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Natural Medications in Psychiatry


Key Points

  • Complementary and alternative medical therapies are made up of a diverse spectrum of practices (including natural medications) that often overlap with more traditional medical practice.

  • The use of natural medications is growing considerably in the US and around the world, and patients often do not report use of natural medications to their physicians.

  • Historical lack of scientific research in this area has contributed to deficiencies in knowledge with respect to safety and efficacy of many of the natural remedies on the market today.

  • Natural medications are used for the psychiatric indications of mood disorders, anxiety, insomnia, menstrual and menopausal symptoms, and dementia (among others).

Overview

Complementary and alternative medical therapies are made up of a diverse spectrum of practices and beliefs that often overlap with current medical practice. The National Institutes of Health (NIH) defines complementary and alternative medicine (CAM) as “healthcare practices outside the realm of conventional medicine, which are yet to be validated using scientific methods.” The National Center for Complementary and Alternative Medicine (NCCAM) is one of the NIH institutes and is the federal government's lead agency responsible for scientific research on complementary and alternative medicine. NCCAM distinguishes four domains within complementary medicine: mind–body medicine, energy medicine, manipulative and body-based practices, and biologically-based practices. This chapter will focus on the biologically-based practices including natural medications. Natural medications are medications that are derived from natural products, and are not approved by the Food and Drug Administration (FDA) for their proposed indication. Natural medications may include a wide variety of types of products such as hormones, vitamins, plants, herbs, fatty acids, amino acid derivatives, and homeopathic preparations. Natural medications have been used in Asia for thousands of years. Their use in the US has, however, been much more recent, with a dramatic increase over the past decade and a half. In fact, the National Health Interview Survey conducted in 2002 revealed that 62% of a randomly-sampled US population used some form of CAM, including prayer, for health reasons within the past year. When prayer was excluded, 36% of those sampled admitted to using some form of CAM. Moreover, between 1990 and 1997 the prevalence of herbal remedy use increased by 380%, while high-dose vitamin use increased by 130%. Between 1998 and 2002 CAM use doubled in the over-65 population. Ethnic considerations also appear to be important, with African Americans being the group least likely in the US to try natural remedies and Hispanics being the most prone to their use. Given the considerable portion of the US population trying natural remedies, it is clearly becoming increasingly important to be informed about these medications in order to provide comprehensive patient care. This chapter provides an overview of the use of natural medications in psychiatry. General safety and efficacy are discussed first. This is followed by an examination of some of the primary remedies used for psychiatric indications including mood disorders, anxiety and sleep disorders, menstrual disorders, and dementia.

Efficacy and Safety

Although both governmental agencies (including the NIH and NCCAM) and the pharmaceutical industry are sponsoring more clinical research involving natural medications, data regarding effectiveness still lag behind. The actual benefits of natural remedies are often unclear in a setting where relatively few systematic studies have adequately addressed the question of effectiveness. The FDA does not routinely regulate natural medications, leaving questions of safety at the forefront. Consumers often believe that because a remedy is “natural,” it is therefore safe. Moreover, since these remedies are most often purchased over the counter (OTC), there is no clear mechanism for reports of toxicity to reach those who use them. Another significant problem lies in the limited information regarding the safety and efficacy of combining natural medications with more conventional ones. In cases where interactions are known, the psychiatrist faces the reality that patients frequently do not disclose their use of CAM therapies to their physicians. In one study, fewer than 40% of CAM therapies used were disclosed to a physician. Asking very specific questions about a patient's use of both prescribed and OTC medications may improve disclosures in this regard. Finally, since natural medications are not regulated as more conventional ones are, significant variability exists among different preparations. Preparations often vary in purity, quality, potency, and efficacy while side effects may vary. The increase in government- and industry-sponsored studies may further clarify the potential uses, safety, and efficacy of these medications; until such results are available, caution should still be used in recommending those that are less well understood. The remainder of this chapter outlines the current understanding of some of the primary natural medications with potential psychiatric indications.

Mood Disorders

Numerous natural medications have been used to treat mood disorders, including omega-3 fatty acids, St. John's wort (SJW), S- adenosylmethionine (SAMe), folic acid, vitamin B 12 , and inositol ( Table 13-1 ). Dehydroepiandrosterone (DHEA) may also have a role in the treatment of depression; however, further description of this adrenal steroid is reserved for the cognition and dementia section later in this chapter. The efficacy, possible mechanisms of action, dosing, adverse effects, and drug interactions of each of these medications are discussed in the following section.

TABLE 13-1
Natural Medications for Mood Disorders
(Adapted from Mischoulon D, Nierenberg AA. Natural medications in psychiatry . In Stern TA, Herman JB, editors: Psychiatry update and board preparation , ed 2, New York, 2004, McGraw-Hill.)
Medication Active Components Possible Indications Possible Mechanisms of Action Suggested Doses Adverse Events
Omega-3 fatty acids Essential fatty acids (primarily EPA and DHA) Depression, bipolar disorder, schizophrenia, ADHD Effects on neurotransmitter signaling receptors; inhibition of inflammatory cytokines; lowering plasma norepinephrine (noradrenaline) 1,000–2,000 mg/day Fishy taste and odor, GI upset, theoretical risk of bleeding
Folic acid Vitamin Depression, dementia Neurotransmitter synthesis 400–800 mcg/day; 15 mg/day 5-MTHF (Deplin) Masking of B 12 deficiency, lowers seizure threshold in high doses, and adverse interactions with other drugs
Inositol Six-carbon ring natural isomer of glucose Depression, panic, OCD, and possibly bipolar disorder Second messenger synthesis 12–18 g/day Mild GI upset, headache, dizziness, sedation, and insomnia
SAMe Biological compound involved in methylation reactions Depression Neurotransmitter synthesis 300–1,600 mg/day Mild anxiety, agitation, insomnia, dry mouth, GI disturbance; also possible switch to mania and serotonin syndrome
St. John's wort (Hypericum perforatum L.) Hypericin, hyperforin, polycyclic phenols, pseudohypericin Depression Inhibition of cytokines, decreased serotonin receptor density, decreased neurotransmitter reuptake, MAOI activity 900–1,800 mg/day Dry mouth, dizziness, GI disturbance, and phototoxicity; also possible serotonin syndrome when taken with SSRIs and adverse interactions with other drugs
Vitamin B 12 Vitamin Depression Neurotransmitter synthesis 500–1,000 mcg/day None
ADHD, Attention-deficit/hyperactivity disorder; DHA, docosahexaenoic acid; EPA, eicosapentaenoic acid; GI, gastrointestinal; MAOI, monoamine oxidase inhibitor; OCD, obsessive-compulsive disorder; SAMe, S -adenosylmethionine; SSRI, selective serotonin reuptake inhibitor.

Omega-3 Fatty Acids

Omega-3 fatty acids are polyunsaturated lipids derived from fish oil and certain land-based plants (e.g., flax). Omega-3 fatty acids have been shown to have benefits in numerous medical conditions, including rheumatoid arthritis, Crohn's disease, ulcerative colitis, psoriasis, immunoglobulin A (IgA) nephropathy, systemic lupus erythematosus, multiple sclerosis, and migraine headache, among others. Cardioprotective benefits have also been demonstrated, although recent systematic reviews have been less supportive of their role as preventive agents for cardiovascular disease. From a psychiatric standpoint, omega-3 fatty acids may have a role in the treatment of unipolar depression, post-partum depression, bipolar disorder, schizophrenia, and attention-deficit/hyperactivity disorder (ADHD). The most promising data, however, are in the treatment of both bipolar disorder and unipolar depression; positive studies have been reported in each of these domains, yet recent meta-analyses have also cast doubt on the degree of antidepressant efficacy of the omega-3s. In countries with higher fish consumption, lower rates of depression and bipolar disorder provide a clue that omega-3 fatty acids may play a protective role in these disorders. Although there are several types of omega-3 fatty acids, eicosa­pentaenoic acid (EPA) and docosahexaenoic acid (DHA) are thought to be psychotropically active. While their mechanism of action is not completely clear, several have been proposed. These run the gamut from effects on membrane-bound receptors and enzymes that regulate neurotransmitter signaling, to the regulation of calcium ion influx through calcium channels, to the lowering of plasma norepinephrine (noradrenaline) levels, or possibly to the inhibition of secretion of inflammatory cytokines that result in decreased corticosteroid release from the adrenal gland. Omega-3 fatty acids may be consumed naturally from a variety of sources, including fatty fish (e.g., salmon), flax seeds, chia seeds, hemp seeds, and enriched eggs. Commercially available preparations of omega-3 fatty acids in pill form vary in composition, and the suggested ratio of EPA : DHA is at least 3 : 2 in favor of EPA. Psychotropically-active doses are generally thought to be in the range of 1 to 2 g per day, with dose-related gastrointestinal (GI) distress being the major side effect. There is also a theoretical risk of increased bleeding, so concomitant use with high-dose non-steroidal anti-inflammatory drugs (NSAIDs) or anticoagulants is not recommended. There are thus far no known interactions with other mood stabilizers or antidepressants.

In sum, the use of omega-3 fatty acids remains promising, particularly given the range of potential benefits and the relatively low toxicity seen thus far. However, larger and more definitive studies are still needed.

St. John's Wort

St. John's wort (SJW) (Hypericum perforatum) is one of the biggest-selling natural medications on the market. It has been shown to be more effective than placebo in the treatment of mild-to-moderate depression. Studies have further suggested that SJW is as effective as low-dose tricyclic antidepressants (TCAs) (e.g., imipramine 75 mg, maprotiline 75 mg, or amitriptyline 75 mg). When compared with selective serotonin reuptake inhibitors (SSRIs), the efficacy of SJW has been comparable and better than placebo in some studies of mild depression. For example, SJW was shown to be as effective as sertraline and fluoxetine in the treatment of mild-to-moderate depression in at least two cases. However, in other studies, SJW has not shown an advantage over placebo. These mixed results may be explained by more severely depressed study populations in studies with negative outcomes. Hypericum is thought to be the main antidepressant ingredient in SJW, while polycyclic phenols, pseudohypericin, and hyperforin are also thought to be active ingredients. As far as the mechanism of action of SJW is concerned, there are several proposed theories. These include the inhibition of cytokines, a decrease in serotonin (5-HT) receptor density, a decrease in reuptake of neurotransmitters, and monoamine oxidase inhibitor (MAOI) activity. Since SJW has MAOI activity, it should not be combined with SSRIs because of the possible development of serotonin syndrome. Suggested doses range from 900 to 1,800 mg per day depending on the preparation, and adverse effects include dry mouth, dizziness, constipation, and phototoxicity. Care should be taken in patients with bipolar disorder due to the possibility of a switch to mania. Finally, there are a number of important drug–drug interactions with SJW that are of particular note. Hyperforin is metabolized through the liver and induces cytochrome P-3A4 expression, which may reduce the therapeutic activity of a number of common medications, including warfarin, cyclosporine, oral contraceptives, theophylline, digoxin, and indinavir. Transplant recipients should not use SJW since transplant rejections have been reported as a result of interactions between SJW and cyclosporine. Individuals with human immunodeficiency virus (HIV) infection on protease inhibitors also should avoid SJW because of drug interactions.

In sum, SJW appears to be better than placebo and equivalent to low-dose TCAs for the treatment of mild depression. Emerging data also suggest that SJW may also compare favorably to SSRIs for mild depression. Data also seem to suggest that SJW may not be effective for more severe forms of depression. There are important drug–drug interactions that should be considered as outlined previously.

S- Adenosylmethionine

S- Adenosylmethionine (SAMe) is a compound found in all living cells that is involved in essential methyl group transfers. It is the principal methyl donor in the one-carbon cycle with SAMe levels depending on levels of the vitamins folate and B 12 ( Figure 13-1 ). SAMe is involved in the methylation of neurotransmitters, nucleic acids, proteins, hormones, and phospholipids—its role in the production of norepinephrine, serotonin, and dopamine may explain SAMe's antidepressant properties. SAMe has been shown to elevate mood in depressed patients in doses of between 300 and 1,600 mg per day. Studies support antidepressant efficacy of SAMe when compared with placebo and TCAs. Recent studies have demonstrated efficacy as augmentation for SSRI and SNRI partial responders. Oral preparations of SAMe are somewhat unstable, making high doses required for adequate bioavailability. Since the medication is relatively expensive (and not covered by conventional medical insurance plans), the high cost may be prohibitive for many patients. Potential adverse effects are relatively minor and include anxiety, agitation, insomnia, dry mouth, bowel changes, and anorexia. Sweating, dizziness, palpitations, and headaches have also been reported. Psychiatrists should also watch for a potential switch to mania. Furthermore, suspected serotonin syndrome was reported when SAMe was combined with clomipramine in an elderly woman. Finally, there have not yet been reports of significant drug–drug interactions or hepatoxicity with SAMe.

Figure 13-1, One-carbon cycle with SAMe, folate, and vitamin B 12 .

SAMe therefore is a natural medication that appears to be relatively safe and shows promise as an antidepressant. Further study will help clarify its efficacy and safety.

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