MEDICAL JOURNALS/PROFESSIONAL RESOURCES:
HERBAL MEDICINES WITH PSYCHIATRIC INDICATIONS: A REVIEW FOR PRACTITIONERS

The use of herbal and other alternative medicines continues to be controversial among United States physicians. This review 1) summarizes recent literature documenting the popularity of herbal products, 2) presents the reputed indications and potential problems associated with herbal medicines commonly used for psychiatric indications, and 3) gives recommendations for assessing patients who may be using alternative medicines. This review is limited to those herbals mentioned in multiple sources as having psychiatric indications. It does not include vitamins and other nutritional supplements, the consequences of excessive use of various "natural" substances, such as vitamin A toxicity, caffeineism, and mental status changes secondary to steroids, or herbs that are widely known as drugs of abuse, such as cocaine and marijuana.

Published studies report that 20% to 40% of the general U.S. population use herbal and other alternative medicines.1,2 In a 1993 study, one in five patients taking a prescribed drug was also taking an alternative medicine.1 These studies found that patients in all educational, socioeconomic, age, and racial groups purchase these products, that they are most commonly used for chronic conditions, and that in most cases the primary care physician does not know that the patient is using an alternative medicine. Among the seven most frequently cited health problems for which alternative therapies were used, two were psychiatric (anxiety and addiction in 31% and 25% of respondents, respectively), and two others (chronic fatigue syndrome and headaches) can be associated with, secondary to, or present as psychiatric disorders.

Herbal medicines have been widely used for centuries, but their potential adverse effects often are overlooked. Many people assume that herbs are safe. Most U.S. physicians have received no formal training in herbal medicine and if unfamiliar with a given product may fail to recognize its side effects or the consequences of its interaction with a prescribed drug. A further complication is that patients may not spontaneously report their use of these products and may not acknowledge it even if asked directly. Another potential problem is that an herb's effects, therapeutic or adverse, can vary from one occasion to another because most of these products are sold in a variety of preparations, combinations, and dosages. This lack of standardization and the limited understanding of the mechanisms of action and pharmacokinetics of these drugs can complicate diagnostic and treatment decisions. Even when there is no side effect or interaction of concern, taking herbal medicines may prevent correct and timely diagnosis and thereby delay effective treatment. By contemporary Western scientific standards, the data supporting the efficacy of herbal medicines are limited, and their potential side effects and interactions incompletely understood.

While these cautions apply to all alternative medicines, those intended to alter mental or emotional functioning may be of particular concern. The herbal preparation may not be regarded by the patient as a medicine, and in some cases it may be taken to enhance capacity rather than to treat illness. Patients may also be reticent to report use of a product if they think they will be criticized or told to stop, as might be the case with herbals intended to decrease appetite, promote weight loss, or enhance sexual performance. Some patients may not readily acknowledge depression or other mental symptoms, and physicians may be less inclined to ask specific questions about substances taken to counter dysphoria or other psychiatric problems not part of the presenting complaint. Questions about products used to enhance mood, memory, or other mental function are not routinely asked, especially if the patient is not taking a prescribed medication and has no neuro-psychiatric complaints of which the practitioner is aware. While no research has directly addressed how and to what extent physicians ask about patients' use of herbal medicines, a number of studies have shown that psychiatric disorders are both underrecognized and undertreated by nonpsychiatrists, in part because of limited attention to the mental status and to complaints related to the psyche.3-9

The classification system developed by the NIH Center for Complementary and Alternative Medicine (NCCAM) lists six broad categories of treatments including the "biologically-based therapies" that utilize herbal products (plant-derived preparations) and nutrients (orthomolecular medicine).10 Table 1 lists the 15 herbal products most frequently cited as having a psychiatric indication, and each is discussed below. For most of these agents there is insufficient data to establish efficacy or a definitive list of adverse effects and drug-drug interactions (Table 2). Many published reports are largely anecdotal, and the pharmacokinetics, mechanisms of action, and in some cases even the active ingredient of these substances are not completely understood.

St. John's Wort has been known since the time of Hippocrates. It is used to treat depression and is perhaps the most rigorously researched of the alternative medicines. A number of studies, most of which were conducted in Germany, support its efficacy as an antidepressant, but recent reviews raise questions about the adequacy of this research.11,12 There is little data to suggest that St. John's Wort is effective in severe depression, and its use could delay initiation of a more effective treatment. A recent report suggests that this herb can precipitate a manic episode in bipolar patients, a potential problem with FDA-approved antidepressants as well.13 In addition, there have been several recently reported interactions involving St. John's Wort, including with the protease inhibitor indinavir (suggesting caution in the use of this herb with any medication for HIV) and with the SSRI antidepressants (and by extension perhaps all antidepressants).14,15 Gingko (Gingko biloba) is most frequently used to enhance memory and treat other symptoms of Alzheimer's disease. As recently reviewed by Fugh-Berman et al, there is considerable support for its efficacy in dementia, although the improvements in functioning compared to controls are modest.16 Gingko is sometimes used to treat depression and impotence.17 Because gingko can cause bleeding, it probably should not be used in patients taking anticoagulants or aspirin (whether used for anticoagulation or other purposes). Side effects are not common but include headache and gastrointestinal upset, either of which could be misattributed to a prescribed antidepressant.

Melatonin is used to treat insomnia and regulate the sleep-wake cycle and has been touted as a possible remedy for jet lag.18-21 Among potential side effects are excessive sleepiness and confusion, headache, and diminished sexual drive in males.18.19 Melatonin should be used with caution, if at all, in patients with mental illnesses, and in patients taking steroids. It is also contraindicated in a number of medical disorders, especially autoimmune diseases.20

Evening Primrose (Oenothera blennis) use is primarily used as a sedative. Wong et al have noted the occasional reports about the benefits of this herb in schizophrenia, childhood hyperactivity, and dementia, presumably because of the fatty acids in evening primrose and their link to the treatment of these disorders.17 While not likely to be common, such use is of concern because this herb can exacerbate mania and epilepsy and can interact adversely with antipsychotics and beta blockers as well as with some nonpsychiatric medications.22-24 Despite these concerns evening primrose is generally regarded as safe.25

Passionflower (Passiflora incarnata) is used as a sedative and as an anxiolytic. No adverse reactions have been reported and there is little to suggest significant interactions with other substances. However, it is most commonly used in combination with other herbs, and a patient using passionflower, especially on a regular basis, may be consuming significant quantities of other herbals of potential concern.

Skullcap (Scutellaria laterifolia labiatae) is used as a sedative but may be consumed for a variety of purposes, including any perceived "nervous condition" or dysphoric state.

Valerian (Valeriana officinalis) is most commonly used as a soporific but it may be used by patients seeking relief from anxiety or depression, a potential problem since this herb is a depressant. When used short-term, as is usually recommended, there is little to indicate that there are side effects or drug interactions of concern, although its sedative effects may be additive when used in combination with sedating prescription medications. Long-term use is occasionally associated with headache, restlessness, decreased sleep, mydriasis, and cardiac dysfunction, and there is a report of dystonia and hepatoxicity after overdose.26,27

Kava (Piper methysticum) is reputed to be useful as an anxiolytic and sedative, and several German studies, recently reviewed by Fugh-Berman, found it equal in efficacy to benzodiazepines.16 Little is known about the long-term use of this herb, including its effects on sleep architecture (ie, as with benzodiazepines, short-term benefits may be outweighed by the complications of chronic administration) and its usefulness in disorders associated with persistent anxiety. Kava should not be used in depressed patients, in Parkinson's disease, or in combination with other sedating drugs.28

German Chamomile (Matricaria recutila) is indicated for insomnia and anxiety but has a wide variety of uses in general medicine as well. There is little evidence to suggest side effects or drug-drug interactions of concern.

Lemon balm (Melissa officinalis) is used as an anxiolytic. There appear to be no common side effects, but it may interact with thyroid medications, a potential problem in treating patients with thyroid disease and when augmenting antidepressants with thyroid supplement.29-31

Black Cohosh (Cimicifuga racemosa) is described as useful for anxiety, dysphoria, and other symptoms associated with menopause.32 However, dysphoria is among its side effects, as are headaches and gastric upset, potentially complicating treatment and the differential diagnosis. This herb probably should not be used in patients taking other hormonal therapies.32

Hops is used as a sedative, often in combination with other herbs.33 It has not been well studied as a single agent. It can disrupt the menstrual cycle and should be avoided in depressed patients.32,33

Ginseng (Panax ginseng, and others) is often taken as a daily tonic intended to improve overall endurance and quality of life. It is also used to treat stress and fatigue. Insomnia is a common side effect as are anxiety, restlessness, euphoria, and hypertension.34,35 It should be used only with caution in patients on MAO inhibitors, stimulants, and haloperidol, and, by extension, in any patient on psychotropic medications.36,37

Ma-Huang (Ephedra sinica) is a CNS stimulant used as an appetite suppressant. Contraindications and side effects are those associated with other stimulants and can include death.38 It should be used cautiously, if at all, in psychiatric patients, especially those taking prescription antidepressants.

Yohimbe (Pausinystalia yohimbe) is said to have aphrodisiac properties and is used in the treatment of erectile dysfunction.39,40 It is well established that this herb can produce psychiatric symptoms. It is used in laboratory studies of anxiety to provoke symptoms and should not be taken by patients with a pre-existing diagnosis of panic disorder.42,43 There are also reports that yohimbe can produce psychotic symptoms, manic episodes, and seizures.33,44-46

Medical practice is increasingly grounded in evidence-based guidelines, and in this environment it is unlikely that herbal medicines will be rapidly accepted by physicians in this country. Further research is clearly needed to resolve the controversies about the role of herbal preparations in medicine. Given their wide use, however, it is imperative that physicians specifically inquire about what herbal medicines patients may be consuming. Doctors cannot depend upon patients to report such use independently or to disclose everything they are taking in response to general questions. A thorough assessment of a patient's mental status and psychosocial functioning may be impractical for most nonpsychiatric physicians. However, practitioners can ask if patients are taking anything to enhance functioning or to remedy a problem in seven specific areas: "nerves," depression or mood, anxiety, sleep, memory/attention/concentration, appetite/weight control, and sexual pleasure/performance. For child and adolescent patients, parents should be asked if the patient is taking alternative medicines for any of the above reasons, for hyperactivity, or for academic or behavior problems.

There are several sources of up-to-date information about herbal medicines physicians can consult. Hospital pharmacies and drug information services have begun to maintain databases about these products. In 1993 the FDA established the Office of Special Nutritionals and the Special Nutritionals Adverse Event Monitoring System (SN/EMS).10

Future studies may establish the effectiveness of the herbal products discussed above and lead to their routine use by physicians. To date, however, there is no psychiatric equivalent of, for example, the Madagascar rosy periwinkle (Catharanthus roseus) from which vencristine and vinblastine are made, or the foxglove plant, the leaves of which were the original source of digitalis.