Imipramine and buspirone in treatment of patients with generalized anxiety disorder 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 enrolled in a benzodiazepine discontinuation program that assessed the effectiveness of concomitant imipramine (180 mg/day) and buspirone (38 mg/day) compared to placebo in facilitating benzodiazepine discontinuation.


METHODS
After a benzodiazepine stabilization period taking either diazepam, lorazepam, or alprazolam, patients were treated for 4 weeks with imipramine, 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, buspirone, and placebo treatment being continued until 3 weeks into the posttaper phase, at which time all patients were switched to placebo for 2 weeks. Benzodiazepine plasma levels were assayed weekly. Benzodiazepine-free status was 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 effect remained highly significant even after the analysis adjusted for three other 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 facilitated significantly by co-prescribing imipramine before and during the benzodiazepine taper. Daily benzodiazepine dose, severity of baseline symptoms of anxiety and depression, and duration of benzodiazepine use were additional significant predictors of successful taper outcome.
Rickels
K
K
Department of Psychiatry, University of Pennsylvania, Philadelphia, USA. krickels@mail.med.upenn.edu
DeMartinis
N
N
García-España
F
F
Greenblatt
D J
DJ
Mandos
L A
LA
Rynn
M
M
D000328:Adult; D000368:Aged; D014151:Anti-Anxiety Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D000929:Antidepressive Agents, Tricyclic / Q000008:administration & dosage / Q000627:therapeutic use*; D001008:Anxiety Disorders / Q000188:drug therapy* / Q000523:psychology; D001569:Benzodiazepines / Q000008:administration & dosage* / Q000009:adverse effects* / Q000627:therapeutic use; D002065:Buspirone / Q000008:administration & dosage / Q000627:therapeutic use*; D003866:Depressive Disorder / Q000188:drug therapy / Q000523:psychology; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007099:Imipramine / Q000008:administration & dosage / Q000627:therapeutic use*; D008297:Male; D010919:Placebos; D013375:Substance Withdrawal Syndrome / Q000209:etiology*; D016896:Treatment Outcome
D014151:Anti-Anxiety Agents; D000929:Antidepressive Agents, Tricyclic; D010919:Placebos; D001569:Benzodiazepines; D007099:Imipramine; D002065:Buspirone