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Alprazolam and Exposure Alone and Combined in Panic Disorder with Agoraphobia

A Controlled Study in London and Toronto

Published online by Cambridge University Press:  02 January 2018

Isaac M. Marks*
Institute of Psychiatry and Bethlem-Maudsley Hospital, London SE5 8AF
Richard P. Swinson
Toronto General Hospital and University of Toronto, Canada
Metin Başoǧlu
Institute of Psychiatry, London
Klaus Kuch
Toronto General Hospital and University of Toronto
Homa Noshirvani
Institute of Psychiatry, London
Geraldine O'Sullivan
Institute of Psychiatry, London
Paul T. Lelliott
Institute of Psychiatry, London
Marlene Kirby
Toronto General Hospital and University of Toronto
Gary McNamee
Institute of Psychiatry, London
Seda Sengun
Institute of Psychiatry, London
Kim Wickwire
Toronto General Hospital and University of Toronto


A cross-national randomised trial of alprazolam for chronic panic disorder with agoraphobia was run. Compared with previous trials it had three new features: an exposure therapy contrast group, a six-month treatment-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 patients had eight weeks of: alprazolam and exposure (combined treatment); or alprazolam and relaxation (a psychological placebo); or placebo and 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-panic measures, by the end of treatment, both alprazolam and exposure were effective, but exposure had twice the effect size of alprazolam. During taper and follow-up, gains after alprazolam were lost, while gains after exposure were maintained. Combining alprazolam with exposure marginally enhanced gains during treatment, but impaired improvement thereafter. The new features put previous trials in a fresh light. By the end of treatment, though gains on alprazolam were largely as in previous studies, on phobias and disability they were half those with exposure. Relapse was usual after alprazolam was stopped, whereas gains persisted to six-month follow-up after exposure ceased. Panic improved as much with placebo as with alprazolam or exposure.

Research Article
Copyright © The Royal College of Psychiatrists 

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