Abstract
A large proportion of 138 panic disorder patients entered into a 32-week double-blind trial of alprazolam (n = 78) versus placebo (n = 60) demonstrated early and progressive clinical improvement irrespective of treatment. Long-term therapeutic superiority of alprazolam over placebo was evident only on more global measures such as Clinician and Patient Global Impression scores and the greater placebo dropout rate over time. Plasma benzodiazepine levels indicated that the robust placebo response could not be accounted for by illicit use of benzodiazepines. Differentiation of patients by diagnostic subtype, primary panic disorder with minimal agoraphobia (n = 68), panic disorder and moderate to severe phobic avoidance (n = 42), and primary depression with secondary panic attacks (n = 28), revealed greater drug-placebo differences specifically for the agoraphobic group. Following a 4-week tapered discontinuation, drug-treated patients compared to placebo-treated patients demonstrated greater increases in generalized levels of anxiety relative to both the beginning and end of treatment. There were significantly higher rates of unauthorized benzodiazepine use among the drug-treated group versus placebo group at the completion of the 1-month tapered discontinuation period.