Despite the lack of guidance available for practitioners, extensive polypharmacy has become the primary method of treating patients with severe and chronic mood, anxiety, psychotic or behavioral disorders. This ground-breaking new book provides an overview of psychopharmacology knowledge and decision-making strategies, integrating findings from evidence-based trials with real-world clinical presentations. It adopts the approach and mind-set of a clinical investigator and reveals how prescribers can practice 'bespoke psychopharmacology', tailoring care to the individualized needs of patients.
Novel Drug Therapeutics: Nutraceuticals, Steroids, Probiotics, and Other Dietary Supplements
Let not thy food be confused with thy medicine.
▢ Understand safety concerns for patients who take nutraceutical products, from both a pharmacokinetic and a pharmacodynamic perspective
▢ Recognize the distinction between repletion versus supplementation of dietary vitamins or other nutritional supplements
▢ Appreciate the highly variable evidence base for claims of psychotropic efficacy for specific nutritional supplements
The relationship between food products and pharmacodynamically active agents traces at least to antiquity, even if Hippocrates never actually did say “let food be thy medicine and medicine be thy food” (Cardenas, 2013). In modern times the relationship between dietary supplements and medicine has come to pose a rather peculiar dichotomy between what might be called “legitimate” or “mainstream” medicine and nonstandard or “alternative” medicine. Interventions in the latter category suffer from issues of credibility due to an often less rigorous RCT database, at times poorly established rationales and/or mechanisms of action, and lack of regulatory agency product oversight for quality assurance purposes. Many patients obtain information about herbal products or dietary supplements simply from internet searches with little awareness of the scientific rigor or credibility behind advertising claims or consumer postings and testimonials, or cognizance of potential pharmacokinetic interactions.
Proponents of nutritional supplements sometimes conflate “natural” with “safe,” despite the plethora of poisonous natural substances (e.g., hemlock, arsenic, cyanide, strychnine, mercury, and tetrodotoxin) devoid of therapeutic value except perhaps as defenses against predators. A study of 121 Ayurvedic or Chinese herbal natural health products found that most contained measurable levels of toxic elements (notably, lead, mercury, cadmium, arsenic, and aluminum), though fewer than 10% of products tested had levels exceeding the established daily limit of toxicant exposure (Genuis et al., 2012). Safety and efficacy command equal importance throughout medicine, no more nor less for psychopharmacology in particular, regardless of whether a compound is “natural” or synthetic. And while even placebos can have adverse effects, and sometimes exert astonishing potency (see Chapter 4), products that are entirely harmless still pose the hazard of being ineffective as compared to those that are better (and have large effect sizes) relative to placebo.
In the eighteenth century, tobacco smoke enemas were considered state-of-the-art remedies for both epilepsy and respiratory failure; fried pigeon dung was a first-line treatment for dyspepsia; white lead was used to stop hemorrhaging or diarrhea; and dried toad was believed to cure asthma. Such practices have long been abandoned by traditional medicine without the necessity of RCTs to establish their lack of efficacy.
When leaping from an airplane (recall from Chapter 1), note that altitude is a critical moderator of response to parachute efficacy; parachutes have been shown not to reduce death or major trauma when deployed from stationary aircraft on the ground (Yeh et al., 2018).
When little or no data exist to guide treatment decisions, practitioners are more vulnerable to clinical impressionism or other low-tier levels of evidence (see Chapter 1, Figure 1.1). Many nutraceutical products that predate modern practices have garnered popularity because their perceived pharmacodynamic effects have been reinforced by cultural lore (e.g., “used for centuries” by ancient civilizations) or anecdote, sometimes underscored by dramatic endorsements from sufferers or practitioners. Certainly, there are times when the potential value of an intervention is so intuitively obvious and compelling that RCTs appear unnecessary – as in the utility of parachutes during airplane jumps. (But, consider that comparative trials would still be needed to judge how well parachutes fare in comparison to, say, jet packs, or knowing when two or three parachutes may produce a better effect than just one or two, or deciding when dome-canopy versus annular or ram-air designs deliver a better result, or whether nylon versus silk versus terylene construction tends to land jumpers more safely and soundly.) Lead – albeit a natural substance – probably makes a parachute less useful than having none at all.
Psychotropic drugs are parachutes for when mental health enters into free fall. Marketers of dietary supplements often tout nonspecific and/or nebulous mental health benefits such as “relief of nervous tension or stress,” “improves mental and physical performance,” “enhances overall vitality,” or “body cleansers” – variables that are difficult to quantify or translate into tangible targets when treating psychopathology. In this chapter, we will direct our focus on the existing evidence base for the relative safety and psychotropic efficacy of nutritional or dietary supplements, examining specific intended targets of mental health treatment.
Exact terminology varies across countries, but broadly speaking, food products that may have pharmacodynamic effects have been referred to as dietary supplements, nutraceuticals, functional foods, phytochemicals, biochemopreventatives, or designer foods. In Japan, such products are called foods for special health use (FOSHU). “Natural health products” is the preferred category descriptor in Canada (where a government database maintains up-to-date information on product safety and efficacy (www.canada.ca/en/health-canada/services/drugs-health-products/natural-non-prescription/applications-submissions/product-licensing/licensed-natural-health-products-database.html)). The term nutraceutical was coined in 1989 by Stephen DeFelice of the Foundation of Innovative Medicine and encompasses dietary supplements, isolated nutrients, and herbal products. Under the Dietary Supplement Health and Education Act, “dietary ingredients” found in dietary supplements may include “vitamins, minerals, herbs, amino acids, enzymes, organ tissues, glandulars, and metabolites.”
The National Institute of Health’s Center for Complementary and Integrative Health estimates that about 59 million Americans annually spend over $30 billion out of pocket on dietary health supplements (https://nccih.nih.gov/research/statistics/NHIS/2012).
The Dietary Supplement Health and Education Act (DSHEA) of 1984 defined “dietary supplements” as food exempt from FDA oversight or regulation. There is no federal scrutiny over the safety or efficacy of dietary supplements or their promotional marketing, although regulation 21 CFR part 111 requires “good manufacturing practice conditions” for US-made dietary supplements.