Clinician guidelines for the treatment of psychiatric disorders with nutraceuticals and phytoceuticals: The World Federation of Societies of Biological Psychiatry (WFSBP) and Canadian Network for Mood and Anxiety Treatments (CANMAT) Taskforce

The 'Micronutrient Formula' rated by this international taskforce was Daily Essential Nutrients, and was given an 'Evidence Grade' of 'A', due to a statistically significant meta-analysis (k = 2, n = 173) with statistically significant RCTs in adult and child samples. They gave the following supporting statements for Daily Essential Nutrients:

  • Meta-analytic level results have shown supportive evidence for efficacy in ADHD as a monotherapy

  • More replicated evidence required (in both adults and children)

  • This particular micronutrient formula’s efficacy cannot necessarily be extended to other multi-nutrient formulas

  • Dosing may need to be supervised (and titrated) via a health profession

  • Cost and compliance may be an issue due to a recommended dosage of 8–12 capsules per day

  • Acceptable safety data

Abstract

Objectives: The therapeutic use of nutrient-based 'nutraceuticals' and plant-based 'phytoceuticals' for the treatment of mental disorders is common; however, despite recent research progress, there have not been any updated global clinical guidelines since 2015. To address this, the World Federation of Societies of Biological Psychiatry (WFSBP) and the Canadian Network for Mood and Anxiety Disorders (CANMAT) convened an international taskforce involving 31 leading academics and clinicians from 15 countries, between 2019 and 2021. These guidelines are aimed at providing a definitive evidence-informed approach to assist clinicians in making decisions around the use of such agents for major psychiatric disorders. We also provide detail on safety and tolerability, and clinical advice regarding prescription (e.g. indications, dosage), in addition to consideration for use in specialised populations.

Methods: The methodology was based on the WFSBP guidelines development process. Evidence was assessed based on the WFSBP grading of evidence (and was modified to focus on Grade A level evidence - meta-analysis or two or more RCTs - due to the breadth of data available across all nutraceuticals and phytoceuticals across major psychiatric disorders). The taskforce assessed both the 'level of evidence' (LoE) (i.e. meta-analyses or RCTs) and the assessment of the direction of the evidence, to determine whether the intervention was 'Recommended' (+++), 'Provisionally Recommended' (++), 'Weakly Recommended' (+), 'Not Currently Recommended' (+/-), or 'Not Recommended' (-) for a particular condition. Due to the number of clinical trials now available in the field, we firstly examined the data from our two meta-reviews of meta-analyses (nutraceuticals conducted in 2019, and phytoceuticals in 2020). We then performed a search of additional relevant RCTs and reported on both these data as the primary drivers supporting our clinical recommendations. Lower levels of evidence, including isolated RCTs, open label studies, case studies, preclinical research, and interventions with only traditional or anecdotal use, were not assessed.

Conclusions: Based on the current data and clinician input, a range of nutraceuticals and phytoceuticals were given either a supportive recommendation or a provisional recommendation across a range of various psychiatric disorders. However several had only a weak endorsement for potential use; for a few it was not possible to reach a clear recommendation direction, largely due to mixed study findings; while some other agents showed no obvious therapeutic benefit and were clearly not recommended for use. It is the intention of these guidelines to inform psychiatric/medical, and health professional practice globally.

Clinician guidelines for the treatment of psychiatric disorders with nutraceuticals and phytoceuticals: The World Federation of Societies of Biological Psychiatry (WFSBP) and Canadian Network for Mood and Anxiety Treatments (CANMAT) Taskforce

Sarris J, Ravindran A, Yatham LN, Marx W, Rucklidge JJ, McIntyre RS, Akhondzadeh S, Benedetti F, Caneo C, Cramer H, Cribb L, de Manincor M, Dean O, Deslandes AC, Freeman MP, Gangadhar B, Harvey BH, Kasper S, Lake J, Lopresti A, Lu L, Metri NJ, Mischoulon D, Ng CH, Nishi D, Rahimi R, Seedat S, Sinclair J, Su KP, Zhang ZJ, Berk M. Clinician guidelines for the treatment of psychiatric disorders with nutraceuticals and phytoceuticals: The World Federation of Societies of Biological Psychiatry (WFSBP) and Canadian Network for Mood and Anxiety Treatments (CANMAT) Taskforce. World J Biol Psychiatry. 2022 Jul;23(6):424-455.

An Observational Preliminary Study on the Safety of Long-Term Consumption of Micronutrients for the Treatment of Psychiatric Symptoms

Abstract

Objectives: There is an increasing body of literature documenting the efficacy of micronutrients (vitamins and minerals) interventions for the treatment of psychiatric problems in the short term; however, long-term safety is largely unexplored. The goal of this observational study was to investigate the safety of two commercially available broad-spectrum micronutrient formulas (EMPowerplus and Daily Essential Nutrients) given at doses above the Recommended Dietary Allowances for the long-term treatment of individuals with psychiatric symptoms. 

Design: Participants on long-term treatment with micronutrients (medication-free) for psychiatric problems (attention-deficit hyperactivity disorder [ADHD, n = 21], anxiety/depression [n = 13]) were identified from ongoing research studies and the community through purchasing records. Seventeen children and 17 adults had blood tests to assess their full blood count, coagulation profile, liver and kidney function, fasting glucose, iron studies, key nutrients, and prolactin. Questionnaires assessed psychological/psychiatric functioning. Seventeen of the participants had completed the same measures pretreatment. 

Results: The average length of consuming micronutrients was 2.66 years (standard deviation = 2.86). Excluding B12 (which was elevated for almost all participants), 94.6% of all blood test results were within the test reference ranges. One participant was diagnosed with hemochromatosis based on iron studies. No other clinically relevant adverse changes in blood results were identified pre- and post-treatment. No clinically significant adverse effects were reported. Post-treatment psychometrics identified that 85% of the participants were in nonclinical ranges for measures of ADHD, depression, anxiety, and stress. 

Conclusions: We report preliminary evidence for the safety of long-term commercially available micronutrients, although questions remain. Overall, the substantial psychiatric benefits observed appear to outweigh the minimal observed risks in these participants. Screening for potential medical problems is recommended before initiating treatment. Long-term pharmacovigilance monitoring is required to ascertain any rare but significant adverse events.

An Observational Preliminary Study on the Safety of Long-Term Consumption of Micronutrients for the Treatment of Psychiatric Symptoms

Julia J. Rucklidge, PhD, Matthew J. F. Eggleston, MD, Breanne Ealam, BA (Hons), Ben Beaglehole, MD, and Roger T. Mulder, MD. J Altern Complement Med. 2019 Jun;25(6):613-622. doi: 10.1089/acm.2018.0352. Epub 2019 May 13.

Vitamin–mineral treatment of attention-deficit hyperactivity disorder in adults: double-blind randomised placebo-controlled trial.

A micronutrient formulation co-developed by Hardy Nutritionals® founder David Hardy, showed “statistically robust improvements” in the first-ever double-blind study to test the effectiveness and safety of a multivitamin-mineral supplement in adults with ADHD. Researchers from the University of Canterbury and the University of Otago, New Zealand, randomized 80 adults diagnosed with ADHD to take either the micronutrient formulation or identical-looking placebo pills for 8 weeks. Most of the study participants had at least one psychiatric diagnosis in addition to ADHD. Additional diagnoses included multiple anxiety disorders, major depressive disorder, dysthymia, bipolar disorder, reading disability, and alcohol/substance misuse or dependence. The nutrient group reported more than double the improvement in attention, hyperactivity, and impulsivity symptoms, compared with the placebo group. Clinical psychologists rated more than twice as many people in the nutrient group ‘very much’ or ‘much’ improved in overall symptoms. They also rated moderate and severely depressed participants in the nutrient group as having nearly double the improvement in depression symptoms. Researchers found that the micronutrients were completely safe; there were no differences in side effects between the two groups.

British Journal of Psychiatry Daily Essential Nutrients Hardy Nutritionals Study on ADHD

Vitamin–mineral treatment of attention-deficit hyperactivity disorder in adults: double-blind randomised placebo-controlled trial.

Rucklidge JJ, Frampton CMA, Gorman B, Boggis A. The British Journal of Psychiatry. 2014 Feb;204(2): doi: 10.1192/bjp.bp.113.132126 [Epub ahead of print]

Safety and tolerability of Micronutrient formulations.

Scientists compiled safety data from all published and unpublished studies that used a micronutrient formulation co-developed by Hardy Nutritionals® founder David Hardy which has been widely researched in the mental health field. Biological safety data from six sources, including 144 children and adults, showed no occurrences of clinically meaningful negative outcomes/effects or abnormal blood tests that could be attributed to toxicity. Adverse event information from six studies involving 157 children and adults included reports of minor, transitory headache and nausea. Only one of the studies permitted a direct comparison between tolerability of the micronutrient treatment and medications: children and adults treated with micronutrients showed significantly fewer adverse events and significantly less weight gain compared with those taking medications.

Systematic review of safety and tolerability of a complex micronutrient formula used in mental health.

Simpson JS, Crawford SG, Goldstein ET, Field C, Burgess E, Kaplan BJ. BioMed Central Psychiatry. 2011 Apr 18;11:62.

Micronutrient formulation outperforms medications in 88 patients with autism.

Researchers compared psychiatric medication and micronutrient treatment approaches in 88 children with autism spectrum disorder. The micronutrient group (taking predominately a micronutrient formulation co-developed by Hardy Nutritionals® founder David Hardy) improved significantly more than the medication group in key ways, including notably reduced irritability, anger, and intensity of self-injurious behaviors. The micronutrient-treated group also had dramatically lower treatment side-effects.

Micronutrients versus standard medication management in autism: a naturalistic case-control study.

Mehl-Madrona L, Leung B, Kennedy C, Paul S, Kaplan BJ. Journal of Child and Adolescent Psychopharmacology. 2010 Apr;20(2):95-103.

†The micronutrient formulation studied was a pre-2013 version of Truehope EMPowerplus which was co-formulated by David Hardy and Anthony Stephan. Truehope EMPowerplus is a registered trademark of The Synergy Group of Canada Inc., which was co-founded by David Hardy and Anthony Stephan in 1999. David Hardy officially resigned as a shareholder of The Synergy Group of Canada Inc. and director of Truehope Nutritional Support Ltd. in 2013 to focus his efforts exclusively on Hardy Nutritionals®.