The treatment approach involves short-term coadministration of the benzodiazepine alprazolam and the selective serotonin reuptake inhibitor (SSRI) sertraline, said lead author, Andrew Goddard, MD, director of outpatient psychiatry services, Indiana University Hospital, Indianapolis, Indiana, United States.

This combination, he said, is showing promise in alleviating severe symptoms and could be provided safely in both the inpatient and outpatient settings.

"It promotes rapid stabilization, yet because of the early tapering of benzodiazepine, does not commit patients to long-term benzodiazepine therapy," Goddard said.

He added that "attendant problems of physiological dependence and, occasionally, tolerance" associated with benzodiazepines have understandably deterred the use of alprazolam despite its effectiveness.

The combination approach, he said, involves tapering the benzodiazepine after 4 weeks, after patients have demonstrated early improvement.

In their ongoing randomised, double-blind, multicenter, prospective study, Dr. Goddard and colleagues are comparing the efficacy of sertraline in combination with either alprazolam or placebo. Patients in the two-drug arm receive flexible-dose sertraline for 12 weeks, with a target dose of 150 mg daily, in combination with 2 mg to 4 mg daily of extended-release alprazolam for 4 weeks. The tapering period is 3 weeks.

Patients are deemed to be treatment responders if they show a decrease of 50% or more on the Panic Disorder Severity Scale (PDSS).

The study is designed to enroll 150 patients and is based on an earlier single-institution study that found the combination treatment effective in acute panic disorder. The objective is to provide a definitive answer as to whether this combination provides long-term benefits.

The study's preliminary results are based on 22 patients enrolled so far, whose mean age is 42 years.

Dr. Goddard noted that some patients are experiencing early rapid improvement, presumably due to benzodiazepine co-administration, and that despite benzodiazepine withdrawal symptoms, retention rates have been good, suggesting that those symptoms are tolerable.

"Our hope is that the combination treatment approach will eventually be a valuable therapeutic tool in a variety of primary care and medical settings -- the ER, PCP's office and cardiology clinic, for example--where panic patients first present," he said.


[Presentation title: A Randomized, Double-Blind, Comparison of Sertraline with Early Alprazolam XR Co-Administration vs. Sertraline/placebo for Panic Disorder. Poster 151]

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