Some biochemical correlates of panic attacks with agoraphobia and their response to a new treatment

Thirty-two patients with chronic debilitating agoraphobia and panic attacks participated in a comparative study of the triazolobenzodiazepine alprazolam and the anti-inflammatory agent ibuprofen. After a 2-week placebo washout period, patients were randomly assigned to 8 weeks of treatment with alprazolam (2 to 6 mg/day) or ibuprofen (0.8 to 2.4 g/day). Medication was identically packaged and patients were blind to the treatment condition, but investigators were aware of which medication was dispensed. Alprazolam recipients (mean daily dose: 5.4 mg) improved markedly with respect to physician and patient global rating of disease severity, frequency and severity of panic attacks, and phobic anxiety target symptoms on the 90-Item Hopkins Symptom Check List. Ibuprofen recipients (mean daily dose: 2.13 g) experienced significantly less clinical improvement than patients on alprazolam. After 8 weeks of treatment, ibuprofen patients were crossed over to alprazolam, while the original alprazolam group continued on that drug. The daily dosage ceiling was increased to 10 mg. In the ensuing 4 weeks (mean daily alprazolam dose: 6.3 mg), all patients achieved comparably marked clinical improvement relative to baseline. Pretreatment plasma concentrations of platelet factor 4 and beta-thromboglobulin--two measures of platelet turnover and release--were significantly elevated in patients relative to normal controls. The elevated platelet factor 4 and beta-thromboglobulin normalized during treatment with both drugs. Alprazolam appears to produce rapid and specific clinical improvement in patients with severe agoraphobia and panic attacks and deserves further evaluation under double-blind conditions.