Cross-cultural evaluation of the Panic Disorder Severity Scale in Japan

The Panic Disorder Severity Scale (PDSS) [Shear et al., 1997] is rapidly gaining world-wide acceptance as a standard global severity measure of panic disorder, however, its cross-cultural validity and reliability have not been reported yet. We developed the Japanese version of the PDSS and examined its factor structure, internal consistency and inter-rater reliability and concurrent validity among Japanese patients with panic disorder with or without agoraphobia. We also established rules of thumb for interpreting PDSS total scores, taking the Clinical Global Impression severity scale as the anchoring criterion. The identical one-factor structure of the PDSS was confirmed among the Japanese patients as among the United States patients. Both internal and inter-rater reliability was excellent (Cronbach's alpha was 0.86, and ANOVA ICCs were all above 0.90). Concurrent validity of the PDSS items with self-report questionnaires tapping similar or overlapping domains was satisfactory (Pearson correlation coefficients were mostly above 0.5). Using the anchor-based approach, the following interpretative guides are suggested: among those with established panic disorder diagnosis, PDSS total scores up to 10 correspond with "mild," those between 11 and 15 with "moderate," and those at or above 16 correspond with "severe" panic disorder. The present findings support the cross-cultural generalizability of panic disorder symptomatology and of the PDSS, in particular.     

Headache types and panic disorder: directionality and specificity

OBJECTIVE: To examine the relationship of migraine and other severe headaches with panic disorder. METHODS: Representative samples of persons with migraine, non-migrainous severe headaches, and controls with no history of severe headaches, identified by a telephone survey, were interviewed in person, using a standardized psychiatric interview. Cox proportional hazards models with time-dependent covariates were used to examine the relationship of headaches with first-onset panic disorder and vice versa. RESULTS: Lifetime prevalence of panic disorder was significantly higher in persons with migraine and in persons with other severe headaches, compared with controls. Migraine and other severe headaches were associated with an increased risk for first onset of panic disorder (hazards ratios = 3.55 and 5.75). Panic disorder was associated with an increased risk for first onset of migraine and for first onset of other severe headaches, although the influences in this direction were lower (hazards ratios = 2.10 and 1.85). CONCLUSIONS: Comorbidity of panic disorder is not specific to migraine and applies also to other severe headaches. The influence is primarily from headaches to panic disorders, with a weaker influence in the reverse direction. The bidirectional associations, despite the difference in the strength of the associations, suggest that shared environmental or genetic factors might be involved in the comorbidity of panic disorder with migraine and other severe headaches.     

Maintaining reliability in a long-term psychiatric study: an ongoing inter-rater reliability monitoring program using the longitudinal interval follow-up evaluation

The Longitudinal Interval Follow-up Evaluation (LIFE), has been shown to be a valid and reliable instrument for characterizing the week-by-week course of anxiety disorders examined retrospectively over the period of 1 year. Due to the chronic nature of these disorders, there is a need for reliable, valid instruments for measuring course over periods of several years if we are to learn more about the natural history of these disorders. This paper describes a rater-monitoring program designed to ensure long-term inter-rater reliability and prevent "rater drift". In this program, clinical interviewers score taped interviews and are required to maintain a median intra-class correlation coefficient (ICC) of at least 0.80 with the other raters. Raters also assess tapes from previous years, to ensure that they are using the same diagnostic criteria as earlier generations of interviewers. A reliability study was conducted to compare psychiatric status ratings (PSRs) collected using biweekly telephone interviews with the semi-annual interviews. The ICCs for panic, agoraphobia, social phobia, and generalized anxiety disorder were very good to excellent. Another reliability study examined the PSRs of subjects who had been previously lost to follow-up. ICCs for panic, agoraphobia, generalized anxiety disorder and depression were good to excellent. These results show that the LIFE, when used in conjunction with an intensive training and rater monitoring system, is a reliable instrument for use in longitudinal studies of the course of anxiety disorders.     

International reliability of a diagnostic intake procedure for panic disorder.

Test-retest diagnostic reliability interviews using the Upjohn version of the Structured Clinical Interview for DSM-III (SCID) were conducted with 72 patients at 13 international sites of the Cross-National Collaborative Panic Study. Agreement on the diagnosis of panic disorder was very good. For the subtypes (uncomplicated, with limited phobic avoidance, and agoraphobia), agreement was fair to good.     

Comorbid bipolar disorder and panic disorder in families with a high prevalence of bipolar disorder.

OBJECTIVE: Panic attacks are a common complication of affective disorder, although the etiologic relationship of panic and affective symptoms has not been determined. Evidence from a family study suggests that panic attacks and panic disorder may be related genetically to bipolar disorder. This study used diagnostic data from the NIMH Bipolar Disorder Genetics Initiative to assess in a separate, larger family set the familiality of panic combined with bipolar disorder. METHOD: First-degree relatives (N=966) of probands with bipolar I disorder (N=192) and schizoaffective disorder, bipolar type, (N=11) were included in the study. All subjects were interviewed directly and were assigned best-estimate diagnoses for major affective and other psychiatric disorders. The risk of a family member being diagnosed with panic disorder if the proband with bipolar disorder had panic attacks or panic disorder was calculated with logistic regression analysis with generalized estimating equations that controlled for sex and affective disorder subdiagnosis. RESULTS: More than 90% of the probands and first-degree relatives with panic disorder also had an affective disorder diagnosis. Panic disorder was present in 17% of the relatives with recurrent major affective disorder and in 3% of the relatives without recurrent major affective disorder. Risk of panic disorder in relatives with bipolar disorder was increased significantly if the proband had panic attacks or panic disorder. CONCLUSIONS: Risk for panic disorder with familial bipolar disorder appears to be inherited. Inherited risk for panic disorder with bipolar disorder may indicate a shared genetic etiology for both disorders in some families. The patterns of bipolar disorder and panic disorder comorbidity observed in families imply a complex genetic etiology, which may be elucidated by using endophenotypes.     

Association of rapid mood switching with panic disorder and familial panic risk in familial bipolar disorder

OBJECTIVE: Comorbid bipolar and panic disorders aggregate in families. A phenotypic trait shared by both disorders is the sudden shift in affect observed in panic attacks and some rapid cycling states. The authors investigated whether comorbidity of bipolar disorder and panic disorder is associated with rapid mood switching in families with a high rate of bipolar disorder. METHOD: Six hundred six subjects with bipolar disorder from the NIMH Bipolar Disorder Genetics Initiative were included in the study. Logistic regression analysis was used to analyze rapid mood switching as a function of panic disorder diagnosis, sex, and familial risk for panic. RESULTS: Familial panic and the diagnosis of panic disorder in an individual subject increased the odds for rapid mood switching. The familial effect persisted when individuals with panic disorder were excluded from the analysis. CONCLUSIONS: Panic and rapid mood switching occurring together in familial bipolar disorder may define a useful subphenotype for future studies.     

Diagnosis and management of panic disorder in psychiatry (PANDA Study)

Panic disorder is a genuine public health problem given by their frequency and the various and repeated consultations that they involve. PD is underdiagnosed in primary care and in medical specialist. A public campaign might lead to improved diagnosis and better treatment of panic disorder, with a beneficial effect on medico-economic indicators. Intervention by the psychiatrist is of key importance, although it has not been evaluated to any great extend. The objective of the PANDA study was to look at the prevalence and diagnostic of panic disorder, the conditions of access to and use of care, as well as the method of treatment. Four hundred and twenty three psychiatrists participated in the study and 8,137 patients seen consecutively were included. The prevalence of actual panic disorder evaluated using the Mini International Neuropsychiatric Interview (MINI) systematic is 9%. In two third of cases coexisted agoraphobia and in one third a depression. Eighty six percent of patients with actual panic disorder were treated by the psychiatrists. The diagnosis and suitable treatment of panic disorder would appear to be a significant objective in term of public health, leading to a reduction in medical and social cost of this disorder.     

Response to sodium lactate infusion in alcoholics with panic attacks

The authors studied the response to sodium lactate infusion of 12 alcoholics with a history of panic attacks, 10 alcoholics without a history of panic attacks, and 16 nonalcoholic patients with panic disorder. The rate of lactate-induced panic was significantly higher in alcoholics with panic attacks than in alcoholics without panic attacks. Alcoholics with panic attacks were similar to nonalcoholic patients with panic disorder in their response to lactate. These findings support the specificity of lactate-induced panic for panic states and suggest that panic attacks in alcoholics resemble those in nonalcoholics. Lactate infusion may prove useful in the diagnosis of panic disorder in alcoholics.     

Comorbidity of ictal fear and panic disorder

Purpose. We sought to determine the prevalence of psychiatric conditions, particularly panic disorder, in epilepsy patients with ictal fear.Methods. A consecutive series of 12 patients with ictal fear underwent psychiatric evaluation, via either formal consultation with a psychiatrist or standardized interview using the Mini International Neuropsychiatric Interview; the latter was addended to create an instrument specifically for use in epilepsy patients (MINI-Epi).Results. Four of the twelve patients (33%) with ictal fear had a comorbid diagnosis of panic disorder. One of these developed panic attacks only after epilepsy surgery, and another worsened after surgery, while in the other two panic attacks were not related to any surgical procedure. Two patients had other anxiety disorders. Eight patients (67%) had current or past depression; this did not appear to be related to the presence of panic disorder.Conclusion. A specific comorbidity exists between focal epilepsy with ictal fear and panic disorder. Involvement of the amygdala in both temporal lobe epilepsy and panic disorder may underlie this. The predisposition to panic disorder in these patients may be exacerbated by anterior temporal lobectomy.     

Does the association between mitral valve prolapse and panic disorder really exist?

Objective: Although the possible relationship between panic disorder and mitral valve prolapse (MVP) attracted considerable research interest in the 1980s and 1990s, the reported prevalence of MVP in these patients has been inconsistent and widely variable. Clinical and epidemiologic studies have produced controversial data on possible association or definite causal relationship between these 2 entities. The primary objective of the present review was to summarize the current state of knowledge on the association between panic disorder and MVP, including the influence of diagnostic criteria for MVP on the controversial results.Data Sources: We searched MEDLINE, LILACS, and EMBASE databases using the keywords panic and mitral. Inclusion criteria were articles concerning the reciprocal association of MVP and panic disorder, published from the earliest dates available through December 2006.Study Selection: All relevant articles published in English, Spanish, or Portuguese and reporting original data related to the association of MVP and panic disorder were included. Forty articles fulfilling the criteria for inclusion in this review were identified.Data Synthesis: Even though the reported prevalence of MVP in panic disorder varied from 0% to 57%, a significant association between the 2 disorders was documented in 17 of the 40 studies. Such inconsistent results were due to sampling biases in case or control groups, widely different diagnostic criteria for MVP, and lack of reliability of MVP diagnosis. None of the reviewed studies used the current state-of-the-art diagnostic criteria for MVP to evaluate the volunteers. Apparently, the more elaborate the study methodology, the lower the chance to observe a significant relationship between these 2 conditions.Conclusions: Published results are insufficient to definitely establish or to exclude an association between MVP and panic disorder. If any relationship does actually exist, it could be said to be infrequent and mainly occur in subjects with minor variants of MVP. To clarify this intriguing issue, future studies should mainly focus on the observed methodological biases and particularly should use the current criteria for MVP as the standard for evaluation.     

Is childhood separation anxiety disorder a predictor of adult panic disorder and agoraphobia? A seven-year longitudinal study

OBJECTIVE: To examine whether separation anxiety disorder (SAD) in childhood is a risk factor for panic disorder and agoraphobia in adulthood. METHOD: Patients (n = 85) who had completed treatment for SAD, generalized anxiety disorder, and/or social phobia 7.42 years earlier (on average) were reassessed using structured diagnostic interviews. RESULTS: Subjects with a childhood diagnosis of SAD did not display a greater risk for developing panic disorder and agoraphobia in young adulthood than those with other childhood anxiety diagnoses. Subjects with a childhood diagnosis of SAD did not more frequently meet full diagnostic criteria for panic disorder and agoraphobia, generalized anxiety disorder, social phobia, or major depressive disorder in adulthood than subjects with childhood diagnoses of generalized anxiety disorder or social phobia, but were more likely to meet criteria for other anxiety disorders (i.e., specific phobia, obsessive compulsive disorder, posttraumatic stress disorder, and acute stress disorder). CONCLUSIONS: These results argue against the hypothesis that childhood SAD is a specific risk factor for adult panic disorder and agoraphobia.     

Panic Disorder in Clinically Referred Children and Adolescents

The present study examined the frequency and characteristics of panic disorder in children and adolescents who had been referred to a pediatric psychopharmacology clinic. Of the 280 children and adolescents evaluated in this clinic, 35 were diagnosed with panic disorder using a semi-structured clinical interview (K-SADS) and other objective measures. Approximately half of the youngsters with panic disorder also met criteria for the diagnosis of agoraphobia. There was extensive comorbidity between panic disorder and other internalizing and externalizing disorders. Parents reported clinically significant levels of child symptomatology on the CBCL. Teacher-and child-reported symptomatology on the CBCL was within the normal range. At the same time, it was notable that no child had been referred specifically for evaluation or treatment of panic disorder or agoraphobia. Implications for clinical assessment/identification and treatment are discussed. This paper was presented at the 39th Annual Convention of the Association for Behavioral and Cognitive Therapies, November 18, 2005, Washington, DC.     

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.     

Multidimensional assessment of the Panic-Agoraphobic Spectrum: reliability and validity of the Spanish version of the PAS-SR

The present study reports on the psychometric properties of the adaptation into Spanish of the Panic-Agoraphobic Spectrum Self-Report (PAS-SR). Drawing on a dimensional and longitudinal perspective of psychopathology, the PAS-SR was designed to measure a wide array of lifetime Panic-Agoraphobic features. Participants included outpatients with a DSM-IV-TR diagnosis of panic disorder (n=26) or major depression (n=28), and a normal control group (n=41). Internal consistency and test-retest reliability were excellent for the total score, and moderate to excellent for most domains. Significant and high correlations between PAS-SR scores and instruments measuring similar constructs indicated good concurrent validity. The findings support the discriminant validity of the questionnaire. Patients with a diagnosis of panic disorder attained higher scores than normal controls on all domains, and displayed higher scores than patients with major depression on five of the eight domains.     

Panic disorder history in the families of patients with angiographically normal coronary arteries.

OBJECTIVE: The authors evaluated the diagnostic validity of an interview-based panic disorder diagnosis in cardiology chest pain patients with angiographically normal coronary arteries. METHOD: Patient probands with normal coronary arteries (N = 65) were first contracted immediately after their normal angiogram and were given a structured diagnostic interview. On the basis of the results of the interview, probands were grouped as having panic disorder (N = 19), panic attacks that did not meet frequency criteria for panic disorder (N = 17), or no panic (N = 29). At a later time, patient probands were recontacted and given a structured family history interview that inquired about psychopathology in their first-degree biological relatives (N = 544). RESULTS: As predicted, panic disorder was significantly more prevalent among the first-degree relatives of probands with normal coronary arteries diagnosed with panic disorder or panic attacks than among the family members of probands with normal coronary arteries without panic (17.4% versus 15.7% versus 4.0%). Family members of probands with panic attacks were significantly more likely to be diagnosed with major depression than were the family members of probands with no panic; however, differences did not reach significance for family members of the panic disorder proband group. Groups did not differ significantly in familial alcoholism. CONCLUSIONS: These data support the construct validity of an interview-based panic disorder diagnosis among patients with chest pain and normal coronary arteries and suggest that these patients could benefit from treatment for panic disorder.     

Panic disorder without fear in patients with angiographically normal coronary arteries

By DSM-III-R criteria, patients may be diagnosed as having panic disorder without reporting the experience of intense fear. However, if such patients do not report subjective fear, they may be less likely to receive a panic diagnosis. The authors studied 32 subjects with angiographically normal coronary arteries who fit panic disorder criteria. A total of 13 (41%) reported no fear during their last major attack. These subjects were contrasted with those who did report fear. Few differences were found in group demographic data or responses to self-report questionnaires. We conclude that there appear to be few differences between the nonfear panic disorder subjects and those who do report fear. This conclusion awaits further support using challenge tests, medication trials, biological indices, alexithymia inventories, and family studies. The recognition of the existence of this subtype is likely to increase the number of patients receiving the panic disorder diagnosis in cardiology settings, in psychiatric settings, and in research projects using structured clinical interviews.     

Major depression and agoraphobia in patients with angiographically normal coronary arteries and panic disorder

Patients with panic disorder and/or agoraphobia appearing in psychiatric settings report rates for lifetime major depression between 24% and 91%. Between 40% and 90% of patients with panic disorder in psychiatric populations report concomitant agoraphobia. A recent study of panic disorder subjects appearing in an outpatient cardiology clinic confirmed the strong link between panic and depression but found only a weak association between panic disorder and agoraphobia. In order to test the reliability of these outpatient cardiology findings, the authors studied major depression and agoraphobia in patients with angiographically normal coronary arteries and panic disorder. Twelve of the 32 (37.5%) panic disorder subjects reported a lifetime history of major depression (nine current, three past only). Only two of the 32 (six percent) reported any phobic avoidance. This study confirms the previous findings which suggest that major depression is common in cardiology populations with panic disorder and that phobic avoidance is uncommon in this group.     

The diagnosis and management of panic disorder

The diagnosis of panic disorder without agoraphobia can very often be quite difficult because of the similarity with physical disorders particularly in the cardiac, gastrointestinal or neurological systems. The distinction must be made between panic attacks appearing as medical problems and medical problems appearing as panic attacks. Sometimes the diagnosis of panic attacks is made only after the medical diagnoses have been excluded. Panic disorder with agoraphobia however is much easier to detect if one carefully traces the historical development of agoraphobia and carefully distinguishes between the anxiety produced by agoraphobia and the panic attacks related to panic disorder. Panic disorder must also be distinguished from other anxiety disorders since the treatment for panic disorder still is quite specific. Once diagnosed however, the treatment of panic disorder without agoraphobia is rather simple. It involves the use of a benzodiazepine, either alprazolam or clonazopam, and perhaps the concomitant use of either imipramine or phenelzine sulfate for the rapid control of anxiety symptoms and continued treatment of the disorder. It is also very helpful to have the patient in psychotherapy either using a supportive or cognitive approach. If the patient has a panic disorder with agoraphobia, the pharmacological approach is the same, with the initiation of treatment using either alprazolam or clonazopam, but the psychotherapeutic approach is somewhat different in that behavioral therapy is emphasized rather than purely supportive or cognitive approaches. Given the fact that 1%-2% of the population is at risk for panic disorder, it is important that the condition be rapidly recognized and treated effectively since the currently available modalities of treatment result in almost total resolution of symptoms. Some individuals will remain on medication for several years while others will find it possible to decrease and/or discontinue their medications after only a few months or a few years. There is little excuse at this point for this disorder to be ineffectively diagnosed or treated.     

Specificity of panic response to CO(2) inhalation in panic disorder: a comparison with major depression and premenstrual dysphoric disorder

OBJECTIVE: The behavioral response to CO(2) inhalation has been used to differentiate panic disorder patients from normal subjects and other clinical populations. This study extended examination of the diagnostic specificity of CO(2)-induced anxiety by testing panic disorder patients and clinical populations with reported low and high sensitivity to CO(2) inhalation (patients with major depression and patients with premenstrual dysphoric disorder, respectively). METHOD: The behavioral responses to inhalation of 5% and 7% CO(2), administered by means of a respiratory canopy, were studied in 50 patients with panic disorder, 21 with major depression, and 10 with premenstrual dysphoric disorder and in 34 normal comparison subjects. Occurrence of panic attacks was judged with DSM-IV criteria by a blind rater. Subjects were rated on three behavioral scales at baseline and after each CO(2) inhalation. RESULTS: Panic disorder patients had a higher rate of CO(2)-induced panic attacks than depressed patients and normal subjects, whose panic rates were not distinguishable. The panic rate for patients with premenstrual dysphoric disorder was similar to that for panic disorder patients and higher than that for normal subjects. Subjects with CO(2)-induced panic attacks had similarly high ratings on the behavioral scales, regardless of diagnosis, including the small number of panicking normal subjects. Seven percent CO(2) was a more robust panicogen than 5%, and response to 7% CO(2 )better distinguished panic disorder patients from normal subjects than response to 5% CO(2). CONCLUSIONS: Patients with panic disorder and patients with premenstrual dysphoric disorder are highly susceptible to CO(2)-induced panic attacks, and depressed patients appear to be insensitive to CO(2) inhalation. The symptoms of CO(2)-induced panic attacks have a similar intensity regardless of the subject's diagnosis.