Prior Benzodiazepine Exposure and Benzodiazepine Treatment Outcome

Background: We examined discontinuation symptomsfollowing brief benzodiazepine therapy (8 weeks) and intermittentbenzodiazepine therapy (2 weeks with at least 2 weeks withoutdrug) and associations with prior benzodiazepine use. Thehypothesis was that prior benzodiazepine use would predisposepatients to more severe discontinuation symptoms.

Method: Data were drawn from 3double-blind, randomized, placebo-controlled, published treatmenttrials: alprazolam for patients with premenstrual syndrome (PMS)and diazepam and lorazepam for patients with generalized anxietydisorder (GAD). The PMS group provided prospective daily symptomratings, which allowed ongoing investigation of effects of priortreatment. In the GAD groups, taper outcome was examined after 8weeks of benzodiazepine therapy as a function of priorbenzodiazepine use and as a function of time since last priorbenzodiazepine use. Symptom scores were analyzed using tstatistics in the PMS group and analysis of covariance with8-week scores as the covariate in the GAD groups.

Results: The PMS subjects reported no increasein symptom scores and no significant difference fromplacebo-treated subjects during taper and discontinuation ofalprazolam in the follicular phase of each treatment cycle. Inthe GAD trials, the results of treatment discontinuation did notdiffer significantly as a function of presence or absence ofprior benzodiazepine use or as a function of time since lastbenzodiazepine use.

Conclusion: These preliminary data failto support the hypothesis that prior benzodiazepine usepredisposes patients to more severe discontinuation symptoms whentreatment is brief and doses are low.