Imipramine and buspirone in treatment of patients with generalized anxietydisorder who are discontinuing long-term benzodiazepine therapy

Objective: Patients with generalized anxiety disorder (N=107) who had been long-term benzodiazepine users (average duration of use=8.5 years) were enr olled in a benzodiazepine discontinuation program that assessed the effecti veness of concomitant imipramine (180 mg/day) and buspirone (38 mg/day) com pared to placebo in facilitating benzodiazepine discontinuation. Method: After a benzodiazepine stabilization period taking either diazepam, lorazepam, or alprazolam, patients were treated for 4 weeks with imipramin e, buspirone, or placebo under double-blind conditions while benzodiazepine intake was kept stable (treatment phase). Patients then entered a 4-6 week benzodiazepine taper and a 5-week posttaper phase with imipramine, buspiro ne, and placebo treatment being continued until 3 weeks into the posttaper phase, at which time all patients were switched to placebo for 2 weeks. Ben zodiazepine plasma levels were assayed weekly. Benzodiazepine-free status w as assessed 3 and 12 months posttaper. Results: Study subjects were long-term benzodiazepine users with an average of three unsuccessful prior taper attempts. The success rate of the taper in this study was significantly higher for patients who received imipramine (82.6%), and nonsignificantly higher for patients who received buspirone ( 67.9%), than for patients who received placebo (37.5%). The imipramine effe ct remained highly significant even after the analysis adjusted for three o ther independent predictors of taper success: benzodiazepine dose, level of anxious symptoms at baseline, and duration of benzodiazepine therapy. Conclusions: Management of benzodiazepine discontinuation can be facilitate d significantly by co-prescribing imipramine before and during the benzodia zepine taper. Daily benzodiazepine dose, severity of baseline symptoms of a nxiety and depression, and duration of benzodiazepine use were additional s ignificant predictors of successful taper outcome.