Jerome Sarris

Rosenroot (Rhodiola rosea): traditional use, chemical composition, pharmacology and clinical efficacy.

The aim of this review article was to summarize accumulated information related to chemical composition, pharmacological activity, traditional and official use of Rhodiola rosea L. in medicine. In total approximately 140 compounds were isolated from roots and rhizome - monoterpene alcohols and their glycosides, cyanogenic glycosides, aryl glycosides, phenylethanoids, phenylpropanoids and their glycosides, flavonoids, flavonlignans, proanthocyanidins and gallic acid derivatives. Studies on isolated organs, tissues, cells and enzymes have revealed that Rhodiola preparations exhibit adaptogenic effect including, neuroprotective, cardioprotectiv e, anti-fatigue, antidepressive, anxiolytic, nootropic, life-span increasing effects and CNS stimulating activity. A number of clinical trials demonstrate that repeated administration of R. rosea extract SHR-5 exerts an anti-fatigue effect that increases mental performance (particularly the ability to concentrate in healthy subjects), and reduces burnout in patients with fatigue syndrome. Encouraging results exist for the use of Rhodiola in mild to moderate depression, and generalized anxiety. Several mechanisms of action possibly contributing to the clinical effect have been identified for Rhodiola extracts. They include interactions with HPA-system (cortisol-reducing), protein kinases p-JNK, nitric oxide, and defense mechanism proteins (e.g. heat shock proteins Hsp 70 and FoxO/DAF-16). Lack of interaction with other drugs and adverse effects in the course of clinical trials make it potentially attractive for use as a safe medication. In conclusion, Rhodiola rosea has robust traditional and pharmacological evidence of use in fatigue, and emerging evidence supporting cognition and mood.

A systematic review of insomnia and complementary medicine

In concert with growing public interest in complementary and alternative medicine (CAM), these therapies and products have been increasingly studied over the past two decades for the treatment of sleep disorders. While systematic reviews have been conducted on acupuncture and valerian in the treatment of insomnia, to date no comprehensive review has been conducted on all major CAM treatments. We sought to address this via a rigorous systematic review of hypnotic CAM interventions, including herbal and nutritional medicine, acupuncture, acupressure, yoga, tai chi, massage, aromatherapy and homoeopathy. The electronic databases MEDLINE (PubMed), CINAHL, PsycINFO, and The Cochrane Library were accessed during late 2009 for CAM randomized controlled trials (RCTs) in the treatment of chronic insomnia. Sixty-four RCTs were identified, of which 20 studies involving eight CAM interventions met final inclusion criteria. Effect size calculations (where possible) and a quality control analysis using a modified Jadad scale were undertaken. Many RCTs lacked methodological rigor, and were commonly excluded due to small sample size or an inadequate control condition. Among the studies that met inclusion criteria, there was evidentiary support in the treatment of chronic insomnia for acupressure (d=1.42-2.12), tai chi (d=0.22-2.15), yoga (d=0.66-1.20), mixed evidence for acupuncture and L-tryptophan, and weak and unsupportive evidence for herbal medicines such as valerian. Surprisingly, studies involving several mainstream CAM therapies (e.g., homoeopathy, massage, or aromatherapy) were not located or did not meet basic inclusion criteria. If CAM interventions are to be considered as viable stand-alone or adjuvant treatments for sleep disorders, future researchers are urged to use acceptable methodology, including appropriate sample sizes and adequate controls. RCTs evaluating other untested CAM therapies such as massage, homoeopathy, or osteopathy are encouraged, as is the exploration of using CAM therapies adjuvantly with conventional therapies.

Nutritional medicine as mainstream in psychiatry

Psychiatry is at an important juncture, with the current pharmacologically focused model having achieved modest benefits in addressing the burden of poor mental health worldwide. Although the determinants of mental health are complex, the emerging and compelling evidence for nutrition as a crucial factor in the high prevalence and incidence of mental disorders suggests that diet is as important to psychiatry as it is to cardiology, endocrinology, and gastroenterology. Evidence is steadily growing for the relation between dietary quality (and potential nutritional deficiencies) and mental health, and for the select use of nutrient-based supplements to address deficiencies, or as monotherapies or augmentation therapies. We present a viewpoint from an international collaboration of academics (members of the International Society for Nutritional Psychiatry Research), in which we provide a context and overview of the current evidence in this emerging field of research, and discuss the future direction. We advocate recognition of diet and nutrition as central determinants of both physical and mental health.

Omega-3 for bipolar disorder: meta-analyses of use in mania and bipolar depression.

OBJECTIVE Studies using augmentation of pharmacotherapies with omega-3 in bipolar disorder have been conducted; however, to date a specific meta-analysis in this area has not been published. Thus, we present the significant findings from meta-analyses of omega-3 in the treatment of bipolar depression and bipolar mania. DATA SOURCES PubMed, CINAHL, Web of Science, and Cochrane Library databases were searched for clinical trials up to September 1, 2010, using the search terms bipolar disorder OR bipolar depression OR bipolar mania OR mania OR hypomania OR cyclothymia with the search terms omega 3 OR essential fatty acids OR polyunsaturated fatty acids OR DHA OR EPA OR fish oil OR flax oil. Clinical trial registries and gray literature (published or unpublished data not readily accessible via main databases) were also searched. DATA SELECTION The analysis included randomized controlled studies 4 weeks or longer, with a sample size > 10, written in English, using omega-3 for diagnosed bipolar depression or mania. No criteria were set for age, gender, or ethnicity. DATA EXTRACTION A random-effects model was used. The model analyzed the standard mean difference between treatment and placebo between baseline and endpoint, combining the effect size (Hedges g) data. Funnel plot and heterogeneity analyses (I²) were also performed. DATA SYNTHESIS The findings of 5 pooled datasets (n = 291) on the outcome of bipolar depression revealed a significant effect in favor of omega-3 (P = .029), with a moderate effect size of 0.34. On the outcome of mania, 5 pooled datasets (n = 291) revealed a nonsignificant effect in favor of omega-3 (P = .099), with an effect size of 0.20. Minor heterogeneity between studies on the outcome of bipolar depression was found (I² = 30%; P = .213), which was not present on the outcome of bipolar mania (I² = 0%; P = .98). Funnel plot symmetry suggested no significant likelihood of publication bias. Meta-regression analysis between sample size and effect size, however, revealed that studies with smaller sample sizes had larger effect sizes (P = .05). CONCLUSIONS The meta-analytic findings provide strong evidence that bipolar depressive symptoms may be improved by adjunctive use of omega-3. The evidence, however, does not support its adjunctive use in attenuating mania.

The effects of dietary and nutrient interventions on arterial stiffness: a systematic review

BACKGROUND Although dietary and nutrient interventions have been extensively studied as a means of improving arterial stiffness, to our knowledge no systematic analysis of the data has been conducted. OBJECTIVE The aim of the current study was to systematically review the human clinical trial data and qualitatively examine the efficacy of dietary and nutrient interventions in the treatment of arterial stiffness. DESIGN We systematically searched multiple databases until July 2010 for relevant randomized controlled human clinical trials of common dietary and nutrient interventions in the treatment of arterial stiffness. Located studies were subject to strict inclusion criteria and objectively assessed for scientific quality. RESULTS Of the 75 relevant studies located, we considered 38 studies to be appropriate for review. Results revealed support for intakes of omega-3 (n-3) fish oils (Cohens d = 0.21-0.81) and soy isoflavones (Cohens d = 0.35-0.39) in the treatment of arterial stiffness. There was limited but consistent evidence to suggest that salt restriction (Cohens d = 0.28-0.37) as well as consumption of fermented-milk products (Cohens d = 0.15-0.33) that contain bioactive peptides improved arterial stiffness. The evidentiary support for intakes of vitamins, micronutrients, and herbal medicines was insufficient. Limited but consistent evidence suggested that caffeine intake acutely increased arterial stiffness (Cohens d = 0.34-0.51). CONCLUSIONS Current evidence from several small studies suggests that omega-3 and soy isoflavone supplementation provides an effective means of reducing arterial stiffness. There was little research that explored intakes of herbal medicines or micronutrients in the treatment of arterial stiffness, and this remains an area of potential research.

Kava and St. John's Wort: Current Evidence for Use in Mood and Anxiety Disorders

BACKGROUND Mood and anxiety disorders pose significant health burdens on the community. Kava and St. Johns wort (SJW) are the most commonly used herbal medicines in the treatment of anxiety and depressive disorders, respectively. OBJECTIVES The objective of this study was to conduct a comprehensive review of kava and SJW, to review any evidence of efficacy, mode of action, pharmacokinetics, safety and use in major depressive disorder, bipolar disorder, seasonal affective disorder (SAD), generalized anxiety disorder, social phobia (SP), panic disorder (PD), obsessive-compulsive disorder (OCD), and post-traumatic stress disorder (PTSD). METHODS A systematic review was conducted using the electronic databases MEDLINE, CINAHL, and The Cochrane Library during late 2008. The search criteria involved mood and anxiety disorder search terms in combination with kava, Piper methysticum, kavalactones, St. Johns wort, Hypericum perforatum, hypericin, and hyperforin. Additional search criteria for safety, pharmacodynamics, and pharmacokinetics were employed. A subsequent forward search was conducted of the papers using Web of Science cited reference search. RESULTS Current evidence supports the use of SJW in treating mild-moderate depression, and for kava in treatment of generalized anxiety. In respect to the other disorders, only weak preliminary evidence exists for use of SJW in SAD. Currently there is no published human trial on use of kava in affective disorders, or in OCD, PTSD, PD, or SP. These disorders constitute potential applications that warrant exploration. CONCLUSIONS Current evidence for herbal medicines in the treatment of depression and anxiety only supports the use of Hypericum perforatum for depression, and Piper methysticum for generalized anxiety.

Kava: a comprehensive review of efficacy, safety, and psychopharmacology.

Overview: Kava (Piper methysticum) is a South Pacific psychotropic plant medicine that has anxiolytic activity. This effect is achieved from modulation of GABA activity via alteration of lipid membrane structure and sodium channel function, monoamine oxidase B inhibition, and noradrenaline and dopamine re-uptake inhibition. Kava is available over the counter in jurisdictions such as the USA, Australia and New Zealand. Due to this, a review of efficacy, safety and clinical recommendations is advised. Objective: To conduct a comprehensive review of kava, in respect to efficacy, psychopharmacology, and safety, and to provide clinical recommendations for use in psychiatry to treat generalized anxiety disorder (GAD). Methods: A review was conducted using the electronic databases MEDLINE, CINAHL, PsycINFO and the Cochrane Library during mid 2010 of search terms relating to kava and GAD. A subsequent forward search was conducted of key papers using Web of Science cited reference search. Results: The current weight of evidence supports the use of kava in treatment of anxiety with a significant result occurring in four out of six studies reviewed (mean Cohens d = 1.1). Safety issues should however be considered. Use of traditional water soluble extracts of the rhizome (root) of appropriate kava cultivars is advised, in addition to avoidance of use with alcohol and caution with other psychotropic medications. Avoidance of high doses if driving or operating heavy machinery should be mandatory. For regular users routine liver function tests are advised. Conclusions: While current evidence supports kava for generalized anxiety, more studies are required to assess comparative efficacy and safety (on the liver, cognition, driving, and sexual effects) versus established pharmaceutical comparators.

Lifestyle medicine for depression

The prevalence of depression appears to have increased over the past three decades. While this may be an artefact of diagnostic practices, it is likely that there are factors about modernity that are contributing to this rise. There is now compelling evidence that a range of lifestyle factors are involved in the pathogenesis of depression. Many of these factors can potentially be modified, yet they receive little consideration in the contemporary treatment of depression, where medication and psychological intervention remain the first line treatments. “Lifestyle Medicine” provides a nexus between public health promotion and clinical treatments, involving the application of environmental, behavioural, and psychological principles to enhance physical and mental wellbeing. This may also provide opportunities for general health promotion and potential prevention of depression. In this paper we provide a narrative discussion of the major components of Lifestyle Medicine, consisting of the evidence-based adoption of physical activity or exercise, dietary modification, adequate relaxation/sleep and social interaction, use of mindfulness-based meditation techniques, and the reduction of recreational substances such as nicotine, drugs, and alcohol. We also discuss other potential lifestyle factors that have a more nascent evidence base, such as environmental issues (e.g. urbanisation, and exposure to air, water, noise, and chemical pollution), and the increasing human interface with technology. Clinical considerations are also outlined. While data supports that some of these individual elements are modifiers of overall mental health, and in many cases depression, rigorous research needs to address the long-term application of Lifestyle Medicine for depression prevention and management. Critically, studies exploring lifestyle modification involving multiple lifestyle elements are needed. While the judicious use of medication and psychological techniques are still advocated, due to the complexity of human illness/wellbeing, the emerging evidence encourages a more integrative approach for depression, and an acknowledgment that lifestyle modification should be a routine part of treatment and preventative efforts.

The Cognitive-Enhancing Effects of Bacopa monnieri: A Systematic Review of Randomized, Controlled Human Clinical Trials

OBJECTIVES Traditional knowledge suggests that Bacopa monnieri enhances cognitive performance. Such traditional beliefs have now been scientifically tested through a handful of randomized, controlled human clinical trials. The current systematic review aimed to examine the scientific evidence as to whether Bacopa can enhance cognitive performance in humans. DESIGN A systematic review of randomized controlled trials is presented. Multiple databases were systematically searched by multiple authors. Relevant trials were objectively assessed for methodological quality. SUBJECTS The subjects studied were adult humans without dementia or significant cognitive impairment. INTERVENTIONS B. monnieri, including Bacopa extracts, were administered over long-term supplementation periods. OUTCOME MEASURES Any validated cognitive test, whether a primary or secondary outcome. RESULTS Six (6) studies met the final inclusion criteria and were included in review. Trials were all conducted over 12 weeks. Across trials, three different Bacopa extracts were used at dosages of 300-450 mg extract per day. All reviewed trials examined the effects of Bacopa on memory, while other cognitive domains were less well studied. There were no cognitive tests in the areas of auditory perceptual abilities or idea production and only a paucity of research in the domains of reasoning, number facility, and language behavior. Across studies, Bacopa improved performance on 9 of 17 tests in the domain of memory free recall. There was little evidence of enhancement in any other cognitive domains. CONCLUSIONS There is some evidence to suggest that Bacopa improves memory free recall with evidence for enhancement in other cognitive abilities currently lacking perhaps due to inconsistent measures employed by studies across these cognitive domains. Research into the nootropic effects of Bacopa is in its infancy, with research still yet to investigate the effects of Bacopa across all human cognitive abilities. Similarly, future research should examine the nootropic effects of Bacopa at varied dosages and across different extracts.

A Randomized, Controlled Trial of Meditation for Work Stress, Anxiety and Depressed Mood in Full-Time Workers

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.