Discontinuation of Alprazolam After Successful Treatment of Panic Disorder: A Naturalistic Follow-up Study

Low rates of benzodiazepine discontinuation have been seen in longterm outcome studies of alprazolam-treated panic disorder. Discontinuation studies reveal high rates of relapse when alprazolam is stopped. Available data may lack relevance to clinical practice, however, because drug taper rates are often more rapid than those used in many clinical settings. In order to obtain naturalistic data on the longterm course of alprazolam treatment of panic, we obtained follow-up data on 18 of 20 patients who had been enrolled one to two years earlier in a study of alprazolam effects on hypothalamic-pituitary-adrenal (HPA) axis functioning. The HPA protocol provided measures of symptom severity, biological markers, and short-term treatment response (12 weeks). Routine clinical care was then provided, with dosage adjustments dictated by individual clinical needs. The follow-up study repeated clinical measures at a mean of 21 months after initiation of treatment. AIprazolam was discontinued in 78% of patients. Relapse occurred in 36% of these. At follow-up, 61% were medication-free. Only 28% were on a benzodiazepine. The four patients remaining on alprazokrm were on reduced doses and had maintained clinical gains. HPA axis activity did not predict dose or outcome. Factors related to successful alprazohun discontinuation are discussed. Alprazolam is now an approved treatment for panic disorder, but discontinuation difficulties raise concerns about the long-term course of alprazolamtreated patients. Complications of alprazolam discontinuation include the following: (a) relapse, which is the recurrence of the anxiety symptoms for which treatment was originally sought; (b) rebound, which is relapse in which symptom intensity exceeds pretreatment baselines; and (c) withdrawal, which is the occurrence of specific symptoms associated with benzodiazepine discontinuation that were not present prior to treatment (Pecknold et al., 1988). Discontinuation studies have demonstrated high rates of all three phenomena Patients described in this follow-up study entered treatment via a biological research protocol that was supported in part by a research grant from The Upjohn Company and in part by Clinical Research Center grant MOlRROOO42. We are indebted to Pamela B. Schweitzer, M.S., for the excellent clinical care she provided to many of the patients. Address correspondence to James L. Abelson, M.D., Ph.D., University of Michigan Medical Center/Box 0840, 1500 E. Medical Center Drive, Ann Arbor, MI 48109-0840.