Is the Precipitation of Anxiety Symptoms Associated with Bolus Doses of Flumazenil a Barrier to Its Use at Low Continuous Doses in Benzodiazepine Withdrawal?

INTRODUCTION: Benzodiazepines (BZDs) are used in the management of anxiety and sleep disorders; however, chronic use is associated with tolerance and dependence. During withdrawal, symptoms of anxiety are often severe and problematic for patients and may lead to relapse or maintenance on low doses of BZDs. Low, continuous doses of flumazenil reduce BZD withdrawal symptoms in several studies; however, bolus doses are known to induce anxiety and precipitate panic. Accordingly, this study aimed to determine whether continuous low-dose flumazenil is anxiogenic like bolus doses. METHOD: In a randomised control cross over design, participants received a continuous low-dose flumazenil infusion for eight days at an approximate rate of 4 mg/24 h or placebo before crossing over to the alternate study arm. Participants were able to request diazepam as needed. The primary outcome was the change in state anxiety levels. Trait anxiety was also recorded at baseline and one month after the flumazenil/placebo infusion period. RESULTS: BZD use was significantly reduced in both groups. There were no significant differences between state anxiety and the 95% confidence interval showed no evidence of a clinically significant anxiogenic effect from low-dose flumazenil. Trait anxiety was significantly reduced one month after the infusion period. CONCLUSION: There is no evidence that continuous low-dose flumazenil infusion significantly increases state anxiety levels to a clinically significant level. Interestingly, flumazenil may decrease state anxiety during BZD withdrawal, unlike bolus doses of flumazenil. Flumazenil may have an anxiolytic effect on trait anxiety, which was evident one month after treatment.

Identifying and treating codeine dependence: a systematic review.

OBJECTIVES: Codeine dependence is a significant public health problem, motivating the recent rescheduling of codeine in Australia (1 February 2018). To provide information for informing clinical responses, we undertook a systematic review of what is known about identifying and treating codeine dependence. STUDY DESIGN: Articles published in English that described people who were codeine-dependent or a clinical approach to treating people who were codeine-dependent, without restriction on year of publication, were reviewed. Articles not including empirical data were excluded. One researcher screened each abstract; two researchers independently reviewed full text articles. Study quality was assessed, and data were extracted with standardised tools. DATA SOURCES: MEDLINE and EMBASE were searched for relevant publications on 22 November 2016. The reference lists of eligible studies were searched to identify further relevant publications. 2150 articles were initially identified, of which 41 were eligible for inclusion in our analysis. DATA SYNTHESIS: Studies consistently reported specific characteristics associated with codeine dependence, including mental health comorbidity and escalation of codeine use attributed to psychiatric problems. Case reports and series described codeine dependence masked by complications associated with overusing simple analgesics and delayed detection. Ten studies described the treatment of codeine dependence. Three reports identified a role for behavioural therapy; the efficacy of CYP inhibitors in a small open label trial was not confirmed in a randomised controlled trial; four case series/chart reviews described opioid agonist therapy and medicated inpatient withdrawal; two qualitative studies identified barriers related to perceptions of codeine-dependent people and treatment providers, and confirmed positive perceptions and treatment outcomes achieved with opioid agonist treatments. CONCLUSION: Strategies for identifying problematic codeine use are needed. Identifying codeine dependence in clinical settings is often delayed, contributing to serious morbidity. Commonly described approaches for managing codeine dependence include opioid taper, opioid agonist treatment, and psychological therapies. These approaches are consistent with published evidence for pharmaceutical opioid dependence treatment and with broader frameworks for treating opioid dependence. PROSPERO registration: CRD42016052129.

Psychiatry versus general physicians: who is better at differentiating epileptic from psychogenic non-epileptic seizures?

OBJECTIVE: To determine how accurately psychiatry and general medical doctors can differentiate epileptic and psychogenic non-epileptic seizures based on videotaped events (closest proxy to witnessed events). This study aims to establish how confidently this distinction can be made, the reasons why a particular diagnosis is reached, and inter-rater agreement. METHODS: 18 videos of patients demonstrating a heterogeneous mixture of epileptic and psychogenic non-epileptic seizures were collected and ordered in a random mix. These videos were shown to groups of general physicians, medical registrars and residents (n=19) as well as to psychiatrists and psychiatry registrars (n=8) who were provided with a questionnaire. RESULTS: A total of 27 doctors participated in the study. The overall percentage of correct diagnoses was 55.4%. There were no significant differences in correct diagnosis rates between psychiatry and general medical doctors. There was poor inter-rater agreement (Kappa = 0.159). Neither group was particularly confident in reaching a diagnosis, and diverse reasons underpinned the diagnoses given. CONCLUSION: Among the participants, merely observing an epileptic or non-epileptic event is insufficient to establish a definitive diagnosis. The results indicate poor diagnostic accuracy and agreement among psychiatry and general medical doctors. This may have important implications for both education and clinical practice.