Monica Vermani, Hon.BSc, MA Stress, Trauma, Anxiety, Rehabilitation Treatment (S.T.A.R.T.) Clinic for Mood & Anxiety Disorders, Toronto, Canada; Adler School of Professional Psychology, Chicago, Ill
Irena Milosevic, Hon.BSc University of Toronto, Toronto, Canada
Fraser Smith, BA, ND Canadian College of Naturopathic Medicine, Toronto, Canada
Martin A. Katzman, BSc, MD, FRCPC Stress, Trauma, Anxiety, Rehabilitation Treatment (S.T.A.R.T.) Clinic for Mood & Anxiety Disorders, Toronto, Canada; Department of Psychiatry, Faculty of Medicine, University of Toronto
Efficacy. Evidence for ginkgo’s efficacy is encouraging, but more rigorous research is needed. Kleijnen and Knipschild80 reviewed 40 controlled trials on the use of ginkgo to treat “chronic cerebral insufficiency.” Only 8 of the studies were deemed to be of good quality, although all but 1 found clinically significant improvement in symptoms including memory loss, concentration difficulties, fatigue, anxiety, and depressed mood.
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Ginkgo was superior to placebo in delaying the course of dementia
Another meta-analysis79 identified more than 50 articles on the effect of ginkgo on the cognitive function in Alzheimer patients, but only 4 studies were found to be properly blinded and placebo-controlled with well-characterized subjects. The authors concluded that gingko appears to have a modest effect on cognitive function in Alzheimer’s but note that further research is necessary.
A systematic review by Ernst and colleagues81 concluded that ginkgo was superior to a placebo in delaying the clinical course of dementia. The authors reported on 9 placebo controlled, double-blind randomized trials including 1497 patients in their analysis.
Ginkgo has also been used to treat impotence, including antidepressant-induced sexual dysfunction. In 1 trial, 60 patients with proven arterial erectile dysfunction who had not previously responded to papaverine showed improvement with a daily dose of 60 mg of ginkgo over 12 to 18 months.9 However, further research must be undertaken in this domain, in part because this trial was not blinded, with both doctors and patients aware of who was receiving the ginkgo treatment.
Thus, SOR=A for the evidence in support of ginkgo as a cognitive enhancer in mild to moderate dementia, and B for the evidence in support of ginkgo as a treatment for erectile dysfunction.
Mechanisms of action. Ginkgo leaves contain several bioactive compounds, including flavonoids, terpenoids (ginkgolide, bilbobide), and organic acids. Although the mechanisms of action are only partially understood, the main effects appear to be related to its antioxidant properties, which require the synergistic action of the principal constituents.82 These compounds act as free radical scavengers.83 Other pharmacologic actions involve antihypoxic and antiplatelet effects.84
Herb-drug interactions. Researchers have suggested that ginkgo may potentiate other anticoagulants or increase bleeding over time,85,86 which can be attributed to ginkgolide B, a potent inhibitor of platelet-activating factor needed for inducing arachidonate-independent platelet aggregation.87 Caution should be exercised when ginkgo is taken in conjunction with anticoagulant treatment (including aspirin) or when there is a risk of bleeding (eg, peptic ulcer disease and subdural hematoma).9,86
Adverse effects. Side effects from ginkgo appear to be relatively uncommon; however, they may include headaches, gastrointestinal tract upset, nausea, vomiting, and a skin allergy to the ginkgo fruit.17,88
Sexual dysfunction
Yohimbine
Yohimbine is an alkaloid derived from the cortex of the Central African tree Corianthe yohimbe.89 The bark of the tree was used traditionally to enhance virility. Today, yohimbine is still reputed as an aphrodisiac and used as a remedy for erectile problems.90
Efficacy. Overall, the efficacy of yohimbine in the treatment of erectile dysfunction appears promising, although, as with studies of other herbal products, clinical trials often suffer from methodological flaws. Carey and Johnson91 conducted 4 independent meta-analyses to examine the effects of yohimbine alone or in combination with other drugs in controlled and uncontrolled trials. The authors found positive results for yohimbine across all 4 analyses, but they note that the highest-quality data were derived from controlled clinical trials when yohimbine was administered on its own. In their analysis, this included 242 patients across 4 studies. Another systematic review yielded similar results: a meta-analysis of 7 randomized, placebo-controlled trials including 419 patients demonstrated that yohimbine is superior to placebo as a treatment for erectile dysfunction.89 Thus, SOR=A for the evidence in support of yohimbine as a treatment for erectile dysfunction.
Mechanisms of action. Yohimbine is an alpha2-adrenergic antagonist. Its blocking activity increases the release of noradrenaline and the firing rate of noradrenergic neurons in the central nervous system.92
Herb-drug interactions. Yohimbine should not be taken with sibutramine, a serotonin and norepinephrine reuptake inhibitor. The concomitant use of the 2 products could unmask the peripheral effect of sibutramine and produce negative cardiovascular effects.93 Potential interactions also exist with heart or blood pressure medications,94 lithium,95 morphine,96 and alcohol.97
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Yohimbine is superior to placebo as a treatment for erectile dysfunction
Adverse effects. Adverse effects are not common with yohimbine; however, they may include headaches, sweating, agitation, hypertension, and restlessness.98 Yohimbine has also been reported to contribute to psychotic symptoms, mania, and seizures, though such occurrences are not well documented.9
