ALPRAZOLAM AND EXPOSURE ALONE AND COMBINED IN PANIC DISORDER WITH AGORAPHOBIA - A CONTROLLED-STUDY IN LONDON AND TORONTO

A cross-national randomised trial of alprazolam for chronic panic diso rder with agoraphobia was run. Compared with previous trials it had th ree new features: an exposure therapy contrast group, a six-month trea tment-free follow-up, and a low rate of early placebo drop-outs ('non- evaluables'). The dose of alprazolam was high (5 mg/day). The 154 pati ents had eight weeks of: alprazolam and exposure (combined treatment); or alprazolam and relaxation (a psychological placebo); or placebo an d exposure; or placebo and relaxation (double placebo). Drug taper was from weeks 8 to 16. Follow-up was to week 43. Results were similar at both sites. Treatment integrity was good. All four treatment groups, including double placebo, improved well on panic throughout. On non-pa nic measures, by the end of treatment, both alprazolam and exposure we re effective, but exposure had twice the effect size of alprazolam. Du ring taper and follow-up, gains after alprazolam were lost, while gain s after exposure were maintained. Combining alprazolam with exposure m arginally enhanced gains during treatment, but impaired improvement th ereafter. The new features put previous trials in a fresh light. By th e end of treatment, though gains on alprazolam were largely as in prev ious studies, on phobias and disability they were half those with expo sure. Relapse was usual after alprazolam was stopped, whereas gains pe rsisted to six-month follow-up after exposure ceased. Panic improved a s much with placebo as with alprazolam or exposure.