Kava for the treatment of generalised anxiety disorder (K-GAD): study protocol for a randomised controlled trial Pharmacotherapy of anxiety. Investigation of the anxiolytic effects of xanthohumol, a component of humulus lupulus (Hops), in the male Sprague-Dawley rat. An investigation into the efficacy of Scutellaria lateriflora in healthy volunteers. The Sedative Effect of Non-Alcoholic Beer in Healthy Female Nurses Cannabidiol in Humans—The Quest for Therapeutic Targets The selective GABA reuptake inhibitor tiagabine for the treatment of generalized anxiety disorder: results of a placebo-controlled study. Efficacy of progesterone vaginal suppositories in alleviation of nervous symptoms in patients with premenstrual syndrome Efficacy of Agomelatine in Generalized Anxiety Disorder: A Randomized, Double-Blind, Placebo-Controlled Study The effect of modafinil on counter-regulatory and cognitive responses to hypoglycaemia Mindfulness-Based Stress Reduction for Older Adults With Stress Disorders and Neurocognitive Difficulties: A Randomized Controlled Trial. Heart Failure 2012 Virtual reality in the treatment of generalized anxiety disorders. Effects of music listening on adult patients' pre‐procedural state anxiety in hospital Effects of music listening on adult patients' pre-procedural state anxiety in hospital. A Review of Vilazodone, Serotonin, and Major Depressive Disorder Mirtazapine for chronic breathlessness? A review of mechanistic insights and therapeutic potential A systematic review of cognitive and behavioral treatments for individuals with psoriasis The role of captodiamine in the withdrawal from long-term benzodiazepine treatment Mind-Body Interventions, Psychological Stressors, and Quality of Life in Stroke Survivors: A Systematic Review A controlled trial of ondansetron, a 5-HT3 antagonist, in benzodiazepine discontinuation. A Randomized Dose-Ranging Study of Neuropeptide Y in Patients with Posttraumatic Stress Disorder Comparing group-based acceptance and commitment therapy (ACT) with enhanced usual care for adolescents with functional somatic syndromes: a study protocol for a randomised trial
Background Generalised anxiety disorder ( GAD ) is a chronic and pervasive condition that generates high levels of psychological stress , and it is difficult to treat in the long term . Current pharmacotherapeutic options for GAD are in some cases only modestly effective , and may elicit undesirable side effects . Through targeted actions on the gamma-aminobutyric acid ( GABA ) pathway , the South Pacific medicinal plant kava ( Piper methysticum ) is a non-addictive , non-hypnotic anxiolytic with the potential to treat GAD . The evidence for the efficacy of kava for treating anxiety has been affirmed through clinical trials and meta-analyses . Recent research has also served to lessen safety concerns regarding the use of kava due to hepatotoxic risk , which is reflected in a recent German court overturning the previous kava ban in that country ( which may in turn influence a reinstatement by the European Union ) . The aim of current research is to assess the efficacy of an ‘ aqueous noble cultivar rootstock extract ’ of kava in GAD in a larger longer term study . In addition , we plan to investigate the pharmacogenomic influence of GABA transporters on response , effects of kava on gene expression , and for the first time , the neurobiological correlates of treatment response via functional and metabolic imaging . Methods / Design This clinical trial is funded by the Australian National Health and Medical Research Council ( APP1063383 ) and co-funded by MediHerb ( Integria Healthcare ( Australia ) Pty . Ltd ) . The study is a phase III , multi-site , two-arm , 18-week , r and omised , double-blind , placebo-controlled study using an aqueous extract of noble kava cultivar ( st and ardised to 240 mg of kavalactones per day ) versus matching placebo in 210 currently anxious participants with diagnosed GAD who are non-medicated . The study takes place at two sites : the Centre for Human Psychopharmacology ( Swinburne University of Technology ) , Hawthorn , Melbourne , Australia ; and the Academic Discipline of Psychiatry ( The University of Queensl and ) based at the Royal Brisbane and Women ’s Hospital , Herston , Brisbane , Australia . Written informed consent will be obtained from each participant prior to commencement in the study . The primary outcome is the Structured Interview Guide for the Hamilton Anxiety Rating Scale ( SIGH-A ) . The secondary outcomes involve a range of scales that assess affective disorder symptoms and quality of life outcomes , in addition to the study of mediating biomarkers of response ( assessed via genomics and neuroimaging ) . Discussion If this study demonstrates positive findings in support of the superiority of kava over placebo in the treatment of GAD , and also is shown to be safe , then this plant-medicine can be considered a ’ first-line ‘ therapy for GAD . Genomic and neuroimaging data may reveal clinical response patterns and provide more evidence of the neurobiological activity of the plant extract . Trial Registration Information Clinical Trials.gov : NCT02219880 Date : 13 August 2014 The pharmacological treatment of anxiety has a long and chequered history , and recent years have seen a rich development in the options available to prescribers . Most of the currently used anxiolytic agents act via monoaminergic ( chiefly serotonin ) or amino acid ( GABA or glutamate ) neurotransmitters , and this chapter describes the pharmacology of the major drug groups . Clinical applications are discussed with respect to the five major anxiety disorders , as well as simple phobia and depression with concomitant anxiety . Prospect i ve future developments in the field are considered The purpose of this study was to investigate the anxiolytic effects of xanthohumol , a component of Humulus lupulus ( hops ) , and its potential interaction with the benzodiazepine binding site on the y-aminobutyric acid ( GABAA ) receptor in the male Sprague-Dawley rat . This was a prospect i ve , r and omized , between-subjects experimental study . Fifty-five rats were assigned to 1 Sof 5 groups with 11 rats per group : control ( vehicle ) , xanthohumol , midazolam , midazolam with xanthohumol , and flumazenil with xanthohumol . In this study the elevated plus maze measured the behavioral components of anxiety and motor movements . A 2-tailed multivariate analysis of variance and least significant difference post hoc test was used to determine if a significant difference existed . Our data suggest that xanthohumol does not produce anxiolysis by modulation of the GABAA receptor ; however , there may be a possible interaction between xanthohumol and midazolam , or xanthohumol may influence the modulation of another neurotransmitter site in the central nervous system . Alone , xanthohumol does not show significant modulation of the benzodiazepine receptor . Additional research should investigate if xanthohumol acts as a benzodiazepine GABAA partial agonist or antagonist or if it modulates another neurotransmitter system in the central nervous system Scutellaria lateriflora is an herbal medicine with long-st and ing traditional use as a relaxing nervine . There has been controversy in the literature with regards to its efficacy , and this study was design ed to clarify its effectiveness in reducing anxiety , one of the phytotherapeutic indications . A double blind , placebo-controlled study of healthy subjects demonstrated noteworthy anxiolytic effects . The use of phytomedicines for the treatment of anxiety is review ed , as is the published literature on S. lateriflora and its putative toxicity Introduction The hop ( Humulus lupulus L. ) , a component of beer , is a sedative plant whose pharmacological activity is principally due to its bitter resins , in particular to the α-acid degradation product 2-methyl-3-buten-2-ol . The mechanism of action of hop resin consists of raising the levels of the neurotransmitter γ-aminobutyric acid ( GABA ) , an inhibitory neurotransmitter acting in the central nervous system ( CNS ) . Objectives To analyze the sedative effect of hops as a component of non-alcoholic beer on the sleep/wake rhythm in a work-stressed population . Methods The experiment was conducted with healthy female nurses ( n = 17 ) working rotating and /or night shifts .  Overnight sleep and chronobiological parameters were assessed by actigraphy ( Actiwatch ® ) after moderate ingestion of non-alcoholic beer containing hops ( 333 ml with 0,0 % alcohol ) with supper for 14 days ( treatment ) . Data were obtained in comparison with her own control group without consumption of beer during supper . Results Actigraphy results demonstrated improvement of night sleep quality as regards the most important parameters : Sleep Latency diminished ( p≤0.05 ) in the Treatment group ( 12.01±1.19 min ) when compared to the Control group ( 20.50±4.21 min ) , as also did Total Activity ( p≤0.05 ; Treatment group = 5284.78±836.99 activity pulses vs Control = 7258.78±898.89 activity pulses ) . In addition , anxiety as indexed by the State-Trait Anxiety Inventory ( STAI ) decreased in the Treatment group ( State Anxiety 18.09±3.8 vs Control 20.69±2.14 ) . Conclusion The moderate consumption of non-alcoholic beer will favour night-time rest , due in particular to its hop components , in addition to its other confirmed benefits for the organism Cannabidiol ( CBD ) , a major phytocannabinoid constituent of cannabis , is attracting growing attention in medicine for its anxiolytic , antipsychotic , antiemetic and anti-inflammatory properties . However , up to this point , a comprehensive literature review of the effects of CBD in humans is lacking . The aim of the present systematic review is to examine the r and omized and crossover studies that administered CBD  to healthy controls and to clinical patients . A systematic search was performed in the electronic data bases PubMed and EMBASE using the key word “ cannabidiol ” . Both monotherapy and combination studies ( e.g. , CBD + ∆9-THC ) were included . A total of 34 studies were identified : 16 of these were experimental studies , conducted in healthy subjects , and 18 were conducted in clinical population s , including multiple sclerosis ( six studies ) , schizophrenia and bipolar mania ( four studies ) , social anxiety disorder ( two studies ) , neuropathic and cancer pain ( two studies ) , cancer anorexia ( one study ) , Huntington ’s disease ( one study ) , insomnia ( one study ) , and epilepsy ( one study ) . Experimental studies indicate that a high-dose of inhaled/intravenous CBD is required to inhibit the effects of a lower dose of ∆9-THC . Moreover , some experimental and clinical studies suggest that oral/oromucosal CBD may prolong and /or intensify ∆9-THC-induced effects , whereas others suggest that it may inhibit ∆9-THC-induced effects . Finally , preliminary clinical trials suggest that high-dose oral CBD ( 150–600 mg/d ) may exert a therapeutic effect for social anxiety disorder , insomnia and epilepsy , but also that it may cause mental sedation . Potential pharmacokinetic and pharmacodynamic explanations for these results are discussed OBJECTIVE To evaluate the efficacy and tolerability of tiagabine , a selective gamma-aminobutyric acid ( GABA ) reuptake inhibitor , in adults with generalized anxiety disorder ( GAD ) . METHOD This 8-week , r and omized , double-blind , multicenter , placebo-controlled study enrolled patients with GAD ( DSM-IV ) .  Tiagabine was initiated at 4 mg/day and then flexibly dosed twice a day to a maximum dose of 16 mg/day . Study drug was tapered after week 8 in decrements of 2 mg every other day . Efficacy assessment s included the Hamilton Rating Scale for Anxiety ( HAM-A ) and Sheehan Disability Scale . Adverse events , sexual functioning , and change in depressive symptoms were monitored . Data were collected from May 2003 to January 2004 . RESULTS A total of 266 patients ( tiagabine , N = 134 ; placebo , N = 132 ) were included in safety analyses ; 260 patients ( tiagabine N = 130 ; placebo N = 130 ) were included in efficacy analyses . Tiagabine reduced symptoms of GAD according to the observed case and mixed models repeated- measures ( MMRM ) analyses but not the primary last-observation-carried-forward ( LOCF ) analysis . At final visit , the reduction from baseline in mean HAM-A total score was 11.8 for tiagabine , compared with 10.2 for placebo ( LOCF analysis , p = .27 ) . In a post hoc MMRM analysis , a significant difference in the mean reduction in HAM-A total score over the efficacy evaluation period was found , favoring tiagabine over placebo ( p < .01 ) . Tiagabine had an early onset of effect , as shown by significant reduction from baseline in mean HAM-A total score compared with placebo at week 1 ( observed cases , p < .05 ) . Tiagabine was generally well tolerated and not associated with changes in sexual functioning or depressive status . Symptoms of a discontinuation syndrome during taper were not observed . CONCLUSION The primary LOCF analysis was negative ; however , results from the observed case and MMRM analyses suggest that tiagabine may be a useful treatment option for adult patients diagnosed with GAD . These findings warrant further evaluation in r and omized clinical studies Purpose To further investigate the efficacy of progesterone in the treatment of the symptoms of premenstrual syndrome ( PMS ) .  Material s and Methods From an initial cohort of 25 subjects diagnosed with moderate to severe PMS , 17 reproductive age females completed the 7-month , doubleblind , placebo controlled trial using 200-mg vaginal progestone suppositories . Multiple modalities for evaluating symptoms were employed , including the Spielberger self-evaluation rating , the Beck depression inventory , and the Hamilton anxiety scale . In addition , each subject was interviewed by a psychiatrist on a monthly basis ; ovulation was determined monthly using a basal body temperature chart ; serum hormonal assays included beta endorphin , progesterone , follicle stimulating hormone , luteinizing hormone , estradiol , and prolactin . Results Hormonal assays confirmed no differences between treatment and control groups . Overall scores on all test vehicles were likewise not significantly different between the two groups ; however , in the subcategory of nervous symptoms , a significant improvement was found in symptoms relating to tension , mood swings , irritability , anxiety and lack of control . Conclusions Metabolites of progesterone ( pregnanolone and allopregnanolone ) may play a physiologic role as anxiolytic agents , perhaps modifying mood and anxiety ; the current study confirms the utility of twice daily , 200-mg progesterone vaginal suppositories , in the alleviation of some PMS symptoms relating to anxiety and irritability . Further evaluation may be warranted to ascertain which patients in the known heterogeneous PMS population may be most likely to benefit from such treatment Background : Agomelatine is a novel agent that acts on melatonergic ( MT1 , MT2 ) receptors and serotonergic ( 5-HT2C ) receptors . Pre clinical data and data from clinical trials in major depression suggest that agomelatine may have anxiolytic properties . A r and omized , double-blind , placebo-controlled trial was design ed to assess the efficacy of agomelatine in generalized anxiety disorder ( GAD ) . Methods : One hundred twenty-one patients with Diagnostic and Statistical Manual of Mental Disorders , Fourth Edition GAD and no comorbid disorders were r and omized to agomelatine ( 25 - 50 mg/d ) or placebo for 12 weeks . The primary outcome measure was the Hamilton Anxiety Rating Scale , whereas secondary outcome measures included the Clinical Global Impression scales , the Leeds Sleep Evaluation Question naire , and the Sheehan Disability Scale . Safety measures included assessment of spontaneously reported adverse events , laboratory monitoring , and the Discontinuation Emergent Signs and Symptoms Scale to evaluate discontinuation symptoms . Results : Analysis of covariance of change in the last Hamilton Anxiety Rating Scale total score from baseline demonstrated significant superiority of agomelatine 25 to 50 mg as compared with placebo ( E [ SE ] = −3.28 [ 1.58 ] ; 95 % confidence interval = −6.41 to −0.15 ; P = 0.040 ) . Data on secondary outcome measures , including clinical response , symptoms of insomnia , and improvement in associated disability , were consistent with the efficacy of agomelatine . Safety analysis indicated that agomelatine was tolerated as well as placebo and was devoid of discontinuation emergent symptoms . Conclusions : This study suggests that agomelatine is effective in the treatment of GAD and is well tolerated . Additional trials , using an active comparator and extending over a longer period , are needed to delineate the place of agomelatine in the contemporary pharmacotherapy for anxiety disorders Aims /hypothesisOur hypothesis is that reducing release of the inhibitory neurotransmitter gamma-aminobutyric acid ( GABA ) with modafinil will enhance symptomatic and hormonal responses to hypoglycaemia . Methods Nine healthy men received , in r and om order , two 100-mg doses of modafinil or placebo , followed by an insulin clamp in which plasma glucose was either reduced stepwise to 2.4 mmol/l or was sustained at euglycaemia ( four studies ) . Catecholamines , symptom scores and cognitive function were measured . Results Modafinil had no effect on the measured parameters during euglycaemia . During hypoglycaemia , autonomic symptom scores were significantly higher with modafinil ( increase at lowest plasma glucose concentration 271.3±118.9 vs 211.2±80.4/40 min , p=0.019 ) , and the heart rate response was increased ( 12,928±184 vs 6773±148 bpm/140 min , p=0.016 ) . Deterioration in performance of two cognitive tasks was reduced : Stroop colour – word test ( 613±204 vs 2375±161/65 min , p=0.009 ) and accuracy of a simple reaction task ( 11.3±1.8 vs 9.4±3.7 , p=0.039 ) . Conclusions /interpretationWe conclude that modafinil improves adrenergic sensitivity and some aspects of cognitive function at hypoglycaemia , possibly by reducing neuronal central GABA concentrations OBJECTIVE To determine whether neurocognitive performance and clinical outcomes can be enhanced by a mindfulness intervention in older adults with stress disorders and cognitive complaints . To explore decreased hypothalamic-pituitary-adrenal ( HPA ) axis activity as a possible mechanism . METHODS 103 adults aged 65 years or older with an anxiety or depressive disorder ( diagnosed according to DSM-IV criteria ) and subjective neurocognitive difficulties were recruited in St. Louis , Missouri , or San Diego , California , from September 2012 through August 2013 and r and omly assigned in groups of 5 - 8 to  mindfulness-based stress reduction ( MBSR ) or a health education control condition matched for time , attention , and credibility . The primary outcomes were memory ( assessed by immediate and delayed paragraph and list recall ) and cognitive control ( Delis-Kaplan Executive Function System Verbal Fluency Test and Color Word Interference Test ) . Other outcomes included clinical symptoms ( worry , depression , anxiety , and global improvement ) . HPA axis activity was assessed using peak salivary cortisol . Outcomes were measured immediately post-intervention and ( for clinical outcomes only ) at 3- and 6-month follow up . RESULTS On the basis of intent-to-treat principles using data from all 103 participants , the mindfulness group experienced greater improvement on a memory composite score ( P = .046 ) . Groups did not differ on change in cognitive control . Participants receiving MBSR also improved more on measures of worry ( P = .042 ) and depression ( P = .049 ) at posttreatment and on worry ( P = .02 ) , depression ( P = .002 ) , and anxiety ( P = .002 ) at follow-up and were more likely to be rated as much or very much improved as rated by the Clinical Global Impressions-Improvement scale ( 47 % vs 27 % , χ² = 4.5 , P = .03 ) . Cortisol level decreased to a greater extent in the mindfulness group , but only among those participants with high baseline cortisol . CONCLUSIONS In this population of older adults with stress disorders and neurocognitive difficulties , a mindfulness intervention improves clinical outcomes such as excessive worry and depression and may include some forms of immediate memory performance . TRIAL REGISTRATION Clinical Trials.gov identifier : NCT01693874 Heart failure has been named “ the growing epidemic . ” Over the last decade , the annual number of heart failure hospitalizations has almost doubled with approximately 50 % of patients being rehospitalized within 6 months of discharge [ 1 ] . The complex array of physiologic , psychological , social , and health care delivery issues makes it a challenging chronic disease to manage . Underst and ing the epidemiology and pathophysiology of the syndrome , identifying the predictors and their strength of association with outcomes , and using the available diagnostic modalities cost-effectively are essential in order to devise effective prevention interventions and implement novel therapeutic approaches to curb this epidemic . In this special issue , we have invited a few papers that address such issues and explain why despite the emergence of novel therapeutic approaches , that promise life prolongation and hospital length reduction , this patient population will still be needing rehospitalization and will often have a poor prognosis . This special issue is the extension of an effort that was initiated in 2011 with the first heart-failure-focused issue [ 2 ] . In the pathophysiology section , S. M. R. Kazemi-Bajestani et al. describe the opportunities and challenges of targeting the angiotensin converting enzyme 2 (ACE2)/Ang II/Ang1–7 and apelin/APJ pathways as novel therapeutic modalities in heart failure [ 3 ] . ACE2 and the apelin/APJ are two important peptide systems which exert diverse effects on the cardiovascular system . Dysregulation of such systems may be involved in the predisposition to cardiovascular diseases whereas enhancing their action may have important therapeutic effects . In the same section , D. Lindner et al. provide a comprehensive review on the protective function of signal transducer and activator of transcription 3 ( STAT3 ) in CVB3-induced myocarditis [ 4 ] . The transcription factor ( STAT3 ) is an important mediator of the inflammatory process , and in this original research the investigators examine the role of STAT3 in viral myocarditis and its possible role in the development to dilated cardiomyopathy . Considering the high mortality rate and the availability of life-saving therapies like transplantation and left ventricular assist devices , accurate prognosis determination in HF is clinical ly important . Taking into account the mediocre performance of current established prediction models , such as the Seattle Heart Failure Model [ 5–7 ] , the work by H. Fukuta et al. [ 8 ] on the prognostic value of left ventricular diastolic dysfunction in patients undergoing cardiac catheterization for coronary artery disease sheds light on this extremely important topic . A shared underst and ing of medical conditions between patients and their health care providers has been shown to improve self-care and outcomes [ 9 ] . In the comorbidity section , we demonstrate how certain comorbid conditions may affect patients ' decision-making capacity and interfere with their ability to comply with treatment requirements , recognize and self-manage disease worsening symptoms . Among others , cognitive impairment is increasingly recognized as a common adverse consequence of HF , whereby phenomena such as microembolism , chronic or intermittent cerebral hypoperfusion , and /or impaired cerebral vessel reactivity may lead to cerebral hypoxia and ischemic brain damage . Cognitive decline in HF is characterized by deficits in one or more cognition domains , including attention , memory , executive function , and psychomotor speed . E. Dardiotis et al. [ 10 ] , in a comprehensive review , underscore the importance for healthcare professionals to become familiar with assessment of cognitive performance using st and ardized screening instruments in their routine evaluations of HF patients . Another comorbidity gaining increasing attention in HF patients is depression . There are several pathophysiological mechanisms as well as behavioral processes linking depression and HF . Equally important is screening for depression and there are several valid and reliable screening tools to identify patients at greater risk . Consultation should be provided by a multidisciplinary team , consisting of cardiologists , psychiatrists , and hospital or community nurses so as to carefully plan , execute , and evaluate medical intervention and implement lifestyle changes . D. Mastrogiannis et al. [ 11 ] systematic ally review the existing knowledge regarding current definitions , prognostic implication s , pathophysiological mechanisms , and current and future treatment options in patients with depression and HF . Evidence from the literature supports the possibility of a pathophysiological relationship between cognitive impairment , depression , and HF . Yet , very few studies have sought to investigate this relationship . The paper by Z. N. Sohani and Z. Samaan review s current literature on the association between depression and cognitive impairment  in persons with HF and explores possible mechanisms explaining this complex triad [ 12 ] . Heart failure through neurohumoral activation induces alterations of cardiac metabolism , such as insulin resistance , and promotes increased utilization of noncarbohydrate substrates for energy production [ 13 , 14 ] . Fasting blood ketone bodies as well as fat oxidation have been shown to be increased in this patient population . The result is depletion of myocardial ATP , phosphocreatine , and creatine kinase , leading to decreased efficiency of mechanical work . A direct approach to manipulate cardiac energy metabolism consists in modifying substrate utilization by the failing heart . Trimetazidine , perhexiline , and ranolazine directly inhibit fatty acid oxidation and have been used to increase the ischemic threshold in patients with effort angina . Current research is supporting the concept that shifting the energy substrate preference away from fatty acid metabolism and toward glucose metabolism could be an effective adjunctive treatment in patients with HF . These agents have been shown to improve both glucose metabolism and left ventricular function in diabetic patients with left ventricular dysfunction . In the pharmacotherapy section , we provide a systematic review , in which N. Signoretta et al. [ 15 ] discuss the beneficial therapeutic effects of modulation of cardiac metabolic substrates utilization in patients with HF . In the advanced heart failure section , we provide a thorough review on the current status of mechanical circulatory support in patients with advanced HF . Management of the advanced HF patients with the numerous comorbidities [ 16 , 17 ] requires a significant amount of health care re sources and is becoming a major public health problem . As therapeutical strategies for HF have been refined , the number of patients suffering from the end-stage disease has exp and ed dramatically . Although heart transplantation still represents the gold st and ard therapeutical approach , the shortage of donors universally has made the implantation of mechanical circulatory support devices a well-established management for this disease . The systematic review by K. Spiliopoulos et al. [ 18 ] , outlines the current status of mechanical circulatory support in this patient population . In the chronic follow-up section , we deal with telemonitoring , a novel diagnostic modality that has been suggested to be beneficial for HF patients , targeting optimization of their chronic followup . Telemonitoring is viewed as a means of recording physiological data ( such as body weight , heart rate , arterial blood pressure electrocardiogram recordings , and other data ) by portable devices and transmitting these data remotely ( via a telephone line , a mobile phone , or a computer ) to a server where they can be stored , review ed , and analyzed by the research team . In a systematic review of all r and omized clinical trials evaluating telemonitoring in chronic HF , G. Giamouzis et al. [ 19 ] assess whether telemonitoring provides any substantial benefit in this patient population . We hope that the readers of the journal will find the topics as interesting and important as we did . Gregory Giamouzis George Giannakoulas Javed Butler John A. Elefteriades Carsten Tschope Filippos Generalized anxiety disorder ( GAD ) is a common anxiety disorder characterized by 6 months of " excessive anxiety and worry " about a variety of events and situations . Anxiety and worry are often accompanied by additional symptoms like restlessness , being easily fatigued , difficulty concentrating , irritability , muscle tension and disturbed sleep . GAD is usually treated with medications and /or psychotherapy . In particular , the two most promising treatments seem to be cognitive therapy and applied relaxation . In this study we integrated these approaches through the use of a biofeedback enhanced virtual reality ( VR ) system used both for relaxation and controlled exposure . Moreover , this experience is strengthened by the use of a mobile phone that allows patients to perform the virtual experience even in an outpatient setting . This paper describe the results of a controlled trial ( NCT00602212 ) involving 20 GAD patients r and omly assigned to the following groups :  ( 1 ) the VR and Mobile group ( VRMB ) including biofeedback ; ( 2 ) the VR and Mobile group ( VRM ) without biofeedback ; ( 3 ) the waiting list ( WL ) group . The clinical data underlined that ( a ) VR can be used also in the treatment of GAD ; ( b ) in a VR treatment , patients take advantage of a mobile device that delivers in an outpatient setting guided experiences , similar to the one experienced in VR Background Anticipation of an invasive procedure in hospital is likely to provoke feelings of anxiety and stress in patients . An unfamiliar environment , loss of control , perceived or actual physical risk , dependence on strangers and separation from friends and family are all factors that can contribute to the development of such feelings . Recently , there has been considerable interest in the anxiolytic potential of music listening in a variety of clinical setting s , yet thus far , little is known about the impact of music listening on the pre‐procedural patient population . A systematic review of all literature to date was indicated to improve underst and ing of outcomes and impact of music listening on pre‐procedural anxiety , thus helping nurses decide whether or not to incorporate music listening into practice and to highlight a need , or otherwise , for a related primary research agenda . Objective The objective of this review was to determine the best available evidence on the effectiveness of music listening in reducing adult hospital patients ' pre‐procedural state anxiety . Inclusion criteria Types of studies This review included r and omised controlled trials and quasi‐experimental research design s that examined the efficacy of music listening in reducing state anxiety among pre‐procedural hospital patients published between January 1985 and February 2006 . The search was limited to publications after 1985 to coincide with the increasing interest and use of complementary therapies within health care during the 1980s and 1990s . Types of participants Participants of interest to the review were adult day patients , ambulatory patients and in patients who were about to undergo any type of clinical procedure . Types of intervention The review focused on studies that investigated pre‐procedural music listening employed and prescribed as a potentially therapeutic activity . It excluded any other form of music therapy . Types of outcome measures The primary outcome measures examined were alterations in state anxiety and a variety of physiological variables such as blood pressure and respiration and heart rates . Search strategy A search for published and unpublished literature between January 1985 and February 2006 was conducted using all major electronic data bases . A three‐step search strategy was devised which consisted of using high‐precision MeSH terminology and keywords to ensure that all material relevant to the review was captured . Critical appraisal The method ological quality of included studies was assessed by two review ers , who appraised each study independently , using the st and ard Joanna Briggs Institute ( JBI ) critical appraisal tools . Data extraction and synthesis Data were extracted from the studies that were identified as meeting the criteria for method ological quality using a data ‐ extraction tool developed for the review . Studies were grouped by outcome measure and summarised using tabular and narrative formats . Results The review demonstrated that state anxiety is defined and measured using both psychological and physiological parameters . Music listening had a consistently positive and statistically significant effect on reducing psychological parameters of pre‐ procedural state anxiety . However , the results from the measurement of various pre‐ procedural physiological parameters failed to reveal any consistent positive changes in patients who had listened to music . This calls into question the adequacy of the theories in this area which link anxiety and the automated and central nervous systems and the effect that music listening may have on these processes and physiological responses . Conclusions / implication s for practice In order to reduce anxiety , it is likely that patients will benefit psychologically from having the opportunity to listen to music in the immediate pre‐procedural period . Patients do not appear to experience any alteration in physiological status as a result of listening to music . Further research is indicated in order to replicate existing studies , to strengthen the evidence to support such interventions and to establish intervention parameters . Further research is needed analysing the physiological mechanisms by which music listening is believed to reduce state anxiety and the contribution of the automated and other nervous systems to this reduction UNLABELLED EXECUTIVE SUMMARY : BACKGROUND Anticipation of an invasive procedure in hospital is likely to provoke feelings of anxiety and stress in patients . An unfamiliar environment , loss of control , perceived or actual physical risk , dependence on strangers and separation from friends and family are all factors that can contribute to the development of such feelings . Recently , there has been considerable interest in the anxiolytic potential of music listening in a variety of clinical setting s , yet thus far , little is known about the impact of music listening on the pre-procedural patient population . A systematic review of all literature to date was indicated to improve underst and ing of outcomes and impact of music listening on pre-procedural anxiety , thus helping nurses decide whether or not to incorporate music listening into practice and to highlight a need , or otherwise , for a related primary research agenda . OBJECTIVE The objective of this review was to determine the best available evidence on the effectiveness of music listening in reducing adult hospital patients ' pre-procedural state anxiety .  INCLUSION CRITERIA Types of studies This review included r and omised controlled trials and quasi-experimental research design s that examined the efficacy of music listening in reducing state anxiety among pre-procedural hospital patients published between January 1985 and February 2006 . The search was limited to publications after 1985 to coincide with the increasing interest and use of complementary therapies within health care during the 1980s and 1990s . Types of participants Participants of interest to the review were adult day patients , ambulatory patients and in patients who were about to undergo any type of clinical procedure . Types of intervention The review focused on studies that investigated pre-procedural music listening employed and prescribed as a potentially therapeutic activity . It excluded any other form of music therapy . Types of outcome measures The primary outcome measures examined were alterations in state anxiety and a variety of physiological variables such as blood pressure and respiration and heart rates . SEARCH STRATEGY A search for published and unpublished literature between January 1985 and February 2006 was conducted using all major electronic data bases . A three-step search strategy was devised which consisted of using high-precision MeSH terminology and keywords to ensure that all material relevant to the review was captured . CRITICAL APPRAISAL : The method ological quality of included studies was assessed by two review ers , who appraised each study independently , using the st and ard Joanna Briggs Institute ( JBI ) critical appraisal tools . DATA EXTRACTION AND SYNTHESIS Data were extracted from the studies that were identified as meeting the criteria for method ological quality using a data - extraction tool developed for the review . Studies were grouped by outcome measure and summarised using tabular and narrative formats . RESULTS The review demonstrated that state anxiety is defined and measured using both psychological and physiological parameters . Music listening had a consistently positive and statistically significant effect on reducing psychological parameters of pre-procedural state anxiety . However , the results from the measurement of various pre-procedural physiological parameters failed to reveal any consistent positive changes in patients who had listened to music .  This calls into question the adequacy of the theories in this area which link anxiety and the automated and central nervous systems and the effect that music listening may have on these processes and physiological responses . CONCLUSIONS / IMPLICATION S FOR PRACTICE 1 In order to reduce anxiety , it is likely that patients will benefit psychologically from having the opportunity to listen to music in the immediate pre-procedural period . 2 Patients do not appear to experience any alteration in physiological status as a result of listening to music . 3 Further research is indicated in order to replicate existing studies , to strengthen the evidence to support such interventions and to establish intervention parameters . 4 Further research is needed analysing the physiological mechanisms by which music listening is believed to reduce state anxiety and the contribution of the automated and other nervous systems to this reduction Objective : To review the mechanism of selective serotonin reuptake inhibitor (SSRI)–mediated serotonergic neurotransmission , focusing on serotonin 1A ( 5-HT1A ) autoreceptors , which are proposed to be involved in delaying therapeutic efficacy . Vilazodone was specifically design ed to function both as an SSRI and a partial agonist at 5-HT1A receptors . This combined mechanism is proposed to decrease time to efficacy , minimize sexual side effects , and provide concomitant anxiolytic properties . Data Sources : A PubMed search of all English- language articles from January 1990 to January 2013 was conducted using the search terms depression and 5-HT1A , depression and buspirone , depression and pindolol , and vilazodone . Study Selection : We found 47 articles and abstract s that were selected for inclusion on the basis of information about the pharmacology of 5-HT1A receptors and the clinical data on pindolol , buspirone , and vilazodone in depression . Data Extraction : This review summarizes current literature involving antidepressant activity , the role of 5-HT1A autoreceptors , and clinical trials involving serotonin reuptake inhibition in conjunction with 5-HT1A agonists and partial agonists , with a focus on vilazodone . Results : Vilazodone has demonstrated efficacy in 2 large , r and omized , double-blind , placebo-controlled trials in major depressive disorder . Results suggest that vilazodone has a low incidence of sexual side effects and is effective in patients with high levels of anxiety . A pooled analysis shows evidence of significant symptom reduction after only 1 week of therapy . Conclusions : If future studies corroborate the clinical benefits attributed to its mechanism of action , vilazodone may show potential advantages in terms of onset of action , sexual side effects , and anxiolytic activity in patients with major depressive disorder ABSTRACT Introduction :  Chronic breathlessness  is a common and distressing symptom of advanced disease with few effective treatments . Central nervous system mechanisms are important in respiratory sensation and control . Consequently , drugs which may modify processing and perception of afferent information in the brain may have a role . Antidepressants have been proposed ; however , current evidence is limited . Of potentially suitable antidepressants , mirtazapine is an attractive option given its tolerability profile , low cost , and wide availability , along with additional potential benefits . Areas covered : The paper provides an overview of the physiology of breathlessness , with an emphasis on central mechanisms , particularly the role of fear circuits and the associated neurotransmitters . It provides a potential rationale for how mirtazapine may improve chronic breathlessness and quality of life in patients with advanced disease . The evidence was identified by a literature search performed in PubMed through to October 2018 . Expert opinion : Currently , there is insufficient evidence to support the routine use of antidepressants for chronic breathlessness in advanced disease . Mirtazapine is a promising c and i date to pursue , with definitive r and omized controlled trials required to determine its efficacy and safety in this setting Abstract Background : Although there are effective dermatological treatments for psoriasis , a proportion of individuals also experience psychological distress not addressed by these treatments . Psychological factors may be targeted by cognitive behavioral therapy ( CBT ) which may in turn also decrease psoriasis severity . Method : A systematic review using PsycINFO , PubMed , and SCOPUS data bases was performed in 2019 to examine the efficacy of treatments that delivered psychotherapy with a major cognitive/behavioral component to patients with psoriasis . Quality of included studies was assessed . Results : Nine r and omized controlled trials with 8 unique sample s met inclusion criteria . Study quality ranged from fair to good . Half of the studies found improved psoriasis severity following treatment . Several studies found improvements following treatment in anxiety , depression , and stress . The studies that reported non-significant findings on psychological outcomes had sample s with healthy baseline psychological functioning . Nearly all studies that examined quality of life as an outcome found improvements following treatment . Conclusion : CBT as an adjunct to conventional dermatological treatments may be particularly beneficial for individuals with more severe pretreatment psychopathology in improving psoriasis severity , anxiety , and depression symptoms .  CBT appears to be generally effective in improving quality of life . Greater method ological rigor is needed in future research SUMMARY Background and objectives : Discontinuation of benzodiazepines can be associated with the emergence of a withdrawal syndrome which compromises successful termination of treatment . The objective of the present study was to evaluate whether a six week administration of captodiamine during benzodiazepine discontinuation could prevent emergence of a benzodiazepine withdrawal syndrome and thus facilitate discontinuation of these drugs . Subjects and methods : A controlled , r and omised , double-blind trial of captodiamine versus placebo was conducted in 81 subjects presenting mild to moderate anxiety and treated for at least 6 months with a stable dose of benzodiazepine . Each subject was gradually weaned from benzodiazepines over a 14 day period using a tapering dose schedule and received captodiamine ( 150 mg/d ) or placebo for 45 days from the beginning of the weaning period . Outcome measures : The primary outcome criterion was the extent of withdrawal symptoms assessed using the Tyrer Benzodiazepine Withdrawal Symptom Question naire . Secondary outcome criteria were ; self-evaluation of tension , anxiety , drowsiness and slowing of physical and mental performance using visual analogue scales ; quality of sleep using the Spiegel question naire ; anxiety using the Hamilton Anxiety Rating Scale ; and cognitive function using a driving stimulation test . Results : Analysis of the primary study criterion revealed a statistically significant difference ( p < 0.0001 ) in the emergence of withdrawal symptoms between the two groups in favour of captodiamine at two , six and eight weeks following initiation of therapy . These results were supported by significant beneficial effects of captodiamine on the majority of secondary outcome measures . The switch to captodiamine was associated with an improvement in vigilance , which may be an advantage for the overall safety of the anxiolytic treatment , for example with regard to road safety . Discontinuation of captodiamine was not associated with the emergence of rebound anxiety . Conclusion : Captodiamine represents an interesting strategy for achieving benzodiazepine substitution with a low risk of dependence or impairment of cognitive function . Further clinical studies addressing the anxiolytic activity and safety of captodiamine in such subjects are merited Background and Purpose — Psychological stressors , including poststroke depression , poststroke anxiety , and posttraumatic stress disorder , are highly prevalent in stroke survivors . These symptoms exact a significant toll on stroke survivors . Clinical and research efforts in stroke recovery focus on motor disability , speech and language deficits , and cognitive dysfunction while largely neglecting psychological stressors . Evidence suggests mind-body interventions in other chronic illness population s decrease symptoms of depression , regulate immune responses , and promote resilience , yet similar studies are lacking in stroke population s. This review aims to synthesize evidence of the effects of mind-body interventions on psychological stressors , quality of life , and biological outcomes for stroke survivors . Methods — A systematic search of PubMed , PsycINFO , and CINAHL was conducted from data base inception to November 2017 . Results — Eight studies were included in the review , with a total of 292 participants .  Mind-body interventions included yoga or tai chi . Of the 5 included r and omized controlled trials , most were pilot or feasibility studies with small sample sizes . Psychological stressors , including poststroke depression and anxiety , along with the quality of life , improved over time , but statistically significant between-group differences were largely absent . The 3 included studies with a qualitative design reported themes reflecting improvement in psychological stressors and quality of life . No included studies reported biological outcomes . Conclusions — Studies of mind-body interventions suggest a possible benefit on psychological stressors and quality of life ; however , rigorously design ed , sufficiently powered r and omized controlled trials with mixed- methods design are warranted to delineate specific treatment effects of these interventions . Studies with both biological and psychological stressors as outcomes would provide evidence about interaction effects of these factors on stroke-survivor responses to mind-body interventions Serotonin is implicated in the etiology of anxiety disorders and in the anxiolytic actions of benzodiazepines . Pre clinical studies with 5-HT3 receptor antagonists , including ondansetron , show they have anxiolytic properties and that ondansetron suppresses withdrawal anxiety after abrupt discontinuation of chronic benzodiazepine treatment . We evaluated the efficacy of ondansetron as an adjunctive medication in the discontinuation of benzodiazepines in long-term users . One hundred eight patients who had used alprazolam or lorazepam regularly for > 3 months entered , and 97 completed a r and omized double-blind discontinuation treatment program during which they received either ondansetron 2 mg twice daily or placebo and flexibly tapered their benzodiazepine over a 6-week period . There were no significant differences between the patients who had entered and completed treatment . Three weeks postmedication , 63 % of the patients discontinued use of benzodiazepine . The percentage of reduction of benzodiazepine daily dosage at all time points in the treatment trial was similar for the ondansetron and placebo groups . Ondansetron had no significant effects on severity of withdrawal symptoms or levels of anxiety . High placebo response may have prevented detection of an ondansetron effect . At 1 year follow-up , 68 % of patients reported that they stopped using  benzodiazepine . Patient characteristics were more important than ondansetron in tapered benzodiazepine discontinuation Abstract Background Anxiety and trauma-related disorders are among the most prevalent and disabling medical conditions in the United States , and posttraumatic stress disorder in particular exacts a tremendous public health toll . We examined the tolerability and anxiolytic efficacy of neuropeptide Y administered via an intranasal route in patients with posttraumatic stress disorder . Methods Twenty-six individuals were r and omized in a cross-over , single ascending dose study into 1 of 5 cohorts : 1.4 mg ( n=3 ) , 2.8 mg ( n=6 ) , 4.6 mg ( n=5 ) , 6.8 mg ( n=6 ) , and 9.6 mg ( n=6 ) . Each individual was dosed with neuropeptide Y or placebo on separate treatment days 1 week apart in r and om order under double-blind conditions . Assessment s were conducted at baseline and following a trauma script symptom provocation procedure subsequent to dosing . Occurrence of adverse events represented the primary tolerability outcome . The difference between treatment conditions on anxiety as measured by the Beck Anxiety Inventory and the State-Trait Anxiety Inventory immediately following the trauma script represented efficacy outcomes . Results Twenty-four individuals completed both treatment days . Neuropeptide Y was well tolerated up to and including the highest dose . There was a significant interaction between treatment and dose ; higher doses of neuropeptide Y were associated with a greater treatment effect , favoring neuropeptide Y over placebo on Beck Anxiety Inventory score ( F1,20=4.95 , P=.038 ) . There was no significant interaction for State-Trait Anxiety Inventory score . Conclusions Our study suggests that a single dose of neuropeptide Y is well tolerated up to 9.6 mg and may be associated with anxiolytic effects . Future studies exploring the safety and efficacy of neuropeptide Y in stress-related disorders are warranted . The reported study is registered at : http:// clinical trials.gov ( ID : NCT01533519 ) Introduction Functional somatic syndromes ( FSS ) are common in adolescents , characterised by severe disability and reduced quality of life .  Behavioural treatments such as acceptance and commitment therapy ( ACT ) has shown promising results in children and adolescents with FSS , but has focused on specific syndromes such as functional pain . The current study will compare the efficacy of group-based ACT with that of enhanced usual care ( EUC ) in adolescents with a range of FSS operationalised by the unifying construct of multiorgan bodily distress syndrome ( BDS ) . Methods and analysis A total of 120 adolescents aged 15–19 and diagnosed with multiorgan BDS , of at least 12 months duration , will be assessed and r and omised to either : ( 1 ) EUC : a manualised consultation with a child and adolescent psychiatrist and individualised treatment plan or ( 2 ) manualised ACT-based group therapy plus EUC . The ACT programme consists of 9 modules ( ie , 27 hours ) and 1 follow-up meeting ( 3 hours ) . The primary outcome is physical health , assessed by an Short Form Health Survey ( SF-36 ) aggregate score 12 months after r and omisation . Secondary outcomes include self-reported symptom severity , symptom interference , depression and anxiety , illness worry , perceived stress and global improvement ; as well as objective physical activity and bodily stress response measured by heart rate variability , hair cortisol and inflammatory biomarkers . Process measures are illness perception , illness-related behaviour and psychological flexibility . Ethics and dissemination The study is conducted in accordance with Helsinki Declaration II . Approval has been obtained from the Science Ethics Committee of the Central Denmark Region and the Danish Data Protection . The results will be sought to be published according to the CONSORT statement in peer- review ed journals . Discussion This is one of the first larger r and omised clinical trials evaluating the effect of a group-based intervention for adolescents with a range of severe FSS . Trial registration number NCT02346071 ; Pre- results
Collectively , the literature reveals pre clinical and clinical evidence for various phytomedicines modulating GABA-pathways , with comparative anxiolytic effect to the current array of pharmaceuticals , along with good safety and tolerability profiles
Anxiety disorders are chronic and functionally disabling conditions with high psychological stress , characterised by cognitive symptoms of excessive worry and focus difficulties and physiological symptoms such as muscle tension and insomnia .
Gamma-aminobutyric acid ( GABA ) is an inhibitory neurotransmitter within the central nervous system and is a key target of pharmacotherapies in the treatment of anxiety .
Although current pharmaceutical treatments are often efficacious , they may cause undesirable side effects including cognitive decrements and withdrawal symptoms .
Plant-based " phytomedicines " may provide novel treatment options , to act as an adjunctive or alternative to existing anxiolytic medications .
As such , we conducted a systematic review to assess the current body of literature on anxiolytic phytomedicines and /or phytoconstituents .