Can Kampo and Dietary Supplement Address Unmet Need? – A Commentary on Tatsumi et al. and Hoffmann et al.

Although a variety of evidence-based guidelines have been published for the treatment of psychiatric disorders, a certain proportion of patients cannot achieve remission or recovery. In addition, there are some patients who cannot take psychotropic drugs because of their poor acceptability. These facts leave room for psychosocial treatment and complementary and alternative medicine in psychiatry and suggest the importance of reviewing the clinical impact of Kampo therapy and dietary supplementation.

In a literature review of a Japanese traditional medicinal system for psychiatric conditions, Tatsumi et al. summarized the clinical effectiveness of Kampo for various psychiatric disorders [1]. Yokukansan was effective for the treatment of behavioral and psychological symptoms of dementia and for the treatment of schizophrenia as an add-on to antipsychotics in patients with treatment-resistant schizophrenia. Kamikihito might be useful for treating mild elderly depression. Moreover, Tatsumi et al. suggested that Kampo mitigated the adverse drug reactions to psychotropics and therefore may be useful in improving drug adherence. In a narrative review of dietary supplements in psychiatric treatment, Hoffmann et al. suggested that there were many indications of the complementary positive effects of Vitamin D and polyunsaturated fatty acids (PUFA) on depressive symptoms, anxiety and pain [2]. They postulated that because these agents are associated with a low frequency of adverse events, there should be no reason to exclude their use as additions to standard therapy. Both reviews pointed out the paucity of evidence derived from large-scale, randomized controlled clinical trials in patients with psychiatric conditions and concluded that further research is needed.

While the author is aware of the importance of investigating the curative efficacy and safety of Kampo and dietary supplements for psychiatric disorders, this commentary focused on the preventive potential of Kampo and dietary supplementation therapies. Specifically, their efficacy for early intervention and frailty management in psychiatry was briefly reviewed.

The first topic is the preventive potential of omega-3 fatty acids in psychiatric disorders, including depression, psychosis, and dementia. Omega-3 fatty acids refer to a group of PUFA represented by eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), contained in fish oil, and α-linolenic acid, richly present in perilla seed oil. The possible benefit of omega-3 PUFA in preventing depression may be considered from the major depressive disorder algorithms of the Texas Medication Algorithm Project (TMAP) [3]. These TMAP algorithms described that omega-3 fatty acids could be recommended as a treatment option for major depressive disorder, along with evidence-based psychotherapy administered alone or in combination with pharmacotherapy. Moreover, several meta-analyses showed that EPA was the active component of PUFA in the treatment of major depressive episodes [4] [5]. In addition, since another meta-analysis reported that omega-3 fatty acids were effective on depressive patients without diagnosis of major depressive disorder [6], it suggested that omega-3 PUFA may be effective for preventing depression.

What about the effectiveness of omega-3 PUFA for preventing schizophrenia and other psychotic disorders? A randomized, double-blind, placebo-controlled trial in 81 patients with an ultra-high risk of psychotic disorder demonstrated that a 12-week intervention with 1.2 g/day omega-3 acids significantly reduced the risk of developing psychosis [7]. A longer-term follow-up of the study population at a median of 6.7 years showed a reduced risk of progression to psychotic disorder [8].

Regarding the ability of various supplements to prevent dementia, a randomized, double-blind, placebo-controlled clinical trial was conducted in which participants daily received either placebo or a combination of 290 mg EPA, 203 mg DHA, 240 mg ginkgo biloba extract, and 5 mg lycopene [9]. Participants who received the active treatment for 3 years showed significantly better cognitive function than those who received placebo. This clinical trial demonstrated the potential benefit of administering multiple agents with different antioxidant properties for preventing dementia symptoms.

The next topic deals with the clinical potentials of early intervention by Kampo for psychiatric disorders. Although Kampo formulae are covered by the national insurance system in Japan, few clinical trials have been conducted in Japan to investigate the effect of Kampo in preventing psychiatric disorders, not treating them. Here, the author focused on the concept of frailty, which would be close to the pre-disease condition in the elderly, because of its growing significance in the context of global ageing. Frailty is a state of increased vulnerability and a consequence of age-related decline in reserve and function across multiple physiologic systems. Fried et al. identified frailty based on the presence of three or more of the following: shrinking, weakness, exhaustion, slowness, and low activity [10]. A systematic review and meta-analysis demonstrated a reciprocal interaction between depression and frailty in elderly patients [11]. Each condition is associated with the increased prevalence and incidence of the other, and each may be a risk factor for the other’s development. The prevention of frailty could thus play a significant role in preventing depression. Ninjin'yoeito (NYT) is an agent that can be expected to be effective especially in frailty management. NYT consists of the following ingredients: Ginseng, glycyrrhiza, Atractylodes rhizome, Japanese angelica root, Poria sclerotium, Cinnamon bark, Polygala root, Citrus unshiu peel, Astragalus root, Schisandra fruit, Peony root, and Rehmannia root. NYT is indicated for the relief of the following symptoms: declined constitution after recovery from disease, fatigue and malaise, anorexia, perspiration during sleep, cold limbs, and anemia. From the composition and effect mechanism of NYT, the benefit potential of this Kampo for frailty was explained [12]. Because a clinical study showed that Ninjin’yoeito possibly had a protective effect against frailty [13], its use in preventing depression deserves research attention.

Finally, the author concluded by proposing that more well-designed clinical research be done to investigate the effects of herbal medicine and nutrient supplementation to early intervention and frailty management in psychiatry. The accumulation of evidence in this field will help decrease the burden of people with mental health problems.

• References

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