Lila Massoumi, MD
Chairperson, Caucus on Complementary, Alternative, and Integrative Medicine, American Psychiatric Association
Dr. Massoumi has disclosed that she has no relevant financial or other interests in any commercial companies pertaining to this educational activity.
Patients are increasingly asking us about complementary and alternative treatments for their psychiatric issues. If you don’t know much about these treatments, you may end up saying something like, “Well, we don’t have as much data on these as we do for standard treatments—they might help, but we just don’t know. Let me refer you to….”
There’s nothing inherently wrong with that approach, but it’s also a missed opportunity. Why not combine conventional psychopharmacology with complementary and alternative medicine (CAM) treatment? As an integrative holistic psychiatrist, I combine the conventional care of psychiatric medications and counseling with non-medication treatments, including supplements and electromagnetic devices, and have had good success. In this article, I’ll review some of my practices and discuss various nutritional and herbal supplements that you might consider prescribing for your patients.
The nature of the evidence In order to practice evidence-based medicine, we typically limit our prescribing to treatments that either have been FDA-approved, or, if off-label, are at least somewhat supported by high-quality clinical trials—typically randomized controlled trials (RCT). Unfortunately, natural supplements cannot be patented. For this reason, supplement manufacturers have no financial incentive to do expensive RCTs. Because of this, the studies you’ll find will vary in quality. Some will be very small case series; other supplements may be supported by a few uncontrolled clinical trials of 30 patients or so. Occasionally you’ll see randomized placebo-controlled trials, but the numbers of subjects are often lower than we’d like. The bottom line is that you will have to make your own judgments based on your evaluation of the evidence for particular natural treatments.
Evaluating patients Some patients are better candidates than others for CAM. Clearly, those who have milder symptoms who come right out and ask for alternative treatments are appropriate. Other good candidates include patients who are very sensitive to the side effects of conventional meds, are somatically preoccupied, or who have responded only partially to conventional medications (in which case the supplement is used as an augmenting agent).
There are also patients who, perhaps due to a history of developmental trauma, simply do not trust psychiatric medications. Rather, they prefer the feeling of control they get by buying their own supplements (vs. having to rely on a prescriber or a prescription). For such patients, you can start with a natural supplement until you have gained their trust. The supplement may have a smaller effect size than a pharmaceutical, but by starting with something natural, you are enhancing the therapeutic alliance. Additionally, as we’ve learned more about the power of the placebo response, especially in psychiatry, many of us are willing to prescribe an agent for which the evidence may be insufficient—in order to activate the placebo response and enhance the agent’s efficacy.
One of the realistic challenges for using integrative medicines is that there are so many supplement options that patients can end up taking too many pills per day—often a dozen or more. Compliance becomes a real issue. It’s a good idea to assess your patients’ motivation before recommending a multitude of supplements. For example, if you have a patient with skin-picking disorder and you are considering prescribing NAC (discussed later in the article), you’d want to ask, “If there’s a supplement that you would have to take twice a day that could get rid of your desire to pick at your skin, and which could take 3 months to see full effect, would you want to try it?” If you hear “Yes, absolutely,” then you proceed from there.
Lab testing Many psychiatrists order basic labs during the psychiatric evaluation, such as a CBC, electrolytes, liver function tests, thyroid tests, and a lipid panel. As an integrative practitioner, I will usually order additional testing, and may also interpret results differently. For example, I usually check high sensitivity C-reactive protein (hsCRP), which is a measure of the degree of inflammation within the blood vessels. Recent studies have shown a relationship between inflammation and mood disorders. Specifically, there may be a subgroup of treatment resistant patients with elevated inflammatory markers, such as hsCRP, whose mood disorder may respond to anti-inflammatories (Rosenblat JD et al, Bipolar Disord 2016;18(2):89–101).
In terms of thyroid, integrative practitioners have a lower threshold for considering a TSH (thyroid stimulating hormone) result treatable. Recall that hypothyroidism causes the brain to produce increased quantities of TSH in order to increase production of the hormone. Most laboratories define the “normal” range as 0.5–4.0, but some patients may have subtle clinical symptoms of hypothyroidism even when the TSH is lower than 4. Like many other integrative practitioners, I will often treat any TSH above 2.5 if the patient is exhibiting clinical symptoms, particularly a history of always feeling colder than others.
For nutritional lab work before starting supplements, the following basic checklist is a good start:
Vitamin B12 level
Vitamin D level–-specifically 25-hydroxyvitamin D (not
Ferritin level (storage iron)
RBC magnesium level* (intracellular magnesium)
RBC zinc level* (intracellular zinc)
*RBC levels of magnesium and zinc are better indicators of the status of these minerals than standard serum levels.
Which supplements should you prescribe? If a patient’s lab work shows a clear deficiency, you would use the relevant supplement for replenishment. However, even if there is no frank deficiency, for the most part I want my patients to be on the upper end of normal levels, if for no other reason than to prevent a future depletion. Often, patients say they feel healthier and more energetic when their nutritional levels are on the high side. Based on the results of your patients’ lab work, here are some guidelines that I recommend for optimum nutritional levels.
Vitamins and minerals Vitamin B12 The standard normal B12 level is anything above 200 picograms/milliliter (pg/mL), which is enough to avoid peripheral neuropathy and overt signs of dementia. Most doctors practicing integrative medicine want to see these levels above 500 pg/mL, sometimes even closer to 1,000 pg/mL. In recent preventative studies on dementia, “normal” levels are listed as above 500 pg/mL and ideally closer to 1,000 pg/mL (Gröber U, Nutrients 2013;5(12):5031–5045). In Japan, levels above 500 are standard. Many practitioners also include a folic acid supplement when repleting B12.
Be aware that vitamin B12 can act as a stimulant. I’ve had a few cases when I’ve repleted people with low levels and they’ve experienced anxiety or mania. So for patients with bipolar disorder, I may avoid repleting B12 or use a much lower dose until I feel that mania is well-controlled with a conventional mood stabilizer.
The vitamin B12/folic acid combination product I currently recommend to my patients is “Active B12 with L-5-MTHF,” under the Seeking Health brand. This is a lozenge that can be melted under the tongue, so I don’t need to worry about lack of intrinsic factor or stomach acid for absorption. [Editor’s note: Most of the supplements recommended by Dr. Massoumi can be purchased on Amazon.com.]
Vitamin D Research over the last 10 years has indicated that a large percent of the world’s population is low in vitamin D (Holick MF et al, J Clin Endocrinol Metab 2011;96(7):1911–1930). In the U.S., a range above 30 ng/mL is considered normal. Most integrative practitioners recommend a level significantly higher than that—50 ng/mL or above on the conservative side. Many also supplement vitamin D with vitamin K2, as studies have indicated that these two vitamins work synergistically to prevent osteoporosis (Ushiroyama T et al, Maturitas 2002;41(3):211–221).
If a patient’s vitamin D level is greater than 20 ng/mL, then standard practice is to prescribe 5,000 IU daily and then recheck in several months. Once patients get to 50, you want to keep them on that daily dose for maintenance purposes. If a patient’s vitamin D level is less than 20, prescribe 10,000 IU daily for a month, dropping the patient back down to 5,000 IU when the level reaches 50. Historically, there’s been a concern about vitamin D being fat-soluble and the consequent risk of toxicity; however, most practitioners will say it’s a rare patient whose vitamin D level reaches a toxic level of 80 or above on a regimen of 5,000 IU daily.
I prefer to use “Vitamin D3 5000 IU with Vitamin K2,” under the Michael’s Naturopathic Programs brand—it is tiny, inexpensive, chewable, and good-tasting, so I get more compliance. However, if a patient is on anticoagulant therapy (vitamin K blockers), then I avoid use of vitamin K2 and suggest taking vitamin D3 alone.
Magnesium Magnesium is the best natural supplement for the treatment and prevention of headaches, including migraine headaches. Approximately 40% of Americans are deficient in magnesium (Moshfegh A. What We Eat in America, NHANES. U.S. Department of Agriculture, Agriculture Research Services, 2005–2006). In my practice, I routinely ask about headaches and migraines. If I have a patient experiencing them, I will be pretty suspicious about the patient’s RBC magnesium levels. Most integrative practitioners want to see a RBC magnesium level in the upper half of normal, or > 5 mg/dL.
If a supplement is necessary, the main thing to keep in mind is that most forms of magnesium cause a laxative side effect. Most integrative doctors use magnesium glycinate, which tends to cause less diarrhea than other forms. Magnesium L-threonate (the patented form is called Magtein) does not cause a laxative side effect and also has some very preliminary evidence suggesting that it’s beneficial for brain health (Slutsky I et al, Neuron 2010;28:65(2):165–177).
Iron Low iron levels are one of the nutritional deficiencies that can cause restless leg syndrome. If a patient’s ferritin (storage iron) level is < 30 ng/mL, I’ll recommend an iron supplement. Usually the RLS goes away, and you have just saved the patient from a prescription for a dopamine agonist. One nice product is “Ferritin,” under the Cardiovascular Research brand, and the usual dose is 5 mg two capsules per day (10 mg daily total).
Iron, zinc, and ADHD You’ll often see low ferritin and RBC zinc in patients who are diagnosed with ADHD. Restless leg syndrome due to low iron in children may be misinterpreted as hyperactivity. Meanwhile, zinc supplementation has been shown to (modestly) reduce hyperactivity and impulsivity. If the zinc is in the lower half of normal (with a typical lab’s normal range being 9–15 mg/L), I’ll recommend a zinc supplement. Keep in mind this is not a substitute for traditional prescribing patterns for ADD. You’re not going to necessarily notice a dramatic behavioral difference with these supplements, but it prevents prescribing excessive stimulants to compensate for a nutritional deficiency (Arnold LE et al, J Child Adolesc Psychopharmacol 2011;21(1):1–19).
Amino acids and other molecules CoQ10 Coenzyme Q10 (CoQ10) is a molecule produced in the body and does not necessarily need to be supplemented. However, several diseases are associated with low CoQ10 levels (particularly fibromyalgia), and statin drugs are known to deplete CoQ10 levels. If I learn that a patient is on a statin, I will prescribe CoQ10, because this will significantly decrease the patient’s chances of developing statin-induced myalgias or rhabdomyolysis. I have had patients report improved energy and improved aerobic capacity while taking CoQ10. In adults, CoQ10 100 mg taken once daily with a meal (relies on food for absorption) is the most cost-effective dose. For CoQ10, I do not care about the brand or form; Costco is a good place to buy CoQ10 inexpensively.
N-acetylcysteine (NAC) NAC has pretty good clinical evidence for both skin-excoriation disorder and trichotillomania (Grant JE et al, Arch Gen Psychiatry 2009;66(7):756–763), and it might help adjunctively for treatment resistant OCD (Deat et al, J Psychiatry Neurosci 2011;36(2):78–86). I prescribe it for those conditions, as well as for those who have OCD but who don’t want to be on psychiatric medication. The ideal therapeutic dose is two 600 mg pills (1,200 mg) twice a day, although if I’m concerned about compliance, I will have patients start with 1 pill twice a day (or 2 pills once per day). Generally, it will take about 3 months for patients to note the full therapeutic effect of NAC. An additional benefit of NAC is that it repletes glutathione, an important antioxidant.
y-Aminobutyric acid (gaba) GABA is the major inhibitory neurotransmitter in the brain. Supplemental GABA has been shown to increase alpha waves (brain waves associated with relaxed alertness) and decrease beta waves (associated with high stress and difficulty concentrating) (Akhondzadeh S et al, Psychiatr Clin North Am 2013;36(1):25–36). The product I like to use is actually a combination product called “Chewable GABA,” under the NOW Foods brand. I tell my patients it’s like a mild Xanax, only it is not abusable. Patients having anxiety attacks can just chew it in public without anyone noticing that they have taken a pill. The NOW formulation also includes some other molecules that may contribute to its usefulness, such as L-theanine, which we know is a calming agent without being sedating; taurine, which is an amino acid that some people feel has mood-stabilizing effects; and inositol. Inositol by itself is available as a powder, and there is good clinical evidence that it helps with conditions for which we’d normally prescribe SSRIs, such as depression, anxiety, panic, binge eating, and OCD (Gelber D et al, Int J Eat Disord 2001;29(3):345–348). Unfortunately, I stopped using standalone inositol in my practice despite its good clinical evidence because all of my patients experienced severe, life-interfering flatulence.
S-adenosylmethionine (SAM-e) SAM-e is involved in the formation, activation, or breakdown of other chemicals in the body, including hormones and proteins. Studies clearly show that for depression, it’s as effective and possibly better tolerated than some SSRIs and tricyclics (Brown R et al, Clin Pract Intern Med 2000;1:230–241). SAM-e is highly stimulating, and my experience with patients on the bipolar spectrum is that it results in mood cycling. I end up seeing things like increased agitation, anxiety, and irritability or insomnia. From the first moment I see a depressed patient, I always think in terms of mood cycling, so I’m very cautious about this effect. One recommendation is to start SAM-e at a smaller dose and add something calming with it until the highly stimulating effects go away. If someone is completely mood-controlled—eg, on a mood stabilizer to prevent mania—I might add SAM-e to the mood stabilizer, either alone or as an adjunct to a conventional antidepressant. SAM-e comes in 200 mg and 400 mg tablets. Good brands include Nature Made, Jarrow Formulas, or Vitacost (available from Vitacost.com). The maximum dose I would use is 800 mg in the morning, at least 20 minutes before food, and 800 mg in the early afternoon. You don’t want your patients to take it too late in the day because it can cause insomnia. After 1 week, increase to 2 pills every morning, but if anxiety, insomnia, or jitteriness develops, back down on the dose.
Natural hormones Melatonin Melatonin is normally produced by the pineal gland, and its level increases throughout the night, causing sleepiness. As a supplement, melatonin is an effective sleeping aid, and comes in both an immediate-release form, which helps with sleep onset, and an extended (or sustained) release form, which assists with sleep maintenance. Sometimes I’ll have patients take one of each if they’re having trouble with both sleep-onset and sleep-maintenance insomnia. The therapeutic dose ranges from 0.3 mg to 5 mg; next-day sedation is a dose-related effect, and patients should lower their dose if they experience it. It’s important to explain that melatonin does not work like Xanax or Ambien in adults; it may take 2 weeks to start working. (In contrast, it seems to work immediately in children.) If it doesn’t work after 2–3 weeks, then I just tell my patients to stop taking it.
Contrary to many consumers’ concerns, melatonin supplementation is not associated with negative feedback (ie, it does not cause the body to produce less of the hormone); there is no withdrawal, and it is not addictive. I also use melatonin quite effectively for night terrors and parasomnias. Some practitioners use a higher dose for parasomnias—up to 6 mg—with full effect taking 2–3 months (McGrane IR et al, Sleep Med 2015;16(1):19–26). Sometimes I will prescribe melatonin alone (the brand makes no difference), or I will use a combination product such as “NightRest with Melatonin,” under the Source Naturals brand (containing 5 mg of melatonin as well as magnesium, GABA, taurine, glycine, passionflower, chamomile, and lemon balm). As an aside, melatonin also is notably effective for symptoms of GERD and has a protective effect against ulcers (Celinski K et al, J Physiol Pharmacol 2011;62(5):521–526).
Herbal adaptogens The herbal medicines I use most frequently fall under the category of “adaptogens,” or herbs that increase our ability to adapt to stress. The stress-protective activity of adaptogens is associated with regulation of homeostasis via several mechanisms of action, linked with the hypothalamic-pituitary-adrenal axis and the regulation of key mediators of the stress response, including cortisol, nitric oxide, neuropeptide Y, and others (Panossian A and Wikman G, Pharmaceuticals 2010;3(1):188–224). The clinical result is increased energy or a feeling of psychological and physical well-being. Thus, adaptogens may help with fatigue or depression.
They also appear to be neuroprotective. Clinical research supports—as have the results in my practice—the use of adaptogens to decrease akathisia and Parkinsonian symptoms from antipsychotics (Muskin et al, Psychiatr Clin of North Am 2013;36(1):54). Whether they help prevent tardive dyskinesia is unclear, but I would speculate that they do, and I try to get my patients who take antipsychotics to also take a daily adaptogen.
The best way to learn about the different adaptogens is to read the book The Rhodiola Revolution by Richard Brown, MD and Patricia Gerbarg, MD (New York, NY: Rodale; 2005)—it is how I learned to use them. Below, I describe the three adaptogens that I use the most in my practice. All of them are best consumed on an empty stomach approximately 20 minutes before eating. Also, I always provide patients with a handout showing which brand to purchase and emphasize that I do not support using any other product. This is because herbal quality varies considerably across manufacturers, and the best way to achieve “pharmaceutical grade” is to stick with the manufacturer used in the actual studies.
Rhodiola rosea Rhodiola acts as both a stimulant and an anti-anxiety agent. In the original studies done in Russia, rhodiola was found to be more helpful for increased energy than stimulants like methylphenidate and caffeine, because unlike stimulants, it did not exacerbate anxiety, and patients did not experience an energy crash when the effects of the substance wore off. As a stimulant, it is a natural treatment for ADHD, and my adult patients have been able to decrease their stimulant doses (as well as their coffee intake) when they have used it. Anything that increases energy has the risk of precipitating mania, so I’m unlikely to use rhodiola with bipolar I patients.
I prescribe rhodiola in two ways: either as the single herb, or as a combination of three adaptogens in a commercial product called “Adapt Life” (containing Rhodiola rosea, Eleutherococcus senticosus, and Schisandra chinensis). The product I recommend for simple Rhodiola rosea is “Rosavin Plus,” under the Ameriden International brand. Dosing for both is 1 pill in the morning, and if there is no effect after several days, then increase to 2 pills every morning. If patients develop anxiety or irritability, I tell them to stop using the product immediately. For patients who do not have bipolar disorder, I consider Rhodiola rosea to be anxiolytic, and Adapt Life to be anxiety-neutral. For patients on the bipolar spectrum, either of these agents could exacerbate anxiety.
Ashwagandha Ashwagandha is an adaptogen used for calming that is popular in Ayurvedic medicine (traditional Indian medicine). I prefer a combination product called “Cortisol Manager,” under the Integrative Therapeutics brand; it includes ashwagandha, phosphatidylserine, and a few other calming agents. Instructions are to take 1 pill at bedtime. With ashwagandha, I have never seen precipitation of mania, and I am comfortable using it in bipolar disorder.
Maca Maca is an adaptogen from Peru that was traditionally used to enhance fertility and libido. I use it to regulate female hormones in women of all ages—for example, to normalize period duration, decrease pain, and decrease mood and physical symptoms of PMS and menopause (Meisner HO, Int J Biomed Sci 2006;2(4):360–374). Most of my patients do very well with it. You do need to caution women of reproductive age, however, that if they go on maca, they will be more fertile and more likely to get pregnant. Also, maca isn’t effective for patients on birth control pills, bioidentical hormones, or exogenously administered hormones.
The product I use is Natural Health International Maca. Natural Health International has three products for reproductive-age women, perimenopausal women, and postmenopausal women. It takes about 3 months for patients to get the full benefits of maca. Women of reproductive age may notice that their first cycle can be the opposite of what they’re used to. So if women are used to very heavy periods, maca might cause the first month of their period to be abnormally light. Usual dosage is to start with 1 pill in the morning, preferably on an empty stomach, for 10 days, and if no side effects occur such as worsening of mood symptoms, go up to 2 pills in the morning and remain at that dose. If there are still some residual issues after a couple of months or the treatment doesn’t seem to be working, I’ll increase the dosage by adding an extra 1 or 2 pills about 2 hours after lunch.
Supplements I don’t use and why St. John’s wort (SJW) SJW is one of a small handful of supplements with clinically relevant P450 supplement-drug interactions. Specifically, it increases the activity of several hepatic enzymes and therefore decreases serum levels of a number of medications. I consider SJW like a mild SSRI without the sexual side effects, but with drug interaction risks and the problem of needing to avoid sunlight because it can cause a phototoxic rash. [Editor’s note: Some clinicians do prescribe SJW, especially to young people, because it is one of the only antidepressants that does not carry a black box warning regarding the risk of suicidality.]
Kava Although kava is an effective anti-anxiety compound, it has the marked disadvantage of potentially causing liver damage. It also may be addictive for some patients (like benzodiazepines), and there are few if any studies documenting the safety of its long-term use. Better CAM anti-anxiety treatments include GABA, the combination product containing ashwagandha, and cranial electric stimulation devices, which I discuss in more detail in this issue’s expert interview.
Fish oil (Omega-3 fatty acids) Fish oil is a combination of two fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). EPA is an antidepressant (think “EPA for Emotions”], and DHA has some positive data on improving cognition in both dementia and ADHD (think “DHA for Dementia”]. While that may sound great, the reality is that in order to match the doses used in the clinical trials, EPA+DHA needs to equal 1000–2000 mg. This can mean up to 8 pills per day, or alternatively having to drink fish oil liquid (albeit flavored). The pills are fairly large and smell unpleasantly fishy to some patients, although a good tip is to freeze them before taking them, which eliminates the odor. In general, I haven’t seen a large enough effect size using fish oil to justify adding it to the rest of the supplements that I am asking my patients to take. Rather, I prefer to advise patients to eat seafood, and in particular salmon, at least three times per week.
Conclusion This has been a whirlwind introduction to CAM treatments in psychiatry, and it can be overwhelming to decide how to introduce these supplements to your patients. One thing to keep in mind before implementing CAM interventions is that they are best used for patients who are less severely ill or as augmentation strategies. Specifically, consider CAM for:
Patients with milder forms of psychiatric illness
Patients who specifically state they are opposed to psychiatric medications, leading you to recommend an appropriate supplement as a means of establishing a therapeutic alliance
Patients who are treatment resistant or medication sensitive
Patients on conventional meds for whom the supplement augments their current treatment
If you are new to CAM, I recommend starting with checking vitamin B12 and vitamin D and repleting those if necessary, and using melatonin for insomnia in those patients who are willing to wait the several weeks it might take to be fully effective.
Beyond this, I encourage you to gradually explore these treatments over time. You may find, as I have, that your patients benefit from, and appreciate, CAM treatments in your psychiatric practice.
Brown R, Gerbarg P, Muskin P. How to Use Herbs, Nutrients and Yoga in Mental Health Care. New York, NY: W.W. Norton & Company; 2012.
Muskin P et al, eds. Complementary and integrative therapies for psychiatric disorders. Psychiatric Clinics of North America 2013;36(1).
Gerbarg P et al, eds. Complementary and Integrative Treatments in Psychiatric Practice. American Psychiatric Association Press, estimated publication date June 2017.
IntPsychiatry.com: American Psychiatric Association (APA) Caucus on Complementary & Alternative Medicine. This APA special interest group offers a monthly newsletter and webinar on topics pertaining to CAM.
Examine.com (most of this site is free). A multidisciplinary team (including PhDs, MDs, and PharmDs) based in Canada that evaluates the research and then summarizes the literature on a given supplement in a concise table called the “Human Effect Matrix.” At a glance, the table lists the indications for which the supplement has been evaluated, the quality of the evidence, the reported magnitude of benefit (effect size), and the consistency of the research results. Clicking an item within the matrix brings up a pop-up window with more information and direct links to PubMed abstracts. The site has a strong commitment to being free of industry bias.
Consumerlab.com (requires membership, approximately $45/year). Purchases supplements off the shelf and tests whether each supplement contains the claimed ingredient at the claimed dose; the site also evaluates for concerning contaminants.