William Matuzas

Panic disorder, agoraphobia, and anxiety-relevant cognitive style

We attempted to identify factors differentiating Agoraphobia with Panic Attacks (AG) from Panic Disorder (PD) patients. Twenty-three AG and 27 PD patients were compared. No significant difference in severity of illness was found. As predicted, the groups differed on a measure of anxiety-relevant cognitions developed for this study, the Anxious Thoughts and Tendencies scale (AT&T) (P less than 0.02). We suggest that differences in interpretation of panic attacks account for the development of of phobic avoidance behavior in some but not all PD patients. The intercorrelations among measures suggest that Panic Disorder may be conceptualized as having several independent although related components (panic attacks, general anxiety, phobic anxiety, and cognitive distortions).

Interactive model of therapeutic response in panic disorder: moclobemide, a case in point.

It was proposed that pre-post regression slopes be used to index treatment response when the effect of baseline scores differed among treatments (interaction between treatment and baseline score). Reanalyses of two studies using imipramine and fluoxetine in panic disorder showed doserelated decreases in pre-post slopes for the frequency of unexpected panic attacks, but not for the frequency of situational panic attacks or measures of agoraphobia. This report presents similar analyses of data from a study using moclobemide. Patients (N = 452) with panic disorder were randomized to placebo or a fixed dose of moclobemide (75, 150, 300, 600, or 900 mg/day). They were treated double-blindly and evaluated at baseline and 1, 2, 3, 4, 6, and 8 weeks later. The authors analyzed the frequency of unexpected and situational panic attacks compiled from a daily diary, and fear and avoidance ratings based on the patient’s main phobia using baseline (pre) and end-point (post) values for all randomized patients. Adjoining dose groups were combined. Both unexpected and situational panic attacks showed systematic doserelated suppression of pre-post treatment slopes. Neither pre-post slopes nor adjusted posttreatment means for fear and avoidance differed reliably between treatment arms. This study replicates the authors’ earlier findings, except for situational panic attacks, which probably were not reliably identified. Antidepressants selectively suppress panic attacks, especially unexpected attacks, but not agoraphobia. The findings are consistent with the hypothesis that panic disorder with agoraphobia has clinically separable biologic and cognitive components that respond differentially to treatment. Antidepressants benefit primarily patients with many unexpected panic attacks. Investigators should evaluate pre-post treatment slopes before comparing adjusted posttreatment means (analysis of covariance).

Abrupt discontinuation of alprazolam and cognitive style in patients with panic disorder: early effects on mood, performance, and vital signs.

Abstract: The objective of this study was to ascertain the relationship of alprazolam plasma levels and an anxiety-prone cognitive style to the characteristics and severity of early withdrawal after abrupt discontinuation of alprazolam in 26 patients with panic disorder. After 8 and 9 weeks of fixed-dose treatment, patients were hospitalized for 24 hours. On 1 admission, ordered at random, treatment was maintained; on the other, placebo was substituted double blind. The Anxious Thoughts and Tendencies questionnaire was administered before treatment. Alprazolam plasma levels were measured 7 times on the day after each admission. Before each blood sampling, the Profile of Mood States and performance tasks were administered, and vital signs were recorded. On the day after abrupt discontinuation of alprazolam, Profile of Mood States anxiety, depression, fatigue, and confusion increased; vigor and elation decreased; speed on the digit symbol substitution task improved; and systolic blood pressure increased substantially over time. High Anxious Thoughts and Tendencies scores were related specifically to more anxiety. Our findings (1) confirm that dysphoric mood, fatigue, low energy, confusion, and elevated systolic blood pressure are part of the early syndrome of withdrawal from alprazolam in patients with panic disorder, notably as the drop in plasma levels approaches 50%; (2) indicate a psychomotor deficit persisting beyond dose stabilization; (3) suggest that an anxiety-prone cognitive style measurable before undertaking treatment may be a risk factor for more severe anxiety upon discontinuation; and (4) provide a rationale for applying cognitive behavior therapy during benzodiazepine taper.

Correlates of mitral valve prolapse among patients with panic disorder

Mitral valve prolapse (MVP) has been observed more frequently than expected among patients who report the current experience of panic attacks. The MVP observed has been generally of a mild variety and has not been associated with clinically meaningful variables in studies to date. In the current study, 82 patients with panic disorder (PD) who were recruited for a study of the drug treatment of PD were assessed for the presence of MVP, and patients with and without MVP were compared on several variables. Statistically significant findings were that patients with MVP were younger and more often female; reported an earlier age of onset of PD and more frequent panic attacks; and had a higher ponderal index, lower weight, and lower levels of triiodothyronine than patients without MVP. Contrary to previous studies, these results suggest that the presence of MVP among patients with PD is associated with potentially meaningful differences. While generalizability may be limited and causal relationships speculative at this time, the variables identified in this study deserve more explicit attention in future studies of PD and MVP.

Subject-own-control design in evaluating clinical antidepressant effects.

This study tested the use of a subject-own-control, multiple crossover design for evaluating the clinical effects of an established tricyclic antidepressant drug, imipramine. Although significant physiological and cognitive performance effects were demonstrated, only one clinical measure, target symptom change rated by the patients, showed a statistically significant drug-placebo difference. This result is in considerable contrast to the sensitivity of similar designs in detecting the clinical effects of antianxiety drugs in studies employing less than 20 patients. Crossover designs appear to be most successful when the treated condition is continuous, rather than episodic, and the treatment effects have a rapid onset and offset.

Plasma Concentration Monitoring of Antipsychotic and Tricyclic Antidepressant Treatment

The history of plasma levels in psychiatry goes back to World War II, when the pharmacologist Shannon (later head of NIH) was trying to develop synthetic antimalarial drugs as substitutes for quinine. Until more was known in this field, differing rates of metabolism obscured important clinical findings. B.B. Brodie, a student of Shannon’s, developed fundamental knowledge about the clinical pharmacology of many drugs used in internal medicine. His student, Julius Axelrode (later to win the Nobel Prize), became interested in the metabolism of amphetamine and, as a consequence, discovered the liver microsomal enzymes that metabolize amphetamine. Subsequent work indicated that these liver microsomal enzymes metabolize a great variety of drugs including antipsychotics and tricyclic antidepressants. A student of Axelrode’s, Snyder, developed an assay for antipsychotic drugs which involved measuring the dopamine-receptor properties of drug and/or metabolites in plasma, rather than a chemical measure of the drug itself. Another student of Brodie’s, Stephen Curry, developed a method for measuring chlorpromazine [1]. Davis, Janowsky, and Marshall (students of Curry’s) determined correlations between antipsychotic drug plasma levels and clinical effects in man [2–5]. Yet another student of Brodie’s, Sjoqvist [6], developed a method for monitoring plasma tricyclic levels. Subsequently, students of his in Sweden and Denmark related tricyclic plasma levels to clinical response.