Herbal Remedies in Psychiatric Practice

It is currently estimated that alternative/complementary medicine is used by 20% to 30% of the general North American population, and use appears to be most common in patients with chronic conditions.^{1 - 2} It is estimated that North Americans spend more than $11 billion dollars for chiropractic, naturopathic, and herbal therapies not covered by health plans each year,^{1 ,3} and the current annual growth rate of the alternative/complementary medicine industry is estimated to be 20%.⁴ Patients' growing interest in alternative/complementary medicine has created the need for accurate information that is accessible to physicians. While this review cannot be comprehensive, especially in covering remedies used in less developed countries, the botanicals commonly encountered in North America that have particular relevance to psychiatry will be discussed. The herbal remedies reviewed herein will be divided into 3 sections: (1) herbs that are commonly used to treat psychiatric symptoms (Table 1), (2) herbs that have psychotropic effects, and (3) herbs that may interact with either psychiatric illnesses or the drugs used to treat these illnesses.

Information included in this review was drawn from comprehensive MEDLINE (1986-1997) searches, frequently cited or landmark articles, sources commonly used by the alternative health care community in North America (eg, The Canadian College of Naturopathic Medicine reference library), and consensus reports from expert committees (eg, The German Commission E⁵ and the European Scientific Cooperative on Phytotherapy). The efficacy of herbal interventions was rated according to criteria derived from the 1994 Canadian Guide to Clinical Preventive Health Care by the Canadian Task Force on the Periodic Health Examination⁶ and the 1996 Guide to Clinical Preventive Services by the US Preventive Services Task Force.⁷ This rating system was designed to provide clinically relevant guidance regarding the use of these herbs by patients. The ratings assigned to each herb, and the rating system, may be found in Table 1.

Many of the herbs discussed in this article have a variety of constituents and putative therapeutic indications. Only the information relevant to psychiatric illness, symptoms, or treatments will be considered because of space limitations. This review focuses primarily on the English-language literature. A further caveat concerns the lack of standardization, quality control, and regulation of commercial herbal products in much of the world.^{8 - 9} The studies cited herein report results of a wide range of herbal preparations, some of which may not be applicable to other preparations of the same herb.

Black cohosh (Cimicifuga racemosa [L] Nutt) has a history of use among North American aboriginal peoples as a treatment for the hot flashes, anxiety, and dysphoria associated with menopause; as an analgesic; and to promote lactation and menses.¹⁰ Its putative action is on the gonadotropin system, through direct estrogen ligands that suppress luteinizing hormone release, and through nonestrogen ligands that appear to decrease luteinizing hormone secretion with long-term use.¹¹ A variety of uncontrolled studies have demonstrated some clinical benefit in the treatment of ovarian insufficiency symptoms.^{12 - 15}

A randomized study comparing a commercial product of C racemosa (Remifemin) with conventional hormonal therapy for the treatment of ovarian insufficiency symptoms showed comparable efficacy with both treatments (n=60).¹⁶ A randomized, double-blind, placebo-controlled trial with the same product (n=80) found superior efficacy to placebo or conjugated estrogen therapy for the treatment of both physical and mental menopausal symptoms.¹⁷ The long-term benefits of postmenopausal hormone treatment have not been compared with those of C racemosa. The dose of black cohosh ranges from 40 to 200 mg daily, and the onset of action is reported to be up to 2 weeks.¹⁸

Potential side effects include gastric upset, throbbing headaches, dysphoria, and cardiovascular depression. Caution should be exercised if the herb is taken with other hormonal therapies, since C racemosa likely interacts with the sex hormone system, although such interaction has not been documented. It should be avoided during pregnancy and lactation.^{18 - 19}

German chamomile (Matricaria recutita L) has been used for the treatment of gastrointestinal tract discomfort, peptic ulcer disease, mouth and skin irritation, pediatric colic and teething, and mild insomnia and anxiety.^{18 ,20} The herb contains the flavonoid apigenin, which may have an affinity for the benzodiazepine receptor²¹ and may also interact with the histamine system.²² A mild hypnotic effect has been reported in mice²¹ and in humans,^{23 - 25} but no randomized or controlled clinical studies were identified. Doses commonly range from 2 to 4 g of dried flower heads 3 times daily, normally prepared as a tea.^{5 ,18} Chamomile is also commercially available as a liquid extract (1:1, 45% ethanol), which is dosed as 1 to 4 mL 3 times daily,¹⁸ and as a tincture (1:5, 45% ethanol), of which 3 to 10 mL is taken 3 times daily.¹⁸ Potential adverse reactions are rare and mainly allergic in nature.^{19 ,23 - 24 ,26 - 28}

Some authors have proposed the use of evening primrose (Oenothera biennis L) in the treatment of schizophrenia, childhood hyperactivity, and dementia, apparently on the basis of isolated reports of prostaglandin abnormalities in schizophrenia²⁹ and attention-deficit/hyperactivity disorder.^{30 - 32} There is little scientific evidence or cultural tradition to support this usage. The pharmacological constituents of interest are the essential and nonessential fatty acids: cis-linoleic acid, cis-γ-linolenic acid, oleic acid, palmitic acid, and stearic acid.^{19 ,33 - 34} However, the empirical evidence for changes in fatty acid levels after oral administration is sparse,³⁵ and the literature on the efficacy of fatty acid administration in the treatment of schizophrenia and attention-deficit/hyperactivity disorder is contradictory.^{36 - 38} In addition, there is currently insufficient information to recommend evening primrose in the treatment of dementia.^{19 ,39} The majority of evening primrose oil supplements contain 8% cis-γ-linolenic acid, and the daily adult dose ranges from 6 to 8 g, normally given in divided doses.¹⁹

In general, evening primrose oil is relatively safe,^{40 - 42} but it should be used with caution in mania⁴³ and epilepsy.^{19 ,41 ,43} There have been cases in which evening primrose oil appears to have exacerbated epilepsy. Drugs that may interact adversely with evening primrose include phenothiazines,^{37 ,39 ,44} nonsteroidal anti-inflammatory drugs, corticosteroids,⁴⁵ β-blockers,³⁹ and anticoagulants.⁴³

The ginkgo tree (Ginkgo biloba L) is one of the oldest deciduous tree species on earth.⁴⁶ It has been used for medicinal purposes extensively in Europe and has a minor role in traditional Chinese medicine.^{47 - 49} Its indications are varied and include dementia, "chronic cerebrovascular insufficiency," and "cerebral trauma."^{47 - 48} Standardized commercial preparations are widely available and usually contain the active constituents flavone glycosides (24%) and terpenoids (6%).^{50 - 51} Most clinical studies have used specific extracts of Ginkgo (EGb 761 and LI 1370) that are equivalent to the commercial preparations. The dose for most indications is 40 mg of standardized extract 3 times daily,^{20 ,48} which must be given for 1 to 3 months before the full therapeutic effects are apparent.^{48 ,52}

There is considerable evidence that Ginkgo extracts can improve vascular perfusion^{53 - 59} by modulating vessel wall tone^{60 - 69} and can decrease thrombosis⁷⁰ through antagonism of platelet activating factor.^{71 - 75} Ischemic sites may benefit in particular from ginkgo treatment.^{76 - 84} The antioxidant properties that have been attributed to the flavonoid components found in ginkgo are believed to play an important role in its postulated neuroprotective and ischemia-reperfusion–protective effects.^{85 - 91} The extract EGb 761 has been shown to have both hydroxyl radical scavenging activity and superoxide dismutase–like activity.^{68 ,92}

Kleijnen and Knipschild⁵³ reviewed 40 controlled trials on the use of ginkgo in the treatment of "chronic cerebral insufficiency." Although only 8 of the studies were deemed to be of good quality, all but 1 found clinically significant improvement in symptoms, such as memory loss, concentration difficulties, fatigue, anxiety, and depressed mood. Studies investigating the use of ginkgo to augment memory or treat memory loss have produced conflicting results. Generally, some improvement is reported in patients with moderate to severe memory impairment, but no significant improvement is seen in those with mild to no memory impairment.^{93 - 103}

There is also evidence, derived from randomized, controlled trials, that ginkgo extracts are effective in the treatment of psychopathological conditions and memory impairment caused by Alzheimer and vascular dementia.^{104 - 107} For example, 1 multicenter, randomized, double-blind, placebo-controlled trial (N=216) assessed the use of ginkgo in the treatment of outpatients diagnosed with primary degenerative dementia of the Alzheimer type or multi-infarct dementia of mild to moderate severity (DSM-III-R¹⁰⁸ criteria). The participants were given either 120 mg of G biloba extract (EGb 761) or placebo twice daily. Response to treatment was defined as response to a minimum of 2 of the 3 primary outcome variables: the Clinical Global Impressions (item 2) to assess psychopathology, the Syndrom-Kurztest to assess memory and attention, and the Nurnberger Alters-Beobachtungsskala rating scale to assess the ability to perform the activities of daily life. The investigators reported that the frequency of response was significantly (P<.005) higher in the ginkgo-treated group, which was confirmed by intention-to-treat analyses.¹⁰⁴

A recent North American multicenter, randomized, controlled trial in a similar patient population (outpatients with mild to severe Alzheimer disease or multi-infarct dementia) followed 309 patients for 52 weeks and reported similar results. Patients in this study received 40 mg of G biloba extract (EGb 761) or placebo 3 times daily, and the following outcome measures were used: the Alzheimer's Disease Assessment Scale–Cognitive subscale, the Geriatric Evaluation by Relative's Rating Instrument, and the Clinical Global Impression of Change. With an intention-to-treat analysis, those taking ginkgo scored significantly higher on both the Alzheimer's Disease Assessment Scale–Cognitive subscale (P=.04) and the Geriatric Evaluation by Relative's Rating Instrument (P=.005). There was no difference reported between the 2 groups in the Clinical Global Impression of Change scores. The investigators concluded that, although the changes in the ginkgo-treated groups were modest, they were of sufficient magnitude to be recognized by caregivers.¹⁰⁷

Ginkgo has been used by patients in an attempt to treat impotence, including antidepressant-induced sexual dysfunction. In one open trial (N=60), patients with proved arterial erectile dysfunction who had not previously responded to papaverine ingested 60 mg of G biloba extract daily for 12 to 18 months. Fifty percent of the men had gained potency after 6 months of therapy; however, the role of Ginkgo in this recovery is difficult to determine, given the large psychological component of impotence and the fact that this trial was not blinded. There are no reports cited in the MEDLINE literature that investigated the use of ginkgo for antidepressant-induced sexual dysfunction.

There is one randomized, controlled trial showing improvement in resistant depression with ginkgo as an augmenting agent with conventional antidepressants.¹⁰⁹ One in vitro study reported that compounds present in both dried and fresh Ginkgo leaves have monoamine oxidase (MAO) (both A and B) inhibitory activity¹¹⁰ ; however, there is currently no evidence that G biloba extracts ingested in normal dosages by humans will inhibit MAO activity in the brain. Finally, there is evidence from animal studies that ginkolide B may have a neuroprotective effect in brain injury.^{84 ,111 - 112}

Side effects from ginkgo appear to be relatively uncommon, but include headache, gastrointestinal tract upset, and skin allergy to the Ginkgo fruit.^{48 - 49 ,53 ,61 ,113 - 115} Of these, headache is the most common, and it is best prevented by starting with a low dose and gradually titrating to the required dose. Many researchers have suggested that ginkgo theoretically may potentiate other anticoagulants or increase bleeding time; however, these effects rarely have clinically significant implications. Millions of people take ginkgo every year, yet only 2 reported cases of bleeding problems (neither a confirmed drug interaction) may be found in the literature.^{116 - 117} Caution should still be exercised when ginkgo is taken in conjunction with anticoagulant treatment (including aspirin) or where there is a risk of bleeding (eg, peptic ulcer disease, subdural hematoma). Safety in pregnancy and lactation has not been established.

Although hops (Humulus lupulus L) is used by the brewing industry to produce beer, the female flowers of the plant also have a long medicinal history as a mild sedative.^{25 ,118} Hops is also currently used as a mild hypnotic agent^{18 ,33 ,119 - 121} ; however, there are no clinical studies of its use as a single agent to treat specific symptoms or illnesses, such as insomnia or anxiety disorders. The sedating effects of hops may be mediated by one of its constituent volatile oils, 2-methyl-3-butene-2-ol,^{20 ,121 - 122} but there is insufficient information to confirm this. Adverse effects include allergy and disruption of menstrual cycles.^{19 ,25 ,123 - 124} Hops is commonly given 3 times daily and before bed in the following doses: 0.5 to 1 g of dried flowers, 0.5 to 1 mL of liquid extract (1:1, 45% ethanol), or 1 to 2 mL of tincture (1:5, 60% ethanol).¹⁸ The use of hops should be avoided in depression, in pregnancy, and during lactation.^{18 - 19 ,25} Although there are currently no documented case examples, care should be taken when hops is used with sedative-hypnotic agents and alcohol, as a potentiation of their effect may be seen.

Preparations made from the roots of kava (Piper methysticum, Forst) have been used extensively by the peoples of the South Pacific for both medicinal and cultural purposes.¹²⁵ Medicinally, it is reputed to have anxiolytic, anticonvulsant, sedative, and muscle relaxant properties.^{125 - 126} While a number of pharmacologically active agents have been identified, most interest has centered on the α-pyrones commonly referred to as kavalactones. Conflicting evidence exists regarding the affinity of kava pyrones for various γ-aminobutyric acid (GABA) or benzodiazepine-binding sites.^{127 - 128} Kavain, a kavalactone, has been shown to block the voltage-dependent sodium ion channel.¹²⁹ In animals, kava has been reported to exhibit neuroprotective effects against ischemia.¹³⁰ Anticonvulsive effects have also been noted.^{131 - 133} Many published works regarding kava are in German, but a number of reviews are available in English.^{125 ,134}

Kava has been reported to produce changes on the electroencephalogram similar to those seen with diazepam.¹³⁵ Several human clinical trials suggest that kava products standardized for kavalactone content (70%) may be beneficial in the management of anxiety and tension of nonpsychotic origin.^{136 - 137} Kava appears not to adversely affect cognitive function, mental acuity, or coordination^{125 ,138} in comparison with oxazepam, as measured by event-related potentials during cognitive testing.^{139 - 140} Clinical trials with kava have used doses of standardized preparations that range from 100 to 200 mg of kavalactones daily in divided doses or a single dose at bedtime.¹²⁶

Long-term administration with higher doses (eg, 400 mg of kavalactones) may result in scaling of the skin on the extremities.^{125 - 126} It has been hypothesized that kava produces a vitamin B deficiency that results in the scaling. However, administration of nicotinamide (100 mg daily for 3 weeks) did not resolve the condition.¹⁴¹ Kava may interact with benzodiazepines; there is 1 controversial case report involving alprazolam.¹⁴² While the consumption of large amounts of alcohol has been noted to potentiate the actions of kava in mice,¹⁴³ administration of a standardized kava extract in a placebo-controlled, double-blind study showed few adverse effects.¹⁴⁴ The possibility exists that concomitant administration may potentiate the action of other centrally mediated agents.¹²⁶

An aromatic member of the mint family, lemon balm (Melissa officinalis L) has a history of use as an anxiolytic.^{25 ,121} Although 1 article has reported hypnotic and analgesic effects in mice,¹⁴⁵ there are currently no clinical studies demonstrating hypnotic or anxiolytic effects in humans, even though some authors endorse this use.^{25 ,118 - 119} One study using a combination product containing valerian and lemon balm showed a sleep-promoting effect, but it is difficult to conclude what role lemon balm played in this effect.¹⁴⁶ Doses of lemon balm range from 1 to 4 g daily.²⁵ No side effects have been reported from ingestion of lemon balm; however, safety in pregnancy and lactation has not been established. Lemon balm may potentiate the effects of other central nervous system (CNS) depressants, including alcohol,¹⁴⁵ and may interact with thyroid medications or thyroid disease.^{33 ,147 - 150}

Passion flower (Passiflora incarnata L) is native to the Americas, where its perennial vine leaves have been used as a sedative by indigenous peoples such as the Aztecs.^{19 ,33 ,151} Its current use as a sedative-hypnotic^{118 - 119 ,151 - 153} is supported by the findings of some animal studies^{153 - 157} ; however, the active ingredients^{118 ,151 ,158 - 159} and mechanism of action remain obscure. No clinical studies of P incarnata alone have been found, although one randomized, controlled trial that used a commercial preparation containing P incarnata in addition to valerian showed benefit in the treatment of adjustment disorder with anxious mood.¹⁶⁰ Passion flower is often given 3 times daily in the following doses: 0.25 to 1 g of dried herb (commonly taken as a tea); 0.5 to 1 mL of liquid extract (1:1; 25% alcohol); or 0.5 to 2.0 mL of tincture (1:8; 45% alcohol).^{18 - 19}

Hypersensitivity vasculitits¹⁶¹ and "altered consciousness"¹⁶² have been reported with products containing passion flower. Passion flower may cause sedation, and so the usual precautions regarding operation of a motor vehicle or machinery should be observed.¹⁵³ Excessive use during pregnancy and lactation should be avoided.¹⁹ Interactions with other psychotropic medications have not been adequately studied.

Members of the genus Scutellaria have a long history of medicinal use; the roots in traditional Chinese medicine and the aerial parts in western herbalism.^{19 ,163} Skullcap (Scutellaria laterifolia L) has been used as a sedative and anticonvulsant.^{119 ,164} The active ingredients and pharmacology are not well documented. In addition, existing studies are not necessarily applicable to preparations that patients may be taking, because different species and parts of the plant are used.¹¹³ Skullcap is available in several dosage forms that are commonly taken 3 times daily: 1 to 2 g of dried herb or 2 to 4 mL of liquid extract (1:1; 25% alcohol).¹⁸ Adverse reactions include giddiness, confusion, sedation, seizures,^{165 - 166} and possibly hepatotoxic effects¹⁶⁶ (the hepatotoxic effect in this case was later attributed to another ingredient of the preparation¹⁶⁷ ). Although there is insufficient information to make specific recommendations regarding safety, skullcap should be avoided in pregnancy and lactation, and may interact with other CNS drugs.¹⁶⁸

The use of St John's wort (Hypericum perforatum L) may be traced back to the texts of the ancient Greek physicians Hippocrates, Pliny, and Galen, and continued through the Classical, Renaissance, and Victorian eras.^{169 - 170} Its contemporary usage has been as an antidepressant, for which there is more rigorous evidence than for any other herbal remedy.^{171 - 172} The active ingredients responsible for antidepressant action have been investigated (mainly hypericin and pseudohypericin),^{173 - 177} but the putative mechanism of action of St John's wort extracts remains controversial.

The hypericins were found to be absorbed within 2 hours, in a dose-dependent manner. These compounds are widely distributed and have a plasma half-life of 24 hours, allowing steady-state concentrations to be reached in 4 days.^{175 - 176} It is estimated that 14% to 21% of the compounds are systemically available.¹⁷⁶ In vitro experiments found hypericin mainly in the cytoplasmic membrane and cytoplasm, with smaller amounts found in the nucleus.¹⁷⁸

Hypericum extracts show affinity for a variety of neurotransmitter receptors, including: adenosine, GABA_A, GABA_B, serotonin (5-HT)₁, central benzodiazepine, forskolin, inositol triphosphate, and the MAO A and B enzymes.¹⁷⁹ Hypericin by itself has an affinity for the N-methyl-D-aspartate receptor.¹⁸⁰ However, the concentrations required for in vivo activity are unlikely to be attained after oral administration, except for activity at the GABA receptors.¹⁸⁰ Various authors have proposed serotonin reuptake inhibition,^{181 - 182} decreased serotonin receptor expression,¹⁸³ altered receptor regulation,¹⁸² inhibition of benzodiazepine binding,¹⁸⁴ increased excretion of adrenergic metabolites,¹⁸⁵ and inhibition of MAO^{186 - 187} to explain the clinically observed antidepressant effects. Although MAO inhibitor activity is an attractive explanation for the antidepressant actions of St John's wort, studies are unable to confirm that putative MAO inhibition is responsible for antidepressant effects.^{187 - 189}

Animal studies show changes, similar to those seen with other antidepressants, on behavioral tests.¹⁹⁰ Changes are seen in assays of motor activity, exploratory behavior, analgesia, ketamine sleeping time, and temperature.^{191 - 192} Rats treated for 6 months with LI 160 (a commercial hypericum extract) were found to have significantly increased numbers (50% more) of both 5-HT_1A and 5-HT_2A serotonin receptors, without changes in affinity.¹⁹³ Human studies show electroencephalographic changes with St John's wort that are different from those seen with tricyclic antidepressants: shortening of evoked potential latencies and enhancement of theta and beta-2 regions of the resting electroencephalogram in the absence of sleep changes.^{194 - 195}

There is strong evidence of efficacy in mild to moderate depression, as reviewed by Linde et al.¹⁷¹ That meta-analysis included 23 randomized trials with a total of 1757 outpatients, in which extracts of St John's wort alone (20 of 23 trials) or in combination with other herbs (3 of 23) were tested against placebo (15 trials) or antidepressant drugs (8 trials). Outcome was assessed by means of a pooled estimate of the "responder rate ratio" (response rate in the hypericum group vs the control group). St John's wort was reported to be clearly superior to placebo and comparable with conventional drug treatment, with lower side-effect and dropout rates in the hypericum group. Concerns raised in the article by Linde et al include the heterogeneity of patients, interventions, extract preparations, and diagnostic classifications among the various trials. A more recent review (but not meta-analysis) of 12 randomized trials (11 of which were included in the meta-analysis by Volz¹⁷² ) expressed similar concerns regarding the methods of the original studies, the possibility of subtherapeutic control drug dosing, and the variability of hypericum preparations. Overall, there are inadequate data regarding long-term use and efficacy in severe depression. There are concerns regarding the standardization and quality control of commercial preparations.^{196 - 197} Clearly, more research is needed to address these shortcomings in the literature.

Many commercial St John's wort products are standardized extracts (0.3% hypericin) of which 300 to 900 mg are given daily in 3 divided doses.¹⁷¹ This is approximately equivalent to 2 to 4 g of the dried herb.¹⁹ In general, fewer adverse effects are seen with hypericum than with conventional antidepressants,^{171 ,198} but they may include photodermatitis,¹⁹⁹ delayed hypersensitivity, gastrointestinal tract upset, dizziness, dry mouth, sedation, restlessness, and constipation.^{19 ,171 ,200 - 201} There do not appear to be significant adverse effects on cardiac conduction with hypericum extracts.²⁰² The use of St John's wort is contraindicated in pregnancy, lactation, exposure to strong sunlight, and pheochromocytoma.¹⁹ Because of the lack of information regarding the mechanism of action of H perforatum extracts, the potential for MAO inhibitor–like drug interactions cannot be excluded.^{19 ,203}

Valerian (Valeriana officalis L and Valeriana species) has a rich history of use throughout the world for a variety of indications, including as a sedative.²⁰ Research on the mechanism of action has yielded contradictory findings. Extracts of valerian have affinity for GABA_A receptors,^{204 - 205} likely because of the relatively high content of GABA itself that has been documented to be a constituent of valerian.^{206 - 207} The amount of GABA present in aqueous extracts of valerian is sufficient to induce release of GABA in synaptosomes and may also inhibit GABA reuptake.^{208 - 209} However, since GABA does not readily cross the blood-brain barrier, the relevance of these findings to central sedating effects is questionable. Other postulated mechanisms of action include inhibition of the catabolism of GABA by valerenolic acid and acetylvalerenolic acid²¹⁰ and affinity for the 5-HT_A receptor by another constituent of valerian, hydroxypinoresinal.²¹¹ Adenosine receptors may also be a target of valerian extracts.²¹²

Animal behavioral tests with valerian show results consistent with other hypnotic agents such as the benzodiazepines,^{211 ,213 - 222} as well as contradictory reports of anticonvulsant activity^{223 - 224} and possible antidepressant effects.^{219 ,225} Imaging with cerebral nuclear medicine scans in rats showed CNS depressant effects.^{211 ,226 - 227}

Human clinical studies of valerian confirm a mild sedative effect,²²⁸ although the exact effects on sleep architecture, quality, and the electroencephalogram are inconsistent.^{229 - 235} These results are based on a relatively small number of subjects and do not evaluate the efficacy of valerian as a treatment for primary or secondary insomnia. There is no evidence to suggest that valerian is superior to existing hypnotic medications or other treatments for insomnia. This review found only 1 English-language report of a subjective anxiolytic effect.²²⁹

The dosage for valerian ranges from 2 to 3 g of the dried root given 3 times daily or at bedtime.²¹¹ Adverse effects include reports of hepatotoxic effects, although the offending preparations often contained a mixture of ingredients, making it difficult to draw definitive conclusions.^{236 - 240} There is currently insufficient information to recommend valerian in pregnancy and during lactation,^{241 - 243} although no reports of teratogenicity were found. The sedative effects of valerian may potentiate the effects of other CNS depressants,^{213 ,221 ,244 - 245} and the usual precautions taken with other sedating agents also apply to valerian.

Commonly encountered in the form of chili or cayenne pepper, capsicum (Capsicum annuum L) has been used topically for pain relief in a variety of healing traditions.^{25 ,246} The active ingredients form a class referred to as the capsaicinoids, of which the most important is capsaicin.^{247 - 248} Capsaicin depletes substance P, thus inhibiting substance P–mediated pain transmission.^{249 - 252} Numerous trials have concluded that 0.075% capsaicin cream is a safe and effective treatment for painful diabetic neuropathy.^{253 - 258} There is also some evidence that 0.025% capsaicin cream may be useful in relieving the pain of postherpetic neuralgia.^{259 - 264} Several proprietary creams containing capsaicin (eg, Axsain and Zostrix) are available in North America. Traditionally, Capsicum has been ingested as a treatment for gastrointestinal tract complaints, such as colic and dyspepsia. In addition, it is thought to improve peripheral circulation in patients with cardiovascular conditions.¹⁹ These indications have not been investigated scientifically. CapsicumL. products used internally may elevate the secretion of catecholamines,²⁶⁵ thus caution with concurrent MAO inhibitor treatment is recommended.

Found in the Mediterranean and central Asia, chaste tree (Vitex Agnus-castus L) has been used medicinally since the times of ancient Greece and Rome to treat symptoms of premenstrual syndrome, mastodynia, menopause, hyperprolactinemia, and menstrual irregularity.^{266 - 269} The exact mechanism of action is unclear but likely involves modulating the prolactin axis.^{118 ,270 - 271} Affinity for D₁ and D₂ dopamine receptors has also been reported.^{272 - 273} These data point to a potential interaction with other dopaminergic drugs, such as the antipsychotics and metoclopramide.²⁷⁰

Siberian ginseng (Eleuthrococcus senticosus [Rupr and Maxim] Maxim), a member of the Araliaceae family and also known as eleuthero, is native to the northern parts of China, Japan, Korea, and eastern Russia. Used in traditional Chinese medicine for more than 400 years, the roots are thought to help fatigue and stress and to improve endurance.^{274 - 275} This type of "ginseng" must be distinguished from plants of the genus Panax (eg, Panax ginseng, Panax quinquefolius), which are discussed below. The eleutherosides contained in Siberian ginseng are thought to mediate the antifatigue and immunostimulatory properties attributed to this plant.^{19 ,274 ,276} Eleuthero should be used cautiously with sedative-hypnotic agents, as some studies report alteration of barbiturate-induced sleeping time.^{18 ,274 ,277}

Often confused with E senticosus (Siberian ginseng), P ginseng CA Meyer (ie, ginseng, Chinese ginseng, Korean ginseng) and P quinquefolius L (ie, Canadian ginseng, American ginseng) have a long list of indications, including treating stress and fatigue and improving endurance. Although many mechanisms of action have been postulated, it probably affects the hypothalamic-pituitary-adrenal axis, resulting in elevated plasma corticotropin and corticosteroid levels.^{278 - 284} One of the most common side effects is insomnia,²⁸⁵ while others include hypertension, diarrhea, restlessness, anxiety, and euphoria.^{286 - 287} Ginseng should be used with caution in patients with hypertension and diabetes and in conjunction with centrally acting medications.^{25 ,276} In addition, ginseng may potentiate the effect of MAO inhibitors,^{45 ,288 - 290} stimulants (including caffeine), and haloperidol.²⁹¹

Yohimbe (Pausinystalia yohimbe [K Schum]) is a botanical medicine derived from the bark of the P yohimbe (K Schum) tree.²⁰ The active constituents are the alkaloids, notably one of the yohimbane derivatives called yohimbine.²⁹² Yohimbine appears to act as an α₂-adrenoceptor antagonist,^{292 - 293} and the hydrochloride salt is used in the treatment of erectile dysfunction.^{294 - 295} Yohimbe bark is reputed to have aphrodisiac properties and is widely sold for this purpose.²⁰

When administered to humans, yohimbine causes a variety of symptoms, including anxiety, nervousness, palpitations, and restlessness, as well as signs such as elevated 3-methoxy-4-hydroxyphenylglycol and cortisol levels.^{292 ,296 - 297} In fact, yohimbine is one of the agents commonly used to provoke panic attacks and anxiety in studies of the pathophysiology, psychopharmacology, and treatment of anxiety disorders.^{298 - 299} Tricyclic antidepressants, medications with central α-adrenergic blocking properties, centrally acting sympathomimetics, MAO inhibitors, and antimuscarinic agents are all known to potentiate the action of yohimbine.²⁹² Yohimbine also may contribute to psychotic symptoms,²⁹⁶ mania,³⁰⁰ and seizures,³⁰¹ but these effects are not well documented.

Clearly, yohimbine-containing products have the potential to produce psychiatric symptoms, primarily anxiety or panic, especially in patients with preexisting panic disorder.³⁰² While it is important to be aware of this in examining patients with anxiety who are also taking herbal remedies, many commercial products containing yohimbe bark actually have little or no yohimbine.³⁰³

We have reviewed the most common herbal products used in North America that are likely to be encountered in psychiatric practice. With the exception of St John's wort for depression and ginkgo for dementia, there is insufficient evidence to recommend the use of herbal medicines in the treatment of psychiatric illness. None of these herbal remedies is clearly superior to current conventional treatments. Because these products are widely available and often used by the general public, more clinical research is needed to establish safety and efficacy. A working knowledge of the pharmacological data and clinical literature is necessary to properly counsel, diagnose, and treat patients who may be using herbal products. The advances of modern medicine, science, and technology are greater than at any other time in history, and the rate of discovery of new knowledge and techniques is accelerating. However, the experience and healing traditions of other cultures, whether in less developed countries or in history, should not be ignored. Contemporary medical research may finally allow us to separate the traditional remedies that can effectively treat disease from those that are superstition and myth. In addition, research into the biochemical and pharmacological effects of these herbs may uncover novel treatments for psychiatric illness or yield fresh insights into basic disease mechanisms.

Accepted for publication August 7, 1998.

Reprints: Albert H. C. Wong, MD, FRCPC, G39, Clarke Institute of Psychiatry, 250 College St, Toronto, Ontario, Canada M5T 1R8 (e-mail: albert.wong@utoronto.ca).