Psychiatry - Research Publications

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    GABA-modulating phytomedicines for anxiety: A systematic review of preclinical and clinical evidence
    Savage, K ; Firth, J ; Stough, C ; Sarris, J (WILEY, 2018-01)
    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. An open-ended search to 5 July 2017 was conducted using MEDLINE (PubMed), Scopus, and Cochrane library online databases and performed in a stepped format from preclinical to clinical investigations. Eligible studies must have had (a) in vitro evidence of GABA-modulating activity, (b) animal studies using anxiety models to test an anxiolytic effect, and (c) human clinical trials. Ten phytomedicines were identified as having preclinical investigations showing interaction with the GABA system, in addition to human clinical trials: kava, valerian, pennywort, hops, chamomile, Ginkgo biloba, passionflower, ashwagandha, skullcap, and lemon balm. Collectively, the literature reveals preclinical 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.
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    Herbal medicines in the treatment of psychiatric disorders: 10-year updated review
    Sarris, J (WILEY, 2018-07)
    This paper provides a 10-year update of the 2007 systematic review of herbal medicines studied in a broad range of psychiatric disorders, including depression, anxiety, obsessive-compulsive, seasonal affective, bipolar, psychotic, phobic, somatoform, and attention-deficit hyperactivity disorders. Ovid Medline, PubMed, and the Cochrane Library were searched for herbal medicines with both pharmacological and clinical evidence of psychotropic activity. This updated review now covers clinical trial evidence for 24 herbal medicines in 11 psychiatric disorders. High-quality evidence was found to exist for the use of Piper methysticum (Kava), Passiflora spp. (passionflower) and Galphimia glauca (galphimia) for anxiety disorders; and Hypericum perforatum (St John's wort) and Crocus sativus (saffron) for major depressive disorder. Other encouraging herbal medicines with preliminary evidence include Curcuma longa (turmeric) in depression, Withania somnifera (ashwagandha) in affective disorders, and Ginkgo biloba (ginkgo) as an adjunctive treatment in Schizophrenia. Although depression and anxiety are commonly researched, many other mental disorders still require further prospective investigation. Although the previous review suggested increasing the adjunctive study of select herbal medicines with pharmaceuticals, this was still only found to sparingly occur in research designs. Aside from this, future focus should involve the incorporation of more biomarker analysis, in particular pharmacogenomics, to determine genetic factors moderating response to herbal medicines.
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    A Randomized, Controlled Trial of Meditation for Work Stress, Anxiety and Depressed Mood in Full-Time Workers
    Manocha, R ; Black, D ; Sarris, J ; Stough, C (HINDAWI LTD, 2011)
    Objective. To assess the effect of meditation on work stress, anxiety and mood in full-time workers. Methods. 178 adult workers participated in an 8-week, 3-arm randomized controlled trial comparing a "mental silence" approach to meditation (n = 59) to a "relaxation" active control (n = 56) and a wait-list control (n = 63). Participants were assessed before and after using Psychological Strain Questionnaire (PSQ), a subscale of the larger Occupational Stress Inventory (OSI), the State component of the State/Trait Anxiety Inventory for Adults (STAI), and the depression-dejection (DD) subscale of the Profile of Mood States (POMS). Results. There was a significant improvement for the meditation group compared to both the relaxation control and the wait-list groups the PSQ (P = .026), and DD (P = .019). Conclusions. Mental silence-orientated meditation, in this case Sahaja Yoga meditation, is a safe and effective strategy for dealing with work stress and depressive feelings. The findings suggest that "thought reduction" or "mental silence" may have specific effects relevant to work stress and hence occupational health.
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    The Effects of Multivitamin Supplementation on Diurnal Cortisol Secretion and Perceived Stress
    Camfield, DA ; Wetherell, MA ; Scholey, AB ; Cox, KHM ; Fogg, E ; White, DJ ; Sarris, J ; Kras, M ; Stough, C ; Sali, A ; Pipingas, A (MDPI AG, 2013-11)
    Recent evidence suggests that dietary intake of vitamins, in particular the B-vitamins including B6, B9 and B12 may have a number of positive effects on mood and stress. Given the effects of stress on a range of biological mechanisms including the endocrine system, it could be reasonably expected that multivitamin supplementation may also affect markers of these mechanisms such as diurnal cortisol secretion. In the current double-blind placebo-controlled study 138 adults (aged 20 to 50 years) were administered a multivitamin containing B-vitamins versus placebo over a 16-week period. Salivary cortisol measurements were taken at waking, 15-min, 30-min and at bedtime, at baseline, 8-weeks and 16-weeks. Perceived Stress (PSS) was measured at baseline, 8-weeks and 16-weeks, while blood serum measures of B6, B12 and homocysteine (HCy) as well as red cell folate (B9) were also collected at these time points. A significant interaction was found between treatment group and study visit for the Cortisol Awakening Response (CAR). Compared to placebo, at 16-weeks multivitamin supplementation was found to be associated with a near-significant trend towards an increased CAR. No significant differences in PSS were found between groups, with PSS increasing in both groups across the course of the study. Red cell folate was found to be significantly correlated with the CAR response at 16-weeks while HCy levels were not found to be associated with the CAR response, although HCy significantly correlated with waking cortisol levels at 8-weeks. A possible interpretation of the elevation in CAR associated with multivitamin supplementation is that this represents an adaptive response to everyday demands in healthy participants.
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    A randomized controlled trial investigating the effects of PCSO-524®, a patented oil extract of the New Zealand green lipped mussel (Perna canaliculus), on the behaviour, mood, cognition and neurophysiology of children and adolescents (aged 6-14 years) experiencing clinical and subclinical levels of hyperactivity and inattention: study protocol ACTRN12610000978066
    Kean, JD ; Camfield, D ; Sarris, J ; Kras, M ; Silberstein, R ; Scholey, A ; Stough, C (BMC, 2013-07-16)
    BACKGROUND: The prevalence rate of attention-deficit/hyperactivity disorder (ADHD) within Western cultures is between 5% and 12%, and is the most common psychiatric illness among school-aged children, with an estimated 50% of these children retaining ADHD symptoms for the rest of their lives. Children with ADHD have lower blood levels of long-chain Poly Unsaturated Fatty Acids (LC PUFAs) compared with children without ADHD, and following PUFA supplementation, have shown improvements in ADHD-related symptoms. One highly promising marine based LC PUFA preparation is the Omega-3-rich Lyprinol/Omega XL which is a natural formulation containing standardised lipid extract of the New Zealand green lipped mussel (Perna canaliculus) known as PCSO-524® which contains a unique combination of free fatty acids, sterol esters, polar lipids and carotenoids. It is this unique combination of marine lipids that may assist in correcting the decreased levels of LC PUFA levels in children with symptoms of ADHD. The compound is a mixture belonging to a lipid group called sterol esters (SE). The fatty acids in the SE fraction are mainly myristic acid, palmitic acid, palmitoleic acid, stearic acid, oleic acid, linoleic acid, eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA). Lyprinol/Omega XL has previously been shown to contain a potent group of Omega-3 lipids that block the 5 - lipoxygenase metabolic pathway responsible for inflammation in the body. METHODS: A randomized double blind placebo controlled trial will be utilized to assess the effects of 14 weeks administration of Lyprinol/Omega XL versus placebo in 150 children aged 6 to 14 years with high levels of hyperactivity and inattention. Additionally, a range of cognitive, mood and central electrophysiological measures will be undertaken during the 14 week supplementation trial. The primary outcome measure, the Conners' Parent Rating Scales will be completed initially at baseline, then in weeks 4, 8, 10, 14 and then again at 4 weeks post-administration (week 18). The results will contribute to our understanding of the efficacy of marine based Omega-3 s with high anti-inflammatory actions on inattention and hyperactivity in children aged 6 to 14 years.
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    A Randomized Controlled Trial Investigating the Effects of a Special Extract of Bacopa monnieri (CDRI 08) on Hyperactivity and Inattention in Male Children and Adolescents: BACHI Study Protocol (ANZCTRN12612000827831)
    Kean, JD ; Kaufman, J ; Lomas, J ; Goh, A ; White, D ; Simpson, D ; Scholey, A ; Singh, H ; Sarris, J ; Zangara, A ; Stough, C (MDPI, 2015-12)
    UNLABELLED: Clinical diagnoses of Attention Deficit Hyperactivity Disorder (ADHD) and the use of prescription medications for its treatment have increased in recent years. Current treatments may involve the administration of amphetamine-type substances, a treatment path many parents are apprehensive to take. Therefore, alternative pharmacological treatments are required. Few nutritional or pharmacological alternatives that reduce ADHD associated symptoms (hyperactivity and inattention) have been subjected to rigorous clinical trials. Bacopa monnieri is a perennial creeping herb. CDRI 08 is a special extract of Bacopa monnieri which has been subjected to hundreds of scientific studies and has been shown in human randomized controlled trials (RCTs) to improve memory, attention, and mood. It is hypothesised that chronic administration of CDRI 08 will improve attention, concentration and behaviour in children with high levels of hyperactivity and/or inattention. This paper reports the protocol for the first 16-week, randomized, placebo-controlled, double-blind, parallel groups trial examining the efficacy and safety of CDRI 08 in male children aged 6-14 years with high levels of inattention and hyperactivity. The primary outcome variable will be the level of hyperactivity and inattention measured by the Conners' Parent Rating Scale (CPRS). Secondary outcome variables include cognition, mood, sleep, and EEG. TRIAL REGISTRATION: Australia and New Zealand Clinical Trials Register (ANZCTR): ACTRN12612000827831.
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    Herbal medicine use behaviour in Australian adults who experience anxiety: a descriptive study
    McIntyre, E ; Saliba, AJ ; Wiener, KK ; Sarris, J (BMC, 2016-02-11)
    BACKGROUND: Anxiety disorders are the most prevalent mental health condition in Australia. In addition, there are many people who experience problematic anxiety symptoms who do not receive an anxiety disorder diagnosis but require treatment. As herbal medicine use is popular in Australia, and little is known about how adults experiencing anxiety are using these medicines, this study aimed to identify how Australian adults who experience anxiety are using herbal medicines. METHODS: An online cross-sectional descriptive study was conducted using purposive convenience sampling to recruit Australian adults who have experienced anxiety symptoms and have used herbal medicines (N = 400). Descriptive statistics, chi-square test of contingency, analysis of variance, and simple logistic regression was used to analyse the data. RESULTS: Eighty two percent of participants experienced anxiety symptoms in the previous 12 months, with 47% reporting having previously been diagnosed with an anxiety disorder. In addition, 72.8% had used herbal medicines specifically for anxiety symptoms in their lifetime, while 55.3% had used prescribed pharmaceuticals, with 27.5% having used herbal medicines concurrently with prescribed pharmaceuticals. The Internet and family and friends were the most frequently used sources of information about herbal medicines. Forty eight percent of participants did not disclose their herbal medicine use to their doctor. CONCLUSIONS: Herbal medicines are being used by adults with anxiety and are commonly self-prescribed for anxiety symptoms. Health practitioners who are experts in herbal medicine prescribing are consulted infrequently. In addition, herbal medicine use is often not disclosed to health practitioners. These behaviours are concerning as people may not be receiving the most suitable treatments, and their use of herbal medicines may even be dangerous. It is critical we develop a better understanding of why people are using these medicines, and how we can develop improved health literacy to help with treatment decision making to ensure people receive optimal care.
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    Kava for the treatment of generalised anxiety disorder (K-GAD): study protocol for a randomised controlled trial
    Savage, KM ; Stough, CK ; Byrne, GJ ; Scholey, A ; Bousman, C ; Murphy, J ; Macdonald, P ; Suo, C ; Hughes, M ; Thomas, S ; Teschke, R ; Xing, C ; Sarris, J (BMC, 2015-11-02)
    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, randomised, double-blind, placebo-controlled study using an aqueous extract of noble kava cultivar (standardised 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 Queensland) 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: ClinicalTrials.gov: NCT02219880 Date: 13 August 2014:.
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    N-Acetyl Cysteine in the Treatment of Obsessive Compulsive and Related Disorders: A Systematic Review
    Oliver, G ; Dean, O ; Camfield, D ; Blair-West, S ; Ng, C ; Berk, M ; Sarris, J (KOREAN COLL NEUROPSYCHOPHARMACOLOGY, 2015-04)
    OBJECTIVE: Obsessive compulsive and related disorders are a collection of debilitating psychiatric disorders in which the role of glutamate dysfunction in the underpinning neurobiology is becoming well established. N-acetyl cysteine (NAC) is a glutamate modulator with promising therapeutic effect. This paper presents a systematic review of clinical trials and case reports exploring the use of NAC for these disorders. A further objective was to detail the methodology of current clinical trials being conducted in the area. METHODS: PubMed, Web of Science and Cochrane Library Database were searched for human clinical trials or case reports investigating NAC in the treatment of obsessive compulsive disorder (OCD) or obsessive compulsive related disorders. Researchers with known involvement in NAC studies were contacted for any unpublished data. RESULTS: Four clinical trials and five case reports/series were identified. Study durations were commonly 12-weeks, using 2,400-3,000 mg/day of NAC. Overall, NAC demonstrates activity in reducing the severity of symptoms, with a good tolerability profile and minimal adverse effects. Currently there are three ongoing randomized controlled trials using NAC for OCD (two adults and one pediatric), and one for excoriation. CONCLUSIONS: Encouraging results have been demonstrated from the few pilot studies that have been conducted. These results are detailed, in addition to a discussion of future potential research.
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    Exploring the Effect of LactiumTM and Zizyphus Complex on Sleep Quality: A Double-Blind, Randomized Placebo-Controlled Trial
    Scholey, A ; Benson, S ; Gibbs, A ; Perry, N ; Sarris, J ; Murray, G (MDPI, 2017-02)
    Acute, non-clinical insomnia is not uncommon. Sufferers commonly turn to short-term use of herbal supplements to alleviate the symptoms. This placebo-controlled, double-blind study investigated the efficacy of LZComplex3 (lactiumâ„¢, Zizyphus, Humulus lupulus, magnesium and vitamin B6), in otherwise healthy adults with mild insomnia. After a 7-day single-blind placebo run-in, eligible volunteers (n = 171) were randomized (1:1) to receive daily treatment for 2 weeks with LZComplex3 or placebo. Results revealed that sleep quality measured by change in Pittsburgh Sleep Quality Index (PSQI) score improved in both the LZComplex3 and placebo groups. There were no significant between group differences between baseline and endpoint on the primary outcome. The majority of secondary outcomes, which included daytime functioning and physical fatigue, mood and anxiety, cognitive performance, and stress reactivity, showed similar improvements in the LZComplex3 and placebo groups. A similar proportion of participants reported adverse events (AEs) in both groups, with two of four treatment-related AEs in the LZComplex3 group resulting in permanent discontinuation. It currently cannot be concluded that administration of LZComplex3 for 2 weeks improves sleep quality, however, a marked placebo response (despite placebo run-in) and/or short duration of treatment may have masked a potential beneficial effect on sleep quality.