Efficient allocation of patients to treatment cells in clinical trials with more than two treatment conditions.

OBJECTIVE: Clinical trials generally allocate patients to equal-sized treatment groups. The authors propose that it may be more efficient to allocate unequal proportions of the total sample size to treatments when more than two treatments are being compared. METHOD: This proposal is illustrated with two examples. One involved a comparison of three treatments and used a dichotomous categorical outcome. The other involved comparison of three treatments and used a continuous measure. RESULTS: In both examples, a considerable increase in efficiency was realized by reducing the number of patients assigned to the placebo cell. CONCLUSIONS: Unequal allocation of patients to treatments should be considered when more than two groups are compared.

Multicenter collaborative panic disorder severity scale.

OBJECTIVE: To address the lack of a simple and standardized instrument to assess overall panic disorder severity, the authors developed a scale for the measurement of panic disorder severity. METHOD: Ten independent evaluators used the seven-item Panic Disorder Severity Scale to assess 186 patients with principal DSM-III-R diagnoses of panic disorder (with no or mild agoraphobia) who were participating in the Multicenter Collaborative Treatment Study of Panic Disorder. In addition, 89 of these patients were reevaluated with the same scale after short-term treatment. A subset of 24 patients underwent two independent assessments to establish interrater reliability. Internal consistency, convergent and discriminant validity, and sensitivity to change were also determined. RESULTS: The Panic Disorder Severity Scale was associated with excellent interrater reliability, moderate internal consistency, and favorable levels of validity and sensitivity to change. Individual items showed good convergent and discriminant validity. Analysis suggested a two-factor model fit the data best. CONCLUSIONS: The Panic Disorder Severity Scale is a simple, efficient way for clinicians to rate severity in patients with established diagnoses of panic disorder. However, further research with more diverse groups of panic disorder patients and with a broader range of convergent and discriminant validity measures is needed.

Response to meta-chlorophenylpiperazine in panic disorder patients and healthy subjects: influence of reduction in intravenous dosage.

As a further test of the hypothesis of serotonin hypersensitivity in panic disorder (PD), the serotonin agonist meta-chlorophenylpiperazine (MCPP) was administered intravenously in a dose of 0.05 mg/kg to 27 PD patients and 22 normal control subjects. This is one-half the dose used in our previous study of PD patients, where the dose may have been too high to provide evidence of hypersensitivity to the agent. Responses of anxiety and nervousness were statistically indistinguishable by analysis of variance in the two groups, replicating our previous findings. Panic attack symptom score (PASS) ratings were significantly higher in the PD group, compared with a trend toward higher PASS ratings in the 0.1 mg/kg study. Cortisol, human growth hormone, and male prolactin responses showed no significant differences in the two groups by analysis of variance. Prolactin responses were significantly blunted in the female patients. The unexpected blunted prolactin response to MCPP in female PD patients may reflect a nonspecific blunting of prolactin response to stress. The PASS data provide some evidence of serotonergic hypersensitivity in PD.

Postpartum onset of panic disorder: a coincidental event?

BACKGROUND: This study investigated whether the onset of panic for the first time during the postpartum period represented a coincidental occurrence. METHOD: Sixty-four childbearing women diagnosed with panic disorder who had been treated at the Yale Anxiety Research Clinic were interviewed. Postpartum panic was defined as the first panic occurring within 12 weeks of the woman's first childbirth. RESULTS: Seven women (10.9%) met criteria for postpartum onset, which is significantly greater than the expected age-corrected percentage of 0.92%, Z = 2.29, p < .02. CONCLUSION: The onset of panic in the first postpartum period is not a coincidental event.

Effects of the serotonin reuptake inhibitor fluvoxamine on yohimbine-induced anxiety in panic disorder.

To assess the effects of the selective serotonin reuptake blocker fluvoxamine on noradrenergic function in patients with panic disorder, an intravenous yohimbine challenge test was administered to eight patients with panic disorder before and after 8 weeks of fluvoxamine treatment and to a parallel group of eight patients treated with placebo. Fluvoxamine treatment reduced yohimbine-induced anxiety while placebo treatment had no effect on this variable. Both fluvoxamine and placebo treatment had little effect on biochemical or physiologic responses to yohimbine.

Lifetime course of chronic depression in older men.

The lifetime course of illness in older outpatient men who remained symptomatic despite adequate pharmacologic treatment for depression was examined. A bimodal distribution of age of onset of first major depression was found, with 75% having onset before age 35 years and 25% having onset after age 50 years. At all ages, episodes of chronic depression developed after episodes of major depression and appeared to be partially resolved major depression. In 88% of patients, anxiety disorders developed before age 35 years, preceded onset of other disorders, and continued throughout the patient's lifetime. Seventy percent developed alcoholism and 25% had a medical illness that impaired function to a significant degree. The importance of obtaining a lifetime course of illness in older patients is discussed.