[Panic disorder. The pattern of somatic contacts in patients]. / Panikangst. Patienters somatiske kontaktmønster.

The epidemiology, phenomenology and treatment of panic disorder have been thoroughly studied in recent years. The symptomatology of panic attacks may mimic cardiopulmonary, neurological and gastrointestinal disease. Forty Danish panic patients with panic disorder of ten years' duration had had contact with several medical specialists, hospital emergency and outpatient services. Thus, 28% had visited neurologists, 8% cardiologists and 20% an emergency service. One third had been admitted to hospital departments. Almost all patients had consulted psychiatrists or psychologists. Ninety had been treated with a benzodiazepine, 35% with tricyclic antidepressants and 57% with neuroleptics. To prevent costly medical testings and delay in accurate diagnosis in psychiatric and somatic settings, the phenomenology of panic disorders should be recognized by all medical specialists and general practitioners.

The sequence of improvement of the symptoms encountered in patients with panic disorder.

Patients who meet DSM-III-R criteria for a diagnosis of panic disorder often show a complex mixture of psychopathological symptoms, including panic attacks (spontaneous and situational), anxiety (anticipatory and generalized), phobias (fear and avoidance), depression/dysphoria, and social and occupational disability. Various theories about the pathogenesis of these symptoms have been advanced that focus on a given symptom (e.g., panic, phobia) being primary in these disorders, with concurrent symptoms seen as epiphenomena or as secondary and reactive to a core symptom. This study, conducted on a large sample of panic disorder patients (N = 1,168), examines the temporal sequential pattern of symptom improvement in these patients, and explores how these relationships relate to various pathogenic theories. Our multiple analyses, when considered together, tend not to support any pathogenic theory that views a given symptom as being central to the overall disorder; our findings have obvious implications for theoreticians and clinicians interested in the study and treatment of panic and anxiety disorders.

Efficacy and safety of alprazolam, imipramine and placebo in treating panic disorder. A Scandinavian multicenter study.

As part of the cross-national collaborative panic study, a double-blind comparison of alprazolam, imipramine and placebo was performed in Scandinavian outpatients with panic disorder according to DSM-III; 41 patients were randomly allocated to each drug. Doses were increased for 3 weeks to an average of about 6 mg alprazolam, 150 mg imipramine and a corresponding number of placebo capsules, which were then given for 5 weeks. No more than supportive psychotherapy was given. Key symptoms were rated weekly. The drugs were tapered for 4 or 8 weeks and the patients were followed up for 6 months. Compliance at 3 weeks was 95% for alprazolam, 83% for imipramine and 88% for placebo; at 8 weeks 95% for alprazolam, 73% for imipramine and 46% for placebo. At 3 weeks plasma determination showed that the proportion taking diazepam outside the protocol was 0% for alprazolam, 19% for imipramine and 31% for placebo; at 8 weeks the corresponding proportions were 3%, 11% and 16%. Intention-to-treat analysis showed that freedom from panic attacks was obtained for 68% with alprazolam, 61% with imipramine and 34% with placebo. Alprazolam was more effective than imipramine and placebo on anticipatory anxiety and phobic symptoms. Globally rated by physicians and patients, about 60% had complete remission with alprazolam and imipramine and 30% on placebo. At least partial remission was obtained in about 85% with alprazolam, 70% with imipramine and 40% with placebo. Alprazolam had a more rapid onset of action than imipramine on all symptoms. Side effects were generally mild, with a preponderance of drowsiness for alprazolam and anticholinergic effects for imipramine. Tapering was uneventful without significant discontinuation phenomena. During taper and follow-up, several patients in remission relapsed, leaving approximately 30% patients in complete remission in all groups. To obtain more stable improvement, either long-term drug treatment or combinations of drug treatment and psychotherapy should be evaluated.

A trend analysis of changes during treatment of panic disorder with alprazolam and imipramine.

A total of 123 Scandinavian patients participated in a cross-national study of panic disorder. Twelve outcome measures, including number of panic attacks and phobias, have been used to describe changes in symptoms during treatment. This article gives a trend analysis of remission for each variable, analysing changes through the total period from baseline to week 8 and also changes in first and second half of this period, separately. Important differences between treatments are demonstrated. Alprazolam had an early effect on variables relating to panic attacks, such as severity of spontaneous attacks and avoidance, whereas imipramine showed a more delayed effect on global measures. Duration of illness, sex and the occurrence of depression in patients' history all affected the sequence of improvement.

Characteristics of panic disorder patients responding to placebo.

Forty-one panic disorder patients receiving placebo were investigated in a double-blind comparison of alprazolam, imipramine and placebo in panic disorder. A significantly higher drop-out rate was found in the placebo group than in the active treatment groups, but placebo response was found in 34% of the patients, defined as reduction of panic attacks to zero, and in 23%, defined as a score of greater than or equal to 8 on the Physician Global Improvement Scale (0-10 points). Several predictors of response to placebo were found. The responders had fewer panic attacks than the nonresponders at baseline. They also reported less psychopathology and were less help-seeking than the nonresponders. The implications for psychopathology and possible response to psychotherapy among responders and nonresponders are discussed. It is hypothesized that the responders show more signs of realistic processing of internal and external stimuli and fewer signs of subjective distress than the nonresponders. Responders will therefore probably be more responsive to psychotherapy than nonresponders.

Secondary depression in panic disorder: an indicator of severity with a weak effect on outcome in alprazolam and imipramine treatment.

Depressive symptoms are frequent in panic disorder. Among 123 Scandinavian patients participating in a placebo-controlled multicenter study of the efficacy of alprazolam and imipramine treatment in panic disorder, 21% and 23% fulfilled the DSM-III criteria of current and past major depressive episode, respectively, and 17% had dysthymia, even when melancholia and depressive episode with onset prior to the panic symptoms were excluded. According to a subscale of the Hamilton Rating Scale for Depression (HRSD) with higher validity than the full scale, 18% were classified as major depression and 57% as minor depression. A major finding was that patients with affective symptoms had higher scores on many psychopathological measures, including several Symptom Checklist-90 factors. Accordingly, secondary depression was suggested as an indicator of the severity of panic disorder. Depressed and nondepressed patients significantly improved on major outcome measures, but patients with current minor or major depression improved less. Although the sample was too small for detailed analysis of differences in drug efficacy, there was no indication that imipramine was more effective than alprazolam, considering scores on an HRSD subscale.

Alprazolam, imipramine and placebo treatment of panic disorder: predicting therapeutic response.

Factors that predicted the outcome of drug treatment (alprazolam or imipramine) of panic disorder were studied in a sample of 123 Scandinavian patients participating in a multicenter placebo-controlled 8-week trial. The attrition rate was 95% for alprazolam, 73% for imipramine and 46% for placebo. For the intention-to-treat and 3-week-completer samples, drugs and anxiety symptoms at baseline were the best predictors of improvement on the Global Improvement Scale and on symptom scales focusing on panic attacks, phobic behavior and anticipatory anxiety. For completers of the 8-week trial, only baseline scores predicted outcome. Generally, more severe symptoms at baseline predicted a worse outcome. A subsample of patients had a marked placebo response. Avoidance, sex, age, childhood psychopathology and previous treatment experience had no or only a weak impact on the outcome. The relationship between panic disorder and mood disorder is presented elsewhere.

Validation criteria for panic disorder as a nosological entity.

Panic disorder (DSM-III, DSM-III-R) has been thoroughly studied in recent years. The main evidence for panic disorder as a nosological entity is reviewed, to delineate some important questions for future research. Validation criteria include epidemiological, phenomenological, genetic, neurobiological, pharmacological and behavioral findings. Biological, behavioral and psychodynamic considerations on etiology, pathogenesis and treatment are presented.

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.

Psychiatric classification as a reflection of uncertainties.

Some problems of psychiatric classification are discussed and a shift of viewpoint is suggested. The existence of a natural and inherent structure for the class of psychiatric disorders is a matter of dispute, and it is postulated that a continuous search for such natural structure may be futile. Clinical psychiatry shall try to answer a series of questions which can be formulated as a hierarchy of uncertainties. It is now suggested that the existing pool of information used for psychiatric description may be a reflection of these uncertainties. The pool shall be analysed for core-syndromes which are the reliable components of an alternative classification.