Treatment of alprazolam withdrawal with chlordiazepoxide substitution and taper

We describe the first case series (n = 6) of using chlordiazepoxide to accomplish a rapid, well-tolerated withdrawal from alprazolam. After abruptly discontinuing alprazolam, we substituted a 50-mg dose of chlordiazepoxide for each 1 mg of alprazolam (except for one elderly patient where we substituted 25 mg) and gave additional chlordiazepoxide doses (25-50 mg every 4-6 hours) as needed for the first 1-2 days of hospitalization. With this approach, the mean "substitution ratio" of chlordiazepoxide to alprazolam was 86 to 1. We then tapered chlordiazepoxide by an average of 10% each day over a 7- to 14-day period according to the symptoms manifested and tolerated by individual patients. No seizures or other serious side effects occurred. Incomplete cross-dependence, as described elsewhere in the literature, was not observed. The rapidity and familiarity of the method are advantages for inpatient units, but careful titration of dosage, diagnostic clarity, and extended follow-ups are necessary when applying this approach.