Psychiatry - Research Publications
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ItemGABA-modulating phytomedicines for anxiety: A systematic review of preclinical and clinical evidence(WILEY, 2018-01-01)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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ItemHerbal medicines in the treatment of psychiatric disorders: 10-year updated review(WILEY, 2018-07-01)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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ItemA 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)(MDPI, 2015-12-01)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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ItemHerbal medicine use behaviour in Australian adults who experience anxiety: a descriptive study(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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ItemKava for the treatment of generalised anxiety disorder (K-GAD): study protocol for a randomised controlled trial(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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ItemN-Acetyl Cysteine in the Treatment of Obsessive Compulsive and Related Disorders: A Systematic Review(KOREAN COLL NEUROPSYCHOPHARMACOLOGY, 2015-04-01)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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ItemExploring the Effect of Lactium(TM) and Zizyphus Complex on Sleep Quality: A Double-Blind, Randomized Placebo-Controlled Trial(MDPI, 2017-02-01)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 (lactium™, 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.
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ItemReduced inattention and hyperactivity and improved cognition after marine oil extract (PCSO-524A (R)) supplementation in children and adolescents with clinical and subclinical symptoms of attention-deficit hyperactivity disorder (ADHD): a randomised, double-blind, placebo-controlled trial(SPRINGER, 2017-02-01)INTRODUCTION: This study investigated the effects of a marine oil extract (PCSO-524®) on inattention, hyperactivity, mood and cognition in children and adolescents. PCSO-524® is a standardised lipid extract of the New Zealand green-lipped mussel and is an inflammatory modulator that inhibits the 5'-lipoxygenase and cyclooxygenase pathways and decreases concentrations of the pro-inflammatory arachidonic acid (AA). METHODS: PCSO-524® or a matched placebo was administered for 14 weeks to 144 participants (123 males/21 females; mean age 8.7 years) with high hyperactivity and inattention in a randomised, double-blind, placebo-controlled study. The primary outcome was the Conners Parent Rating Scale assessing parental reports of behavioural problems. Secondary outcomes assessed changes in cognition and mood. RESULTS: The results of the present study did not support the hypothesis that PCSO-524® improves parental reports of hyperactivity, inattention and impulsivity in children ages 6 to 14 years over placebo. Repeated measures ANOVA on post hoc subsample analysis indicated significant improvements in hyperactivity (p = 0.04), attention (p = 0.02), learning (p = 0.05) and probability of ADHD (p = 0.04) with a medium to large average effect size (d = 0.65) in those children who did not meet criteria for combined hyperactivity and inattention. Furthermore, significant improvements in the PCSO-524® group were indicated in a whole sample repeated measures ANCOVA on recognition memory between baseline and week 8 over placebo (p = 0.02, d = 0.56); this difference was not sustained at week 14. CONCLUSIONS: The results presented indicate that PCSO-524® may be beneficial in reducing levels of hyperactivity and inattention in a population of children with clinical and subclinical symptoms of ADHD.
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ItemNutritional Deficiencies and Clinical Correlates in First-Episode Psychosis: A Systematic Review and Meta-analysis(OXFORD UNIV PRESS, 2018-11-01)OBJECTIVE: Diet is increasingly recognized as a potentially modifiable factor influencing the onset and outcomes of psychiatric disorders. Whereas, previous research has shown long-term schizophrenia is associated with various nutritional deficiencies, this meta-analysis aimed to determine the prevalence and extent of nutritional deficits in first-episode psychosis (FEP). METHOD: A search of electronic databases conducted in July 2017 identified 28 eligible studies, examining blood levels of 6 vitamins and 10 minerals across 2612 individuals: 1221 individuals with FEP and 1391 control subjects. Meta-analyses compared nutrient levels in FEP to nonpsychiatric controls. Clinical correlates of nutritional status in patient samples were systematically reviewed. RESULTS: Significantly lower blood levels of folate (N = 6, n = 827, g = -0.624, 95% confidence interval [CI] = -1.176 to -0.072, P = .027) and vitamin D (N = 7, n = 906, g = -1.055, 95% CI = -1.99 to -0.119, P = .027) were found in FEP compared to healthy controls. Synthesis of clinical correlates found both folate and vitamin D held significant inverse relationships with psychiatric symptoms in FEP. There was also limited evidence for serum level reductions of vitamin C (N = 2, n = 96, g = -2.207, 95% CI = -3.71 to -0.71, P = .004). No differences were found for other vitamins or minerals. CONCLUSIONS: Deficits in vitamin D and folate previously observed in long-term schizophrenia appear to exist from illness onset, and are associated with worse symptomology. Further research must examine the direction and nature of these relationships (ie, mediator, moderator, or marker) with clinical status in FEP. Future trials assessing efficacy of nutrient supplementation in FEP samples should consider targeting and stratifying for baseline deficiency.
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ItemA Review of the Conceptualisation and Risk Factors Associated with Treatment-Resistant Depression.(Hindawi Limited, 2017)Major depression does not always remit. Difficult-to-treat depression is thought to contribute to the large disease burden posed by depression. Treatment-resistant depression (TRD) is the conventional term for nonresponse to treatment in individuals with major depression. Indicators of the phenomenon are the poor response rates to antidepressants in clinical practice and the overestimation of the efficacy of antidepressants in medical scientific literature. Current TRD staging models are based on anecdotal evidence without an empirical rationale to rank one treatment strategy above another. Many factors have been associated with TRD such as inflammatory system activation, abnormal neural activity, neurotransmitter dysfunction, melancholic clinical features, bipolarity, and a higher traumatic load. This narrative review provides an overview of this complex clinical problem and discusses the reconceptualization of depression using an illness staging model in line with other medical fields such as oncology.