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84 HEALTH VITAMINS MINERALS AND SUPPLEMENTS FROM PAGE 83 mild to moderately severe depression (29 RCTs; n=5489) compared treatment for four to 12 weeks with either placebo or standard antidepressants. The authors concluded that available evidence suggested that for the extracts tested in the trials, SJW was superior to placebo in patients with major depression and similarly effective as standard antidepressants with fewer side effects. Authors concluded that if drug-herb interactions could be avoided, SJW is a safer option than conventional drugs.25 • A 2015 systematic review assessed comparative efficacy of hypericum and standard antidepressants in a primary care setting and effects compared with placebo (66 RCTs; n=15161). It found that hypericum extracts are as effective as standard antidepressants and that both are significantly superior to placebo for the treatment of acute depression, but effects compared with placebo for all treatments were relatively small. Hypericum was associated with greater levels of adherence and fewer adverse effects than standard antidepressants. However, despite positive results, authors still concluded that the limitations of current evidence make it difficult to clearly define hypericum’s place in clinical practice.26 • A 2016 systematic review evaluated efficacy and safety of SJW for the treatment of major depressive disorder. (35 RCTs; n=6993). This review was consistent with previous reviews, reporting that SJW is superior to placebo for treatment of mild to moderate depression and not significantly different to antidepressant medication, with greater adherence and fewer adverse events compared with antidepressants. However, quality of evidence was reduced by heterogeneity of studies and some reporting shortfalls, leading the authors to conclude that findings would need to be interpreted with caution.27 SJW can be taken either short or long term but should be taken for at least six weeks to reach maximum effect. It is not recommended for the treatment of specific anxiety conditions as effectiveness for anxiety is strongest for mild to moderate symptoms and GAD. Safety Studies of up to 12 weeks have reported few adverse events. Data on longer term use are lacking. The main caution is in relation to medicine interactions. Medicine interactions Concomitant use is not recommended with a wide range of drugs, including CYP450 enzyme substrates, oral contraceptives, warfarin, protease inhibitors, reverse transcriptase inhibitors, simvastatin, atorvastatin, verapamil, irinotecan, imatinib, methadone, cyclosporin, tacrolimus, fexofenadine, nifedipine, midazolam, omeprazole, voriconazole.13 B complex Recommendation of B vitamins for stress has a physiological basis, with several B vitamins involved in production of neurotransmitters critical to psychological wellbeing. • Occupational stress is a known factor in mental health issues. A 2011 Australian RCT (n=60) examined the efficacy of three months’ administration of high dose B vitamins on mood and psychological strain associated with chronic work stress. After 12 weeks, those taking the B complex formula reported significantly lower personal strain and a reduction in confusion and depressed mood.28 Magnesium Stress and hypomagnesemia share a bidirectional relationship, potentiating each other’s negative effects. Urinary magnesium excretion and plasma magnesium levels are both increased during acute stress, further reinforcing this link. Magnesium has an integral role in central nervous system function, with many nervous system enzymes being magnesium dependent. Magnesium also affects the glutamatergic, serotonergic and adrenergic neurotransmitter systems. Alcohol has a magnesium-depleting effect and poor dietary choices are usually lacking in magnesium, which may further adversely affect magnesium status in some people.29 • A 2017 systematic review of 18 RCTs concluded that there was suggestive but inconclusive evidence for a beneficial effect of magnesium for mild to moderate anxiety, with poor trial quality limiting conclusions.30 The RDI for magnesium is 420mg/day for men and 320mg/day for women (slightly less for those under 30). According to Health Direct, one in three Australians don’t get enough magnesium every day. Diarrhoea is the usual critical endpoint determining an upper limit, being the first sign of excessive intake. LIFESTYLE A growing body of evidence supports the inclusion of lifestyle interventions for all patients with mental health issues. Exercise The relationship between physical activity and mental health is complex. However, the weight of evidence supports the benefit of regular exercise as an anxiolytic and for mental wellbeing. Both aerobic and resistance-style exercise are associated with lower levels of depressive symptoms in clinical trials.5 • A 2018 meta-analysis (11 RCTs; n=455) found that people with major depression who engaged in an average of 45 minutes of supervised moderate-intensity aerobic exercise three days a week for at least two months experienced a large antidepressant effect compared with antidepressant medication or psychological therapies. Authors concluded that “supervised aerobic exercise can significantly support major depression treatment in mental health services”.35 • A 2018 meta-analysis of 49 prospective studies (n=266,939) found that over a two-year period those with high levels of exercise had lower odds of developing depression compared with those with low levels of physical activity. Physical activity also had a protective effect against emergence of depression in youths. Most reports used self-report questionnaires, but controlling for numerous variables still resulted in significant associations between rates of exercise and risk of developing depression.34 Acupuncture, yoga and tai chi • A 2012 literature search found tentative supportive evidence for anxiety disorders. • A 2018 review concluded that yoga may offer benefit as an adjunctive treatment for depression and anxiety disorders, with regular weekly sessions.33 Lack of methodologic rigour has hampered clear recommendations for these approaches but overall, there is positive support for their use as adjunctive interventions. All are well tolerated. Meditation Good quality published literature supports the practice of transcendental meditation (TM) for reducing stress and anxiety. • A 2014 meta-analysis (14 RCTs; n=1295) reported reductions in anxiety for subjects with elevated initial anxiety. 38 • A 2018 RCT (n=203) involved veterans with a current diagnosis of PTSD. This trial assessed symptom severity over three months, comparing TM with a gold- standard prolonged exposure therapy (PE) and health education. Compared RETAIL PHARMACY • MAY 2021