appropriate psychotherapy.     

Genetics of panic disorder on the Faroe Islands: a replication study of chromosome 9 and panic disorder

OBJECTIVE: The population of the Faroe Islands in the North Atlantic Ocean is likely to have the same ancestry as the Icelandic population. An Icelandic study on Panic Disorder has found some evidence for a loci on chromosome 9. METHODS: On the Faroe Islands we have an ongoing genetic project concerning panic disorder among other psychiatric disorders. We searched for shared alleles and haplotypes in distantly related cases from the isolated and recently found population of the Faroe Islands, using 26 more or less evenly distributed microsatellite markers on chromosome 9, with emphasis on the candidate region identified in the Icelandic study. RESULTS: We have not been able to replicate the Icelandic results. Owing to the study design and sample size, we would not be able to detect areas with small impact.     

Marital relationship and the treatment of panic disorder with agoraphobia: a critical review

The purpose of this paper is (1) to specify, among studies on the links between marital relationship and cognitive-behavioral treatment of panic disorder with agoraphobia (PDA), the conceptual and methodological limitations that may have produced inconsistent results in this field so far; and (2) to propose avenues of research that will help in remedying current weaknesses and answering important questions in this area. Following definition of PDA and a survey of its socioeconomic consequences, the authors examine results of the various ways research has tried to specify the links between marital relationship and the development, maintenance, and treatment of this disorder: the study of major life events before and after the onset of PDA, interpersonal problems and quality of marital relationship in the presence of PDA, the links between marital relationship and PDA treatment outcome, variability of experimental outcomes according to types of measure used to study these links, the effect of the spouse as co-therapist in PDA treatment, and the impact of a PDA treatment based on marital communication and problem-solving. Research hypotheses and methodological procedures are proposed to improve understanding of PDA and its treatment outcome.     

Meta-analysis of COMT val158met in panic disorder: ethnic heterogeneity and gender specificity.

There is strong evidence for a genetic contribution to the pathogenesis of panic disorder, with the functional catechol-O-methyltransferase (COMT) val158met polymorphism having been suggested as a potential susceptibility factor. In the present study, a meta-analysis of six available case-control studies (557 patients with panic disorder and 763 healthy controls in total) on the role of the COMT val158met polymorphism in panic disorder was conducted in an attempt to reconcile previous conflicting results and to facilitate evaluation of the role of COMT gene variation in panic disorder. Overall, no significant association, but strong between-study heterogeneity, was discerned. Analysis of studies pooled by ancestry yielded a significant association of the COMT 158val allele with panic disorder in Caucasian samples and, conversely, a trend towards association of the COMT 158met allele with the disorder in Asian samples. Interestingly, stratification for gender as well as ethnicity revealed that association of the 158val allele in Caucasians and, reciprocally, the 158met allele in Asian samples was restricted to females. The present meta-analysis provides tentative support for the COMT val158met polymorphism as a possible risk factor for panic disorder, with differential effects in Caucasian and Asian populations, and suggests a female-specific effect. However, given the relatively small number of case-control studies presently available, several more association studies, preferably including a larger number of family-based studies, are warranted for conclusive evaluation of the COMT val158met polymorphism as a vulnerability factor in panic disorder.     

Subclinical symptoms of panic disorder: new insights into pathophysiology and treatment

The aim of this review was to survey the available literature on prodromal and residual symptoms of panic disorder. Both a computerized (Medline) and a manual search of the literature were performed. In a substantial proportion of patients with panic disorder with agoraphobia a prodromal phase can be identified. Most patients report residual symptoms despite successful treatment. Residual symptoms upon remission have a prognostic value. There appears to be a relationship between residual and prodromal symptomatology (the rollback phenomenon). Appraisal of subclinical symptomatology in panic disorder has important implications as to the pathophysiological model of disease, its conceptualization and treatment.     

Meta-analysis on the treatment of panic disorder with agoraphobia: Review and re-examination

From three meta-analyses on treatment outcome in panic disorder with agoraphobia, method, results and conclusions were reviewed. The meta-analyses differed in methods used and conclusions derived. The conclusions conflicted on the relative efficacy of treatment with antidepressants, high-potency benzodiazepines, psychological panic management, exposure in vivo and combination treatments. These conflicting findings can be caused by confounding variables, present in ‘between-study’ comparisons. In ‘within-study’ comparison, so-called ‘same experiment studies’, these confounding variables are controlled for. Therefore, the literature was reviewed for same experiment studies. The differential efficacy of treatments compared within 25 identified same experiment studies was evaluated by calculating the effect size d between the treatments. Antidepressants and high-potency benzodiazepines were equally effective. The comparison between these drugs and psychological panic management remained inconclusive. Exposure in vivo was superior to psychopharmacological and psychological panic management. The efficacy of exposure in vivo was not enlarged by the addition of psychological panic management. There was some evidence that the addition of psychopharmacological drugs to exposure in vivo enlarged the efficacy of the latter. This observation must be investigated more systematically.     

Serum cholesterol levels and panic symptoms in patients with panic disorder: a preliminary study

BACKGROUND: Although some previous research has focused on the relationship between panic disorder (PD) and a high total cholesterol (TC) level, it is still controversial. Recently, researchers have reported the heterogeneity of clinical symptoms in PD and the complexity of the correlations found among them. Therefore, the controversy on the TC level in PD may be due to the existence of clinical subgroups in PD. It is important to ascertain whether or not an elevated TC level in patients with PD is associated with specific panic symptoms. METHODS: In 104 drug-free patients with PD, we examined the relationship between TC level and each of several panic symptoms occurring at the time of panic attacks (PAs), which included anticipatory anxiety, agoraphobia, and 13 panic symptoms based on the DSM-III-R. RESULTS: Stepwise regression analysis revealed a significant effect of the presence of the symptom 'fear of dying' on TC levels. Patients with a fear of dying had a significantly higher TC level than those without it. LIMITATIONS: The relatively small sample size may limit the generalizability of our findings. DISCUSSION: These data suggest that TC level may be associated with panic symptoms in patients with PD.     

Smoking and panic attacks, panic disorder, and agoraphobia: a review of the empirical literature

The empirical literature regarding panic-spectrum problems (i.e., panic attacks, panic disorder, and agoraphobia) and cigarette smoking is reviewed. In the first section of the paper, empirical studies that document the prevalence of smoking and panic-related problems are presented and discussed. In the second section of the paper, studies pertaining to the role cigarette smoking may play in the onset and maintenance of panic-related problems are critically reviewed. In the third section of the paper, studies related to the association between panic vulnerability factors and the nature of smoking behavior are presented. In the fourth section of the paper, specific areas not otherwise covered in the review are presented to stimulate further development in these areas (e.g., specialized treatment development).     

Psychological treatment of panic disorder with or without agoraphobia: A meta-analysis

Although the efficacy of psychological treatment for panic disorder (PD) with or without agoraphobia has been the subject of a great deal of research, the specific contribution of techniques such as exposure, cognitive therapy, relaxation training and breathing retraining has not yet been clearly established. This paper presents a meta-analysis applying random- and mixed-effects models to a total of 65 comparisons between a treated and a control group, obtained from 42 studies published between 1980 and 2006. The results showed that, after controlling for the methodological quality of the studies and the type of control group, the combination of exposure, relaxation training, and breathing retraining gives the most consistent evidence for treating PD. Other factors that improve the effectiveness of treatments are the inclusion of homework during the intervention and a follow-up program after it has finished. Furthermore, the treatment is more effective when the patients have no comorbid disorders and the shorter the time they have been suffering from the illness. Publication bias and several methodological factors were discarded as a threat against the validity of our results. Finally the implications of the results for clinical practice and for future research are discussed.     

Mitral valve prolapse and panic disorder: a review of their relationship

There has been considerable speculation about a possible relationship between panic disorder and mitral valve prolapse syndrome (MVP), although empirical results have been highly inconsistent. Some studies report low frequencies of 0-8%, others high frequencies of 24-35% "definite" MVP in panic patients (average across 17 studies: 18% of panic patients, 1% of normal controls). Elevated prevalences of MVP were also reported for generalized anxiety disorder, bipolar affective disorder, and anorexia nervosa. Studies of MVP patients generally failed to find elevated prevalence of panic compared to other cardiac patients or normal controls (averages across seven studies: 14%, 10%, and 8%, respectively). Inconsistent results may be due to widely different diagnostic criteria for MVP, low reliability of this diagnosis, inadequate control groups, "non-blind" ratings of panic or MVP, and sampling bias in both patient and control populations. These problems as well as the great variations in the published results preclude any final judgment. If there is concomitance between MVP and panic, it is small and primarily involves subjects with milder or reversible variants of MVP. At present it seems most justified, however, to assume co-morbidity in highly symptomatic individuals rather than a functional relationship.     

Personality disorder and social anxiety predict delayed response in drug and behavioral treatment of panic disorder

BACKGROUND: The aim of this study was to analyze the impact of pretreatment characteristics and personality disorders on the onset of response in the treatment of panic disorder. METHODS: The data of 73 out-patients with panic disorder who had completed at least 6 weeks of a randomized trial of 24 weeks of either paroxetine only or paroxetine combined with cognitive group-therapy were analyzed in a Cox proportional hazards model. RESULTS: The likelihood of having responded to treatment (defined by a CGI rating of improvement) was more than twice as high for patients without a personality disorder or social phobia than for Patients with a personality disorder or social phobia. CONCLUSIONS: We suggest that patients with these characteristics do benefit from prolonged treatment, and they may profit from an additional treatment focused on social anxiety.