Issues in the Long-Term Treatment of Panic Disorder: Proceedings of a symposium held at the 10th Congress of the European College of Neuropsychopharmacology on September 13, 1997, in Vienna, Austria
Synopsis This paper describes a study to assess the validity of a brief household survey measure of psychic distress (PSYDIS). The measure classifies persons according to their pattern of scores on four dimensions, including anxiety and depression. Study subjects were interviewed first respondents from the general population in a cross-sectional household survey. Then, according their ratings on PSYDIS, subsamples were selected for psychiatric evaluation in a clinic a few weeks later. The survey ratings of 287 persons were compared with evaluations of the same persons experienced psychiatrists. Overall levels of concordance ranged from 76% to 80%, depending the psychiatric criterion used. Concordance was very high for women; it was lower for men for persons classified as High on PSYDIS We then applied two analytic strategies for increasing agreement between the clinical judgements and the clinical ratings. Strategy number I augmented the symptom checklist data with additional survey data on the subject's history of episodes of distress. Strategy II revised procedures for constructing the PSYDIS typology by (1) using more rigorous cutting point scores on the component scales, and (2) using a non-typological method of classification. The first strategy improved agreement between the clinic and survey measures; the second did not. The paper also compares PSYDIS with other brief symptom checklist measures.
The reinforcing properties of amphetamine were assessed in two groups of subjects for whom the drug was hypothesized to be a more effective reinforcer than for control subjects. Preference for amphetamine (5 and 10 mg) over placebo was evaluated in subjects who were concerned about being overweight (n = 13), in subjects with depression (n = 15), and in control subjects (n = 25). Subjective effects of the drugs were measured by self-report questionnaires. All three groups chose 5 mg d-amphetamine as often as they chose, placebo. The control and weight-concern group chose 10 mg d-amphetamine significantly more often than placebo. Neither the choice behavior nor the subjective effects of the drug indicated that amphetamine was a more effective positive reinforcer in the experimental groups, because of either its anorectic properties or its presumed antidepressant properties. The results are discussed in terms of the relative risk for stimulant abuse in populations with these characteristics. Clinical Pharmacology and Therapeutics (1987) 42, 127–136; doi:10.1038/clpt.1987.122
This study investigated whether anxious adults desiring treatment for their anxiety would choose to take 10 mg of diazepam (Valium) or placebo after sampling both substances under double-blind conditions. Subjective effects of the drugs were also assessed, and the relationship between self-reported subjective effects and the number of times subjects chose diazepam or placebo was examined. Fourteen male and female volunteers meeting criteria for generalized anxiety disorder were recruited. They participated in a nine-session choice experiment in which they sampled diazepam 10 mg and a placebo on the first four sessions and chose whichever they preferred on the next five sessions. Only three subjects chose diazepam on all five choice occasions, no subjects chose diazepam on three or four occasions, and 11 subjects chose diazepam on two or fewer occasions. Overall, diazepam produced typical, tranquilizer-like subjective effects. However, subjective responses to diazepam differed in the 0–2-times choosers compared with the 5-time choosers: the 0–2-time choosers showed an increase on the measure of confusion, while the 5-time choosers showed decreases on measures of anxiety and confusion and increases on measures of stimulation.
A series of studies has been carried out using a choice procedure to investigate the reinforcing properties of benzodiazepines in adult volunteer subjects. Amphetamine and other drugs with undisputed dependence potential are clearly preferred by the majority of subjects using this procedure. However diazepam has not been found to be an effective reinforcer across a range of doses, using various subject populations and under different experimental conditions. In the present study, lorazepam, a benzodiazepine with a shorter half-life than diazepam, was tested. Twelve normal volunteer subjects were tested in 4 separate experiments in which three doses of lorazepam (0.5, 1.0 and 2.0 mg) were each compared to placebo, and in a separate experiment, 1.0 mg lorazepam was compared to 5.0 mg diazepam. Subjects showed no preference between 0.5 mg lorazepam and placebo or between 1.0 mg lorazepam and 5.0 mg diazepam, but at the 1.0 and 2.0 mg doses of lorazepam they showed a clear preference for placebo. Subjective effects of the drugs were also monitored, and showed changes consistent with the anxiolytic and sedative effects of the drugs. The duration of the effects of lorazepam was unexpectedly long (as long as 6 hours), so the question whether a shorter acting benzodiazepine would be a more effective reinforcer in this situation remains unanswered.
The objective of this study was to assemble expert clinical experience and judgment regarding the treatment of panic disorder in a systematic, quantitative manner, particularly with respect to changes during the past 5 years.A panel of 73 internationally recognized experts in the field of pharmacotherapy of anxiety and depression was constituted by multistage peer nomination. Sixty-six experts completed a questionnaire in 1992, and 51 of those completed a follow-up questionnaire in 1997. This report focuses on the experts' responses to questions about therapeutic options as they relate to a vignette describing a typical case of panic disorder. The preferred initial treatment strategy in 1992 (59%) and in 1997 (55%) was a combination of medication with cognitive behavioral therapy. The vast majority of the expert panel included a medication in their recommendations-91% in 1992 and 90% in 1997. Experts recommending a medication for panic in 1992 chose as first-line treatment a benzodiazepine (35%), a selective serotonin reuptake inhibitor (SSRI, 7%), an older antidepressant (33%), or a combination of medications (25%), principally a benzodiazepine plus an older antidepressant (19%). In 1997, fewer chose a benzodiazepine (15%) or an older antidepressant (11%) alone, whereas 33% chose an SSRI alone. More experts chose a combination of medications in 1997 (39%), and the increase was attributable mainly to the choice of a benzodiazepine plus an SSRI (17%). Overall, there was only a small decline in recommendations for benzodiazepines, whereas the increased choice of SSRIs came largely at the expense of the older antidepressants. As second-line medications for panic should their first-line choice fail, the experts in 1997 recommended a benzodiazepine (7%), an SSRI (15%), an older antidepressant (28%), or a combination of medications (50%), most often a benzodiazepine plus an older antidepressant (21%) or a benzodiazepine plus an SSRI (17%). (Experts were not asked to recommend second-line treatment in 1992.) Thus, in case of unsatisfactory response, the experts' choices shifted from benzodiazepines and SSRIs alone toward the older antidepressants alone or combinations of an antidepressant plus a benzodiazepine. This report concluded that combined cognitive behavioral therapy plus medication was highly favored by the experts as the initial treatment strategy for panic disorder. Over the past 5 years, SSRIs displaced older antidepressants as the experts' choice for first-line pharmacotherapy of panic disorder. In case of an unsatisfactory response, the experts more often recommended an older antidepressant or a combination of an antidepressant plus a benzodiazepine. According to the experts' judgments, the benzodiazepines, especially combined with an antidepressant, remain mainstays of pharmacotherapy for panic disorder. (J Clin Psychopharmacol 1998;18[suppl 2]:27S-31S)
Dr. Finney provides with a charming historical review of the development of questionnaire measures of anxiety, laced as it is with personal anecdotes and references to his interactions with other major workers in this area. Measures that more effectively discriminate anxiety from depression also would represent a definite step forward. The behavioral and cognitive aspects of anxiety in patients also represent neglected areas of measurement. One might suspect that the apparent sensitivity of the Hamilton Anxiety Scale was due to clinical raters picking up sedative side effects in benzodiazepine-treated patients, rather than due to superior sensitivity to the specific antianxiety effects of the drug. The foregoing discussion has placed heavy emphasis on detection of the response to benzodiazepines as a criterion for validating measures of anxiety. This position clearly has heuristic value for investigators concerned with the psychopharmacology of anxiety.
