Raimund Buller

The Hamilton Anxiety Scale: reliability, validity and sensitivity to change in anxiety and depressive disorders

The Hamilton Anxiety Scale (HAM-A) was tested for reliability and validity in two different samples, one sample (n = 97) defined by anxiety disorders, the other sample (n = 101) defined by depressive disorders. The reliability and the concurrent validity of the HAM-A and its subscales proved to be sufficient. Internal validity tested by latent structure analysis was insufficient. The major problems with the HAM-A are that (1) anxiolytic and antidepressant effects cannot be clearly distinguished; (2) the subscale of somatic anxiety is strongly related to somatic side effects. The applicability of the HAM-A in anxiolytic treatment studies is therefore limited. More specific anxiety scales are needed.

Improving depression severity assessment--I. Reliability, internal validity and sensitivity to change of three observer depression scales.

The Hamilton Depression Scale (HAMD) is the most commonly used scale for depression severity assessment and for antidepressant treatment evaluation. Alternative scales have been proposed by Bech and Rafaelsen (BRMS) and by Montgomery and Asberg (MADRS) to try to overcome the shortcomings of HAMD: they are based on different concepts of severity and different scaling procedures. Comparisons with respect to reliability, validity and ability to detect change have been performed using these scales in different samples. The BRMS proved superior. This result makes it necessary to question the usual procedure of testing the efficacy of antidepressants by means of HAMD alone. Problems in defining the severity of depression and in testing the validity of severity scales are discussed.

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.

Drug treatment of panic disorder: early response to treatment as a predictor of final outcome

One of the core problems in clinical research is the detection of early changes in target symptoms that predict future therapeutic outcome. To analyze potential predictors of outcome, data of a multicenter study on patients with panic disorder were used. A total of 1010 patients were randomly allocated either to alprazolam, imipramine or placebo treatment. Early improvement in the number of spontaneous panic attacks within the first week of treatment predicted outcome exclusively in the alprazolam group. In contrast, placebo responders and nonresponders were differentiated by early changes in anticipatory anxiety intensity. For tricyclic antidepressants such as imipramine an evaluation period of more than one week is required to allow conclusions about outcome.

Avoidance behaviour: a predictor of the efficacy of pharmacotherapy in panic disorder?

SummaryThe impact of the avoidance behaviour on the psychopharmacological treatment of panic disorder was explored in the Cross National Collaborative Panic Study (n=1134 patients); in this double blind randomized trial alprazolam, imipramine and placebo were compared during an 8-week treatment period. Patients with extensive avoidance behaviour (agoraphobia) had the most profit from the active drugs. Counter expectancy these specific drug effects were most pronounced in avoidance behaviour. Active drugs (in particular imipramine) were especially more effective than placebo if the patients presented with associated avoidance behaviour. The results suggest that agoraphobia defines more a particular type of anxiety disorder overlapping with panic disorder than merely a severe state of panic disorder.

Chronology of panic and avoidance, age of onset in panic disorder, and prediction of treatment response. A report from the Cross-National Collaborative Panic Study.

SummaryThe relevance of the chronology between panic disorder and avoidance behavior and of an early, medium or late onset of panic disorder was tested. Groups from the sample of the cross-national collaborative panic study (CNCPS) were compared for differences in basic characteristics and for the ability to predict treatment response. Patients who developed avoidance behavior before the full syndrome of panic disorder had less often a full agoraphobia but were not different in their response to treatment. Patients with an early onset of panic disorder suffered more often from agoraphobia. The treatment response was similar in the groups with early, medium or late onset of panic disorder. Neither the chronology between panic disorder and avoidance behavior nor the age of onset of panic disorder predicted outcome in short-term treatment with alprazolam or impiramine.

One-year follow-up of panic disorder

SummaryA 1-year follow-up study was carried out in 77 patients with panic attacks (panic disorder). Of these patients 43% were remitted; avoidance behaviour and chronic anxiety were more persistent than panic attacks within the 1-year period. The main predictor for features of anxiety in the follow-up was avoidance behaviour. The most prominent prognostic factor for features of depression was the history of previous depressive episodes. Female patients had a poorer outcome than male patients.

Differentiation between major and minor depression

Though the concept of Major Depression was generated by clinicians using depressed inpatients as models, a polydiagnostic study in 600 psychiatric inpatients with heterogenous psychological disturbances revealed that all six competing operational definitions of Major Depression (including DSM-III-R and ICD-10) were too restrictive to serve as a general concept of depression. Another polydiagnostic study in 500 primary care outpatients showed that more than two-thirds of all non-chronic depressed cases were below the severity threshold of Major Depression: these patients are classified as Depression Not Otherwise Specified (NOS) by DSM-III-R. Loosening of the over-restrictive time criteria would broaden the concept of Major Depression so as to meet the requirements of a general concept of depression, while the definition of Minor Depression below the threshold of Major Depression would add to a reduction of cases of NOS Depression by more than 80%. For the evaluation of antidepressant drugs in out-patient samples, we propose that patients with these modified definitions of Major and Minor Depression be included, provided they meet a minimum severity criterion of 13 or more points on the Hamilton Depression Scale; four-fifths of the modified Major Depression group and one-third of the Minor Depression group do in fact meet this criterion.

Identification of minor affective disorders and implications for psychopharmacotherapy.

Five hundred general practice patients with functional complaints were studied with the Polydiagnostic Interview (PODI) to see whether DSM-IIIR criteria were able to specify affective disorders satisfactorily. Almost one third of the patients received the diagnosis of depression not otherwise specified (NOS). When Research Diagnostic Criteria were applied to these patients more than 70% received specific diagnoses. A modification of DSM-IIIR algorithms enabled us to further specify diagnoses in subjects with depression NOS. On the 17-item Hamilton Depression Scale many of these patients reached scores of 13 or more which is severe enough to justify a therapy trial with antidepressants.

The cardiac anxiety syndrome--a subtype of panic attacks.

SummaryCardiac anxiety syndrome and the diagnosis of cardiac neurosis respectively are characterized by panic attacks. Panic attacks are the core syndrome of a validated anxiety disorder (panic disorder). The purpose of this study was to investigate if the cardiac anxiety syndrome represents a separate disorder or if it is only a subtype of panic attacks.In a sample of 122 patients with panic attacks, all patients with a cardiac anxiety syndrome were selected (n = 31). Furthermore, parallel to this group—matched in the variables age and sex—a second group of patients with no cardiac anxiety syndrome was selected. There were no significant differences in course; in clinical phenomenology, patients with a cardiac anxiety syndrome were only distinguished by a greater intensity of somatization and phobic avoidance from patients with no cardiac anxiety syndrome. These results confirm the hypothesis that the cardiac anxiety syndrome is a subtype of panic attacks and does not represent a separate disorder.