ADHD = Attention-deficit/hyperactivity disorderADHD-RS = Attention-deficit/hyperactivity disorder Rating ScaleBLT = Bright Light TherapyCBT = Cognitive Behavioural TreatmentIM = Integrative MedicineMBI= Mindfulness Based InterventionMDD- Major Depressive DisorderSD = Standard DeviationUHR = Ultra High Risk

Abbreviations used in this issue:

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Welcome to the inaugural issue of Integrative Medicine Research Review. It is the intention for the reviews in this field to focus on a range of health areas within the Integrative Medicine (IM) paradigm. According to the Australasian Integrative Medical Association: “Integrative medicine is a philosophy of healthcare with a focus on individual patient care and combining the best of conventional western medicine and evidence-based complementary medicine and therapies within current mainstream medical practice. Integrative Medicine reaffirms the importance of the relationship between practitioner and patient, focuses on the whole person, is informed by evidence, and makes use of all appropriate therapeutic approaches, health care professionals and disciplines to achieve optimal health and healing. It takes into account the physical, psychological, social and spiritual wellbeing of the person with the aim of using the most appropriate, safe and evidence-based treatments available.” It is further strongly appreciated that IM is not just about combining pharmaceutical medicines with supplements, and that IM involves a distinct paradigm shift towards treating the person individually using an integrated biological systems approach.

Due to other mental-health focused Research Reviews covering pharmacotherapies and psychological therapies, our IM issues will review the evidence concerning the other elements. Thus the focus of this mental health issue is to highlight some of the research occurring in areas involving Nutraceuticals (nutrient medicines) and Phytoceuticals (plant medicines), Lifestyle Medicine (including diet and exercise), Mind-Body Medicine, and Complementary Therapies. While it is accepted that in some areas the evidence is nascent, it should be noted that research is evolving rapidly in this field, and considering how prolific the use of such approaches are being employed by the public, rigorous appraisal of the research is needed. Below is a snapshot of some of the thought-provoking research occurring recently in the field. It is my hope that future research will also explore the study of more complex integrated models of care involving a range of IM elements that have evidence for the individualised treatment of mental health disorders.

We hope you find this edition of interest and welcome your comments and feedback.

Kind Regards,

Professor Jerome Sarrisjerome.sarris@researchreview.com.au

Effect of ω-3 polyunsaturated fatty acids in young people at ultrahigh risk for psychotic disordersAuthors: McGorry P et al.

Summary: The NEURAPRO double-blind, placebo-controlled randomized clinical trial assessed whether in the presence of psychosocial treatment (cognitive behavioural case management) a daily dietary supplement of 1.4g of ω-3 polyunsaturated fatty acids would reduce or prevent onset of psychosis in young people at high risk for psychotic disorder. The trial was conducted in 304 adult patients (45.7% male, mean (SD) age 19.1 years) between 2010-2014 in 10 specialist early psychosis services in Australia, Asia and Europe. The primary end point was conversion to psychosis at 6 months. General levels of psychopathy and functioning were also measured using a range of scales including the Brief Psychiatric Rating Scale, Scale for Assessment of Negative Symptoms and Montgomery- Åsbery Depression Rating Scale. Kaplan-Meier estimated 6 and 12-month conversion rates were 5.1% and 11.2% for the control group, respectively (95% CI) and 6.7% and 11.5% for the ω-3 PUFA group, respectively (95% CI). As no significant difference was observed between the transition rates to psychosis of the placebo and test groups, it was concluded that in the presence of quality psychosocial treatments ω-3 Polyunsaturated Fatty Acids have no effect on reducing or preventing transition to psychosis.

Comment: This is a follow-up study from the original work of Amminger and colleagues in 2010, showing that omega-3 supplementation attenuated progression to psychosis in adolescents with ultrahigh risk (UHR) of such a transition. While the original trial design used 1.2g of omega-3 over 12 weeks with a 40 week follow up, this study was conducted over a longer period (6 months), in a larger sample, with a slightly larger dose (1.4g per day). The results showing no difference between the active intervention and placebo are disappointing at face value, however upon closer inspection there are reasons for why this occurred. Primarily, the cohort in question had significant medical care, including cognitive behavioural case management and general psychosocial support. In addition, there is the potential that some in the placebo group were using omega-3 due to the publicity around its potential efficacy (I have seen in other non-published study data that participants will take additionally the active nutraceutical, regardless of which group they are randomised into). The reality is that it is difficult to show additional benefits if UHR adolescents are already receiving treatment, and thus the potential utility of fish oil may preferably be as an inexpensive option in countries with little psychiatric care. Additional analysis of the data should reveal if participants responded preferentially to the omega-3 in cases of higher inflammatory markers (such as in depression), or in cases of dietary deficiency. Genomic analyses of the fatty acid desaturase 1 and 2 gene polymorphisms in the sample would also be of potential benefit to see if this was a mediator of response.

Reference: JAMA Psychiatry 2017;74(1):19-27Abstract

In this issue: > ω-3 polyunsaturated fatty acids do not reduce transition to psychosis in young people

> Dietary improvements can improve depression

> Mental health interventions delivered via smartphone applications can reduce depressive symptoms

> affron® a novel saffron extract improves mood in healthy adults

> Treatment of Chinese Americans with depression using Tai Chi

> Chair yoga therapy confers physical fitness benefits to psychiatric patients

> Bright Light Therapy corrects delayed circadian phase and improves ADHD symptoms

> Aromatherapy can reduce anxiety in patients undergoing colonoscopy

> Vegetarian diets and depressive symptoms among men

> Adjunct mindfulness-based intervention for bipolar disorder

> Antenatal nutritional supplementation and autism spectrum disorders in the Stockholm youth cohort

> A Lactium™ and Zizyphus Complex shows no effect on Sleep Quality

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A randomised controlled trial of dietary improvement for adults with major depressionAuthors: Jacka F et al.

Summary: The “SMILES” 12-week parallel-group, single blind randomised clinical trial investigated the therapeutic impact of dietary improvements for the treatment of major depressive episodes. A total of 67 patients were randomised to an intervention group (n=34) who received 7 individual nutritional consulting sessions delivered by a clinical dietician or control group (n=33) who received a social support program delivered to the same visit schedule and length. Depression levels were assessed using the Montgomery–Åsberg Depression Rating Scale (MADRS) at 12 weeks. The dietary intervention group demonstrated significantly greater improvement over the 12 week trial than the social support control group, t(60.7) = 4.38, p < 0.001, Cohen’s d = –1.16. 32.3% (n=10) of the intervention group achieved remission (defined as a MADRS score <10) while 8.0% (n=2) of the control group did (χ 2 (1) = 4.84, p = 0.028).

Comment: The original work from the principal researcher published in the American Journal of Psychiatry, was a landmark paper finding a potential link between a poorer quality ‘Western’ dietary pattern and increased depressive symptoms. There has been high anticipation to see the prospective testing of dietary modification as an intervention. In brief, the research findings of this prospective study were stunning, with a significant large effect size achieved relative to the control group. It is notable that such a dietary intervention was costed as less expensive than the participant’s normal diet. It would be interesting if this was conducted on a macro-scale, analysing the cost saving on both food purchase, and the socioeconomic cost of less depression at a population level. It is recognised however that consumer compliance can be a challenge, due to the intrinsic societal desire for high calorie sweet and savoury foods. There are some challenges noted in interpreting the data from such interventions, with the principle methodological issue being the impossibility of being able to blind lifestyle modifications such as dietary change or exercise etc. The use of an active social support method employed in this study is respectable, however the participant’s active engagement in creating a significant health change in their life is hard to control for. The sample size was also modest, however this points to the known recruitment challenge for any mental disorder group pursuing lifestyle change, especially when being asked to engage in a clinical trial with heavy time commitment. Regardless, there is sound evidence regarding the potential health benefits of a healthy wholefood diet, and reasoning for how this impacts key markers involved in the pathogenesis of clinical depression. Future work is advised to centre on operationalising the intervention to affect a larger population (potentially via internet delivery).

Reference: BMC Medicine 2017;15(23)Abstract

The efficacy of smartphone-based mental health interventions for depressive symptomsAuthors: Firth J et al.

Summary: This meta-analysis evaluated the effects of mental health interventions delivered via smartphone applications in the treatment of depression. A search of Cochrane Central Register of Controlled Trials, Health Technology Assessment Database, Allied and Complementary Medicine (AMED), Health Management Information Consortium (HMIC), Ovid MEDLINE, Embase, and PsycINFO identified 18 randomised controlled trials (n=3414) assessing 22 smartphone apps. Comprehensive random-effects meta-analysis of the data showed a positive effect size of smartphone mental health apps for reducing depressive symptoms in comparison to control conditions (g=0.383, 95% CI: 0.24-0.52, p<0.001). Pre-planned subgroup analyses found that effect sizes were significantly greater when comparing to inactive controls rather than active controls (Q=9.76, p=0.002). Post-hoc subgroup analyses designed to investigate which aspects of smartphone interventions make them effective for management of depressive symptoms found that smartphone-only interventions (as opposed to those that incorporated human feedback), applications focused on mental health (rather than cognitive training) and intervention with “in-app” feedback such as summary statistics and progress scores showed the greatest effects, (g=0.465, 95% CI: 0.30-0.63, p<0.001, g=0.438, 95% CI: 0.28-0.60, p<0.001 and g=0.534, 95% CI: 0.26-0.81, p<0.001, respectively) although not all were significant.

Comment: This new Australian-led research has confirmed that smartphone apps are an effective treatment option for depression, paving the way for safe and accessible interventions for the millions of people around the world diagnosed with this condition. It is an important finding which presents a new opportunity for providing accessible and affordable care for patients who might not otherwise have access to treatment. Using such apps can be part of an ‘integrative’ approach for depression. Curiously, the interventions that used entirely ‘self-contained’ apps – meaning the app did not provide clinician and computer feedback – were found to be significantly more effective than ‘non-self-contained’ apps. Further research is needed in diagnosed MDD, involving studies determining which elements of the interventions in the apps are superior, in which combinations, and at what frequency and intervention duration. The use of mindfulness apps are also growing in popularity, and such an approach in combination with CBT, and mood monitoring, may provide a robust approach to reducing depression.

Reference: World Psychiatry 2017;16(3):287-98Abstract

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affron® a novel saffron extract (Crocus sativus L.) improves mood in healthy adultsAuthors: Kell G et al.

Summary: This 3-arm, randomised, double-blind, placebo-controlled trial investigated the efficacy of affron® (a standardised stigmas extract from saffron Crocus sativus L) for improved mood, stress, anxiety and sleep quality in healthy volunteers self-reporting low mood. 128 participants were randomised to receive affron® at 28mg/day, 22mg/day or placebo for 4 weeks. Mood and sleep were measured using the Primary Outcome Measure, The PANAS questionnaires, the DASS-21 scale and the Sleep Quality Index, respectively. A significant increase in positive mood and decrease in stress and anxiety was observed at the 28mg/day dose. No effect was observed at the 22mg/day dose.

Comment: Saffron has been extensively researched in the last decade in Iran, with a range of small sample size studies showing consistent anti-depressant effects beyond placebo, with equivalence to SSRIs. Larger double-blind RCTs are now needed in Western cohorts. This study goes part way to addressing this need, and it is of note that a dose-dependent effect occurred in favour of 28mg of the stigma. This is in alignment with most of the other research using 30mg per day. One drawback of the study, was that the sample was not diagnosed with major depressive disorder (in addition to excluding many common co-morbidities). Other challenges concern the use of only self-reporting assessments, with the gold-standard being clinician measured scales. Additionally, participants had fairly low baseline mood scores, thus this can’t be generalised to people with more severe clinical depression. However, the inclusion of such a sample does mean that the results are extendable to the general public with low to moderate mood disturbance. In conclusion, this adds to the weight of evidence about the potential application of saffron to elevate mood. My sense is that if a larger international phase III randomised controlled trial were to be conducted and positive results revealed in an MDD sample, this intervention could then be considered as a first-line option for depression treatment.

Reference: Complementary Therapies in Medicine 2017;33:58-64Abstract

A pilot, randomized controlled study of tai chi with passive and active controls in the treatment of depressed Chinese AmericansAuthors: Yeung A et al.

Summary: This study explored the potential of Tai Chi as a primary treatment for depression in Chinese Americans. 67 Chinese Americans with untreated DSM-IV major depressive disorder (72% female, mean age 54±13 years) were recruited into this 12-week 3 arm study that compared a tai chi intervention group, an active control group (education program) and a passive control (waitlisted) group. Depression was quantified using the Hamilton Depression Rating Scale (with remission defined as HDRS17≤7). Primary treatment of depression with Tai Chi showed improvements in treatment response over both passive and active controls, (odds ratio [OR] = 2.11; 95% CI, 1.01–4.46) and (OR = 8.90; 95% CI, 1.17–67.70), respectively and significant improvements in remission rates.

Comment: In Western countries, there is often a disparity between the mental health care afforded to certain ethnic minorities, in part due to language barriers, and cultural stigmas in terms of seeking psychiatric treatment. Tai Chi has been studied for a range of disorders, and has shown to be effective in some research to improve various health outcomes, especially in the elderly. Tai Chi may increase flexibility and strength, improve breathing, and enhance mindfulness. Results of this present study showed that 12-weeks of Yang-style Tai Chi may be effective in reducing depression in Chinese-American patients diagnosed with MDD, compared to waitlist and psychoeducation controls. It should be noted though that significance did not occur between the Tai Chi group and the psychoeducation group for depression remission rates, and also 22% of the sample dropped out of the study post-randomisation. Regardless, considering the small sample and the medium to large effect sizes on the outcome measures, Tai Chi can be considered as potentially beneficial for depression. This intervention is also culturally acceptable for Chinese people, in addition to being safe and cost-effective. Some limitations are recognised, in respect to the small sample size, potential expectancy effects, and it is unknown whether the results can be generalised to other ethnicities.

Reference: J Clinical Psychiatry 2017;78(5):e522-28Abstract

Effects of chair yoga therapy on physical fitness in patients with psychiatric disordersAuthors: Ikai S et al.

Summary: This 12-week, single-blinded randomised controlled trial investigated the benefit to psychiatric patients of chair yoga therapy to increase physical fitness and reduce the risk of falls. 56 inpatients (36 men; mean ± SD age, 55.3 ± 13.7 years; schizophrenia 87.5%) were randomised to an intervention group (twice-weekly 20 min chair yoga sessions over 12 weeks in addition to ongoing treatment) or a control group (treatment-as-usual). There were significant between group differences at 12 weeks with the chair yoga intervention group showing improvements in flexibility, hand-grip, lower limb muscle endurance and on the Modified Falls Efficacy Scale (mean ± SD: 55.1 ± 16.6 to 67.2 ± 14.0 cm, 23.6 ± 10.6 to 26.8 ± 9.7 kg, 4.9 ± 4.0 to 7.0 ± 3.9 kg, and 114.9 ± 29.2 to 134.1 ± 11.6, respectively). These results were sustained at 6 weeks post-intervention. No differences in psychopathology or functioning was noted between the groups.

Comment: Mind-Body therapies such as Yoga and Tai Chi have a growing body of evidence for use across a range of health conditions. Aside from the physiological benefits of physical activity, there is also the potential ancillary benefit of mindfulness practice on increasing psychological wellbeing. One particular challenge in the mental health field, is addressing the deleterious effects of certain medications and the biological effects of the mental disorder itself. This is certainly well-recognised for patients with chronic psychiatric disorders such as schizophrenia. This small novel study showed that just 20-minutes of chair-based yoga twice a week over 12 weeks by a qualified Hatha yoga therapist, improved muscle strength, flexibility, and quality of life, while reducing fear of falls. This is a fairly inexpensive intervention, and one which might be more palatable to patients not wanting to move off their chair while still getting exercise! Confidence in the results however must be tempered due to the lack of an acceptable control group and potential expectation bias. Further work is needed to determine the ideal intensity and duration of the intervention.

Reference: J of Psychiatric Research 2017;94:194-201Abstract

Correcting delayed circadian phase with bright light therapy predicts improvement in ADHD symptoms: A pilot studyAuthors: Fargason R et al.

Summary: This pilot study aimed to improve Attention-deficit/hyperactivity disorder (ADHD) symptoms using Bright Light Therapy (BLT) to treat insomnia caused by delayed circadian phase shift. After a 1-week baseline assessment phase, ADHD- diagnosed patients underwent 2-weeks of BLT (30-min morning 10,000-lux BLT). Sleep parameters were assessed using the Dim Light Melatonin Onset Score at baseline and after 2-weeks of treatment. ADHD symptoms were measured by the ADHD-Rating Scales (ADHD-RS) and Hyperactive-Impulsive sub-scores. BLT therapy significantly advanced both melatonin-onset phase (31 min) and mid-sleep time (57 min) and also significantly decreased ADHD-RS scores.

Comment: Sufferers of ADHD commonly have sleep issues, and this is often associated with a delayed sleep-wake cycle with increased sleep latency. This index study sought to determine whether applying BLT in adults with ADHD would have a beneficial outcome for their sleep pattern and ADHD symptoms. Results revealed that just two weeks of 30 minutes per day of morning BLT significantly advanced the phase of dim light melatonin onset by 31 minutes. Interestingly, phase advances were significantly correlated with decreased ADHD symptom scores and Hyperactive-Impulsive sub-scores. No significant changes were however found in total sleep time, sleep efficiency, wake after sleep onset, or percent wake during sleep interval. While this research is encouraging for the potential of BLT in assisting in reducing ADHD symptoms via better regulation of the circadian rhythm, the small sample size and lack of placebo control hamper confidence in the findings. It is however noted that it is challenging to apply a matched control versus BLT. This intervention may also have even more significance in those with comorbid seasonal affective disorder, or during winter months in the Northern hemisphere.

Reference: J of Psychiatric Research 2017;91:105-10Abstract

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Aromatherapies using Osmanthus fragrans oil and grapefruit oil are effective complementary treatments for anxious patients undergoing colonoscopyAuthors: Engelbertz C et al.

Summary: This randomised controlled trial examined the effects of aromatherapy on anxiety and abdominal discomfort during colonoscopy. 361 total colonoscopy patients were randomised to either a control group (no inhalation), vehicle group (essential-oil-less vapour), Lavender oil group, Grapefruit oil group or Osmanthus fragrans (Sweet Olive) oil group. The Numeric Rating Scale was utilised to approximate each patient’s anxiety and abdominal discomfort. Aromatherapy with Sweet Olive oil resulted in significantly decreased anxiety levels. Aromatherapy during colonoscopy with either Sweet Olive oil or grapefruit oil resulted in decreased abdominal discomfort in patients who experienced strong anxiety during the procedure.

Comment: The application of airborne aromatherapy holds promise as an adjunctive approach to alleviating anxiety for patients undergoing various types of surgical intervention. Previous research has identified aromatherapy as being effective in this regard, however blinding is often a methodological issue. Other natural products such as Passionflower have also been shown to alleviate pre-operative anxiety, with no safety issues regarding anaesthetics or recovery. In this study, aerial exposure to Sweet Olive oil significantly reduced anxiety compared to Lavender and Grapefruit oils (withstanding Bonferroni correction for multiple comparisons). Additionally, in patients with higher levels of anxiety, abdominal discomfort was also alleviated with Sweet Olive or Grapefruit. In light of these results more research is advised considering the very low cost of such an intervention.

Reference: Complementary Therapies in Medicine 2017;34:165-69Abstract

Vegetarian diets and depressive symptoms among menAuthors: Hibbeln J et al.

Summary: This study used self-reported data from adult male partners of pregnant women in the Avon Longitudinal Study of Parents and Children (ALSPAC) to examine the effects of a vegetarian dietary lifestyle choice on depression rates. 9668 men were included in the study and provided information on vegetarian or vegan dietary choices and the Edinburgh Post Natal Depression Scale (EPDS) as well as other confounding variables including age, marital status and employment status. After adjusting for potential confounding factors, vegetarian men [n = 350 (3.6% of sample)], were found to have higher depression scores than non-vegetarians (mean difference 0.96 points [95%CI + 0.53, + 1.40]) and a greater chance of EDPS scored above 10 (adjusted OR = 1.67 [95% CI: 1.14,2.44].

Comment: This is an intriguing finding, and one which could no doubt cause some consternation amongst vegetarians. Interestingly, it does support previous findings that meat-free diets were associated with an increased relationship with depressive and anxious symptoms in a cohort of Australian women. The potential reason for this could be due to meat and fish providing macronutrients such as protein and essential fatty acids, in addition to micronutrients including vitamin B12, zinc, and iron. It should be noted that not all ‘vegetarian’ diets are equal, and a high-quality whole food vegetarian diet has many health benefits, whilst a poor Western diet rich in processed meats and saturated fat has many negative health consequences. Future exploration could involve assessing in a large vegetarian cohort whether the addition of B12, zinc, and iron to a healthy vegetarian diet could attenuate the potential increased depressogenic risk compared to a vegetarian diet without supplementation.

Reference: J of Affective Disorders 2017;225:13-7Abstract

The effectiveness of adjunct mindfulness-based intervention in treatment of bipolar disorder: A systematic review and meta-analysisAuthors: Chu C-S et al.

Summary: This systematic review and meta-analysis of 3 controlled (n=132) and 9 uncontrolled (n=142) studies examined the evidence for the efficacy of mindfulness-based interventions (MBIs) as an adjunctive treatment on psychiatric symptoms in bipolar disorder. The study researchers found in the within-group analysis (symptoms compared to baseline) that MBIs significantly improved depression (7 studies, n=100, Hedges’ g=0.58, p<0.001) and anxiety (4 studies, n=68, Hedges’ g=0.34, p=0.043). However, in between-group analysis (control group to intervention group) no significant difference was observed. The researchers note that the analysis was limited by having only 3 controlled trials comparing MBIs to control conditions.

Comment: Research and clinical interest in MBIs has grown markedly in the past decade, with this approach being recognised as a useful therapeutic tool for a range of psychiatric disorders. The application of MBIs in concert with CBT, is developing strong evidence, and generally has much appeal to the general public. What is unknown is where the evidence sits for such use in people with Bipolar Disorder. This index meta-analysis sought to address this. While results revealed that MBIs did indeed reduce depression in people with Bipolar Disorder, this effect was not significant in comparison to when a control group was employed. It should be noted however that there were only three controlled studies to assess, and these had small sample sizes. The authors note that the quality of studies were rated as being of low methodological quality, and that due to patient disengagement, many drop outs occurred. Due to this, a larger more rigorous study is needed before we can truly judge the effectiveness of MBIs in this mental disorder.

Reference: J of Affective Disorders 2017;225:234-45Abstract

Antenatal nutritional supplementation and autism spectrum disorders in the Stockholm youth cohort: population based cohort studyAuthors: DeVilbiss E et al.

Summary: This Swedish observational study extracted data on 273,107 mother-child pairs (children born between 1996 and 2007) from the Stockholm youth cohort to clarify correlations between maternal nutritional supplementation during pregnancy and the risk of Autism Spectrum Disorder (ASD) with or without intellectual disability. The study examined the use of multivitamins, folic acid and iron supplements at doses recommended by the Swedish government at the time of the study and reported at the first antenatal visit. Multivariable regression analysis, propensity score analysis and sibling analyses were all carried out. ASD with intellectual disability was found in 0.48% (430 cases in 90 480) in the no supplementation group and 0.26% (158 cases in 61 934) in the maternal multivitamin group. The use of either iron or folic acid showed no effect on the prevalence of ASD. Maternal multivitamin supplementation during pregnancy showed an inverse correlation with the presence of ASD with intellectual disability in offspring (odds ratio 0.069, 95%CI, 0.57 to 0.84).

Comment: While the authors are at pains to point out that their findings should be interpreted cautiously, it is still of pronounced significance that in a very large sample, such a strong association was found between maternal multivitamin supplementation during pregnancy, and reduced risk of ASD with intellectual disability in their offspring. The authors’ use of sibling control and propensity score matching, and controlling for multiple confounders, also strengthens the likelihood of this finding. They do note however that they were unable to assess the contribution of the diet and of other potential nutritional supplements used in the cohort. There is some merit as to the application of maternal supplemental and the potential of reducing ASD risk, as this condition is known to have aberrations in oxidative status, and many multivitamins contain antioxidants such as vitamins A, C, E, selenium. There is always controversy regarding any population-based approach to supplementation, with other research noting a slight increase in certain cancers from use of synthetic vitamin E, folic acid, or beta-carotene. Regardless, not all supplement formulations are created equal, and some formulations utilise vitamins in potentially safer and more active forms. More work is needed on firstly replicating this association in other cohorts, and further assessing which nutrients may be responsible for such an effect and the ideal timing of potential supplementation during pregnancy.

Reference: BMJ 2017;359: j4273Abstract

Independent commentary by Professor Jerome Sarris, Professor of Integrative Mental Health and Deputy Director of NICM health research institute at Western Sydney University. He holds an NHMRC Clinical Research Fellowship, in addition to an honorary position at the University of Melbourne, Department of Psychiatry as a Principal Research Fellow. He has a particular interest in anxiety and mood disorder research pertaining to integrative medicine, nutraceutical psychopharmacology and psychotropic plant medicines (such as kava and medicinal cannabis), and lifestyle medicine. His research also utilises genomic technology to examine the pharmacogenomics of individual responses to nutraceuticals in the treatment of psychiatric disorders. Professor Sarris has over 125 publications and has published in many eminent journals in the field including The American Journal of Psychiatry, Lancet Psychiatry, and World Psychiatry. He is currently involved in over a dozen clinical trials in the area of mental health, being Chief-Investigator A on 3 multicentre NHMRC Project Grants in the field. Jerome is a founding Vice Chair of The International Network of Integrative Mental Health & an Executive Committee Member of the International Society of Nutritional Psychiatry Research.

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Exploring the effect of Lactium™ and Zizyphus complex on sleep quality: A double-blind, randomized placebo-controlled trialAuthors: Scholey A et al.

Summary: This double-blind, placebo-controlled trial assessed the efficacy of the herbal complex LZComplex3 (lactium™, Zizyphus, Humulus lupulus, magnesium and vitamin B6) for the treatment of insomnia in otherwise healthy volunteers. A 7-day placebo run in was conducted to exclude placebo-responders and the remaining 171 volunteers were randomised to receive either placebo or LZComplex3 once a day (2 tablets 30 mins before bed) for 14 days. The primary outcome of overall sleep quality was measured using the Pittsburgh Sleep Quality Index. Secondary outcomes such as daytime functioning, physical fatigue, mood and cognitive performance were assessed at days 1, 3, 7 and 14 and 7-days post study using questionnaires such as the Hospital Anxiety and Depression Scale and State-Trait Anxiety Trait subscale. Over the 2-week trial both sleep quality and most secondary outcomes improved in both experimental and control groups with no significant between group differences observed.

Comment: The holy grail of nutraceutical or phytoceutical research at the moment to my mind, is finding an intervention that is clinically effective in treating chronic insomnia. Previous research with herbal medicines such as Valerian and Hops, have been mixed, and some herbal medicines with preclinical hypnotic evidence e.g. Zizyphus, have not been individually studied in robust human trials to assess such efficacy. This study sought to determine whether a combination of nutrients and herbal medicines was effective in treating insomnia (decreasing sleep latency, lengthening sleep time etc.). The results revealed no significant effect beyond placebo, even after a placebo run-in period. Although the formula was not effective in this design in demonstrating a soporific action beyond placebo, a longer study period may have been more beneficial, and in addition it is recommended that during such studies, no attention is paid by the participants to general sleep hygiene elements (which may occur due to increased focus on sleep issues having enrolled in the study). It is difficult though to compete with pharmacotherapies that interact with GABA α1,2,5 receptors, however such a pharmacological effect may cause dependence and withdrawal challenges. The best way forward before future human studies may be to employ preclinical models to see which combinations of nutrients and plant medicines may provide some GABA channel, adenosine or orexin receptor modulatory effects, while also providing supportive anxiolytic effect via modulation of serotonergic pathways.

Reference: Nutrients 2017;9(2); 154Abstract

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