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Concept: Alprazolam

170

BACKGROUND: Social anxiety disorder (SAD) is one of the most common anxiety disorders and is associated with marked impairments. However, a small proportion of individuals with SAD seek and receive treatment. Internet-administrated cognitive behavior therapy (iCBT) has been found to be an effective treatment for SAD. This trial will be the first Internet-delivered guided self-help intervention for SAD in Romania. METHODS: Participants with social anxiety disorder (N = 96) will be recruited via newspapers, online banners and Facebook. Participants will be randomized to either: a) an active treatment, or b) a waiting list control group.The treatment will have a guided iCBT format and will last for nine weeks. Self-report questionnaires on social phobia, anxiety, depression, treatment credibility and irrational thinking will be used. All assessments will be collected pre, post and at follow-up (six months after intervention). Liebowitz Social Anxiety Scale – Self-Report version (LSAS-SR) will be the primary outcome measure and will be administrated on a weekly basis in both conditions. DISCUSSION: The present randomized controlled trial investigates the efficacy of an Internet-administered intervention in reducing social anxiety symptoms in a culture where this form of treatment has not been tested. This trial will add to the body of knowledge on the efficacy of iCBT, and the results might lead to an increase of the accessibility of evidence-based psychological treatment in Romania.Trial registrationClinicalTrials.gov: NCT01557894.

Concepts: Cognitive behavioral therapy, Anxiety disorder, Panic disorder, Alprazolam, Fear, Social anxiety, Anxiety disorders, Social anxiety disorder

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Cognitive theorists relate anxiety disorders to the way in which emotional information is processed. The existing research suggests that patients with anxiety disorders tend to allocate their attention toward threat-related information selectively, and this may differ among different types of anxious subjects. The aim of this study was to explore attentional bias in patients with generalized anxiety disorder (GAD) and panic disorder (PD) using the emotional Stroop task and compare the differences between them.

Concepts: Psychology, Anxiety disorder, Generalized anxiety disorder, Panic disorder, Alprazolam, Fear, Anxiety disorders, Social anxiety disorder

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Objectives To identify trends in concurrent use of a benzodiazepine and an opioid and to identify the impact of these trends on admissions to hospital and emergency room visits for opioid overdose.Design Retrospective analysis of claims data, 2001-13.Setting Administrative health claims database.Participants 315 428 privately insured people aged 18-64 who were continuously enrolled in a health plan with medical and pharmacy benefits during the study period and who also filled at least one prescription for an opioid.Interventions Concurrent benzodiazepine/opioid use, defined as an overlap of at least one day in the time periods covered by prescriptions for each drug. Main outcome measures Annual percentage of opioid users with concurrent benzodiazepine use; annual incidence of visits to emergency room and inpatient admissions for opioid overdose.Results 9% of opioid users also used a benzodiazepine in 2001, increasing to 17% in 2013 (80% relative increase). This increase was driven mainly by increases among intermittent, as opposed to chronic, opioid users. Compared with opioid users who did not use benzodiazepines, concurrent use of both drugs was associated with an increased risk of an emergency room visit or inpatient admission for opioid overdose (adjusted odds ratio 2.14, 95% confidence interval 2.05 to 2.24; P<0.001) among all opioid users. The adjusted odds ratio for an emergency room visit or inpatient admission for opioid overdose was 1.42 (1.33 to 1.51; P<0.001) for intermittent opioid users and 1.81 (1.67 to 1.96; P<0.001) chronic opioid users. If this association is causal, elimination of concurrent benzodiazepine/opioid use could reduce the risk of emergency room visits related to opioid use and inpatient admissions for opioid overdose by an estimated 15% (95% confidence interval 14 to 16).Conclusions From 2001 to 2013, concurrent benzodiazepine/opioid use sharply increased in a large sample of privately insured patients in the US and significantly contributed to the overall population risk of opioid overdose.

Concepts: Pharmacology, Odds ratio, Opioid, Morphine, Alprazolam, Benzodiazepine, Barbiturate, Benzodiazepine overdose

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During pregnancy, many women experience sleep problems and anxiety that require treatment. The long-term safety for the child of maternal benzodiazepine (BZD) and z-hypnotic use during pregnancy remains controversial.

Concepts: Childbirth, Breastfeeding, Alprazolam, Hypnotic, Insomnia

70

Studies have shown that area-level deprivation measured by factors, such as non-home ownership, non-car ownership and household overcrowding, can increase the risk for mental disorders over and above individual-level circumstances, such as education and social class. Whether area-level deprivation is associated with generalised anxiety disorder (GAD) independent of personal circumstances, and whether this association is different between British women and men is unknown.

Concepts: Sociology, Mental disorder, Generalized anxiety disorder, Panic disorder, Alprazolam, Anxiety disorders, Social anxiety disorder, Insomnia

47

Cannabidiol (CBD), a Cannabis sativa constituent, is a pharmacologically broad-spectrum drug that in recent years has drawn increasing interest as a treatment for a range of neuropsychiatric disorders. The purpose of the current review is to determine CBD’s potential as a treatment for anxiety-related disorders, by assessing evidence from preclinical, human experimental, clinical, and epidemiological studies. We found that existing preclinical evidence strongly supports CBD as a treatment for generalized anxiety disorder, panic disorder, social anxiety disorder, obsessive-compulsive disorder, and post-traumatic stress disorder when administered acutely; however, few studies have investigated chronic CBD dosing. Likewise, evidence from human studies supports an anxiolytic role of CBD, but is currently limited to acute dosing, also with few studies in clinical populations. Overall, current evidence indicates CBD has considerable potential as a treatment for multiple anxiety disorders, with need for further study of chronic and therapeutic effects in relevant clinical populations.

Concepts: Selective serotonin reuptake inhibitor, Cognitive behavioral therapy, Anxiety disorder, Generalized anxiety disorder, Panic disorder, Alprazolam, Anxiety disorders, Social anxiety disorder

31

Kappa opioid receptors (KORs) are involved in a variety of aversive behavioral states, including anxiety. To date, a circuit-based mechanism for KOR-driven anxiety has not been described. Here, we show that activation of KORs inhibits glutamate release from basolateral amygdala (BLA) inputs to the bed nucleus of the stria terminalis (BNST) and occludes the anxiolytic phenotype seen with optogenetic activation of BLA-BNST projections. In addition, deletion of KORs from amygdala neurons results in an anxiolytic phenotype. Furthermore, we identify a frequency-dependent, optically evoked local dynorphin-induced heterosynaptic plasticity of glutamate inputs in the BNST. We also find that there is cell type specificity to the KOR modulation of the BLA-BNST input with greater KOR-mediated inhibition of BLA dynorphin-expressing neurons. Collectively, these results provide support for a model in which local dynorphin release can inhibit an anxiolytic pathway, providing a discrete therapeutic target for the treatment of anxiety disorders.

Concepts: DNA, Cell, Enzyme inhibitor, Opioid receptor, Inhibitor, Anxiety disorder, Alprazolam, Kappa Opioid receptor

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Abstract Objective - Silexan is a lavender oil preparation in gelatine capsules containing 80 mg. We review clinical trials investigating the anxiolytic efficacy and tolerability of Silexan as well as its safety and potential for drug interactions. Methods - 7 trials were included. 4 therapeutic trials had a treatment duration of 6 or 10 weeks. Results - In patients with subsyndromal anxiety or generalised anxiety disorder (GAD) an anxiolytic effect of Silexan was evident after 2 weeks. Patients treated with Silexan showed Hamilton Anxiety Scale (HAMA) total score decreases by between 10.4 ? 7.1 and 12.0 ? 7.2 points at Week 6 and between 11.8 ? 7.7 and 16.0 ? 8.3 points at Week 10. HAMA total score reductions between baseline and end of treatment were significantly superior to placebo in patients with subsyndromal anxiety and comparable to lorazepam in its starting dose in patients with GAD. Conclusions - Silexan had beneficial effects on typical co-morbidity symptoms of anxiety disorders, e. g., disturbed sleep, somatic complaints, or decreased quality of life. Except for mild gastrointestinal symptoms the drug was devoid of adverse effects and did not cause drug interactions or withdrawal symptoms at daily doses of 80 or 160 mg.

Concepts: Pharmacology, Generalized anxiety disorder, Panic disorder, Alprazolam, Anxiety disorders, Social anxiety disorder, Insomnia, Anxiolytic

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Many patients with social anxiety disorder (SAD) experience inadequate symptom relief from available treatments. Ketamine is a potent N-methyl-D-aspartate (NMDA) receptor antagonist with a potentially novel mechanism of action for the treatment of anxiety disorders. Therefore, we conducted a double-blind, randomized, placebo-controlled crossover trial in 18 adults with DSM-5 SAD and compared the effects between intravenous ketamine (0.5 mg/kg over 40 min) and placebo (normal saline) on social phobia symptoms. Ketamine and placebo infusions were administered in a random order with a 28-day washout period between infusions. Ratings of anxiety were assessed 3-hours post-infusion and followed for 14 days. We used linear mixed models to assess the impact of ketamine and placebo on anxiety symptoms. Outcomes were blinded ratings on the Liebowitz Social Anxiety Scale (LSAS) and self-reported anxiety on a visual analog scale (VAS-Anxiety). We also used the Wilcoxon signed-rank test to compare the proportion of treatment responders. Based on prior studies, we defined response as a greater than 35% LSAS reduction and 50% VAS-Anxiety reduction. We found ketamine resulted in a significantly greater reduction in anxiety relative to placebo on the LSAS (Time*Treatment: F9,115=2.6, p=0.01) but not the VAS-Anxiety (Time*Treatment: F10,141=0.4, p=0.95). Participants were significantly more likely to exhibit a treatment response after ketamine infusion relative to placebo in the first two weeks following infusion measured on the LSAS (33.33% response ketamine vs 0% response placebo, Wilcoxon signed-rank test z=2.24, p=0.025) and VAS (88.89% response ketamine vs 52.94% response placebo, Wilcoxon signed-rank test z=2.12, p=0.034). In conclusion, this proof-of-concept trial provides initial evidence that ketamine may be effective in reducing anxiety. ClinicalTrials.gov Identifier: NCT02083926Neuropsychopharmacology accepted article preview online, 29 August 2017. doi:10.1038/npp.2017.194.

Concepts: Anxiety disorder, Panic disorder, Alprazolam, Fear, Social anxiety, Anxiety disorders, Social anxiety disorder, Agoraphobia

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We report the current best estimate of the effects of cognitive behavior therapy (CBT) in the treatment of major depression (MDD), generalized anxiety disorder (GAD), panic disorder (PAD) and social anxiety disorder (SAD), taking into account publication bias, the quality of trials, and the influence of waiting list control groups on the outcomes. In our meta-analyses, we included randomized trials comparing CBT with a control condition (waiting list, care-as-usual or pill placebo) in the acute treatment of MDD, GAD, PAD or SAD, diagnosed on the basis of a structured interview. We found that the overall effects in the 144 included trials (184 comparisons) for all four disorders were large, ranging from g=0.75 for MDD to g=0.80 for GAD, g=0.81 for PAD, and g=0.88 for SAD. Publication bias mostly affected the outcomes of CBT in GAD (adjusted g=0.59) and MDD (adjusted g=0.65), but not those in PAD and SAD. Only 17.4% of the included trials were considered to be high-quality, and this mostly affected the outcomes for PAD (g=0.61) and SAD (g=0.76). More than 80% of trials in anxiety disorders used waiting list control groups, and the few studies using other control groups pointed at much smaller effect sizes for CBT. We conclude that CBT is probably effective in the treatment of MDD, GAD, PAD and SAD; that the effects are large when the control condition is waiting list, but small to moderate when it is care-as-usual or pill placebo; and that, because of the small number of high-quality trials, these effects are still uncertain and should be considered with caution.

Concepts: Cognitive behavioral therapy, Anxiety disorder, Generalized anxiety disorder, Panic disorder, Alprazolam, Fear, Anxiety disorders, Social anxiety disorder