Herbs for mental illness: Effectiveness and interaction with conventional medicines

Efficacy. A Cochrane review⁵⁴ of 6 double-blind randomized controlled trials that used a common outcome measure (Hamilton Anxiety Scale) concluded that kava is significantly superior to placebo as a short-term treatment for anxiety. The authors note, however, that further investigation is required to determine long-term efficacy and safety. Another meta-analysis⁵⁵ of 7 double-blind randomized controlled trials also suggests that, relative to a placebo, kava is an efficacious treatment for anxiety. Thus, SOR=A for the evidence in support of short-term efficacy in kava in anxiety. However, long-term data in terms of safety and efficacy has not been shown.

Mechanisms of action. Kavapyrones are the major constituents of this herb and are responsible for its pharmacologic activity. The mechanisms of their anxiolytic effect are still unclear. One line of research suggests that kavapyrones might mediate sedative effects by influencing gamma-aminobutyric acid (GABA)(A) receptor binding,^56-58 whereas another theory posits that kavapyrones are a reversible inhibitor of human platelet MAO-B.⁵² Others have suggested the inhibition of voltage-gated ion channels as a potential mechanism of action.^59,60

Herb-drug interactions. This herb has the potential to interact with benzodiazepines,⁶¹ and the combination with central nervous system depressants like ethanol and barbiturates can produce synergistic effects.^56,62

Adverse effects. Liver damage has been reported in patients who use kava.^63-65 A recent study⁶⁶ analyzed 29 cases of purported liver dysfunction in addition to 7 cases that have already been published; the authors concluded that kava ingestion was the direct cause of liver injury in 3 cases, a probable cause in 21 cases, and a possible cause in 12 cases. The most frequent liver injury was necrosis. Other adverse effects of this herb include dizziness, mild gastrointestinal disturbance, and a temporary yellow discoloration of skin, hair, and nails.⁶⁷ In addition, long-term administration of kava at higher doses my cause scaling of the skin on the extremities, also known as kava dermopathy.⁶⁸

Valerian

Valerian (Valerian officinalis) is a root extract, with purported healing properties that can be traced to ancient Greece and Rome. Today, valerian root preparations are used for their sedative, anxiolytic, and antidepressant properties. The herb, a GABA agonist,⁹ is commonly used in the treatment of sleeplessness and the management of anxiety associated with muscle tension.¹⁰

Efficacy. A recent systematic review of randomized clinical trials (including reports in all languages) assessed the efficacy of valerian in patients with insomnia.⁶⁹ Nine randomized, double-blind, placebo-controlled trials satisfied the inclusion criteria; however, even in these studies questionable methods in randomization, blinding, compliance, withdrawal, confounding variables, diagnostic criteria, and statistical analysis rendered contradictory results, and the authors concluded that evidence for valerian in the treatment of insomnia is inconclusive.

Data to confirm valerian’s effectiveness as an anxiolytic are also minimal. One randomized placebo-controlled pilot study examined the effects of valerian on generalized anxiety disorder; 36 patients were treated with placebo, diazepam, or valerian extract for 4 weeks.⁷⁰ The authors found a significant reduction in the psychic factors of anxiety with diazepam and valerian. However, the study was limited by the small number of patients in each group, relatively low dosages of the active agents, and a short duration of treatment. Similar studies⁷¹ suffer from the same shortcomings, and thus further research is necessary to assess the effect of valerian on anxiety. Thus, SOR=C for the evidence in support of valerian as a somnolent and as a anxiolytic, and further research is necessary to assess the effect of valerian in insomnia and anxiety

Mechanisms of action. Valerian’s constituents include sesquiterpenes of the volatile oil (including valeric acid), iridoids (valepotriates), alkaloids, furanofuran lignans, and free amino acids such as GABA, tyrosine, arginine, and glutamine.⁷² The precise mechanisms of action are still unclear, though it has been suggested that all of the active constituents act synergistically to produce a clinical response. Research has also demonstrated modulation of GABA neurotransmission and receptor function (see Houghton⁷³ for a comprehensive review of valerian’s pharmacology).

Herb-drug interactions. Valerian has the potential to prolong thio-, pental-, and pentobarbital-induced sleep and should, therefore, not be combined with barbiturates.^74,75 It may also potentiate the sedative effects of anesthetics and other central nervous system depressants.⁴⁵

Adverse effects. Adverse affects with this product are rare, but when they occur they may include headaches, excitability, uneasiness, gastrointestinal effects, dizziness, and cardiac disturbances.^76-78

Dementia

Ginkgo

Ginkgo extracts are derived from one of the oldest known tree species (Ginkgo biloba L). They have been used in traditional Chinese medicine for 5000 years for a variety of purposes and are believed to be helpful in the treatment of memory impairment caused by dementia.⁷⁹ The herb is also used to treat stress, fatigue, chronic cerebrovascular insufficiency, and cerebral trauma, and to improve endurance.⁹