Prior benzodiazepine exposure and benzodiazepine treatment outcome.
BACKGROUND
We examined discontinuation symptoms following brief benzodiazepine therapy (8 weeks) and intermittent benzodiazepine therapy (2 weeks with at least 2 weeks without drug) and associations with prior benzodiazepine use. The hypothesis was that prior benzodiazepine use would predispose patients to more severe discontinuation symptoms.


METHODS
Data were drawn from 3 double-blind, randomized, placebo-controlled, published treatment trials: alprazolam for patients with premenstrual syndrome (PMS) and diazepam and lorazepam for patients with generalized anxiety disorder (GAD). The PMS group provided prospective daily symptom ratings, which allowed ongoing investigation of effects of prior treatment. In the GAD groups, taper outcome was examined after 8 weeks of benzodiazepine therapy as a function of prior benzodiazepine use and as a function of time since last prior benzodiazepine use. Symptom scores were analyzed using t statistics in the PMS group and analysis of covariance with 8-week scores as the covariate in the GAD groups.


RESULTS
The PMS subjects reported no increase in symptom scores and no significant difference from placebo-treated subjects during taper and discontinuation of alprazolam in the follicular phase of each treatment cycle. In the GAD trials, the results of treatment discontinuation did not differ significantly as a function of presence or absence of prior benzodiazepine use or as a function of time since last benzodiazepine use.


CONCLUSIONS
These preliminary data fail to support the hypothesis that prior benzodiazepine use predisposes patients to more severe discontinuation symptoms when treatment is brief and doses are low.
Rickels
K
K
Department of Psychiatry, University of Pennsylvania Medical Center, Philadelphia, USA.
Freeman
E W
EW
D000525:Alprazolam / Q000009:adverse effects / Q000627:therapeutic use; D001008:Anxiety Disorders / Q000188:drug therapy* / Q000523:psychology; D001569:Benzodiazepines / Q000009:adverse effects* / Q000627:therapeutic use*; D003975:Diazepam / Q000009:adverse effects / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D008499:Medical Records; D010919:Placebos; D011293:Premenstrual Syndrome / Q000188:drug therapy* / Q000523:psychology; D011446:Prospective Studies; D012720:Severity of Illness Index; D013375:Substance Withdrawal Syndrome / Q000175:diagnosis* / Q000453:epidemiology / Q000209:etiology*; D016896:Treatment Outcome
D010919:Placebos; D001569:Benzodiazepines; D003975:Diazepam; D000525:Alprazolam