Do antidepressants selectively suppress spontaneous (unexpected) panic attacks? A replication

The purpose of this study was to test the following interrelated hypotheses in a larger sample by attempting to replicate supportive results from a sm all therapeutic study: (1) the pathogenesis of panic disorder includes at l east two identifiable components: a biological component represented by spo ntaneous (unexpected) panic attacks, and a cognitive component represented by situational attacks and especially by phobias; (2) these components resp ond differently to treatment; (3) many biological processes respond to an e ffective intervention in proportion to their deviance from "normal" prior t o treatment ("Law of initial Value"); and (4) the response of spontaneous p anic attacks to an effective treatment conforms to that model. Previously, the authors reanalyzed an 8-week therapeutic study of panic disorder that i ncluded groups treated with placebo and with imipramine (225 mg daily). The criteria of response were spontaneous panic attacks (biological component) , situational panic attacks (both components), and agoraphobia ratings (cog nitive component). The analyses compared the regression lines for posttreat ment status on pretreatment status in the imipramine and placebo groups. Th e effect of imipramine on spontaneous panic attacks fitted the hypothesized model: the pre-post slope in the placebo group was approximately 1 (45 deg rees), whereas the slope in the imipramine group was approximately 0. There was no significant difference in pre-post slopes between the imipramine an d placebo groups for situational panic attacks or agoraphobia ratings. For this report, the authors applied the same approach to another larger data s et hom a study using a similar design, but a different antidepressant. In t his multicenter, double-blind study, patients with panic disorder were rand omly assigned to receive 10 weeks of treatment with placebo (N = 78) or flu oxetine 10 mg (N = 84) or 20 mg (N = 81) daily. Spontaneous and situational panic attacks were registered in a daily diary, and agoraphobia was rated at each visit. Using baseline and. endpoint data, fluoxetine had a statisti cally significant, dose-dependent, suppressive effect on spontaneous panic attacks, as measured by the pre-post slopes in the three treatment groups. The placebo group showed some response (slope = 0.69). There were no signif icant drug effects on situational panic attacks. On ratings of agoraphobia, the slopes in the placebo and the fluoxetine 20 mg groups did not differ, but the slope in the fluoxetine 10 mg group was significantly less than tha t in the placebo group, suggesting a therapeutic drug effect on agoraphobia only at the lower dose. These results are consistent with the stated hypot heses. They suggest that the therapeutic effects of antidepressants on pani c disorder may be due primarily to the specific suppression of spontaneous panic attacks among patients with high baseline pathologic findings. Implic ations of these results for concepts of pathogenesis, clinical practice, an d therapeutic research regarding panic disorder are discussed.