ABSTRACT
STUDY OBJECTIVES: Hypnotic medications can adversely affect behavior during unanticipated awakenings during the night. Animals treated with the hypocretin (Hcrt) receptor antagonist almorexant (ALM) have less acute cognitive impairment compared to the GABAA receptor modulator zolpidem (ZOL). This study aimed to determine whether ALM produces less acute cognitive impairment than ZOL in human subjects. METHODS: Healthy, young adult, unmedicated male and female subjects participated in a controlled trial of a single dose of ALM 100 mg (N = 48), ALM 200 mg (N = 53), ZOL 10 mg (N = 49), and placebo (PBO, N = 52). RESULTS: ZOL and both doses of ALM produced similar levels of subjective sleepiness and impaired the ability of subjects to remain awake in a dark, low-stimulus setting relative to PBO. For most cognitive measures, performance under ZOL was significantly worse than ALM or PBO. For tasks involving verbal memory or visual-motor coordination, ZOL impaired performance, whereas the two doses of ALM were no different than PBO. For tasks involving higher-order executive function, ZOL produced impairment in processing speed and inhibitory control, whereas the two doses of ALM were no different than PBO. Performance decrements for ALM were less than ZOL but greater than PBO for some reaction time measures. CONCLUSIONS: The data provide support for the hypothesis that Hcrt receptor antagonists produce less functional impairment than a benzodiazepine receptor agonist (BzRA). These observations are particularly relevant to patients treated with sedative-hypnotics who are at elevated risk for falls and other untoward events during the intended hours for sleep.
Subject(s)
Hypnotics and Sedatives , Pyridines , Acetamides , Animals , Cognition , Double-Blind Method , Female , Humans , Hypnotics and Sedatives/adverse effects , Isoquinolines , Male , Orexin Receptors , Orexins/pharmacology , Psychomotor Performance , Pyridines/adverse effects , Young Adult , Zolpidem/pharmacologyABSTRACT
CONTEXT: Virtual reality exposure therapy (VRET) is an extension of traditional exposure therapy and has been used to treat a variety of anxiety disorders. VRET utilizes a computer-generated virtual environment to present fear-relevant stimuli. Recent studies have evaluated the use of VRET for treatment of PTSD; however, a systematic evaluation of the methodological quality of these studies has yet to be conducted. OBJECTIVES: This review aims to (a) identify treatment outcome studies examining the use of VRET for the treatment of PTSD and (b) appraise the methodological quality of each study using the 2010 Consolidating Standards of Reporting Trials (CONSORT) Statement and its 2008 extension for nonpharmacologic interventions. METHODS: Two independent assessors conducted a database search (PsycINFO, Medline, CINAHL, Google Scholar) of studies published between January 1990 and June 2013 that reported outcome data comparing VRET with another type of treatment or a control condition. Next, a CONSORT quality appraisal of each study was completed. RESULTS: The search yielded nine unique studies. The CONSORT appraisal revealed that the methodological quality of studies examining VRET as a treatment for PTSD was variable. CONCLUSION: Although preliminary findings suggest some positive results for VRET as a form of exposure treatment for PTSD, additional research using well-specified randomization procedures, assessor blinding, and monitoring of treatment adherence is warranted. Movement toward greater standardization of treatment manuals, virtual environments, and equipment would further facilitate interpretation and consolidation of this literature.
