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Objective To compare cognitive-behavioral therapy (CBT), panic-focused psychodynamic psychotherapy (PFPP), and applied relaxation training (ART) for primary DSM-IV panic disorder with and without agoraphobia in a 2-site randomized controlled trial. Method 201 patients were stratified for site and DSM-IV agoraphobia and depression and were randomized to CBT, PFPP, or ART (19-24 sessions) over 12 weeks in a 2:2:1 ratio at Weill Cornell Medical College (New York, New York) and University of Pennsylvania ("Penn"; Philadelphia, Pennsylvania). Any medication was held constant. Results Attrition rates were ART, 41%; CBT, 25%; and PFPP, 22%. The most symptomatic patients were more likely to drop out of ART than CBT or PFPP (P = .013). Outcome analyses revealed site-by-treatment interactions in speed of Panic Disorder Severity Scale (PDSS) change over time (P = .013). At Cornell, no differences emerged on improvement on the primary outcome, estimated speed of change over time on the PDSS; at Penn, ART (P = .025) and CBT (P = .009) showed greater improvement at treatment termination than PFPP. A site-by-treatment interaction (P = .016) for a priori-defined response (40% PDSS reduction) showed significant differences at Cornell: ART 30%, CBT 65%, PFPP 71% (P = .007), but not at Penn: ART 63%, CBT 60%, PFPP 48% (P = .37). Penn patients were more symptomatic, differed demographically from Cornell patients, had a 7.2-fold greater likelihood of taking medication, and had a 28-fold greater likelihood of taking benzodiazepines. However, these differences did not explain site-by-treatment interactions. Conclusions All treatments substantially improved panic disorder with or without agoraphobia, but patients, particularly the most severely ill, found ART less acceptable. CBT showed the most consistent performance across sites; however, the results for PFPP showed the promise of psychodynamic psychotherapy for this disorder. Trial registration ClinicalTrials.gov identifier: NCT00353470.

Background: Little research has addressed moderators of treatment outcome for anxiety disorders, and none has considered interpersonal loss as a predictor of outcome. Purpose: To examine the effect of interpersonal loss events within the 6 weeks preceding panic disorder onset as a moderator of outcome in a randomized controlled trial of Panic-Focused Psychodynamic Therapy (PFPP) and Applied Relaxation Therapy (ART). Researchers hypothesized that such loss events would predict better outcome in PFPP but would not affect ART outcome. Method: Forty-nine subjects with panic disorder were randomly assigned to a 12-week course of PFPP or ART. Independent raters blinded to treatment condition and study hypotheses rated subjects on the Panic Disorder Severity Scale (PDSS) and Sheehan Disability Scale. Exploratory analyses assessed between-group effect size for PFPP and ART following standard moderator analytic procedures. The trial was conducted between February 2000 and January 2005. Results: Three quarters of subjects reported a narrowly defined interpersonal loss (LOSS) in the 6 weeks preceding panic disorder onset. These subjects had a mean (SD) duration of panic disorder of 8.2 (9.5) years. PFPP was more efficacious than ART, but LOSS did not moderate PFPP outcome. An unexpected finding was that LOSS moderated ART outcome: subjects without LOSS showed no response to ART (PDSS mean (SD) change score = 0.00 [2.90]), whereas LOSS had a pre-post mean (SD) change score of 4.29 (5.60). Neither examination of potential confounding variables nor sensitivity analyses of assumptions regarding attrition altered these findings. Conclusions: Interpersonal loss events preceding onset of panic disorder were more common even than in prior studies. These losses moderated outcome in ART, a therapy that does not focus on such losses. Implications and the need for future research before incorporating these findings into clinical practice are discussed. Trial Registration: clinicaltrials.gov Identifier: NCT00128388

OBJECTIVE The American Psychiatric Association (APA) practice guideline for panic disorder recommends psychodynamic psychotherapy for panic disorder patients with comorbid personality disorders. No data underlie this recommendation. This exploratory study assessed the moderating effect of personality disorder on psychodynamic and non-psychodynamic psychotherapy outcome. METHOD Forty-nine subjects with primary DSM-IV panic disorder were randomly assigned to 12 weeks of twice-weekly Panic-Focused Psychodynamic Psychotherapy or Applied Relaxation Training. The primary outcome measure was the Panic Disorder Severity Scale; the moderating effect of Axis II psychopathology on the Sheehan Disability Scale was also tested. The trial was conducted between February 2000 and January 2005. RESULTS Twenty-four subjects (49%) met DSM-IV criteria for a Structured Clinical Interview for DSM-IV Axis II Disorders-diagnosed personality disorder, of whom 19 (79%) had a cluster C diagnosis. Presence of a cluster C diagnosis moderated treatment outcome. Such subjects experienced greater improvements in Panic-Focused Psychodynamic Psychotherapy than subjects without cluster C comorbidity. CONCLUSIONS Despite its small sample size, this exploratory analysis provides initial preliminary evidence corroborating the APA practice guideline recommendation. Future panic disorder clinical trials should explore Axis II moderator effects. CLINICAL TRIALS REGISTRATION ClinicalTrials.gov identifier NCT00128388.