ORCID Profile
0000-0003-2852-7923
Current Organisations
Government of Western Australia Department of Health
,
University of Western Australia
Does something not look right? The information on this page has been harvested from data sources that may not be up to date. We continue to work with information providers to improve coverage and quality. To report an issue, use the Feedback Form.
In Research Link Australia (RLA), "Research Topics" refer to ANZSRC FOR and SEO codes. These topics are either sourced from ANZSRC FOR and SEO codes listed in researchers' related grants or generated by a large language model (LLM) based on their publications.
Mental Health | Secondary Education | Public Health and Health Services | Educational Psychology
Learner and Learning Achievement | Education and Training Systems Policies and Development | Mental Health |
Publisher: BENTHAM SCIENCE PUBLISHERS
Date: 28-03-2012
Publisher: Cold Spring Harbor Laboratory
Date: 23-05-2023
DOI: 10.1101/2023.05.17.23290083
Abstract: Reliable assessment of suicide and self-harm risk in emergency medicine is critical for effective intervention and treatment of patients affected by mental health disorders. Teams of clinicians are faced with the challenge of rapidly integrating medical history, wide-ranging psychosocial factors, and real-time patient observations to inform diagnosis, treatment and referral decisions. Patient outcomes therefore depend on the reliable flow of information though networks of clinical staff and information systems. We studied information flow at a systems-level in a tertiary hospital emergency department using network models and machine learning. Data were gathered by mapping trajectories and recording clinical interactions for patients at suspected risk of suicide or self-harm. A network model constructed from the data revealed communities closely aligned with underlying clinical team structure. By analysing connectivity patterns in the network model we identified a vulnerability in the system with the potential to adversely impact information flow. We then developed an algorithmic strategy to mitigate this risk by targeted strengthening of links between clinical teams. Finally, we investigated a novel application of machine learning for distinguishing specific interactions along a patient’s trajectory which were most likely to precipitate a psychiatric referral. Together, our results demonstrate a new framework for assessing and reinforcing important information pathways that guide clinical decision processes and provide complimentary insights for improving clinical practice and operational models in emergency medicine for patients at risk of suicide or self-harm.
Publisher: Elsevier BV
Date: 07-2003
DOI: 10.1016/S0965-2302(02)00237-0
Abstract: This study evaluated staff perception of a three-month clinical trial of an emergency mental health triage and consultancy service. Eleven night duty emergency department (ED) staff were interviewed on the last night of the trial. Data was analysed according to the standards of qualitative research and through content analysis major themes were identified. Staff-perceived value of the emergency mental health triage and consultancy service to the emergency department was identified under three major themes: "enhancing the quality of service for people requiring psychiatric sychosocial intervention", "the impact on the ED environment" and "providing education and support". The findings of this study show that ED staff perceived that the emergency mental health triage and consultancy service made a valuable contribution to the overall functioning of the ED. The findings also highlight the advanced practice role undertaken by mental health nurses in the ED.
Publisher: SAGE Publications
Date: 22-01-2009
Abstract: Abstract Two-related studies are presented here, detailing our early experience with benzodiazepine-dependent patients treated with a four-day flumazenil infusion using a novel delivery technique. Patients with long-term benzodiazepine dependence who attended the Australian Medical Procedures Research Foundation (AMPRF, Perth, Australia) for treatment were recruited for these studies. Self-reported psychological and physical symptoms, as well as objective vital signs data were collected at intervals before, during and 2 weeks postinfusion. Study A is a case series with cardiovascular measures study B is an open trial that tracks the psychological profiles of 13 subjects. Withdrawal symptoms were tracked, however, the nature and severity of these symptoms differed between patients. No major complications or discomfort prompting study dropout was observed. Significant benzodiazepine abstinence occurred with this flumazenil infusion method despite high levels of initial dependence, comorbid substance use and comorbid psychiatric illness. Low-dose flumazenil infusion appears to be a safe and effective treatment resulting in withdrawal symptoms of lesser severity than any other cessation method currently available. Recommendations for future research are discussed.
Publisher: Bentham Science Publishers Ltd.
Date: 30-10-2008
Publisher: Springer Science and Business Media LLC
Date: 10-08-2018
Publisher: SAGE Publications
Date: 06-2001
DOI: 10.1046/J.1440-1665.2001.00316.X
Abstract: Objective: To review the treatment options for obsessive–compulsive disorder (OCD), with particular reference to treatment resistance, and provide a guideline for clinicians managing these patients, drawing upon evidence from clinical trials and expert consensus. Conclusions: The behavioural technique of exposure and ritual prevention (EX/RP) and serotonergic medications have emerged as effective standard treatments of OCD, although full symptom remission is rare. Predictors of poor and partial response to these treatments may reflect substantial underlying heterogeneity in OCD. Clinicians can now begin to apply psychological and pharmacological augmenting strategies that specifically target these heterogenous subgroups in an attempt to improve response. We offer a treatment algorithm for OCD derived from this understanding.
Publisher: MDPI AG
Date: 02-11-2022
DOI: 10.3390/BS12110430
Abstract: Background: Generalised anxiety disorder (GAD) is a common anxiety disorder associated with social and occupational impairment. Recently, a theory was postulated that dysfunctional gamma aminobutyric acid type A receptors (GABAA) are implicated in anxiety symptomology, which could be corrected by flumazenil, an antagonist at the benzodiazepine binding site on the GABAA receptor. Method: Participants had a primary diagnosis of GAD and were treated initially with an eight-day continuous low-dose flumazenil infusion (total 32 mg at a rate of 4 mg/24 h). Some participants were re-treated with a further four- or eight-day infusion. Treatment response was measured as a 50% reduction in anxiety or stress scores on the Depression Anxiety Stress Scale—21 (DASS-21). Remission was measured as scores ≤3 or ≤7 on the anxiety and stress subscales of the DASS-21, respectively. Results: Eight cases are reported. All cases met the criteria for treatment response on the anxiety and stress subscale of the DASS-21. Remission was achieved in seven participants on the anxiety subscale and in five on the stress subscale. No changes in hepatic, renal, or haematological function were likely attributed to flumazenil. Conclusion: Data suggest that low-dose continuous flumazenil infusion manages GAD symptoms and is safe. Although these results are promising, future randomised control trials are required to confirm these results.
Publisher: SAGE Publications
Date: 10-07-2016
Abstract: The 2002 paper “Does 5-HT restrain panic? A tryptophan depletion study in panic disorder patients recovered on paroxetine” by Bell and colleagues – reprinted in this issue of the Journal – reports on a study undertaken in the halcyon days of David Nutt’s Psychopharmacology Unit at the University of Bristol, England. In this invited commentary authors of the original work discuss the impact of this paper on the field of acute tryptophan depletion research (especially in the field of clinical anxiety disorders) and the development of disorder-specific anxiogenic provocations over the past decade.
Publisher: Informa UK Limited
Date: 26-07-2018
DOI: 10.1080/10641963.2018.1501058
Abstract: To test the role of escitalopram on blood pressure and heart rate of in iduals with hypertension and depression. A total of 30 in iduals participated in this study who were being treated for hypertension and were diagnosed with major depression. Escitalopram (10-20 mg) was administered to 15 in iduals, while the other 15 received placebo. These in iduals were followed for 8 weeks with regular monitoring of blood pressure and heart rate. Scores on the Hamilton Depression Rating Scale were evaluated within the first, second, fourth, and eighth weeks of the study onset. Comparing with placebo, heart rate was lower in the escitalopram group (66.79 ± 9.85 vs. 74.10 ± 9.52 bpm, p = 0.044). There was not a significant decrease of systolic blood pressure (140.80 ± 16.48 vs 139.61 ± 18.92 mmHg, p = 0.85) and diastolic blood pressure (80.55 ± 12.64 vs 80.18 ± 16.36 mmHg, p = 0.94). Escitalopram decreases HR, but not BP, in in iduals with hypertension and depression. Abbreviation: SH: systemic hypertension BP: blood pressure DSM: Diagnostic and Statistical Manual of Mental Disorders SRQ 20: Self-Report Questionnaire SCID: Structured Clinical Interview for DSM-IV HR: heart rate SNS: Sympathetic nervous system HPA: hypothalamus-pituitary-adrenal axis RAA: renin, angiotensin, aldosterone system NE: norepinephrine CSF: cerebrospinal fluid HAM-D: Hamilton Depression Rating Scale CRF: corticotropin releasing factor ACTH: adrenocorticotropic hormone BMI: Body mass index SBP: systolic blood pressure DBP: diastolic blood pressure t: time.
Publisher: SAGE Publications
Date: 03-10-2012
Abstract: Curcumin is the principal curcuminoid of the popular Indian spice turmeric and has attracted increasing attention for the treatment of a range of conditions. Research into its potential as a treatment for depression is still in its infancy, although several potential antidepressant mechanisms of action have been identified. Research completed to date on the multiple effects of curcumin is reviewed in this paper, with a specific emphasis on the biological systems that are compromised in depression. The antidepressant effects of curcumin in animal models of depression are summarised, and its influence on neurotransmitters such as serotonin and dopamine is detailed. The effects of curcumin in moderating hypothalamus–pituitary–adrenal disturbances, lowering inflammation and protecting against oxidative stress, mitochondrial damage, neuroprogression and intestinal hyperpermeability, all of which are compromised in major depressive disorder, are also summarised. With increasing interest in natural treatments for depression, and efforts to enhance current treatment outcomes, curcumin is presented as a promising novel, adjunctive or stand-alone natural antidepressant.
Publisher: Frontiers Media SA
Date: 05-09-2023
Publisher: SAGE Publications
Date: 03-2007
Abstract: The psychometric tools used for the assessment of generalized anxiety disorder (GAD) either do not conform to the current concept of the condition or have important limitations. We aimed to develop and validate a new questionnaire for the assessment of symptom profile and severity of GAD. An original pool of potential scale items was subjected to a series of studies in non-clinical and clinical populations, in order to determine the final composition of the scale. The psychometric properties of the new scale, the Generalized Anxiety Disorder Inventory (GADI), were evaluated using a factor analytic model suitable for ordinal data and the Graded Response Model. The precision of measurement of the GADI was quantified through the item information functions. A total of 197 outpatients and 522 non-clinical subjects participated in four studies and completed the GADI. The final 18-item scale was derived from an original pool of 30 potential items. The GADI showed good reliability, convergent and ergent validity. The scale comprises three factors, relating to cognitive, somatic and sleep symptoms. It accurately distinguished GAD patients from non-patient controls. The cognitive factor also distinguished GAD from other anxiety disorders and depression. The GADI is a useful tool in the assessment of the breadth of symptoms and the severity of generalized anxiety disorder in clinical settings.
Publisher: Bentham Science Publishers Ltd.
Date: 05-2007
Publisher: SAGE Publications
Date: 19-07-2010
Abstract: Anxiety disorders are common both in adults and children. While there have been major advances in understanding the neurobiology of anxiety disorders in adults, progress has been more limited in the elucidation of the mechanisms underlying these disorders in childhood. There is a need to delineate childhood biological models, since anxiety represents a significant clinical problem in children and is a risk factor for the subsequent development of anxiety and depression in adulthood. We conducted a review of the literature regarding pharmacological challenge tests and direct hypothalamic–pituitary–adrenal axis measurement in children with anxiety disorders, with emphasis on panic disorder and social anxiety disorder. Studies identified were contrasted with those in adult panic disorder and social anxiety disorder. Despite this broad approach few studies emerged in children, with only 22 studies meeting inclusion criteria. When contrasted with adult neurobiological models of panic disorder and social anxiety disorder, children studied showed some abnormalities which mirrored those reported in adults, such as altered baseline respiration, altered responses to CO 2 challenge tests and blunted growth hormone response to yohimbine. However, results differed from adults with panic disorder and social anxiety in some aspects of noradrenergic and serotonergic function. For endpoints studied in panic disorder children, unlike adults, displayed a lack of baseline end-tidal CO 2 abnormalities and a different hypothalamic–pituitary–adrenal pattern response under low-dose CO 2 . The biology of these anxiety disorders in children may only partially mirror that of adult anxiety disorders. However, caution is required as the evidence is limited, and many studies combined patients with panic disorder and social anxiety disorder with other disorders or non-specific anxiety. Further research is required to fully understand the biology and progression of childhood anxiety disorders.
Publisher: Elsevier BV
Date: 07-2015
Publisher: Royal College of Psychiatrists
Date: 14-07-2023
DOI: 10.1192/BJP.2023.79
Abstract: Prior trials suggest that intravenous racemic ketamine is a highly effective for treatment-resistant depression (TRD), but phase 3 trials of racemic ketamine are needed. To assess the acute efficacy and safety of a 4-week course of subcutaneous racemic ketamine in participants with TRD. Trial registration: ACTRN12616001096448 at www.anzctr.org.au . This phase 3, double-blind, randomised, active-controlled multicentre trial was conducted at seven mood disorders centres in Australia and New Zealand. Participants received twice-weekly subcutaneous racemic ketamine or midazolam for 4 weeks. Initially, the trial tested fixed-dose ketamine 0.5 mg/kg versus midazolam 0.025 mg/kg (cohort 1). Dosing was revised, after a Data Safety Monitoring Board recommendation, to flexible-dose ketamine 0.5–0.9 mg/kg or midazolam 0.025–0.045 mg/kg, with response-guided dosing increments (cohort 2). The primary outcome was remission (Montgomery-Åsberg Rating Scale for Depression score ≤10) at the end of week 4. The final analysis (those who received at least one treatment) comprised 68 in cohort 1 (fixed-dose), 106 in cohort 2 (flexible-dose). Ketamine was more efficacious than midazolam in cohort 2 (remission rate 19.6% v . 2.0% OR = 12.1, 95% CI 2.1–69.2, P = 0.005), but not different in cohort 1 (remission rate 6.3% v . 8.8% OR = 1.3, 95% CI 0.2–8.2, P = 0.76). Ketamine was well tolerated. Acute adverse effects (psychotomimetic, blood pressure increases) resolved within 2 h. Adequately dosed subcutaneous racemic ketamine was efficacious and safe in treating TRD over a 4-week treatment period. The subcutaneous route is practical and feasible.
Publisher: Springer Science and Business Media LLC
Date: 21-11-2009
DOI: 10.1007/S00213-009-1722-1
Abstract: Serotonergic antidepressants [selective serotonin reuptake inhibitor (SSRI)] are first-line treatments for generalised anxiety disorder (GAD) however, it is not known if synaptic serotonin (5-HT) availability is important for SSRI efficacy. The present study tested the hypothesis that temporary reduction in central 5-HT transmission, through acute tryptophan depletion (ATD), would reverse the therapeutic effect of the SSRIs in GAD patients. Twelve patients (six males) with GAD, who showed sustained clinical improvement with SSRI treatment, underwent ATD in a double-blind, placebo-controlled, within-subjects design over 2 days, 1 week apart. At the peak time of depletion, the participants inhaled 7.5% CO2 and air in random order for at least 12 min each. Psychological responses were measured using the Spielberger State Anxiety Inventory (STAI-S) and GAD-symptom visual analogue scales (VASs e.g., worry and tense) and Profile of Mood States. Free plasma tryptophan to large neutral amino acid (LNAA) ratio decreased by 92% on the depletion day and decreased by 2% on the control day. Irrespective of depletion condition, 7.5% CO(2) inhalation significantly increased STAI-S and GAD-related VAS scores (all p < 0.05) compared with air inhalation. ATD had no effect on any of these measures despite the substantial reduction in free tryptophan/LNAA ratio. Although SSRIs treat GAD effectively, the present results suggest that the mechanism of action is different to that seen in panic, social anxiety, and post-traumatic stress disorders. Successful SSRI treatment of GAD may involve long-term receptor changes or alterations in other neurotransmitter systems downstream of serotonin.
Publisher: SAGE Publications
Date: 02-11-2017
Abstract: Serotonergic antidepressants are first-line medication therapies for obsessive-compulsive disorder, however it is not known if synaptic serotonin availability is important for selective serotonin reuptake inhibitor efficacy. The present study tested the hypothesis that temporary reduction in central serotonin transmission, through acute tryptophan depletion, would result in an increase in anxiety in selective serotonin reuptake inhibitor-remitted obsessive-compulsive disorder patients. Eight patients (four males) with obsessive-compulsive disorder who showed sustained clinical improvement with selective serotonin reuptake inhibitor treatment underwent acute tryptophan depletion in a randomized, double-blind, placebo-controlled, within-subjects design, over two days one week apart. Five hours after consumption of the depleting/sham drink the participants performed a personalized obsessive-compulsive disorder symptom exposure task. Psychological responses were measured using the Spielberger State Anxiety Inventory, Yale-Brown Obsessive Compulsive Scale and Visual Analogue Scales. Free plasma tryptophan to large neutral amino acid ratio decreased by 93% on the depletion day and decreased by 1% on the sham day, as anticipated. Psychological rating scores as measured by Visual Analogue Scale showed a significant decrease in perceived control and increase in interfering thoughts at the time of provocation on the depletion day but not on the sham day. A measure of convergent validity, namely Visual Analogue Scale Similar to past, was significantly higher at the time of provocation on both the depletion and sham days. Both the depletion and time of provocation scores for Visual Analogue Scale Anxiety, Spielberger State Anxiety Inventory, Yale-Brown Obsessive Compulsive Scale and blood pressure were not significant. Acute tryptophan depletion caused a significant decrease in perceived control and increase in interfering thoughts at the time of provocation. Acute tryptophan depletion had no effect on the Spielberger State Anxiety Inventory or Visual Analogue Scale Anxiety measures, which suggests that the mechanism of action of selective serotonin reuptake inhibitors may be different to that seen in panic, social anxiety and post-traumatic stress disorder. Successful selective serotonin reuptake inhibitor treatment of obsessive-compulsive disorder may involve the ability of serotonin to switch habitual responding to goal-directed behaviour.
Publisher: Springer Science and Business Media LLC
Date: 13-12-2008
Publisher: Oxford University Press (OUP)
Date: 19-05-2015
DOI: 10.1093/IJNP/PYV050
Publisher: OMICS Publishing Group
Date: 2013
Publisher: SAGE Publications
Date: 04-12-2018
Publisher: SAGE Publications
Date: 04-07-2017
Abstract: Medical students have higher rates of mental illness compared to the general population. Little is known about services accessed by medical students for mental-health problems. This study aimed to assess the use of mental-health services by Australian medical students and to identify barriers that may prevent students from using mental-health services. A cross-sectional online survey was designed and administered to medical students at the University of Western Australia. Questions focused on self-reported psychological well-being, use of mental-health services, the perceived usefulness of services and barriers to the use of services. The response rate was 41% ( n=286). Sixty-two per cent self-reported experiencing mental-health problems, and of these, 75% had used at least one service. General practitioners and psychiatrists were rated as the most effective service type. The main barriers to seeking help were not enough time, affordability and concerns regarding stigma, including disclosure and peer judgement. A high proportion of students with self-reported mental-health problems had accessed services. However, barriers were also identified. Access to mental-health services needs to be improved, and strategies aimed at reducing stigma and raising awareness of mental-health issues should be encouraged by medical faculties.
Publisher: SAGE Publications
Date: 07-2005
DOI: 10.1080/J.1440-1614.2005.01628.X
Abstract: Objective: This is the second of two articles reviewing the modern dietary technique of acute tryptophan depletion (ATD), a method of transiently reducing central serotonin levels in both healthy volunteers and clinical populations. This article details the clinical studies to date and discusses the implications of this research methodology. Method: The authors present a review of clinical ATD studies collated from a MEDLINE search, unpublished communications and the authors' considerable experience with this paradigm. Results: Following from the initial use of ATD in subjects with depressive illness, studies of anxiety disorders and other psychiatric illnesses have been reported. Sleep, aggressive and cognitive effects are also active areas of research and are reviewed here. Conclusions: Acute tryptophan depletion remains a useful psychiatric research tool. The findings from the clinical studies reviewed here are summarized and implications for future research detailed.
Publisher: Wiley
Date: 22-01-2014
DOI: 10.1111/BCP.12023
Publisher: Elsevier BV
Date: 11-2020
Publisher: Royal College of Psychiatrists
Date: 05-2020
DOI: 10.1192/BJO.2020.31
Abstract: It is clinically imperative to better understand the relationship between trauma, auditory hallucinations and dissociation. The personal narrative of trauma has enormous significance for each in idual and is also important for the clinician, who must use this information to decide on a diagnosis and treatment approach. To better understand whether dissociation contributes in a significant way to hallucinations in in iduals with and without trauma histories. Three groups of participants with auditory hallucinations were recruited, with diagnoses of: schizophrenia (without trauma) ( n = 18), post-traumatic stress disorder (PTSD, n = 27) and comorbid schizophrenia and PTSD (SCZ+PTSD), n = 26). Clinician-administered measures included the PTSD Symptoms Scale Interview (PSSI-5), the Clinician-Administered Dissociative States Scale (CADSS) and the Psychotic Symptom Rating Scales (PSYRATS). Dissociative symptoms were significantly higher in participants with trauma histories (PTSD and SCZ+PTSD groups) and significantly correlated with hallucinations in trauma-exposed participants, but not in participants with schizophrenia (without trauma history). Hallucination severity was correlated with the CADSS amnesia subscale score, but depersonalisation and derealisation were not. Dissociation may be a mechanism in trauma-exposed in iduals who hear voices, but it does not explain all hallucinatory experiences. The SCZ+PTSD group were in an intermediary position between schizophrenia and PTSD on dissociative and hallucination measures. The PTSD and SCZ+PTSD groups experienced dissociative phenomena much more frequently than the schizophrenia group, with a significant trend towards the amnesia subtype of dissociation .
Publisher: SAGE Publications
Date: 02-09-2019
Abstract: As a stand-alone intervention, saffron has efficacy for the treatment of mild-to-moderate depression. However, research as an adjunct agent is limited. The effects of saffron as an adjunct to pharmaceutical antidepressants in adults with persistent depression was investigated. In this eight-week, randomised, double-blind, placebo-controlled study, adults with persistent depression, currently taking a pharmaceutical antidepressant were given a placebo or a saffron extract (affron®, 14 mg b.i.d.). Primary outcome measures included the clinician-rated Montgomery–Åsberg Depression Rating Scale (MADRS) and self-rated MADRS (MADRS-S). Secondary outcome measures included the Antidepressant Side-Effect Checklist (ASEC) and Short Form-36 Health Survey (SF-36). Of the 160 participants enrolled, 139 provided usable data. Based on the MADRS, depressive symptoms decreased more in participants taking saffron compared with a placebo, with reductions of 41 and 21%, respectively ( p = 0.001). However, scores on the MADRS-S decreased 27 and 26% in the saffron and placebo conditions, respectively ( p = 0.831). Saffron was associated with a greater reduction in adverse effects of antidepressants ( p = 0.019), although this was non-significant after covarying for baseline values ( p = 0.449). Quality of life improved in both groups with no significant between-group differences ( p = 0.638). Adjunctive administration of a standardised saffron extract (affron®) for eight weeks was associated with a greater improvement in depressive symptoms as measured by the clinician-rated MADRS but not the self-report MADRS-S. Given the conflicting results, further research is needed to clarify the clinical benefits of saffron as an adjunctive treatment for adults with persistent depressive symptoms despite antidepressant drug treatment.
Publisher: Informa Healthcare
Date: 04-2003
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 08-2001
Publisher: Frontiers Media SA
Date: 19-09-2023
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 11-2006
DOI: 10.1111/J.1572-0241.2006.00811.X
Abstract: To assess the effect of acute changes in serotonin (5-HT) synthesis using the acute tryptophan depletion (ATD) paradigm on gastrointestinal (GI) and mood symptoms in irritable bowel syndrome (IBS). In a randomized double-blind crossover study, 29 subjects (18 patients with ROME II defined IBS and 11 age-matched controls) were studied under ATD and acute tryptophan increase (ATI) conditions. GI symptoms, mood and anxiety ratings, as well as plasma tryptophan concentrations were measured. Total (and free) plasma tryptophan concentrations decreased on the ATD day in patients (73%[82%]) and controls (73%[80%]), and increased on the ATI day in patients (59%[143%]) and controls (61%[381%]). Compared with the ATD day, IBS patients reported more GI symptoms on the ATI day at +210 (p < 0.001) and at +270 (p < 0.05) min post drink. IBS patients also reported less anxiety on the ATI day compared with the ATD day at +270 min (p < 0.001). ATD and ATI did not affect these ratings in control participants. IBS patients had a lower mood compared with controls (p < 0.05), but this did not differ between the ATI and ATD days in either group. IBS patients' GI and anxiety responses to changes in tryptophan load differ from controls. This suggests a difference in serotonergic functioning between these two groups and provides evidence to support the hypothesis that 5-HT dysfunction is involved in IBS.
Publisher: SAGE Publications
Date: 06-10-2008
Abstract: Serotonergic antidepressants (SSRIs) are first-line treatments for social anxiety disorder [SAnD], though there is evidence of dopaminergic system dysfunction. Twenty subjects with DSM-IV SAnD, untreated (n = 10) and SSRI-remitted DSM-IV SAnD (n = 10), were administered a single dose of 1) a dopamine agonist (pramipexole 0.5 mg) and 2) a dopamine antagonist (sulpiride 400 mg), followed by anxiogenic challenges (verbal tasks and autobiographical scripts) in a double-blind crossover design, the two test days being one week apart. Anxiety symptoms were measured by self-reported changes in Visual Analogue Scales, specific SAnD scales and anxiety questionnaires. Plasma levels of prolactin were obtained. Untreated SAnD subjects experienced significant increases in anxiety symptoms following behavioural challenges after either sulpiride or pramipexole. Following remission with SSRIs, the socially anxiogenic effect of behavioural provocation was significantly attenuated under pramipexole, whereas under sulpiride effects remained significantly elevated. There appears to be instability of the dopamine system under behavioural stress in social anxiety subjects that is only partly rectified by successful treatment with an SSRI, which may induce a desensitisation of postsynaptic dopamine D 3 receptors.
Publisher: Elsevier BV
Date: 07-2006
DOI: 10.1016/J.EURONEURO.2006.04.003
Abstract: Generalized anxiety disorder (GAD) frequently occurs comorbidly with other conditions, including depression and somatic complaints. Comorbid GAD sufferers have increased psychologic and social impairment, request additional treatment, and have an extended course and poorer outcome than those with GAD alone therapy should alleviate both the psychic and somatic symptoms of GAD without negatively affecting the comorbid condition. The ideal treatment would provide relief from both GAD and the comorbid condition, reducing the need for polypharmacy. Physicians need suitable tools to assist them in the detection and monitoring of GAD patients-the GADI, a new, self-rating scale, may meet this requirement. Clinical data have shown that various neurobiologic irregularities (e.g., in the GABA and serotonin systems) are associated with the development of anxiety. Prescribing physicians must take into account these abnormalities when choosing a drug. Effective diagnosis and treatment should improve patients' quality of life and their prognosis for recovery.
Publisher: SAGE Publications
Date: 16-05-2013
Abstract: Our group and others internationally have previously reported data on the use of low-dose flumazenil administered intravenously for the management of benzodiazepine withdrawal. This paper describes the first reported use of subcutaneous flumazenil infusion in the management of acute benzodiazepine withdrawal. Self-reported withdrawal symptoms and psychological state and anxiety sequelae were collected at baseline and then at intervals to 5 days following initiation of subcutaneous flumazenil infusion. Data indicate that patient subjective benzodiazepine withdrawal symptoms were well managed, with significant reduction in psychological distress seen over the duration of treatment. Perceived difficulty in performing everyday functions was positively correlated with withdrawal severity and improved over treatment. Patients reported high treatment comfort, willingness to undertake a future subsequent treatment using this technique, and willingness to recommend this treatment to a friend. This small proof-of-concept study indicates that subcutaneous flumazenil infusion has excellent tolerability, efficacy and improvement on measures of psychological distress. Given this technique is less invasive and requires fewer staff resources compared with intravenous administration, it may prove a significant asset in the management of benzodiazepine withdrawal.
Publisher: Royal College of Psychiatrists
Date: 09-2008
DOI: 10.1192/BJP.BP.107.041186
Abstract: The importance of the neurotransmitter serotonin (5-HT) in the pathophysiology of anxiety is well known. A key role for postsynaptic 5-HT 1A receptors has recently been suggested in studies of genetic knockout mice. To measure 5-HT 1A receptor binding in patients with panic disorder in the untreated state and after recovery on treatment with selective serotonin reuptake inhibitors (SSRIs). Nine symptomatic untreated patients with panic disorder, seven patients recovered on SSRI medication and nineteen healthy volunteers underwent a single positron emission tomography (PET) scan using the 5-HT 1A tracer [ 11 C]WAY-100635. In comparison with controls, both presynaptic and postsynaptic 5-HT 1A receptor binding was reduced in untreated patients, with the most significant reductions being in the raphe, orbitofrontal cortex, temporal cortex and amygdala. In recovered patients presynaptic binding was reduced, but there was no significant reduction in postsynaptic binding. Panic disorder is associated with reduced 5-HT 1A receptor availability, which is also known to have a key role in depression.
Publisher: SAGE Publications
Date: 09-2013
DOI: 10.1177/0310057X1304100510
Abstract: This survey was designed to evaluate the factors affecting mental health and welfare in Australian anaesthetists and to investigate current sources of support. An electronic survey was sent to 500 randomly selected Fellows and trainees of the Australian and New Zealand College of Anaesthetists. Questions were related to: anxiety, stress, depression, substance misuse, self-medication, suicide, reporting illness, and help-seeking. Current psychological wellbeing was assessed using the Kessler Psychological Distress Scale (K10). A total of 191 completed surveys were received (a response rate of 38%): 26% had attended their general practitioner for mental health issues, of whom half had been diagnosed with a mental illness 7% of all respondents were currently prescribed medication for this 25% had previously self-prescribed psychoactive medication 17% admitted to using alcohol to deal with stress, anxiety or depression and 8% responded that mental illness had at some point impaired clinical care. Sixteen percent of all respondents reported previous suicidal ideation. Despite a low response rate, and the possibility of responder bias, the mental health of Australian anaesthetists would appear to be subject to common and persistent risk factors, many of which are well described in previous studies. We identify general practitioners as particularly valuable in targeting initiatives for improvements in mental health and welfare. The significant prevalence of suicidal ideation and reluctance to approach senior colleagues with concerns about mental health or welfare issues are specific causes for concern and suggest that further investigation, education and a potential review of support networks is required.
Publisher: Bentham Science Publishers Ltd.
Date: 11-2006
DOI: 10.2174/157488906778773625
Abstract: Anxiety disorders are common and debilitating mental illnesses. Current pharmacological treatments are beset by problems of poor efficacy and side effect profiles. Increasing understanding of novel neurotransmitter systems and the interplay between these systems is broadening the scope of anxiolytic drug treatment. This article aims to describe the areas of current interest and possible future development of anxiolytic drugs by outlining recent patents in this field. A patent database was searched for 17 neurotransmitters and their synonyms as well as 23 compounds of recent known interest from May 2003 to May 2005. The internet resources Pubmed and Google Scholar were searched for peer reviewed literature using the same search parameters. Results were grouped into neurotransmitter systems to present an overview of recent developments in the neuropharmacology of anxiety disorders.
Publisher: SAGE Publications
Date: 11-07-2016
Abstract: There is evidence that mood disorders are associated with impaired parasympathetic nervous system function and consequently increased morbidity and mortality. Our study addresses whether this impairment persists into remission in unipolar and bipolar disorders. Heart Rate Variability was measured in groups of subjects during remission, with Bipolar Affective Disorder I ( n = 29), recurrent Major Depressive Disorder ( n = 41) and a healthy control group ( n = 38), during the bedtime period. Heart Rate Variability was found to be lower in the bipolar and depression groups, compared with control subjects, using the Root Mean Square of Successive Distances variable, and lower in the depression group using the Standard Deviation of Normal to Normal variable and the Standard Deviation, Poincare Plot variable. Autonomic function during bedtime was impaired in subjects with Bipolar I and recurrent Major Depressive Disorder, despite clinical remission. This has significant implications for the morbidity and mortality of patients with major mood disorders.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 08-2006
Publisher: Elsevier BV
Date: 12-2008
DOI: 10.1016/J.JAD.2008.03.003
Abstract: Autonomic nervous system dysfunction may be implicated in the association of hypertension with panic attacks and panic disorder. We hypothesised that panic symptoms of autonomic origin are more common in attacks experienced by hypertensive than normotensive patients, that autonomic panic symptoms cluster together as a distinct factor, and that this factor is more prevalent in hypertensive patients with panic than in normotensives. We analysed all 346 structured questionnaires completed by primary care and hospital clinic patients who had reported experiencing full (n=287) or limited symptom panic attacks (n=59) (268 with hypertension, and 78 never having had hypertension). Frequency of sweating, flushes, and racing heart, symptoms selected prospectively as being most likely of autonomic origin, were compared between hypertensive and normotensive patients. Principal component analysis was performed with varimax orthogonal rotation. Using logistic regression, odds ratios were calculated for association of factor scores with hypertension. Sweating and flushes were significantly more common among hypertensive patients than normotensives (sweating 65% v 46%, p=0.003, flushes 55% v 40%, p=0.019). There was no significant difference between groups for frequency of racing heart nor any of the remaining panic symptoms analysed as secondary endpoints. Principal component analysis yielded four factors with eigenvalues >1.0. Factor 1 was dominated by autonomic symptoms, notably sweating and flushes, which had loadings of 0.68 and 0.61. On regression only this autonomic factor showed a significant association with hypertension, the odds ratio being 1.37 (95% C.I. 1.05 to 1.77, p=0.018). These findings support the possibility that autonomic dysfunction contributes to the association of hypertension with panic.
Publisher: SAGE Publications
Date: 17-09-2012
Abstract: Generalized Anxiety Disorder (GAD) may involve hypo-responsiveness of noradrenaline a2 receptors. To test this hypothesis, we used 99m Tc-hexa-methyl-propylene-amine-oxime (HMPAO) Single Photon Emission Computed Tomography to measure regional cerebral perfusion in patients with untreated GAD, venlafaxine-treated patients and healthy controls during word generation before and after clonidine. Concurrent psychological and physiological measures supported noradrenergic hypofunction in GAD in some cases. A single-day split-dose technique was used. Images were processed using SPM5 (Institute of Neurology). Factorial analysis revealed no significant results. Exploratory analyses were done. Regional perfusion during verbal fluency differed by group pre-clonidine. Compared with healthy controls, patients with untreated GAD displayed increased perfusion in the left Broca’s area and left occipitotemporal region. Treated GAD patients displayed increased cerebellar perfusion bilaterally. Clonidine was associated with different changes in cerebral perfusion in each group. Increases were seen in the right supra-marginal gyrus in healthy subjects, in the left pre-central gyrus in treated GAD patients and in the right cerebellum and middle frontal gyrus in untreated GAD patients. Despite these differences, the findings were not consistent with a noradrenergic hypo-responsiveness hypothesis, as the treated group showed a different pattern of response rather than a normalization of response.
Publisher: SAGE Publications
Date: 08-2015
Abstract: The International Anxiety Disorders Society Conference, held in Melbourne in November 2014, enabled key researchers from Australia and internationally to interact with mental health practitioners with an interest in clinical anxiety disorders. The proceedings of previous conferences in 2006 and 2011 formed the basis of two well-received textbooks on anxiety disorders this time we have taken up the invitation to publish the proceedings as articles in this issue of Australasian Psychiatry. At the end of the first day of the conference a lecture and linked international expert panel explored the topic of guidelines for the management of the anxiety disorders in conjunction with an engaged audience for 90 minutes – key elements of this discussion are presented here. Guidelines for anxiety disorder management should be applied with caution in clinical practice settings.
Publisher: BMJ
Date: 03-2001
DOI: 10.1136/EMJ.18.2.99
Abstract: To assess and improve deployment of a brief test for alcohol misuse: the Paddington Alcohol Test (PAT). Design-Prospective study of the effects of audit feedback. An urban accident and emergency department. Senior house officers (SHO) (n = 13). PAT use and categorisation of patients for each SHO observational analysis of presenting complaints according to PAT. 1062 of 1737 patients (61.1%) were defined as PAT possible-that is, presented with > or = one complaint listed on the PAT test proforma. In month 1, PAT uptake was poor. PAT use improved significantly when feedback was instituted (p collapse (including "fit", "blackout") > head injury (including "facial injury") > assault (including "domestic violence" and 'other') > nonspecific gastrointestinal problem > "unwell" > psychiatric (including "depression", "overdose", "confusion") > cardiac (including "chest pain" and "palpitations") > self neglect > repeat attendance. Ongoing audit with feedback improves both PAT use and detection of alcohol misuse. The PAT is now simpler including only 10 conditions, which should further aid its use.
Publisher: SAGE Publications
Date: 06-09-2021
DOI: 10.1177/10398562211038909
Abstract: To increase awareness of practising clinicians and researchers to the phenomenological distinctions between visual hallucinations and trauma-based, dissociative, visual re-experiencing phenomena seen in psychiatric disease. The experience of visual hallucinations is not exclusive to psychotic disorders in psychiatry. Different forms of experiences that resemble visual hallucinations may occur in patients with a trauma background and may potentially affect diagnosis. Given the paucity of literature around the subject, it is imperative that further research aims to characterise the distinction between visual hallucinations in psychosis and visual phenomena associated with trauma.
Publisher: Informa UK Limited
Date: 09-08-2022
Publisher: SAGE Publications
Date: 21-03-2021
Abstract: The medical use of psychedelic substances (e.g. psilocybin, ayahuasca, lysergic acid diethylamide and 3,4-methylenedioxymeth hetamine) is attracting renewed interest, driven by a pressing need for research and development of novel therapies for psychiatric disorders, as well as promising results of contemporary studies. In this Viewpoint, we reflect upon the ‘Clinical Memorandum on Psychedelics’ recently released by the Royal Australian and New Zealand College of Psychiatrists and note subsequent developments including the application for down-scheduling of psilocybin and 3,4-methylenedioxymeth hetamine presently being considered by the Therapeutic Goods Administration and approvals for access via the Special Access Scheme. We suggest that this field is worthy of rigorous research to assess potential benefits, address safety parameters and clarify therapeutic mechanisms. To this end, we outline recent research findings, provide an overview of current knowledge relating to mechanisms of action and discuss salient aspects of the psychedelic-assisted psychotherapy treatment model. The sum of this research points towards medicinal psychedelics as a potential new class of psychiatric treatments when used within a medically supervised framework with integrated psychotherapeutic support. However, before widespread translation into clinical use can occur, appropriately designed and sufficiently powered trials are required to detect both potential positive and negative outcomes. Unique safety and regulatory challenges also need to be addressed. As for any new medical therapy, psychedelic research needs to be conducted in a rigorous manner, through the dispassionate lens of scientific enquiry. Carte blanche availability to practitioners, without specific protocols and appropriate training, would be potentially harmful to in iduals and detrimental to the field.
Publisher: Mary Ann Liebert Inc
Date: 05-10-2022
Publisher: Royal College of Psychiatrists
Date: 06-2009
DOI: 10.1192/BJP.BP.107.048371
Abstract: Early worsening of anxiety, agitation and irritability are thought to be common among people commencing antidepressants, especially for anxiety disorders. This phenomenon, which may be termed jitteriness/anxiety syndrome, is cited as an explanation for early treatment failure and caution in using selective serotonin reuptake inhibitors (SSRIs). However, we believe that it is inconsistently defined and that robust evidence to support the phenomenon is lacking. To review systematically all evidence relating to jitteriness/ anxiety syndrome to identify: constituent symptoms medications implicated disorders in which it was reported incidence time course management strategies relationship of this syndrome to therapeutic response distinction between syndrome and akathisia relationship between syndrome and suicide and genetic predispositions. A systematic search identified articles and these were included in the review if they addressed one of the above aspects of jitteriness/anxiety syndrome. Of 245 articles identified, 107 articles were included for review. No validated rating scales for jitteriness/anxiety syndrome were identified. There was no robust evidence that the incidence differed between SSRIs and tricyclic antidepressants, or that there was a higher incidence in anxiety disorders. Published incidence rates varied widely from 4 to 65% of people commencing antidepressant treatment. Common treatment strategies for this syndrome included a slower titration of antidepressant and the addition of benzodiazepines. Conclusive evidence for the efficacy of these strategies is lacking. There was conflicting and inconclusive evidence as to whether the emergence of this syndrome had a predictive value on the response to treatment. It appears to be a separate syndrome from akathisia, but evidence for this assertion was limited. The effect of jitteriness/anxiety syndrome on suicide rates has not been evaluated. Three studies examined genetic variations and side-effects from treatment, but none was specifically designed to assess jitteriness/anxiety syndrome. Jitteriness/anxiety syndrome remains poorly characterised. Despite this, clinicians' perception of this syndrome influences prescribing and it is cited to support postulated mechanisms of drug action. We recommend systematised evaluation of side-effects at earlier time points in antidepressant trials to further elucidate this clinically important syndrome.
Publisher: Elsevier BV
Date: 11-2016
DOI: 10.1016/J.JPAIN.2016.07.004
Abstract: In healthy humans, high-frequency electrical stimulation (HFS) of the forearm not only evokes local signs of central sensitization but also triggers broader ipsilateral inhibitory influences on pain akin to a lateralized form of conditioned pain modulation. Paradoxically, some of these inhibitory influences are augmented by α HFS not only evokes local signs of central sensitization but also triggers a broader ipsilateral antinociceptive mechanism mediated by opioid receptors. Dysfunction of this lateralized pain modulation process might contribute to painful unilateral disorders such as migraine or complex regional pain syndrome.
Publisher: Bentham Science Publishers Ltd.
Date: 11-2008
DOI: 10.2174/138161208786848775
Abstract: Anxiety disorders are common and disabling conditions. Current drug treatment methods have limitations including resistance, delayed efficacy and side effects. The advent of sophisticated imaging techniques and the production of highly selective receptor ligands have increased our knowledge of the biological mechanisms underpinning anxiety. Our aim is to review recent discoveries in important neurological systems to provide an understanding of important current anxiolytic targets. Some of these systems, such as GABA, have been implicated in anxiety disorders for decades, but a recent greater understanding is enabling more sophisticated targeting of treatments. In other systems, including the neuropeptides, we have now developed the pharmacological tools in human subjects to begin exploring their relationship to anxiety disorders. We review GABA, serotonin, glutamate, noradrenaline, dopamine and some neuropeptides herein.
Publisher: Elsevier BV
Date: 05-2013
DOI: 10.1016/J.JAD.2013.01.014
Abstract: Research on major depression has confirmed that it is caused by an array of biopsychosocial and lifestyle factors. Diet, exercise and sleep are three such influences that play a significant mediating role in the development, progression and treatment of this condition. This review summarises animal- and human-based studies on the relationship between these three lifestyle factors and major depressive disorder, and their influence on dysregulated pathways associated with depression: namely neurotransmitter processes, immuno-inflammatory pathways, hypothalamic-pituitary-adrenal (HPA) axis disturbances, oxidative stress and antioxidant defence systems, neuroprogression, and mitochondrial disturbances. Increased attention in future clinical studies on the influence of diet, sleep and exercise on major depressive disorder and investigations of their effect on physiological processes will help to expand our understanding and treatment of major depressive disorder. Mental health interventions, taking into account the bidirectional relationship between these lifestyle factors and major depression are also likely to enhance the efficacy of interventions associated with this disorder.
Publisher: Elsevier BV
Date: 07-2009
DOI: 10.1016/J.BIOPSYCH.2009.01.031
Abstract: Selective serotonin reuptake inhibitors (SSRIs) are first-line treatments for posttraumatic stress disorder (PTSD). Serotonergic (5HT) attenuation of stress sensitivity is postulated from SSRIs' effects in other anxiety disorders, and we studied this in PTSD. Ten patients with PTSD fully recovered on SSRIs (Clinical Global Impression Scale-I 1 and 2) were enrolled in the study. Patients were tested on two occasions 1 week apart in each session, they received a drink containing large neutral amino acids (LNAAs) either with (sham tryptophan depletion [STD], control) or without (acute tryptophan depletion [ATD]) tryptophan. At 5.5 hours after the drink, subjects were exposed to a trauma-related exposure challenge. Self-reports of PTSD (visual analogue scales [VAS] and the Davidson Trauma Scale [DTS]), anxiety (Spielberger State Inventory [STAI] Form Y-1), and mood (Profile of Mood States [POMS]) were obtained. Heart rate (HR), systolic (SBP) and diastolic (DBP) blood pressure were also measured. The trauma-related exposure challenge induced anxiety on both days, with more marked responses on the ATD day according to VAS, DTS, POMS, and DBP (p p > .05) was observed for STAI Form Y-1, HR, and SBP. These data demonstrate that ATD accentuates responses to trauma-related stimuli in SSRI-recovered PTSD. They also suggest that SSRI-induced increases in serotonin function restrain PTSD symptoms, especially under provocation, supporting a role for serotonin in mediating stress resilience.
Publisher: Elsevier BV
Date: 10-2006
DOI: 10.1016/J.PSYNEUEN.2006.07.001
Abstract: Acute tryptophan depletion (ATD) is a technique that has been used to evaluate the effects on humans of acutely reducing serotonin neurotransmission. We have developed a model using a single breath of 35% CO(2) that activates the hormonal axis and produces autonomic and behavioural arousal, thus modelling a stress response. This study combines ATD and single breath 35% CO(2) inhalation to study stress responses in volunteers. A randomised, double-blinded, placebo-controlled, cross-over trial involving 14 healthy adult volunteers aged between 18 and 65 years was undertaken. Subjects underwent double-blind tryptophan depletion over 2 days and were then crossed over 1 week later. During each study day, at the time of peak depletion, participants were single blinded to receive a single breath of 35% CO(2) or air. This was followed 40 min later by the other gas. Psychological outcomes were assessed with the Spielberger State Anxiety Inventory (SSAI), Visual Analogue Scales (VAS), Panic Inventory (PI), Panic and Agoraphobia Scale (PSI) and Beck Depression Inventory (BDI). Physiological outcome was measured by serial plasma cortisol, prolactin and tryptophan levels, pulse and blood pressure. Tryptophan depletion did not exacerbate 35% CO(2) inhalation effects on anxiety symptoms. Single breath CO(2) robustly increased plasma cortisol levels in comparison to an air inhalation this was less certain for prolactin levels. ATD influenced the HPA axis (associated with higher cortisol levels), apparently independent of CO(2) or air inhalation stressors. ATD and 35% CO(2) inhalation both induced a pressor response and bradycardia in these normal volunteers. Thirty-five percent CO(2) inhalation and ATD independently activate the human stress response, but do not appear to produce synergistic effects when combined, at least for the conditions produced in this study.
Publisher: Elsevier BV
Date: 2004
DOI: 10.1016/S0965-2302(03)00054-7
Abstract: This article presents the findings of a review of the first year of a night emergency department (ED) mental health triage and consultancy service. During the first 12 months of operation of the service, data on key performance indicators were entered into an emergency mental health triage and consultancy database. Data were also obtained from pre- and post-satisfaction surveys completed by ED staff and from self-appraisal statements generated by the five mental health nurses who undertook the position during the review period. The findings show the ED mental health triage and consultancy service positively impacted on the functioning of the emergency department. This was evidenced by staff' perceptions regarding the value of the service and through shorter "seen by times", a reduction in the number of patients with psychiatric sychosocial problems who left the department without being seen, and the effective management of patients presenting with psychiatric sychosocial problems, particularly those presenting with deliberate self-harm. The review provided evidence regarding the value of the emergency mental health triage and consultancy service and highlighted the advanced practice role undertaken by mental health nurses in this position.
Publisher: Elsevier BV
Date: 10-2004
Publisher: Scientific Research Publishing, Inc.
Date: 2013
Publisher: SAGE Publications
Date: 21-01-2010
Abstract: Serotonin and noradrenaline reuptake inhibitor (SNRI) antidepressants have evidence of efficacy in the treatment of generalized anxiety disorder (GAD) however, it is not clear whether there is an advantage over selective serotonin reuptake inhibitor (SSRI) medicines and there is limited evidence for noradrenergic dysfunction in GAD. We tested whether a dysfunctional alpha-2 adrenoceptor system is present in patients with GAD and the effects of SNRI treatment on this system. The method used was an infusion of clonidine (a selective alpha-2 adrenergic receptor agonist) on psychological and physiological outcomes in three subject groups: 10 untreated GAD patients, five SNRI-treated GAD patients and seven normal controls. The clonidine challenge elicited sedation, a rise in growth hormone, decrease in blood pressure, decline in saccadic eye movement (SEM) variables, and improvement in verbal fluency as anticipated in the 22 subjects examined. Lower cortisol levels were found in controls and higher blood pressure readings in GAD-treated subjects, as well as evidence that GAD-treated subjects had SEMs that were intermediate between control and GAD subjects’ scores and have less clonidine-induced sedation. The implications of these findings with reference to the study hypothesis in this small study are discussed.
Publisher: Bentham Science Publishers Ltd.
Date: 23-07-2015
DOI: 10.2174/1381612821666150619092720
Abstract: This review paper discusses the central role of gamma-aminobutyric acid (GABA) in erse physiological systems and functions and the therapeutic potential of the benzodiazepine antagonist flumazenil (Ro 15- 1788) for a wide range of disorders of the central nervous system (CNS). Our group and others have studied the potential of flumazenil as a treatment for benzodiazepine dependence. A small but growing body of research has indicated that flumazenil may also have clinical application in CNS disorders such as Parkinson's disease, idiopathic hypersomnia and amyotrophic lateral sclerosis. Despite this body of research the therapeutic potential of flumazenil remains poorly understood and largely unrealized. The purpose of this paper is not to provide an exhaustive review of all possible therapeutic applications for flumazenil but rather to stimulate research interest, and discussion of the exciting therapeutic potential of this drug for a range of chronic debilitating conditions.
Publisher: Elsevier BV
Date: 2014
DOI: 10.1016/J.PNPBP.2013.09.017
Abstract: Biomarkers are regularly used in medicine to provide objective indicators of normal biological processes, pathogenic processes or pharmacological responses to therapeutic interventions, and have proved invaluable in expanding our understanding and treatment of medical diseases. In the field of psychiatry, assessment and treatment has, however, primarily relied on patient interviews and questionnaires for diagnostic and treatment purposes. Biomarkers in psychiatry present a promising addition to advance the diagnosis, treatment and prevention of psychiatric diseases. This review provides a summary on the potential of peripheral biomarkers in major depression with a specific emphasis on those related to inflammatory/immune and oxidative stress/antioxidant defences. The complexities associated with biomarker assessment are reviewed specifically around their collection, analysis and interpretation. Focus is placed on the potential of peripheral biomarkers to aid diagnosis, predict treatment response, enhance treatment-matching, and prevent the onset or relapse of major depression.
Publisher: SAGE Publications
Date: 04-2010
DOI: 10.3109/10398560903473686
Abstract: Objective: Prescribers are warned to be vigilant for potential cytochrome P450 mediated drug interactions guidelines separately highlight risks of toxicity associated with zuclopenthixol acuphase. We previously examined potential cytochrome P450 interactions with zuclopenthixol and here describe dangerous side effects in a patient receiving zuclopenthixol acuphase and the selective serotonin reuptake inhibitor fluoxetine at high dose. Method: We present the case of a patient established on fluoxetine 80 mg/day who subsequently received injected zuclopenthixol acuphase 100 mg. Results: Following zuclopenthixol acuphase administration, dangerous extra-pyramidal side effects were observed, including severe laryngeal dystonia necessitating emergency medical treatment. Conclusions: Our observations of symptoms of zuclopenthixol toxicity are consistent with a cytochrome P450 2D6/3A4 interaction with fluoxetine. Previous evidence demonstrating this interaction included only patients taking fluoxetine up to 60 mg/day. This case extends the evidence base. In patients taking high dose fluoxetine, we advise marked reductions in the prescribed dose of zuclopenthixol acuphase.
Publisher: Elsevier BV
Date: 12-2015
Publisher: Elsevier BV
Date: 11-2021
DOI: 10.1016/J.BANDC.2021.105791
Abstract: The development of Vigilant Attention (VA), the ability to focus and maintain our attention to repetitive and cognitively unchallenging tasks over time, has been investigated for more than a decade. The development of this critical executive function across the lifespan has been characterised by a rapid improvement in VA performance throughout childhood and adolescence, a steady improvement in adulthood and a slow decline in older adulthood. However, the development of the neural correlates of VA in children and adolescents remains poorly understood. Using a cross-sectional design, the present study used a meta-analytically defined VA network in children and adolescents to explore the developmental trend of the resting-state functional connectivity (rsFC) within the VA network across two independent cohorts. The results showed a linear and non-linear decrease of rsFC between the left and right VA brain regions across age. However, the results could not be reproduced in the replication cohort, potentially due to a smaller s le size. Based on previous findings from behavioural studies, the present findings suggest that changes in rsFC may underlie a developmental shift in cognitive strategies in neurotypical children and adolescents.
Publisher: SAGE Publications
Date: 2002
DOI: 10.1177/026988110201600116
Abstract: The neurobiological basis of panic disorder has not been clearly established, although a role for serotonin (5-HT) has been postulated. It is clear that drugs which increase 5-HT neurotransmission are effective in treating the condition but how they do so remains a point of debate. The aim of this study was to determine if lowering brain serotonin activity using the technique of tryptophan depletion provoked a short-term relapse of panic symptoms in patients with panic disorder who had responded to drug treatment. Fourteen patients with panic disorder who had responded to treatment with the selective serotonin reuptake inhibitor (SSRI) paroxetine received a tryptophan-free amino acid drink on one occasion and a control drink on the other in a double-blind crossover design. In addition, they received an infusion of flumazenil (used as a pharmacological challenge) and placebo on each day. The tryptophan depleted drink produced an 87% reduction in plasma tryptophan concentration. Flumazenil produced a panic attack (defined by changes in the panic inventory) in seven out of 14 patients when tryptophan depleted and one out of 14 on the control day (p 0.02). Three patients also experienced temporary depressive symptoms when tryptophan depleted, with no mood changes being seen on the control days. We conclude that rapid lowering of brain serotonin function can allow the precipitation of panic symptoms in response to flumazenil in panic disorder patients who have responded to treatment with an SSRI. This implies that in panic disorder increased 5-HT availability is important in maintaining the response to SSRIs.
Publisher: SAGE Publications
Date: 17-07-2015
Abstract: The relationships between serotonin and fear and anxiety disorders have been much studied yet many important questions remain, despite selective serotonin reuptake inhibitors having been the primary treatments for these disorders for some time. In order to explore this issue we performed a pooled analysis of six of our studies in remitted patients with a fear/anxiety disorder who were exposed to syndrome-specific aversive stimulation under acute tryptophan depletion. We based our analysis on the hypothesis that the inconsistencies observed in the studies could be predicted by Deakin and Graeff’s theory about the dual role of serotonin in responses to threats, whereby serotonin is critical to prevent fear (panic) but not anxiety. In accordance with this view, our results give support to a dissociation of the disorders traditionally grouped under fear and anxiety-related disorders in terms of different roles of serotonin in modulation of responses to aversive stimulation. Implications for future studies and psychiatric nosology are discussed.
Publisher: SAGE Publications
Date: 07-2005
DOI: 10.1080/J.1440-1614.2005.01627.X
Abstract: Objective: Acute tryptophan depletion (ATD) is an experimental technique that has been widely used over the last decade to investigate the role of serotonin (5-HT) in a variety of disorders. This review, the first of two articles, describes the rationale behind this technique and provides detail on how it is applied in research settings. Method: The authors outline the development of this technique with reference to the seminal literature and more recent findings from neuroimaging and neuroendocrine studies. This is supplemented by the authors' clinical experience of over 5 years of continuous experimental work with this paradigm in over 50 subjects. Results: Acute tryptophan depletion is a method that significantly reduces central 5-HT in human subjects. Non-serotonergic explanations of the effects of ATD have not been confirmed, supporting the specificity of this method. Conclusions: The ATD technique is a valid method of manipulating central 5-HT levels. The second article in this series will review the application of ATD in depression, anxiety and other psychiatric conditions.
Publisher: SLACK, Inc.
Date: 02-2011
Publisher: Project MUSE
Date: 2007
Publisher: Elsevier BV
Date: 03-2016
Publisher: EDITORA SCIENTIFIC
Date: 12-2006
Publisher: Springer Science and Business Media LLC
Date: 06-2000
Publisher: SAGE Publications
Date: 2023
DOI: 10.1177/20451253231156400
Abstract: Anxiety disorders are highly prevalent and chronic disorders with treatment resistance to current pharmacotherapies occurring in approximately one in three patients. It has been postulated that flumazenil (FMZ) is efficacious in the management of anxiety disorders via the removal of α 4 β2δ gamma-aminobutyric acid A receptors. To assess the safety and feasibility of continuous low-dose FMZ infusions for the management of generalised anxiety disorder (GAD) and collect preliminary efficacy data. Uncontrolled, open-label pilot study. Participants had a primary diagnosis of generalised anxiety disorder (GAD) and received two consecutive subcutaneous continuous low-dose FMZ infusions. Each infusion contained 16 mg of FMZ and was delivered over 96 ± 19.2 h. The total dose of FMZ delivered was 32 mg over approximately 8 days. Sodium valproate was given to participants at risk of seizure. The primary outcome was the change in stress and anxiety subscale scores on the Depression Anxiety Stress Scale–21 between baseline, day 8, and day 28. Nine participants with a primary diagnosis of GAD were treated with subcutaneous continuous low-dose FMZ infusions seven participants met the criteria for treatment resistance. There was a significant decrease in anxiety and stress between baseline and day 8 and baseline and day 28. There was also a significant improvement in subjective sleep quality from baseline to day 28 measured by the Jenkins Sleep Scale. No serious adverse events occurred. This study presents preliminary results for subcutaneous continuous low-dose FMZ’s effectiveness and safety in GAD. The findings suggest that it is a safe, well-tolerated, and feasible treatment option in this group of patients. Future randomised control trials are needed in this field to determine the efficacy of this treatment.
Publisher: Wiley
Date: 04-2001
Publisher: Elsevier BV
Date: 10-2014
DOI: 10.1016/J.JAD.2014.06.001
Abstract: Curcumin, the principal curcuminoid derived from the spice turmeric, influences several biological mechanisms associated with major depression, namely those associated with monoaminergic activity, immune-inflammatory and oxidative and nitrosative stress pathways, hypothalamus-pituitary-adrenal (HPA) axis activity and neuroprogression. We hypothesised that curcumin would be effective for the treatment of depressive symptoms in in iduals with major depressive disorder. In a randomised, double-blind, placebo-controlled study, 56 in iduals with major depressive disorder were treated with curcumin (500 mg twice daily) or placebo for 8 weeks. The primary measure was the Inventory of Depressive Symptomatology self-rated version (IDS-SR30). Secondary outcomes included IDS-SR30 factor scores and the Spielberger State-Trait Anxiety Inventory (STAI). From baseline to week 4, both curcumin and placebo were associated with improvements in IDS-SR30 total score and most secondary outcome measures. From weeks 4 to 8, curcumin was significantly more effective than placebo in improving several mood-related symptoms, demonstrated by a significant group x time interaction for IDS-SR30 total score (F1, 53=4.22, p=.045) and IDS-SR30 mood score (F1, 53=6.51, p=.014), and a non-significant trend for STAI trait score (F1, 48=2.86, p=.097). Greater efficacy from curcumin treatment was identified in a subgroup of in iduals with atypical depression. Partial support is provided for the antidepressant effects of curcumin in people with major depressive disorder, evidenced by benefits occurring 4 to 8 weeks after treatment. Investigations with larger s le sizes, over extended treatment periods, and with varying curcumin dosages are required.
Publisher: Informa UK Limited
Date: 2009
DOI: 10.1080/10253890801976926
Abstract: The responses to inhalation of 35% carbon dioxide (CO(2)) as a stressor were compared in female irritable bowel syndrome (IBS) patients and healthy controls to assess potential differences in cardiovascular, neuroendocrine and behavioural responses to stress. A total of 22 women (12 patients with ROME II defined diarrhoea-predominant IBS and 10 aged-matched controls) were challenged with a single vital capacity breath of 35% CO(2) (with 65% oxygen). Beat-to-beat blood pressure and heart rate were recorded prior to, during and after the inhalation. Serum cortisol concentration and behavioural ratings were measured pre- and post-inhalation. A typical pattern of responses to CO(2) was observed, characterised by a reduction in heart rate and increases in serum cortisol and anxiogenic symptoms however, these responses did not differ between groups. Both groups also demonstrated an increase in systolic blood pressure however, this response was significantly enhanced in IBS patients compared to healthy controls (P < 0.05). These findings demonstrate that females with diarrhoea-predominant IBS have an exaggerated pressor response to 35% CO(2) stress challenge, suggesting a more stress-responsive sympathetic nervous system.
Publisher: EDITORA SCIENTIFIC
Date: 12-2006
Publisher: Springer Science and Business Media LLC
Date: 13-10-2011
DOI: 10.1007/S00213-009-1696-Z
Abstract: The aim of this study was to examine the effect of rapid tryptophan depletion (RTD) combined with a panicogenic challenge in patients with panic disorder who had responded to treatment with cognitive behavioural therapy (CBT). We hypothesised that RTD (compared with the control drink) would result in an increase in anxiety symptoms when provoked by a panicogenic challenge with the benzodiazepine antagonist, flumazenil. Nine patients with panic disorder who had responded to CBT received a tryptophan-free amino acid drink on one occasion and a control drink on the other in a double-blind crossover design. In addition, they received flumazenil and placebo infusions on each day. Our hypothesis regarding the effects of RTD was supported by findings of a significant interaction between RTD and flumazenil on measures from visual analogues scales (total) and the Spielberger State Anxiety inventory. A somewhat unexpected finding was that in this group of CBT responders, the panicogenic effect of flumazenil was not completely blocked by treatment. This meant that although four of the nine subjects (44%) reported a panicogenic effect of flumazenil on the RTD day, this was not significantly different from the rate of panic attacks in response to flumazenil on the control day. We suggest that the partial return of symptoms in response to flumazenil reflects a vulnerability to RTD in this group of panic disorder patients who had responded to treatment with CBT.
Publisher: Elsevier BV
Date: 08-2002
DOI: 10.1016/S0306-4530(01)00075-0
Abstract: The hypothalamo-pituitary-adrenal (HPA) axis is a major stress responsive system in humans. Although there are numerous ways of testing responsiveness of the HPA in experimental animals, this is much more difficult in man. Hypercapnea is a very stressful stimulus for humans and has been used as an anxiogenic probe in psychiatric patients. We have now investigated whether the simple challenge of a single 35% inhalation of CO(2) activates the neuroendocrine system as evidenced by changes in HPA activity, as well as cardiovascular and subjective responses, in healthy volunteers. Fourteen healthy male volunteers were recruited. They underwent single vital capacity inhalation of room air and 35% CO(2), in a single blind fashion. Neuroendocrine, cardiovascular and subjective fear measures were taken at regular intervals. CO(2) inhalation produced significant activation of the HPA axis in all subjects, as measured with plasma cortisol. Heart rate was decreased and systolic blood pressure was significantly increased shortly after the inhalation of CO(2). The subjects reported short-lived symptoms of fear with the experimental gas. Single vital capacity inhalation of 35% CO(2) activated the HPA axis in healthy volunteers. It also had a significant cardiovascular and psychological (anxiogenic) effect, as expected from previous published studies. The test is potentially useful in studying the responsivity of the HPA axis in health and disease.
Location: No location found
Location: Australia
Start Date: 04-2023
End Date: 04-2026
Amount: $395,000.00
Funder: Australian Research Council
View Funded Activity