R Buller’s research while affiliated with Mental Health Center of Denver and other places

The primary objectives of this large multicenter study (n = 578) were to determine the efficacy and safety of moclobemide, 300 or 600 mg per day, for the treatment of social phobia. A double-blind fixed-dose parallel group study was conducted to compare the two different doses of moclobemide to placebo. After a 1-week placebo run-in period, patients were randomly assigned to one of the three treatment groups to receive the test compound for a 12-week period. Assessments were performed at screen, on baseline and on weeks 1, 2, 3, 4, 6, 8, 10, and 12. There were consistent, reliable and clinically meaningful drug effects and indications of a dose-response relationship. Statistical analysis of the results at both weeks 8 and 12 showed that 600 mg of moclobemide was effective and statistically significantly superior to placebo. The 300 mg dose also showed better efficacy than placebo on all measures of efficacy, and about half of them were statistically significantly different from placebo. Moclobemide was well tolerated. Adverse events, except for insomnia, were neither dose-related nor were there significant drug-placebo differences. The results indicate that 600 mg of moclobemide per day given b.i.d. is effective in social phobia, reducing the symptoms and the impairment associated with the disorder. The compound is well tolerated and safe.

This study investigates the naturalistic course of panic disorder over four years and attempts to identify predictors for outcome. 423 DSM-III-R panic disorder patients who had taken part in an international multicentre drug trial were selected for follow-up; we were able to re-interview 367 (87%). For panic attacks, phobic avoidance and disabilities the same rating scales were administered as had been used for the clinical trials. While 61% of all patients experienced at least occasional panic attacks at follow-up, few suffered from serious phobic avoidance (16.7%) or serious disabilities (work 7.9%); family 8.7%; social 13.9%). Panic attack frequency at baseline, original trial medication and continuous use of psychotropic medication during follow-up are not related to outcome, whereas longer duration of illness and more severe phobic avoidance at baseline are unfavourable. The course of panic disorder is not uniform. Since long duration of illness and severe phobic avoidance at baseline are predictors for an unfavourable outcome, more rigorous efforts should be undertaken to detect and treat panic disorder at an early stage.

Seventy-six in- and outpatients seeking help for complaints of dizziness in a neurological clinic were assessed by the Structured Clinical Interview for DSM III (SCID). Neurological assessment included electrophysiological and otological examination. We established criteria to differentiate between dizziness as a symptom of panic disorder and dizziness as a symptom of neurological illness. Criteria for dizziness as a symptom of panic disorder are: adverse life events before the onset of dizziness, current comorbidity with depression, a high number of vegetative symptoms typical for panic attacks, a specific cluster of symptoms and little evidence of a neurological illness. We conclude that patients with complaints of dizziness often suffer from anxiety disorders. Thus we describe a vestibular subtype and contribute to the classification of panic disorder.

The pretreatment anxiety level is supposed to be a very important unspecific treatment factor. Main purpose of this study is to test whether the patients' pretreatment anxiety level is a general or a specific predictor of treatment response and whether mildly, moderately, and severely anxious patients can be differentially characterized by other diagnostic and clinical variables. 103 patients (37 males, 66 females; mean +/- sd age 35.6 +/- 9.5 years), a subsample of the Second Phase of the Cross-National Collaborative Panic Study, were included in the present study. A high positive correlation of initial anxiousness with the number of panic attacks at the end of treatment was found, moreover high positive correlations with most other baseline assessments. Initially severely anxious patients are the severest ill patients with the least treatment response, and that in all treatment groups. The pretreatment anxiety level predicts the number of panic attacks as well as the degree of avoidance behavior in both drug groups, whereas it predicts anticipatory anxiety intensity in the placebo group.

Help-seeking behaviour for treatment of panic disorder was investigated in the sample of the Cross-National Collaborative Panic Study Second Phase. A total of 1168 patients were entered into this trial in 14 countries. Although there were significant center differences in prior treatment and utilization of health services there were also similarities. Treatment had been provided mainly by general practitioners. Drug treatment consisted mostly of prescription of classical tranquilizers and had a longer duration than treatment by psychotherapy. Patients with agoraphobic avoidance, past major depression and longer duration of illness used medical and psychiatric treatment facilities more intensely. Older and more severely disabled subjects were more frequently treated by medical health care providers and were more likely to receive psychotropic drugs. The results indicate that general practitioners carry an important load in the treatment of panic disorders but may need more information about recent development in pharmacotherapy for this condition.

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 outpatient 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.