Effects of Additional Oxazepam in Long-Term Users of Oxazepam

Abstract

Although additional dosages of benzodiazepines in long-term users of benzodiazepines are common, it is unknown whether these additional dosages resort any effect. The effects of an additional 20-mg dosage oxazepam were assessed in a double-blind, balanced-order, crossover randomized study comparing 16 long-term users of oxazepam (patients) with 18 benzodiazepine-naive controls (controls). The effects of 10 and 30 mg oxazepam were assessed at pretest and 2.5 hours after drug administration on: (a) saccadic eye movements as proxy for the sedative effect, (b) acoustic startle response (ASR) as proxy for the anxiolytic effects, (c) memory, (d) reaction time tasks, and (e) subjective measurements. Dose-related effects were found in patients on the peak velocity of saccadic eye movement and on response probability, respectively peak amplitude of the ASR. Comparison with controls, however, suggests that in patients the sedative effects might be mixed up with suppression of sedative withdrawal symptoms, whereas patients were as sensitive as benzodiazepine-naive controls for the effects of an additional dosage on the ASR. Neither 10 nor 30 mg oxazepam challenge affected the reaction time tasks in patients, whereas controls show a dose-related impairment. The memory impairing effects, however, did not differ significantly between patients and controls. In contrast to controls, patients could not discriminate between a 10- and 30-mg dosage as assessed by visual analogue scales and the STAI-DY-1, which might indicate a placebo effect in the 10-mg challenge in patients. We conclude that additional dosages of oxazepam still exert pronounced effects after daily use for more than 10 years.

Long-Term Benzodiazepine Use and Salivary Cortisol

“…In related research on the therapeutic effects of BZDs, an increased dosage of BZDs was found to increase anxiolytic effects even after more than 10 years of daily use. 38 Along with the hypothesis of tolerance development to the cortisol-suppressing effects of long-term BZD use, there are several alternative explanations that may account for discrepancies in the findings. First, BZD users may have had enhanced HPA axis activity before the start of BZD treatment, which was subsequently normalized by long-term BZD treatment.…”

High dose benzodiazepines prolong reaction times in chronic users who have major depressive and/or anxiety disorders

“…Still, several studies did not find associations between BZD use and RT in chronic users [15,16]. Possibly, BZDs still affect RTs in chronic use, but study design issues led to a lack of significant group differences in these studies (small sample size [15,16], absence of adequate statistical transformations [15,16]).…”

“…The inconsistent results regarding chronic BZD use may be caused by the lack of correction for established confounders such as psychopathology [14,16], physical health [14,15] and antidepressant use [14]. Further, differences in sample selection (healthy subjects vs. subjects with psychopathology) may have led to the discrepancies.…”

“…Possibly, BZDs still affect RTs in chronic use, but study design issues led to a lack of significant group differences in these studies (small sample size [15,16], absence of adequate statistical transformations [15,16]). Alternatively, the lack of significant …”

“…Two studies did not report differential RTs among BZD users and non-users [15,16]. When an extra dose of 20 mg oxazepam was administered, RT increased in 18 BZD-naive participants, but not in 18 long term BZD users, suggesting that tolerance to the effects of BZDs on RT may have developed [16].…”