Benzodiazepine side-effects: from the bench to the clinic.

This article introduces a special issue of Current Pharmaceutical Design focusing on the various side effects of benzodiazepine medications. We argue that an increased awareness of the risk of dependence, withdrawal symptoms upon discontinuation, and cognitive side effects of the benzodiazepines has likely contributed to the decline in their prescription rate over the last two decades, as has increased availability of alternative pharmacologic and non-pharmacologic treatments for anxiety and insomnia. The present special issue consists of series of five papers covering current issues in the area of benzodiazepine side effects. These reviews cover a wide range of topics pertaining to adverse, unintended consequences of this class of pharmacologic agents including their potential for tolerance and withdrawal, their profile of associated cognitive impairments, as well as current understanding of means for minimizing these unintended effects. The reviews also cover a variety of methodologies and disciplines from laboratory-based research findings with animals, to laboratory-based studies with healthy human volunteers, to findings obtained in the clinic with anxious patients. All reviews are timely contributions, covering highly relevant topics for consideration of benzodiazepine side effects at present. The papers presented herein should serve to stimulate future research that may ultimately help improve the quality of life of those patients living with debilitating anxiety-related conditions.

As-needed use of benzodiazepines in managing clinical anxiety: incidence and implications.

Benzodiazepines (BZs) have been widely investigated in terms of clinical efficacy, factors underlying dependence, associated cognitive impairments, and interactions with psychotherapy for anxiety control. However, few studies have systematically considered manner of BZ administration in relation to these variables. Studies of chronic BZ users indicate that as-needed or p.r.n. use is a very common practice, increases with chronicity of BZ use, and is preferred compared to regularly scheduled BZ administration. Moreover, a recent study of physician prescription practices indicated that p.r.n. BZ use is a commonly recommended BZ use regimen for anxiety disorder management. Physician advocates of p.r.n. BZ prescriptions for anxiety disorders cite enhanced patient control over symptoms, facilitation of exposure to fear-provoking situations, and reduced frequency of use as rationales supporting this practice. Available data however, do not consistently support these hypothesized advantages of p.r.n. BZ use. And in general, findings from different investigations relevant to this question suggest that p.r.n. BZ administration may be associated with increased patient preference for BZs over placebo, continued use, and greater impairment on cognitive factors associated with positive long-term anxiety management. Ironically, p.r.n. BZ administration may also be associated with reduced anxiolytic efficacy over time. These suggestive findings argue for greater systematic investigation of manner of BZ administration as an important medication use parameter. Such investigations may also yield practical guidelines for navigating BZ discontinuation and promoting more successful long-term management of anxiety.

Cognitive behavioural therapy and pharmacotherapy: complementary or contradictory approaches to the treatment of anxiety?

Considerable controversy exists regarding the practice of combining Cognitive Behavioural Therapy (CBT) with Pharmacotherapy (PT) in the management of anxiety. This paper considers whether these two forms of treating anxiety disorders can be effectively combined to enhance treatment outcome. Despite the theoretical appeal of a combined approach, a critical review of treatment outcome findings across CBT and various anxiolytic medications and their combination, suggests a failure of these treatments to operate in a complementary fashion. A detrimental impact of anxiolytic medication on CBT outcome is particularly salient for high potency benzodiazepines. Low potency benzodiazepines and antidepressants generally have a negligible impact with no clear evidence of treatment enhancement and some negative combined treatment effects on medication withdrawal and at long-term follow-up. Thus, we address potential mechanisms that may explain this treatment noncomplementarity and in some cases, treatment incompatibility. Cognitive factors influencing treatment outcome (catastrophic beliefs, self-efficacy, selective attention, and memory) are highlighted in view of the empirically supported mediating role of these variables in accounting for treatment responsiveness. Potential effects of anxiolytic medication on cognitive change in CBT are postulated. A number of suggestions for future research and clinical practice are proposed on the basis of this review.

Cognitive content specificity in selective attention across four domains of maladjustment.

This research provided a rigorous examination of content-specific selective attention effects across the maladjustment domains of depression, anxiety, bulimia, and Type A behaviour. Study 1 utilized a self-referent endorsement task to obtain a set of empirically validated stimulus adjectives related to each maladjustment domain for use in the attentional paradigm in Study 2. Moreover, Study 1 provided some initial support for content-specificity proposals at the self-schema level Self-descriptive ratings in Study 1 indicated that depressed individuals uniquely identified themselves with adjectives relating to hopelessness, loss and failure. In contrast, the unique self-descriptive adjectives of anxious individuals centered on themes of social threat. Bulimics, in turn, endorsed unique self-descriptors relating to food and weight issues, whereas Type A self-descriptions were uniquely associated with achievement concerns. Content-specificity effects for selective attention were obtained in Study 2 for three of the four domains of interest (i.e. depression anxiety, and bulimia). Using a modified probe detection task, and very stringent criteria for group classification, it was found that individuals in each of these three groups selectively attended to personal adjectives that were hypothesized to be of specific relevance to their underlying cognitive concerns. Limited content-specificity effects were obtained for an incidental recognition measure, with only the depressed and bulimic groups showing enhanced memory performance for personal adjectives uniquely related to their dominant self-views. These findings are discussed in terms of various content-specificity distinctions across the four domains of maladjustment, including possible implications for the expression of differential behaviours for each domain.