LA RESOLUCIÓN DE LA ANÁFORA INDIRECTA

In general, combining an herbal and conventional drug should be advised against when there is a reasonable basis for assuming that their combined use will result in a potentially unsafe interaction or in the absence of clear evidence that the substances can be safely combined. For example, phenothiazines or other drugs that potentially cause photosensitivity reactions should never be used in conjunction with herbals known to cause photosensitivity including kava or St. John’s wort. Kava and valerian potentiate the sedating effects of benzodiazepines and therefore generally should not be used in combination with drugs in this class. Exceptions include the daytime use of kava in a patient who uses a ben- zodiazepine at bedtime to help induce sleep and the careful titration of kava to manage withdrawal effects or recurring anxiety in a patient whose benzodiaz- epine dosage is being gradually tapered. (General considerations of integrative treatment planning in mental health care are addressed in Chapter 4.)

It is prudent to avoid concurrent use of certain herbals or other natural prod- ucts (e.g., tea, coffee, kola nut, soft drinks containing caffeine, ephedra [Mahuang], ginseng, guarana) in bipolar or schizophrenic patients taking con- ventional mood stabilizers or antipsychotics (Brown 1997). All of these herbals can cause insomnia, agitation, and worsening of psychosis or manic symptoms. Although the commercial sale of ephedra in the United States was banned in 2003, it is still relatively easy to obtain the substance at Chinese medical phar- macies or by mail order. Mental health professionals should continue to ask pa- tients who are being treated by a Chinese medical practitioner about the specific herbal formulas that are being used or contact the prescribing Chinese medical practitioner when the patient cannot provide detailed information. Ginseng can also potentiate MAOIs, possibly resulting in a hypertensive crisis. Several case reports of interactions between ginseng and phenelzine have been reported. Al- though most case reports are anecdotal and poorly substantiated, they warrant caution when ginseng or other stimulant herbals are being considered in a pa- tient who is already taking an antidepressant. Guarana, kola nut, and yerba maté are stimulants that should be avoided by bipolar or schizophrenic patients taking conventional synthetic medications because of numerous case reports of agita- tion, mania, and insomnia occurring with their use in this population. Valerian

en t S afe ty 45 problems

Herb Adverse effects Comment

Ginkgo (Ginkgo biloba) Very few adverse effects documented; most common are gastrointestinal discomfort (21 cases), skin allergy, dizziness, headache

Substantiated in pooled clinical trials of almost 10,000 people

Very rare reports of subdural hematoma and hyphema

Case reports

Ginkgo has anticoagulant action (decreases blood viscosity, antiplatelet activity); bleeding risk may be increased if it is used before surgery or labor/delivery

Recurrent seizures in epilepsy patients with prior symptom control

Case reports

Possible electroencephalographic changes

Possible seed contamination of ginkgo leaf products Stevens-Johnson syndrome Case report

Cytotoxic and allergenic alkylphenols (e.g., ginkgolic acids) may be present in some extracts

Toxins removed from approved German products

Anti–vitamin B₆ neurotoxin (ginkgotoxin) in seeds

Possible product contamination problem

Ginkgo seeds are rarely sold to the public, and the leaves of

Co m p le m enta ry a n d A lter na ti ve T rea tm ents i n M ent a l Hea lth C a re

Kava (Piper methysticum) Generally well tolerated Widespread, long-term recreational use in South Pacific seemingly without major problems

Most common adverse effects are

gastrointestinal discomfort (generally mild), allergic skin rashes, mild headache

1.5%–2.3% incidence of untoward reactions reported in two studies involving a total of 7,000 patients using dosages up to 800 mg/day of 30% kavalactone extract; both incidence and severity were dosage dependent

Severe hepatotoxicity (necrotizing hepatitis), liver failure

Case reports

Idiosyncratic reactions?

Germany, Switzerland, and U.K. no longer permit public sales of kava products; American and Canadian

governments are considering stopping sales of kava products

Hepatotoxicity may be related to contamination from materials in the stem; most kava products are prepared from root or rhizome extracts and have no demonstrable hepatotoxicity (Nerurkar et al. 2004)

Caution is required in patients with hepatic risk factors; routine liver function tests are suggested for kava patients problems (continued)

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47

Kava (Piper methysticum)

(continued)

Dystonic reactions Case reports

Increased symptoms in Parkinson disease patient Case report

Dry, scaly rash Due to use of high dosages (400 mg/day kavalactones) over long term; rash disappeared when kava was discontinued St. John’s wort

(Hypericum perforatum)

Low incidence of adverse effects; most common are mild stomach discomfort, allergic skin rashes, tiredness, restlessness

2.4% of 3,250 patients in a study reported side effects; occurrence rates for all effects were 0.6% or less

Manic episodes Case reports

Psychotic episode Case report involving elderly patient with Alzheimer’s disease

Serotonin syndrome–like symptoms Case report Photosensitivity; hypericin known to cause

photosensitivity reactions, especially in animals

Case reports, two involving topical use of herb, one in which individual received intensive ultraviolet B therapy after oral use of herb

Evidence of possible increased risk of cataract occurrence due to hypericin photoactivation in lens of eye

problems (continued)

Co m p le m enta ry a n d A lter na ti ve T rea tm ents i n M ent a l Hea lth C a re Valerian (Valeriana officinalis)

Generally well tolerated Unpleasant odor may be unacceptable to some Morning grogginess; headache Clinical study

Reported in 2 of 61 patients Impaired vigilance for a few hours after

ingestion (no residual morning sedation when used at night)

Use of automobile or other hazardous machinery not recommended immediately after ingestion

Withdrawal syndrome (sinus tachycardia, delirium after no herb postoperatively)

Case report involving patient using high doses over long term

problems (continued)

may potentiate the effects of alcohol and conventional sedative-hypnotics, in- cluding benzodiazepines. Other caveats the clinician should be aware of include the following (Miller 1998):

• Avoid concurrent use of any herbal tincture (which can contain up to 75% alcohol) and alcohol, conventional anxiolytics, or hypnotics.

• Avoid red ginseng or processed Panax ginseng in patients with chronic in- somnia, “nervousness,” or hysterical symptoms or in schizophrenic patients with predominantly positive symptoms (excessive doses can cause insomnia or agitation). However, formulas containing Panax quinquefolius (American ginseng) or Eleutherococcus senticosus (eleutherococcus or Siberian ginseng) is not contraindicated in this population.

• Avoid concurrent use of a herbal diuretic, such as uva ursi, green tea, or dan- delion leaf extract (often contained in over-the-counter weight loss or pre- menstrual syndrome remedies), and lithium carbonate; herbal diuretics can cause decreased renal lithium clearance and increased risk of lithium toxicity. • Evening primrose oil or borage may unmask previously undiagnosed tempo- ral lobe epilepsy due to high levels of γ-linoleic acid. Schizophrenic and other patients taking phenothiazines are at especially high risk for this complication. • Avoid the use of hops (Humulus lupulus) in depressed patients, as hops can further depress central nervous system activity. Avoid concurrent use of herbal sedatives and conventional hypnotics or anxiolytics.

• Avoid concurrent use of MAOIs and herbals with sympathomimetic activity (e.g., ephedra, coffee, black tea, guarana, kola nut, yerba maté, caffeinated soft drinks, Atropa belladonna, Datura, and hyoscyamine. Atropa belladonna, Datura, and hyoscyamine are available only by prescription. Avoid concur- rent use of phenothiazines and herbs with antimuscarinic activity, as this can result in decreased plasma phenothiazine levels.

• Avoid concurrent use of St. John’s wort and an MAOI, as this combination can lead to a hypertensive crisis. Avoid ginseng-containing products in pa- tients taking MAOIs; ginseng can potentiate MAOIs, possibly leading to a hypertensive crisis.

• Recommend that patients taking caffeine, other stimulants (e.g., guarana), or hormonal therapies not take ginseng. Avoid guarana-containing products in schizophrenic or other patients taking hypnotics or anxiolytics.

• Special safety considerations must be addressed when a patient is considering combining Chinese herbal medicines with conventional drugs, including psychotropics. In view of limited available safety information, it is reasonable to consider combining Chinese herbals and Western synthetic drugs only in cases where a licensed traditional Chinese medical practitioner is working collaboratively with a conventionally trained physician (Chen 1998/1999; Huang et al. 1997; Lake 2004).

Table 3–2 lists clinically important interactions that have been documented to occur when herbs commonly used in mental health treatment are combined with prescription drugs or other natural products. (Because documentation evidence is limited, some hypothetical interactions have been included to increase the practi- tioner’s awareness of potentially serious scenarios.) One comprehensive literature review of herb–drug interactions concluded that warfarin was the most frequently reported drug and St. John’s wort the most frequently reported herb in docu- mented incidents of herb–drug interactions from case reports or controlled clinical trials (Brazier 2003). Although many cases of interactions between St. John’s wort and warfarin (or other coumarin anticoagulants) have been reported, most of these probably resulted from additive anticoagulant effects and thus were not true herb– drug interactions. Interpreting reports of herb–warfarin interactions can be prob- lematic, because most cases are from animal studies or individual case data. Further research is needed to determine the clinical significance of these reports (Heck et al. 2000). It is important to note that Ginkgo biloba potentially prolongs bleeding time at the platelet level, specifically by interfering with platelet aggregation factor, and has been associated with bleeding even in the absence of warfarin.

POTENTIAL ADVERSE EFFECTS