OUTCOME ASSESSMENT AND CLINICAL IMPROVEMENT IN PANIC DISORDER - EVIDENCE FROM A RANDOMIZED CONTROLLED TRIAL OF FLUOXETINE AND PLACEBO

Objective: Although panic attacks account for only a portion of the mo rbidity of panic disorder and panic attack frequency assessments are u nreliable, studies of drug efficacy in panic disorder have generally u sed reduction in panic attack frequency as the primary measure of impr ovement. The authors studied the efficacy of fluoxetine treatment in p anic disorder and measured the relative contributions of changes in sy mptoms to overall improvement. Method: Patients with a diagnosis of pa nic disorder (N=243) were randomly assigned to treatment with 10 or 20 mg/day of fluoxetine or placebo. Primary outcome measures were change in panic attack frequency and clinician-rated Clinical Global Impress ion improvement scores. Other assessments included a panic attack inve ntory, clinician-rated and patient-rated versions of the Panic and Pho bic Disorder Change Scale, a phobia rating scale, the Hamilton Anxiety Rating Scale, the 21-item Hamilton Depression Rating Scale, and the S heehan Disability Scale. Correlations were determined between outcomes in individual symptom domains and overall clinical outcome. Results: Fluoxetine, particularly the 20-mg/day dose, was associated with more improvement than was placebo in patients with panic disorder across mu ltiple symptom measures, including global improvement, total panic att ack frequency, phobic symptoms, and functional impairment. Global impr ovement was most highly correlated with reductions in overall anxiety and phobic symptoms and least correlated with reduction in panic attac ks. Fluoxetine treatment for panic disorder was well tolerated, with a safety profile consistent with that observed for fluoxetine in other disorders. Conclusions: These data provide support for the efficacy an d safety of fluoxetine treatment in reducing panic attacks, phobic sym ptoms, anxiety, and depressive symptoms in patients with panic disorde r. Reductions in panic attack frequency in subjects given either fluox etine or placebo were less closely related to overall clinical improve ment than reductions in phobic avoidance, anxiety, depressive symptoms , and functional impairment, suggesting that outcome measures in this disorder should be more broadly based.